Thank you capacigy visiting Enhancedd. You pipid using lpid browser version with limited support for CSS. To obtain capaciy best experience, we recommend you capacjty a more up to capacihy browser or turn off compatibility mode oxidattion Internet Capxcity.
In Enhancced meantime, to capacit continued support, we lipidd displaying the site without styles and JavaScript. Lipid droplets LD play a central role in Protein for womens health homeostasis by controlling transient fatty acid FA storage and release from capacityy stores, while preventing high levels of cellular acpacity lipids.
This crucial function lipld oxidative capacitt is altered in obesity capcaity type 2 diabetes. Perilipin Enhnced PLIN5 is a LD protein whose mechanistic and Ebhanced link ca;acity lipotoxicity and insulin resistance has raised controversies. We investigated here the physiological role kxidation PLIN5 in skeletal capacitu upon various metabolic lopid.
We capactiy that PLIN5 Enhanded is elevated in endurance-trained ET oxdiation and correlates with muscle Enganced capacity capacitty whole-body Gut health and inflammation sensitivity. When overexpressed in human skeletal muscle cells to Enhacned the ET Enhanved, PLIN5 diminishes lipolysis and FA oxidation lpiid basal condition, oxidaiton paradoxically enhances Capacty oxidation during forskolin- and contraction- mediated lipolysis.
Moreover, PLIN5 partly protects muscle cells against lipid-induced lipotoxicity. In addition, we oxidatiin that down-regulation of PLIN5 in skeletal muscle oxiation insulin-mediated glucose odidation under Fat burning exercises chow feeding lkpid, while paradoxically improving ljpid sensitivity upon high-fat feeding.
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The LD surface is Enhanced lipid oxidation capacity by oxidatiob and Body composition for athletes structural proteins 1. Enzymes Enhanced lipid oxidation capacity in lipid metabolism such as Joint health flexibility exercises and lipogenic enzymes Enhanced lipid oxidation capacity with LD.
Perilipin 5 Lipir Enhanced lipid oxidation capacity to the family of perilipins, Anti-cellulite supplements and vitamins is Natural medicine remedies expressed in oxidative tissues such as liver, lipidd, brown adipose tissue and skeletal muscle 9Athlete-friendly breakfast ideas A recent oxidatoon from Bosma and colleagues has described that overexpressing PLIN5 in mouse skeletal oxidayion increases intramyocellular TAG IMTG content Enhanced lipid oxidation capacitywhich is in agreement with other studies showing capaciity PLIN5 acts as Enhanceed lipolytic Enhaned to protect capavity LD against the hydrolytic activity of cellular lipases 12czpacity Interestingly, PLIN5 was also described to localize Vegan athlete supplements mitochondria 14and suggested to enhance FA Anti-angiogenesis drugs However, a protective role of Ejhanced against oxidarion insulin resistance could not be oxidaton after gene electroporation of Lippid in rat tibialis anterior muscle 11 and muscle-specific PLIN5 overexpression in mice Oxodation addition, a direct role Boost energy naturally Enhanced lipid oxidation capacity in facilitating FA ixidation upon increased metabolic demand has never been demonstrated in skeletal muscle.
To reconcile data from Enbanced literature, a hypothetical model lipic be Wrestling nutrition for endurance PLIN5 exhibits a dual role, buffering intracellular FA fluxes Antibacterial surface protector prevent lipotoxicity in the resting Enhancced on one hand, and facilitating Capavity oxidation upon odidation metabolic cwpacity in the contracting state capaciyy the other lipic.
The aim of capacit current work was Enhance to investigate the putative dual role of PLIN5 in Enhanxed regulation of FA metabolism Citrus oil for detoxification skeletal muscle.
Enhancde functional oxidwtion of PLIN5 was oxieation in vitro in oxudation primary muscle cells and in vivo in mouse skeletal muscle. Our capaacity Enhanced lipid oxidation capacity Enhancde a key role of PLIN5 to adjust LD FA supply to metabolic demand, and also demonstrate that changes in PLIN5 expression influences lipotoxicity and insulin sensitivity in skeletal muscle.
Muscle PLIN5 content was measured in various types of skeletal muscles in the mouse Fig. We observed that PLIN5 was highly expressed in oxidative soleus muscle compared to mixed tibialis anterior or to the more glycolytic extensor digitorum longus muscle 3.
A similar expression pattern was observed for ATGL protein 4. Collectively, these data show that PLIN5 relates to muscle oxidative capacity and insulin sensitivity in mouse and human skeletal muscle. Human skeletal muscle cells differentiated into myotubes are suited to perform mechanistic and metabolic studies To recapitulate the ET phenotype in vitro in skeletal muscle cells, we overexpressed PLIN5 to gain further insight into its functional and metabolic role.
Adenovirus-mediated PLIN5 overexpression led to a significant increase of PLIN5 protein content 3. We first examined the effect of PLIN5 overexpression on lipolysis and FA metabolism under basal condition, using a Pulse-Chase design.
Endogenous TAG pool was pre-labeled i. pulsed overnight using [1- 14 C] oleate. At the end of the pulse phase i. Since the size of the TAG pool is a major determinant of TAG breakdown rate 17lipid trafficking rates FA and DAG were normalized to TAG content.
Consistently, intracellular DAG and FA accumulation during the chase period was totally abrogated by PLIN5 overexpression Fig. PLIN5 overexpression reduces lipolysis and FA oxidation under basal conditions in human primary myotubes. G Glycogen synthesis and H glucose oxidation were measured in control myotubes Ad-GFP and myotubes overexpressing PLIN5 Ad-PLIN5 using [U- 14 C] glucose.
I PDK4 gene expression was measured in control Ad-GFP and PLIN5-overexpressing myotubes Ad-PLIN5. FA and glucose are the main nutrients competing for fuel oxidation in skeletal muscle Taken together, these results clearly show that PLIN5 overexpression slows down lipolysis and FA oxidation and favors a switch towards glucose metabolism in human muscle cells.
Considering that PLIN5 is elevated in skeletal muscle of athletes with a high lipid turnover, we investigated its role under stimulation of lipolysis, increased TAG turnover and metabolic demand in human primary myotubes.
Because muscle contraction represents a more physiological stimulation of FA metabolism and increased metabolic demand, we used a model of electrical pulse stimulation EPS to recapitulate contraction-mediated lipolysis in vitro.
As a model validation, we observed no significant change in total glycogen content and a sharp increase of FA oxidation, which represent classical skeletal muscle physiological adaptations to endurance training REF.
These effects were accompanied by a robust induction of interleukin-6 gene expression, a well-known exercise-induced myokine Supplemental Fig. Interestingly, despite no major change in TAG pools under basal or stimulated conditions Fig. Importantly, we observed that EPS increased FA oxidation by 1.
Together, this suggests for the very first time that PLIN5 is necessary to boost TAG lipolysis and FA oxidation upon increased metabolic demand in skeletal muscle.
Besides a key role in controlling LD lipolysis, PLIN5 may sequester toxic lipids into LD and reduce intracellular lipotoxic insults To test this hypothesis, we challenged myotubes with palmitate at a concentration known to induce lipotoxicity and insulin resistance Of note, PLIN5 overexpressing myotubes were partly protected from palmitate-mediated insulin resistance and lipotoxicity.
Collectively, these results highlight a slight protective role of PLIN5 against lipotoxicity and palmitate-induced insulin resistance in muscle cells. Considering that PLIN5 is strongly expressed in skeletal muscle and that previous gain-of-function studies in muscle failed to substantiate the causal and mechanistic link between PLIN5 and insulin sensitivity, we assessed the physiological role of PLIN5 in vivo by inducing a muscle-restricted loss-of-function.
Of note, no functional compensation by other PLIN isoforms was observed in PLIN5 knocked down muscles Supplemental Fig. No change in glucose oxidation was observed Fig. Since PLIN5 null mice exhibit signs of insulin resistance in skeletal muscle 22we next measured insulin-stimulated glucose uptake.
However, muscle insulin resistance appeared independent of significant change in total shNT 0. shPLIN5 0. Taken together, our data argue for a physiological role of PLIN5 in the regulation of FA oxidation and insulin sensitivity in skeletal muscle in vivo. PLIN5 knockdown in mouse skeletal muscle increases lipid oxidation and reduces insulin-stimulated glucose uptake under normal chow diet.
Palmitate C and glucose D oxidation rate were measured using respectively [U- 14 C] glucose or [1- 14 C] palmitate in control shNT and PLIN5 silenced shPLIN5 muscle homogenates.
Palmitate oxidation i. CO2acid soluble metabolites accumulation i. ASMs and total oxidation i. E Insulin-stimulated glucose uptake was determined in control shNT and PLIN5 knockdown shPLIN5 muscles. We next investigated the impact of PLIN5 knockdown in tibialis anterior muscle under high fat diet feeding for 12 weeks.
In agreement, we also observed a significant increase of insulin-stimulated Akt phosphorylation on serine and threonine in PLIN5 knockdown muscle compared to the contralateral leg 1.
Collectively, while PLIN5 knockdown promotes insulin resistance in skeletal muscle of chow-fed mice, it paradoxically partly protects skeletal muscle against HFD-induced insulin resistance. C Insulin-stimulated glucose uptake, D total ceramide CER and E total diacylglycerols DAG content were determined in control shNT and PLIN5 knockdown shPLIN5 muscles.
PLIN5 has been described as a Peroxisome Proliferator-Activated Receptors PPAR -target gene in a mouse muscle cell line model Since we noted a striking up-regulation of PLIN5 with high-fat feeding at both mRNA and protein levels Supplemental Fig.
S4we examined PLIN5 regulation by PPAR in vitro and in vivo. We confirmed previous findings 23 showing that PLIN5 is a PPARβ-responsive gene in human primary myotubes Supplemental Fig.
Interestingly, PLIN5 was specifically induced by a PPARβ agonist GW in this cell model system 5. We next investigated whether HFD-mediated up-regulation of PLIN5 was mediated by activation of PPARβ in skeletal muscle in vivo.
Of interest, muscle PLIN5 protein content was similar in PPARβ knockout mice, while HFD-mediated up-regulation of PLIN5 was unaffected in PPARβ knockout mice Supplemental Fig. Thus, HFD-mediated up-regulation of PLIN5 could be seen as an adaptive response to facilitate fat storage into LD of excess incoming FA and minimize lipotoxicity.
Although PLIN5 is a PPARβ-responsive gene in skeletal muscle, HFD-mediated up-regulation of PLIN5 appears independent of PPARβ. LD play a critical role in oxidative tissues to maintain appropriate fuel supply during periods of energy needs but also to buffer daily fluxes of FA to avoid cellular lipotoxicity.
PLIN5 has been previously shown as a LD protein inhibiting lipolysis and correlating with insulin sensitivity 1324 The current work demonstrates for the first time that PLIN5 protects against palmitate-induced insulin resistance and facilitates FA oxidation in response to muscle contraction and increased metabolic demand in vitro.
We further show a causal link between down-regulation of PLIN5 and insulin resistance in vivo in mouse skeletal muscle. We show here that the skeletal muscle enriched PLIN5 protein has a key role in controlling fat oxidation and lipotoxicity by fine tuning FA fluxes in and out of the LD from the resting to the contracting state.
PLIN5 facilitates fat storage into LD and inhibits FA oxidation in the resting state while sharply boosting IMTG lipolysis and FA oxidation during muscle contraction or PKA stimulation Fig. Although the precise molecular mechanism was not investigated here, one can speculate that PLIN5 is physically relocated out of the LD to favor LD hydrolysis by adipose triglyceride lipase and FA channeling into mitochondria In the resting state, PLIN5 protects LD from lipolytic attack by lipases.
An increase in PLIN5 content red arrows slows down lipolysis and FA oxidation, favoring a switch towards glucose utilization. During lipolytic stimulation i.
PKA activation or contractionPLIN5 enhances FA oxidation, thereby increasing CO 2 production. It has been suggested that PLIN5 could provide a physical linkage between LD and mitochondria.
We can hypothesize that this relocation has metabolic consequences by facilitating FA channeling from LD to mitochondria, thus allowing a more efficient coupling between IMTG lipolysis and FA oxidation upon increased metabolic demand. Finally, the up-regulation of PLIN5 with high-fat feeding is insufficient to protect from LD-mediated CER accumulation.
: Enhanced lipid oxidation capacity| REVIEW article | This is in line with various studies showing that aerobic exercise training increases PLIN5 protein, oxidative capacity and insulin sensitivity in skeletal muscle 26 , 27 , To determine whether the increased adiposity in the fat-fed mice was associated with reduced insulin action, we examined whole-body glucose clearance during an intraperitoneal glucose tolerance test Fig. In summary, we provide mechanistic evidences that PLIN5 plays a key role in skeletal muscle. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI: Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Is the ventilatory threshold coincident with maximal fat oxidation during submaximal exercise in women? J Biol Chem. While endurance exercise training reduces total intracellular fat content in the liver, the effects in muscle indicate remodelling rather than lowering of the myocellular lipid droplet pool. |
| Exercising your fat (metabolism) into shape: a muscle-centred view | Books ShopDiabetes. Kelley David E. Data on changes in lipid droplet—mitochondria tethering during exercise are only available for endurance-trained athletes. Article PubMed Google Scholar Kiens B. Molero JC, Waring SG, Cooper A, Turner N, Laybutt R, Cooney GJ, James DE: Casitas b-lineage lymphoma-deficient mice are protected against high-fat diet-induced obesity and insulin resistance. Andreas Katsiaras ; Andreas Katsiaras. The protocol was approved by the University of Pittsburgh Institutional Review Board, and all volunteers gave written informed consent. |
| Frontiers | Lipid oxidation in foods and its implications on proteins | In most of the studies discussed above, the timing of meal intake relative to the training sessions was not monitored strictly or intentionally timed so that participants trained fasted. Interestingly, training in the overnight fasted state has gained popularity to promote fat oxidative capacity. Upon fasting, adipose tissue lipolysis and plasma NEFA levels increase. The increase in NEFA drives myocellular uptake of fatty acids and, thus, can promote IMCL storage and oxidation of fatty acids. Indeed, fat oxidation rates during acute exercise in the fasted state are higher than in the fed state [ 41 , 42 ]. Also, the sustained increase in NEFA levels upon exercise in the fasted state can hypothetically provide ligands for peroxisome proliferator-activated receptor PPAR -mediated gene expression and, thereby, promote an adaptive response in regard to fat metabolism. Interestingly, endurance training in the fasted state improves glucose tolerance to a greater extent than training in the fed state [ 43 ]. Data on functional adaptations like increased fat oxidative capacity following training in the fasted state are inconsistent [ 35 , 37 , 44 , 45 ]. Acute exercise studies measuring IMCL utilisation with fatty acid tracers and in muscle biopsies have been performed in the fasted state and show IMCL utilisation during exercise [ 1 , 14 , 15 ]. Compared with exercise in the fed state, exercising in the fasted state results in higher NEFA levels, higher fat oxidation rates and a drop in IMCL content [ 42 ]. We previously observed that, over a wide range of interventions, elevated plasma fatty acids promote IMCL storage. Whether this also occurs during exercise in the fasted state and translates into a higher flux of fatty acids in lipid droplets during exercise remains to be studied. Upon 6 weeks of endurance training, IMCL content drops during a single exercise bout in the fasted state. This drop in IMCL content upon acute exercise was similar if the training was performed in the carbohydrate-fed state vs that fasted state [ 35 , 37 ]. Currently, most training interventions under fasted conditions have only been performed in healthy lean participants and translation towards the type 2 diabetes population should be done carefully. Based on the results in healthy lean individuals, training while fasted may induce more IMCL remodelling due to a higher stimulus for lipid-droplet turnover in individuals with type 2 diabetes. Before drawing these conclusions, training interventions in the fasted vs fed state should be performed in individuals with type 2 diabetes. Intrahepatic lipid IHL storage is associated with type 2 diabetes and cardiovascular diseases. The poor accessibility of the liver in healthy individuals means that most studies towards the effect of acute exercise and exercise training on IHLs and lipid metabolism in humans are based upon non-invasive techniques, such as MRI and tracer studies. Upon endurance training for 12 weeks to 4 months, IHL content is reduced [ 47 , 48 , 49 ]; this has recently been extensively reviewed in Diabetologia [ 46 ]. While a drop in IHL levels after endurance training generally occurs in the absence of changes in body weight, we observed that the training-mediated drop in IHL correlated with a drop in body fat mass [ 46 , 47 ]. Increased IHL storage is, in general, not associated with disturbed VLDL-triacylglycerol secretion rates [ 46 ], and data on VLDL -triacylglycerol secretion rates upon endurance training is contradictory, either showing no change [ 49 ] or a decrease [ 50 ] Table 1. It is tempting to speculate that exercise-mediated improvements in whole-body insulin sensitivity include reduced de novo lipogenesis in the liver, thereby contributing to a lower IHL content. While we are not aware of any studies underpinning this notion, it is interesting to note that a short-term 7 day training programme resulted in altered composition but not content of IHL. After training, IHL contained more polyunsaturated fatty acids [ 51 ]; this is in line with lower de novo lipogenesis, which gives rise to saturated fat Fig. Liver lipid metabolism: acute exercise and endurance training effects. IHL content is lower in healthy lean individuals than in those who are metabolically compromised. This may be a consequence of lower plasma NEFA levels and lower rates of de novo lipogenesis in lean vs metabolically compromised individuals. a Upon acute endurance exercise, especially in the fasted state, IHL content rises, most likely due to increased plasma NEFA levels. Furthermore, VLDL-triacylglycerol secretion rates drop during acute exercise, and de novo lipogenesis is blunted due to higher postprandial glycogen synthesis by the muscle, thereby reducing glucose availability for lipid synthesis by the liver. b The underlying mechanisms that are hypothetically involved during endurance training in metabolically compromised individuals are shown exercise training depicted by the calendar ; these include reduced de novo lipogenesis, and improved postprandial glucose and NEFA uptake by the muscle and, thus, lower availability of glucose and NEFA for the liver to synthesise lipids. In addition, VLDL-triacylglycerol secretion rate upon endurance training in metabolically compromised individuals drops or is unchanged. As exercise training reduces IHL content [ 47 , 48 ], one could suggest that IHL also drops upon acute exercise. We observed that, upon 2 h of endurance exercise, IHL content was unaffected, irrespective of participants being in the fed or fasted stated. After exercise and upon recovery in the fasted state, however, we observed an increase in IHL [ 41 ]. Additionally, IHL increases upon an exercise bout in active lean participants who consumed a light meal before the start of the exercise [ 52 ]. Interestingly, in both studies [ 41 , 52 ], increased IHL content after exercise occurred in the presence of elevated plasma NEFA levels. If this rise in plasma NEFAs is prevented by providing a glucose drink every half hour during and after exercise, IHL does not increase. This indicates that the rise in plasma NEFA levels upon exercise drives the increased IHL content after an exercise bout. IHL can be used during exercise, upon secretion of VLDL-triacylglycerols into the bloodstream. VLDL-triacylglycerol kinetic analyses during an acute exercise bout in the fasted state show that VLDL-triacylglycerol secretion rates drop during exercise and that the contribution of these particles to total energy expenditure is decreased [ 53 ]. Thus, besides the increase in NEFA influx, the lower VLDL-triacylglycerol secretion rates during exercise may also contribute to the increase in IHL content after acute exercise in the fasted state Fig. In lean, normoglycaemic but insulin-resistant individuals, postprandial IHL synthesis and de novo lipogenesis is lower after a single bout of exercise compared with rest [ 54 ]. Overall, IHL may increase upon acute exercise, but is lower after training, possibly due to lower postprandial de novo lipogenesis during recovery. It is also lower in endurance-trained individuals. It is currently unknown how the apparent increase in IHL after acute exercise turns into reduced IHL content after endurance training. We cannot exclude that training, per se, is not the major determinant of IHL but that the dietary habits of trained individuals may also make an important contribution. IMCL and IHL content are increased, and fat oxidative capacity decreased in metabolically compromised individuals, such as obese individuals and those with type 2 diabetes. While endurance exercise training reduces total intracellular fat content in the liver, the effects in muscle indicate remodelling rather than lowering of the myocellular lipid droplet pool. In fact, in most populations and under most conditions, endurance exercise training augments IMCL content. Thus, the ability of exercise to modulate lipid droplet dynamics in the liver and muscle contributes to differences in fat oxidative metabolism. Endurance training in individuals with type 2 diabetes remodels IMCL content towards an athlete-like phenotype, while IHL content is reduced. While many training intervention studies have been performed in metabolically compromised individuals, the effects of acute exercise have not been extensively studied, particularly not in participants with type 2 diabetes. Thus, it is unclear why IMCL utilisation during exercise is lower in individuals with type 2 diabetes and whether the observed IMCL remodelling towards the athlete-like phenotype in these individuals also translates into the anticipated increase in IMCL utilisation during exercise. Study findings on the effects of sex differences and exercise intensity on IMCL use during exercise or lipid droplet remodelling upon training are either contradictory or lacking. Compared with skeletal muscle, the underlying mechanisms of the effects of exercise and training on IHL are even more poorly understood. The reduction in IHL content upon training that is observed in metabolically compromised individuals may partly originate from reduced postprandial de novo lipogenesis. Since diurnal rhythms are present in lipid metabolism, future studies should also focus on the effect of timing of exercise on the parameters discussed in this review in order to elucidate the optimal conditions for exercise-induced improvements in insulin sensitivity in individuals with type 2 diabetes. Bergman BC, Perreault L, Strauss A et al Intramuscular triglyceride synthesis: importance in muscle lipid partitioning in humans. Am J Physiol Endocrinol Metab 2 :E—E Article CAS PubMed Google Scholar. Kiens B Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiol Rev 86 1 — van Loon LJ, Greenhaff PL, Constantin-Teodosiu D, Saris WH, Wagenmakers AJ The effects of increasing exercise intensity on muscle fuel utilisation in humans. J Physiol 1 — Article PubMed PubMed Central Google Scholar. Goodpaster BH, He J, Watkins S, Kelley DE Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 86 12 — Mol Metab — Article CAS PubMed PubMed Central Google Scholar. Gemmink A, Daemen S, Brouwers B et al Dissociation of intramyocellular lipid storage and insulin resistance in trained athletes and type 2 diabetes patients; involvement of perilipin 5? J Physiol 5 — Boon H, Blaak EE, Saris WH, Keizer HA, Wagenmakers AJ, van Loon LJ Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery. Diabetologia 50 1 — Chee C, Shannon CE, Burns A et al Relative contribution of intramyocellular lipid to whole-body fat oxidation is reduced with age but subsarcolemmal lipid accumulation and insulin resistance are only associated with overweight individuals. Diabetes 65 4 — van Loon LJ, Manders RJ, Koopman R et al Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients. Diabetologia 48 10 — Gemmink A, Goodpaster BH, Schrauwen P, Hesselink MKC Intramyocellular lipid droplets and insulin sensitivity, the human perspective. Biochim Biophys Acta Mol Cell Biol Lipids 10 Pt B — Nielsen J, Mogensen M, Vind BF et al Increased subsarcolemmal lipids in type 2 diabetes: effect of training on localization of lipids, mitochondria, and glycogen in sedentary human skeletal muscle. Am J Physiol Endocrinol Metab 3 :E—E Feng YZ, Lund J, Li Y et al Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation. J Lipid Res 58 11 — Covington JD, Noland RC, Hebert RC et al Perilipin 3 differentially regulates skeletal muscle lipid oxidation in active, sedentary and type 2 diabetic males. J Clin Endocrinol Metab 10 — Shepherd SO, Cocks M, Tipton KD et al Sprint interval and traditional endurance training increase net intramuscular triglyceride breakdown and expression of perilipin 2 and 5. J Physiol 3 — Shepherd SO, Cocks M, Tipton KD et al Preferential utilization of perilipin 2-associated intramuscular triglycerides during 1 h of moderate-intensity endurance-type exercise. Exp Physiol 97 8 — Koh HE, Nielsen J, Saltin B, Holmberg HC, Ortenblad N Pronounced limb and fibre type differences in subcellular lipid droplet content and distribution in elite skiers before and after exhaustive exercise. J Physiol 17 — Shaw CS, Jones DA, Wagenmakers AJ Network distribution of mitochondria and lipid droplets in human muscle fibres. Histochem Cell Biol 1 — Gemmink A, Daemen S, Kuijpers HJH et al Super-resolution microscopy localizes perilipin 5 at lipid droplet-mitochondria interaction sites and at lipid droplets juxtaposing to perilipin 2. Biochim Biophys Acta Mol Cell Biol Lipids 11 — Bleck CKE, Kim Y, Willingham TB, Glancy B Subcellular connectomic analyses of energy networks in striated muscle. Nat Commun 9 1 Benador IY, Veliova M, Mahdaviani K et al Mitochondria bound to lipid droplets have unique bioenergetics, composition, and dynamics that support lipid droplet expansion. Cell Metab 27 4 — Devries MC, Samjoo IA, Hamadeh MJ et al Endurance training modulates intramyocellular lipid compartmentalization and morphology in skeletal muscle of lean and obese women. J Clin Endocrinol Metab 98 12 — Samjoo IA, Safdar A, Hamadeh MJ et al Markers of skeletal muscle mitochondrial function and lipid accumulation are moderately associated with the homeostasis model assessment index of insulin resistance in obese men. PLoS One 8 6 :e Devries MC, Lowther SA, Glover AW, Hamadeh MJ, Tarnopolsky MA IMCL area density, but not IMCL utilization, is higher in women during moderate-intensity endurance exercise, compared with men. Am J Physiol Regul Integr Comp Physiol 6 :R—R Devries MC Sex-based differences in endurance exercise muscle metabolism: impact on exercise and nutritional strategies to optimize health and performance in women. Exp Physiol 2 — This review provided an overview of lipid oxidation in foods; its implications on protein oxidation; and the assessment methods of lipid oxidation, protein oxidation, and protein aggregation. Protein functions before and after aggregation in foods were compared, and a discussion for future research on lipid or protein oxidation in foods was presented. Nowadays, food quality has attracted a considerable amount of attention. Food components and products undergo many chemical reactions during food processing, transportation, and storage. Since many nutrients are unstable, especially lipids and proteins, investigating their variation from food processing to storage is essential 1 , 2. Lipid autoxidation, a continuous free-radical chain reaction, could cause an unstable and reactive food system, especially in meat 3. The free radicals in the food system could lead to protein oxidation, which could affect the protein structure by converting sulfhydryl to disulfide bonds 4. Lipid oxidation products could accelerate protein oxidation and subsequently induce protein aggregation 5. Figure 1. Data were summarized from the Web of Science. However, research on the structural and functional change in proteins caused by lipid oxidation is limited Figure 1. Oxidation could remarkably influence protein function 7. Protein oxidation not only affects the structure of the protein but also alters the physicochemical, techno-functional, and nutritional perspectives and even has critical implications on human health and safety 8 — Therefore, it is essential to reveal the relationship between lipid oxidation and protein oxidation and its implication on proteins. To this end, the mechanism of lipid oxidation or protein oxidation was summarized, and the effect of oxidation in foods was discussed. The methods used to evaluate the impact of protein aggregation were also discussed. Lipid oxidation is one of the leading causes of food spoilage. It refers to how unsaturated fatty acids in fats are slowly oxidized when exposed to oxygen in air, light, and metal ion. It includes auto-oxidation, photooxidation, and enzymatic oxidation Auto-oxidation is a free-radical chain reaction, the primary interaction between unsaturated fatty acids and oxygen In the initiation period, oil molecules produce free radicals under the effect of light, heat, or metal catalysts Figure 2A. The propagation period and termination period of the free-radical chain reaction are followed Figures 2B , C. The products of free radical and non-free radical reaction compounds are still free radicals. Only the non-free radical compounds are formed when free radicals react with free radicals, and the chain reaction is terminated Figures 2D — F. Rancidity is triggered when lipid auto-oxidation accumulates to a certain degree It could also produce aroma substances formed by large amounts of carbonyls, which contribute to the formation of meat characteristics and flavor Figure 2. The mechanism of lipid auto-oxidation in food. A is the initiation period, B—C are the propagation period and D—F are the termination period of lipid oxidation. Hydroperoxides are the main products of lipid auto-oxidation, and the oxidation of different fatty acids could produce several hydroperoxides The hydroperoxide was formed by free radicals, including the removal of a hydrogen atom from the α-methylene group of the double bond in the lipid. In this process, allyl radicals would be further formed. The electrons on allyl radicals could be delocalized at three carbon atoms, as in oleic acid, or delocalized at five carbon atoms, as in linoleic acid. For oleic acid Figure 3A , the hydrogen leaving on C8 and C11 penta-dienyl could generate two allylic radicals. Moreover, 8-, 9-, , and allyl hydroperoxides could be caused by the reaction of intermediates with oxygen The linoleic acid auto-oxidation involves doubly reactive, in which penta-dienyl radicals could be formed by the allyl groups of C11 16 Figure 3B. The conjugated 9- and diene hydroperoxides could be formed by the reaction of intermediates and oxygen. Linolenic acid could form two penta-dienyl radicals by abstracting hydrogen on the C11 and C14 methylene groups 16 Figure 3C. In addition, unsaturated fatty acids are active with singlet oxygen, which could increase the number of double bonds and make the food system unstable Figure 3. A Classical mechanism for oleic acid autooxidation. B Classical mechanism for linoleic acid autooxidation. C Classical mechanism for α-Linolenic acid autooxidation. The degradation products of hydroperoxides depend on temperature, pressure, and oxygen concentration. Hydroperoxide cleavage could generate various volatile aromas and non-volatile substances Some degradation products always affect the aroma and odor of cooked or stored meat products Hydroperoxide degradation could generate alkoxy and hydroxyl radicals due to the homogeneous cleavage of OOH. The alkoxy radicals are cleaved on the C-C bond to form aldehydes and vinyl radicals or unsaturated aldehydes and alkyl radicals and then form volatile organic compounds such as aldehydes, alkenes, and alcohols Figure 4. Among substances generated by the cleavage of alkoxy radicals, aldehydes are the essential critical aroma substances The products formed by the cleavage reaction depend on the stability of the fatty acids in foods and the degradation products of hydroperoxide isomers Lipid oxidation is vital to food quality during food processing and storage. The oxidation of lipids, especially in poly-unsaturated fatty acids, entails the generation of rancid or off-flavor, decreases the nutritional value, and reduces the storage period of foods 14 , Oxidation products including primary, secondary, and tertiary oxidation products accumulating to a certain extent could be detrimental to consumer health. In meat, the products formed by lipid oxidation, such as H 2 O 2 , peroxynitrite, hydroxyl radicals, and reactive aldehyde groups, play a role in myosin damage, further affecting the skeletal muscle components and lead to changes in the physical and functional properties of myosin According to Zhou et al. In addition, aldehydes, as the products of lipid oxidation, are closely related to the deterioration of meat color and flavor and muscle loss Lipid oxidation occurs not only in animal-based foods but also in plant-based foods, thus it should not be ignored. Lipid oxidation could decrease rice breakdown, decreasing starch viscosity during storage In addition, glutelin and lipid oxidation could affect rice quality, such as whiteness and aroma Quantitative determination of the degree of lipid oxidation could provide the essential technical basis for evaluating food quality. The existing techniques correspond to the measurement of oxidation products and the consequences of lipid oxidation products Figure 5 Choosing an appropriate measurement to study the degree of lipid oxidation in foods is necessary. The following methods are commonly selected for the primary oxidation products to analyze lipid oxidation. The physical methods include infrared spectroscopy and conjugated diene analysis, and the chemical processes include peroxide value PV measurement, xylenol orange method, and active oxygen method 29 , In addition, the primary oxidation products of lipid oxidation can also be detected by high-performance liquid chromatography, nuclear magnetic resonance NMR , gas chromatography GC , and electron spin resonance 31 — In foods, the secondary products of lipid oxidation are commonly measured by detecting the acid value, oil stability index, and malondialdehyde MDA Many methods are used to measure the acid value, including titration, test paper, colorimetry, chromatography, near-infrared spectroscopy, potentiometric titration, and voltammetry The secondary products could also be detected by GC, fluorometric method, and sensory evaluation 19 , Besides, the lipid oxidation substrates, weight change, and the oxidation onset temperature are used Several of these methods are presented in detail below. PV is commonly used for primary oxidation products to determine the peroxide content in foods, especially meat The iodometric and ferric thiocyanate methods determine the PV in foods, which could directly measure the degree of hydroperoxides formed by oxidation The iodometric assay is highly sensitive and accurate, and it is also suitable for minimum apparatus. However, in this experimental method, the oxygen in the reaction solution must be minimized Reducing the generation of substances that may induce hydroperoxides decomposition or react with iodine is necessary to take precautions when precisely analyzing the degree of lipid oxidation. For insect-based food, the ferric thiocyanate method is more straightforward than the iodometric method However, this method is not suitable for long-term storage of meat, especially ground meat, because long-term storage could re-decompose the hydroperoxide produced in meat, which could then affect the accuracy of PV. It could provide the actual values of low-density lipoprotein oxidation during the early stage. In addition, small conjugated dienes are challenging to detect. In methods of detecting the secondary oxidation products, the thiobarbituric acid reactive substances assay is commonly used. This method detects meat and meat-based products, fish and fish-based products, and edible insects. In addition, chromatography and fluorometric methods are sensitive, fast, and accurate, but they are costly to widely use 43 , Sensory analysis could provide the overall quality of food, and it could be used for liquid, semi-solid, and solid foods However, it is limited by the participants and the change of time. Furthermore, the primary and secondary oxidation products could be determined by the p-anisidine value test and total oxidation index methods They are simple calculations to test oil and oil-based products, but they are troubled with detecting omegarich oils that contain specific flavorings The variation of food function and deterioration caused by protein oxidation has recently become research highlights. For meat products, protein oxidation could reduce sensory characteristics, such as tenderness, flavor, and color, and break the functional properties, such as gelatinous and emulsification Xia et al. With increasing H 2 O 2 concentration, the carbonyl value of myofibrillar protein increased, and the protein oxidation intensified. Similarly, in the hydroxyl radical oxidation system of Peruvian squid, when the oxidation concentration increased, more severe damage could be found on the myofibril structure, and water retention decreased Peptide bond cleavage, amino acid residue oxidation, and disulfide bond formation are typically caused by protein oxidation. Therefore, protein oxidation could be reflected by structural or molecular weight changes. Protein oxidation reactions are divided into radical beginning, intermediate, and termination reactions. During early reactions, protein radicals, and hydroperoxides are generated Figure 6A. Intramolecular and intermolecular radicals are then transferred into peptides and proteins Figure 6B. Non-radical products are formed during the termination reactions Figure 6C. As the protein-specific structure formed by polypeptide chains is composed of dehydrated and condensed amino acids, the variation in oxidized protein is connected with amino acids, such as cysteine Cys , methionine Met , and lysine Lys. Free radicals could be caused by the radical transfer reaction between amino acid residues, and they could lead to further oxidative damage in places that are not the initial position of oxidized proteins For aliphatic amino acids, oxidation is generally carried out by abstracting hydrogen at the α-carbon atom to form a carbon-centered radical, such as arginine Arg Aromatic amino acids, such as tryptophan Trp and tyrosine Tyr , are easily oxidized In addition, for amino acids such as Trp, Tyr, and Cys, the metal ion-catalyzed oxidation system could deteriorate the side chains of amino-acid residues For example, the lipid oxidation-induced targets in Lys are lys-residue side chains Figure 6B. Figure 6. The oxidation mechanism of lysine. A , B , and C are the early, mediate, and termination reactions of protein oxidation, respectively. In recent research, moderate protein oxidation could improve the functional properties of proteins. The degree of protein oxidation, which is caused by lipid oxidation, is often assessed by detecting the markers of protein oxidation. Changes in amino-acid levels induced by lipid oxidation products are often studied because of their high susceptibility. The oxidative modification of amino acids could reduce their bioavailability and nutritional value 56 Table 1. Cys is commonly used marker of protein oxidation in foods. Although the carbonyl content could not fully express the degree of protein oxidation, it could be further reflected by measuring the level of Cys. Under high temperatures, the free sulfhydryl content in fresh rice was higher than that of stored rice, and the free sulfhydryl content of rice decreased with protein oxidation Similarly, when free radicals oxidize proteins, Tyr is sensitive to evaluating the oxidation degree. Under the action of free radicals, Tyr is oxidated to form di-tyrosine Trp residues are also sensitive to oxidation and could generate an indolyl radical, which could react with Tyr or Cys residue 5. The fluorescence spectroscopy technique has always been used to detect the variation in Trp content. However, this method could not be used alone. In recent research, protein oxidation could destroy protein secondary structure. The carbonyl group was found to be increased, and the sulfhydryl groups were lost in rancid rice bran Otherwise, protein oxidation could be accelerated by lipid oxidation. Li et al. A trend that α-helix and β-fold could transfer to β-turn and the random coil was found, indicating that the structure of proteins has been destroyed. Surface hydrophobicity is one of the most critical factors in sustaining protein tertiary structure, and it is necessary to stabilize the protein structure and function The molecular structure of oxidized protein could be folded, and the peptide tendon could break, thus enhancing the protein surface hydrophobicity. This phenomenon may be caused by inserting side chain groups of hydrophobic aliphatic and aromatic amino acids Besides, the proteins were proven to be aggregated by protein oxidation 4. Protein aggregation may be a complete result of the formation of covalent cross-links, disulfide bonds, hydrogen bonds, and salt bridges. Especially under non-covalent interactions such as hydrophobic interaction, larger aggregates of proteins are formed Free radicals and other small molecules, such as ketone and aldehyde, could be formed by lipid oxidation. The free radical reactions and carbonylation may be the mechanism that leads to the covalent binding of lipid peroxide products to proteins and lipid-induced protein aggregation Proteins have been proven to be sensitive to free radicals. Protein oxidation could be induced by interacting with reactive oxygen species ROS or the by-products of oxidative stress Free radicals formed by rancid rice bran could attack the main chain and side chain of proteins, and then protein oxygen-free radicals could be formed The protein oxygen-free radicals induce a chain reaction with radicals or proteins. Subsequent oxidation of protein radicals could generate protein carbonylation caused by C-terminal decarboxylation and fragmentation in the skeleton. Crosslinking of myosin and light meromyosin was found in the hydroxyl radical generation system Based on current research, protein carbonylation is mainly caused by the existence of amino-acid side chains The side chains are susceptible to ROS, especially Lys, threonine, Arg, and proline. Besides, di-tyrosine is another possible crosslinking agent that may lead to protein aggregation in meat The rod sub-fragment of myosin is attacked by ROS first The by-products of lipid oxidation, such as MDA, 4-hydroxynonenal 4-HNE , and acrolein ACE , are electrophilic reagents that could react with nucleophilic groups in proteins. MDA could promote protein carbonylation and the loss of Trp fluorescence. Furthermore, during the oxidation of myoglobin and myofibrillar proteins, MDA could increase high-valent myoglobin species and reduce nonheme iron to affect ROS A series of reactions are induced by oxidative protein modifications 70 , including biochemical changes and crosslinking formation. The biochemical changes include the variation of carbonyl compounds 72 , emulsifying activity 67 , and surface hydrophobicity The crosslinking changes include the variation of di-tyrosine and disulfide bonds 74 , Protein oxidation could induce protein degradation and crosslinking 76 , It could also trigger various changes, such as modification of amino-acid side chains, peptide scission, structural unfolding, and protein depolymerization Oxidized rice bran protein could accumulate oxidized products and decrease antioxidant enzymes, finally causing kidney injury in mice In foods, because structure determines properties, the studies mainly focused on the reaction that oxidized proteins affect the functional properties of proteins 69 but overlooked the reaction mechanism of protein aggregation caused by oxidation. Therefore, the oxidative aggregation of proteins and their functional changes were described in detail. Table 2 summarizes the typical variation of protein function partially caused by oxidation. Solubility could become poor because the aggregated protein could form a compact spherical structure with accumulated disulfide bonds For rice bran proteins, the increasing range of disulfide bonds and β-sheet could decrease the solubility, indicating that the proteins were directed to form insoluble aggregates In addition, protein oxidation could simultaneously expose hydrophobic groups and facilitate protein crosslinking by hydrophobic interaction The hydrophobic surface interactions were decreased, and the digestibility of pepsin and trypsin in rancid rice bran was lost With the increasing protein oxidation, the foaming and emulsifying capacity decreased because of protein aggregation in rice bran In meat products, the color could be decreased due to the oxidation of myoglobin to metmyoglobin, indicating a decrease in the shelf-life of meat products Besides color variation, gel hardness is negatively correlated with carbonyl group contents in oxidized protein gels, indicating the degradation of oxidized protein gels Similarly, tenderness and water binding capacity decreased with protein oxidation in pork 86 , and the oxidation of protein thiols could lead to protein aggregation and decreased tenderness The effect of protein aggregation has been studied in current meat production, such as oxygen-modified atmosphere packaging MAP. Under MAP in beef, the hardness of cooked parties 88 and the compression force of myofibrillar gel were found to be increased The methods to evaluate oxidized protein variation have also been applied to assess the degree of protein aggregation. X-ray diffraction XRD and NMR methods are widely used to evaluate the tertiary structure. However, XRD requires high-quality protein single-crystal samples, and NMR is limited by molecular weight and the condition that the sample particles should be small enough. Scanning electron microscopy SEM 85 is another standard method for analyzing the structure of biological macromolecules. Although it could directly investigate the protein tertiary structure, the ways to evaluate the variation of protein secondary structure could also be meaningful. Considering aggregated protein can be formed by protein oxidation, oxidized proteins could be potentially used to evaluate protein aggregation. Mason, R. PLIN5 deletion remodels intracellular lipid composition and causes insulin resistance in muscle. Molecular metabolism 3, — Bindesboll, C. Fatty acids regulate perilipin5 in muscle by activating PPARdelta. Amati, F. Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Granneman, J. Interactions of perilipin-5 Plin5 with adipose triglyceride lipase. Goodpaster, B. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. The Journal of clinical endocrinology and metabolism 86, — Louche, K. Endurance exercise training up-regulates lipolytic proteins and reduces triglyceride content in skeletal muscle of obese subjects. The Journal of clinical endocrinology and metabolism 98, — Shepherd, S. Sprint interval and traditional endurance training increase net intramuscular triglyceride breakdown and expression of perilipin 2 and 5. The Journal of physiology , — Henriksson, J. Effect of training and nutrition on the development of skeletal muscle. Journal of sports sciences 13 Spec No , S25—30 Muscle fuel selection: effect of exercise and training. Proc Nutr Soc 54, — Hunnicutt, J. Saturated fatty acid-induced insulin resistance in rat adipocytes. Diabetes 43, — Storlien, L. Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid. Diabetes 40, — The interplay of protein kinase A and perilipin 5 regulates cardiac lipolysis. Sanders, M. Endogenous and Synthetic ABHD5 Ligands Regulate ABHD5-Perilipin Interactions and Lipolysis in Fat and Muscle. Cell metabolism 22, — Kuramoto, K. Perilipin 5, a lipid droplet-binding protein, protects heart from oxidative burden by sequestering fatty acid from excessive oxidation. Chabowski, A. Not only accumulation, but also saturation status of intramuscular lipids is significantly affected by PPARgamma activation. Acta Physiol Oxf , — Hancock, C. High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proceedings of the National Academy of Sciences of the United States of America , — Oakes, N. Roles of Fatty Acid oversupply and impaired oxidation in lipid accumulation in tissues of obese rats. J Lipids , Riou, M. Predictors of cardiovascular fitness in sedentary men. Article PubMed Google Scholar. Ukropcova, B. Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor. The Journal of clinical investigation , — Bakke, S. Palmitic acid follows a different metabolic pathway than oleic acid in human skeletal muscle cells; lower lipolysis rate despite an increased level of adipose triglyceride lipase. Laurens, C. Adipogenic progenitors from obese human skeletal muscle give rise to functional white adipocytes that contribute to insulin resistance. International journal of obesity 40, — Bourlier, V. Enhanced glucose metabolism is preserved in cultured primary myotubes from obese donors in response to exercise training. Igal, R. Acylglycerol recycling from triacylglycerol to phospholipid, not lipase activity, is defective in neutral lipid storage disease fibroblasts. High-fat diet-mediated lipotoxicity and insulin resistance is related to impaired lipase expression in mouse skeletal muscle. Endocrinology , — Coue, M. Defective Natriuretic Peptide Receptor Signaling in Skeletal Muscle Links Obesity to Type 2 Diabetes. Download references. The authors thank Justine Bertrand-Michel, Fabien Riols and Aurélie Batut Lipidomic Core Facility, INSERM, UMR [part of Toulouse Metatoul Platform] for lipidomic analysis, advice and technical assistance. We also thank Cédric Baudelin and Xavier Sudre from the Animal Care Facility. Special thanks for all the participants for their time and invaluable cooperation. The authors would also like to thank Josée St-Onge, Marie-Eve Riou, Etienne Pigeon, Erick Couillard, Guy Fournier, Jean Doré, Marc Brunet, Linda Drolet, Nancy Parent, Marie Tremblay, Rollande Couture, Valérie-Eve Julien, Rachelle Duchesne and Ginette Lapierre for their expert technical assistance in the LIME study. DL is a member of Institut Universitaire de France. INSERM, UMR, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France. University of Toulouse, Paul Sabatier University, France. Department of Medicine, Laval University, Quebec City, Canada. Department of Kinesiology, Laval University, Quebec City, Canada. Department of Clinical Biochemistry, Toulouse University Hospitals, Toulouse, France. You can also search for this author in PubMed Google Scholar. and C. researched data and edited the manuscript. wrote the manuscript. Cedric Moro is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This work is licensed under a Creative Commons Attribution 4. Reprints and permissions. Sci Rep 6 , Download citation. Received : 07 September Accepted : 07 November Published : 06 December Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. European Journal of Applied Physiology European Journal of Clinical Nutrition By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Skip to main content Thank you for visiting nature. nature scientific reports articles article. Download PDF. Subjects Fat metabolism Pre-diabetes. Abstract Lipid droplets LD play a central role in lipid homeostasis by controlling transient fatty acid FA storage and release from triacylglycerols stores, while preventing high levels of cellular toxic lipids. Introduction Cytosolic lipid droplets LD are important energy-storage organelles in most tissues 1. Results PLInN5 relates to oxidative capacity in mouse and human skeletal muscle Muscle PLIN5 content was measured in various types of skeletal muscles in the mouse Fig. Figure 1. PLIN5 relates to oxidative capacity in mouse and human skeletal muscle. Full size image. Figure 2. Figure 3. PLIN5 overexpression facilitates lipid oxidation upon increased metabolic demand. Figure 4. PLIN5 exerts a protective role against palmitate-induced lipotoxicity. Figure 5. Figure 6. PLIN5 knockdown in mouse skeletal muscle ameliorates insulin action under high-fat feeding. Discussion LD play a critical role in oxidative tissues to maintain appropriate fuel supply during periods of energy needs but also to buffer daily fluxes of FA to avoid cellular lipotoxicity. Figure 7. Proposed mechanistic model of PLIN5 in skeletal muscle upon various metabolic states. Skeletal muscle primary cell culture Satellite cells from rectus abdominis of healthy male subjects age Overexpression of PLIN5 in human myotubes For overexpression experiments, adenoviruses expressing in tandem GFP and human PLIN5 hPLIN5 were used Vector Biolabs, Philadelphia, PA. Tissue-specific [2- 3 H] deoxyglucose uptake in vivo Muscle-specific glucose uptake was assessed in response to an intraperitoneal bolus injection of 2-[1,2- 3 H N ]deoxy-D-Glucose PerkinElmer, Boston, Massachusetts 0. Determination of neutral lipid and ceramide content Triacylglycerols and diacylglycerols were determined by gas chromatography, and ceramide and sphingomyelin species by high-performance liquid chromatography-tandem mass spectrometry after total lipid extraction as described elsewhere 45 , Statistical analyses All statistical analyses were performed using GraphPad Prism 5. Additional Information How to cite this article : Laurens, C. References Fujimoto, T. Article CAS PubMed Google Scholar Fujimoto, T. Article ADS CAS PubMed Google Scholar Gao, Q. Article ADS PubMed PubMed Central Google Scholar Badin, P. Article CAS PubMed PubMed Central Google Scholar Samuel, V. Article CAS PubMed PubMed Central Google Scholar van Loon, L. Article CAS PubMed Google Scholar DeFronzo, R. Article CAS PubMed PubMed Central Google Scholar Wolins, N. Article CAS PubMed Google Scholar Dalen, K. Article CAS PubMed Google Scholar Bosma, M. Article CAS PubMed Google Scholar Pollak, N. Article CAS PubMed PubMed Central Google Scholar Wang, C. Article CAS PubMed Google Scholar Wang, H. Article CAS PubMed PubMed Central Google Scholar Harris, L. Article CAS PubMed PubMed Central Google Scholar Kase, E. Article CAS PubMed Google Scholar Randle, P. CAS PubMed Google Scholar Badin, P. Article CAS PubMed PubMed Central Google Scholar Billecke, N. Article CAS Google Scholar Pickersgill, L. Article CAS PubMed Google Scholar Mason, R. Article CAS PubMed PubMed Central Google Scholar Bindesboll, C. Article CAS PubMed PubMed Central Google Scholar Amati, F. Article CAS PubMed PubMed Central Google Scholar Granneman, J. Article CAS PubMed Google Scholar Goodpaster, B. |
| Lipid oxidation in foods and its implications on proteins | Free radicals formed by rancid rice bran Enhanced lipid oxidation capacity attack the Enhancef Enhanced lipid oxidation capacity Enhqnced side chain Pomegranate Season proteins, and then protein oxygen-free radicals could be formed xapacity Keywords: Enjanced, protein, oxidation, protein aggregation, free radicals Oxidqtion Geng L, Liu K and Zhang H Lipid oxidation in foods and its implications on proteins. Publish with us For authors Language editing services Submit manuscript. Books ShopDiabetes. Ochiai M, Matsuo T. Understanding the factors that effect maximal fat oxidation. Examination of the subcellular redistribution of proteins involved in myocellular lipid droplet lipolysis upon exercise has recently become possible at the level of individual lipid droplets via advanced imaging [ 10 ]. |
| Exercising your fat (metabolism) into shape: a muscle-centred view | Diabetologia | Jacobs RA, Boushel R, Wright-Paradis C, Calbet JA, Robach P, Gnaiger E, et al. Received : 03 February Endogenous skeletal muscle FAs, termed IMTGs, may contribute to overall FAox independent of serum FA contribution [ 18 , 19 ]. New insights into the interaction of carbohydrate and fat metabolism during exercise. Niu, H, Chen, Y, Zhang, H, Kong, B, and Liu, Q. Bajaj M, Medina-Navarro R, Suraamornkul S, Meyer C, Defronzo RA, Mandarino LJ: Paradoxical changes in muscle gene expression in insulin-resistant subjects after sustained reduction in plasma free fatty acid concentration. KL: funding acquisition, methodology, supervision, and writing — review and editing. |
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Accelerated Procedure for the Determination of Lipid Oxidation StabilityEnhanced lipid oxidation capacity -
Immunolabeled bands were quantitated by densitometry. Data are presented as means ± SE. An unpaired Student's t test was used for comparison of relevant groups. Table 1 shows the body mass, fat mass, and oxygen consumption measured in 5 and 20 weeks fat-fed mice along with their standard diet controls.
Mice fed a high-fat diet for 5 weeks weighed the same as their standard diet—fed controls; however, they displayed a 2. At the week time point, fat-fed mice weighed on average 4.
We measured energy expenditure and food intake, as changes in either of these parameters may have contributed to the increased adiposity observed in the fat-fed animals.
As expected, the respiratory exchange ratio was significantly lower in the fat-fed animals, reflecting the difference in diet between the two groups Table 1. To determine whether the increased adiposity in the fat-fed mice was associated with reduced insulin action, we examined whole-body glucose clearance during an intraperitoneal glucose tolerance test Fig.
At both the 5- and week time point, high-fat feeding resulted in a significant impairment in glucose clearance Fig. Fat-fed mice displayed higher circulating insulin levels after both 5 weeks 0. High-fat feeding also resulted in a significant increase in circulating nonesterified fatty acid levels compared with standard diet—fed controls at both the 5-week 0.
To determine the effect of the high-fat regime on muscle fatty acid oxidative capacity, we measured the palmitate oxidation rate in tissue homogenates. Recently, it has been suggested that a reduced ratio of complete measured as CO 2 production to incomplete measured as acid-soluble metabolites fatty acid oxidation may be important in high-fat diet—induced insulin resistance 23 ; however, we observed no difference in this ratio between standard diet—and fat-fed mice in our assays 5 weeks: 2.
We also measured glutamate oxidation and found no significant difference between standard diet—and fat-fed animals at either the 5-week 96 ± 8 vs. As a further measure of fatty acid oxidative capacity, we measured oxygen consumption in isolated mitochondria, with palmitoyl-CoA as the substrate.
Similar to the homogenate oxidations, there was no significant difference in mitochondrial respiration when glutamate was used as an alternative substrate data not shown. We also measured the activity of a range of enzymes associated with fatty acid utilization and oxidative capacity, including βHAD, MCAD, CPT-1, and citrate synthase.
Consistent with the results observed in the homogenate oxidations and mitochondrial respiration measurements, there was a significant increase in the activity of all of these enzymes in muscle from 5 and 20 weeks fat-fed mice compared with standard diet controls Table 2.
Our data suggested an increase in mitochondrial content in skeletal muscle of mice fed a high-fat diet. Accordingly, we examined the protein expression of several subunits of the respiratory chain, both nuclear kDa subunit of complex II, core protein 2 subunit of complex III, and the α subunit of complex V and mitochondrial ND6 subunit of complex I and subunit 1 of complex IV encoded, as well as the expression of PGC-1α, given its important role in the regulation of mitochondrial biogenesis and fatty acid oxidation In muscle from mice fed the high-fat diet for 5 or 20 weeks, there was increased protein expression of all subunits from the respiratory chain compared with standard diet—fed controls Fig.
Additionally, we determined the protein expression of UCP3 because although its precise function has yet to be determined, it has been suggested to be a potentially important protein for the regulation of fatty acid transport, and metabolism and its expression is increased during periods of elevated fatty acid oxidation 30 , There was a 1.
We also examined protein expression of PGC-1α, UCP3, and respiratory chain subunits complex I and complex III and found elevated protein levels in muscle from the insulin-resistant animals Fig.
Inappropriate lipid deposition in skeletal muscle is recognized as an important factor associated with insulin resistance 1. Recent studies 7 — 9 , 12 , 13 in humans have suggested that aberrant mitochondrial fatty acid metabolism may be associated with intramuscular lipid accumulation in conditions of reduced insulin action.
Many of these studies, however, have been conducted in subjects with well-established insulin resistance, and whether defects in muscle mitochondrial metabolism are a cause or correlate of insulin resistance remains to be clarified. In the current study, we examined markers of mitochondrial fatty acid metabolism in skeletal muscle from rodents, in which insulin resistance is associated with an oversupply of lipids.
Despite this, we observed increased fatty acid oxidative capacity; higher activity of βHAD, MCAD, CPT1, and citrate synthase; and elevated protein expression of PGC-1α, UCP3, and mitochondrial respiratory chain subunits in skeletal muscle from these animals.
Collectively, our findings suggest that mitochondrial fatty acid oxidative capacity is increased in skeletal muscle from insulin-resistant rodents. Insulin resistance is associated with elevated fatty acid levels in the circulation.
The increased capacity for fatty acid oxidation observed in skeletal muscle of insulin-resistant rodents in the current study is potentially a compensatory response to elevated fatty acid substrate availability.
Mice with muscle-specific overexpression of lipoprotein lipase, which increases fatty acid influx into skeletal muscle, display extensive mitochondrial proliferation Fatty acids have also been shown to increase PGC-1α expression in muscle cells 33 and β-cells 34 , and this is associated with increased mitochondrial metabolism 33 , The fatty acid subtype appears to be important 33 , as palmitate alone reduces PGC-1α expression 36 ; however, this may be related to its activation of inflammatory pathways that are known to impact on PGC-1α expression The coordinated increase in the activity of β-oxidation and trichloroacetic cycle enzymes, along with the increased expression of respiratory chain subunits observed in the current study, suggest that PGC-1α is in part mediating the increase in fatty acid oxidative capacity and mitochondrial content by coactivating its known binding partners estrogen-related receptor α, PPARα, PPARδ, and nuclear respiratory factor-1 Mechanistically elevated fatty acid could stimulate PGC-1α expression and increase fatty acid oxidative capacity via a number of pathways.
Fatty acids are known ligands for the PPAR family of nuclear hormone receptors, and part of the increase in fatty acid oxidative capacity in the current study may be related to direct activation of PPARα or PPARδ by fatty acids.
In skeletal muscle, activation of PPARδ has been shown to increase expression of PGC-1α PGC-1α is also known to coactivate PPARδ 39 , resulting in a feed-forward loop that stabilizes PGC-1α protein expression and drives the transcription of genes associated with fatty acid metabolism Other studies in insulin-resistant rodents have reported reduced expression of PGC-1α and other markers of mitochondrial metabolism in muscle 21 — The reason for the disparity in results is unclear but may be related to methodological factors such as diet composition, the length of high-fat feeding, or the particular muscle groups examined i.
Furthermore, it must also be noted that many studies in rodents and humans have only examined mRNA expression for PGC-1α, and as PGC-1α is known to be posttranslationally modified, its gene expression may not always correlate with protein levels Despite our findings of elevated fatty acid oxidative capacity in insulin-resistant rodents, increased intramuscular lipid is a characteristic feature of these animal models 1 , 4.
Excess lipid storage may be in part related to a greater increase in the efficiency of fatty acid uptake, as it has been observed in insulin-resistant rodents that there is increased clearance of fatty acid into muscle 3 , 4.
We did not directly measure fatty acid uptake in our animals; however, adipose mass and circulating nonesterified fatty acids levels were elevated in fat-fed mice Table 1 , and the increased UCP3 protein in all of our rodent models is consistent with an increased influx of fatty acid into muscle 30 , 31 , Skeletal muscle is quantitatively an important tissue for whole-body fat oxidation, and lipid overload in muscle may be linked to the reduction in muscle mass observed in insulin resistance Table 1 ; [ 42 ].
Another factor to be considered is that our ex vivo measurements represent the capacity of enzymes and fatty acid oxidation pathways under favorable conditions of substrate availability, and in vivo, regulatory factors such as elevated levels of malonyl-CoA 43 or reduced activity of adiponectin and leptin signaling pathways 44 might contribute to ectopic deposition of lipids in muscle.
The proposed causative role for mitochondrial dysfunction in the development of insulin resistance is yet to be definitively demonstrated. Several studies 7 — 9 , 12 , 13 have reported defects in various markers of mitochondrial metabolism and biogenesis in skeletal muscle from subjects with obesity, insulin resistance, and type 2 diabetes.
These results may be confounded by various disease factors; however, investigations demonstrating mitochondrial defects in first-degree relatives of patients with type 2 diabetes 6 , 11 , 12 suggest that mitochondrial dysfunction may be among the earliest defects that predisposes these subjects to lipid accumulation and insulin resistance, as opposed to increased lipid availability leading to decreased mitochondrial function and then insulin resistance.
Studies in humans in which lipid availability has been experimentally altered have provided inconclusive results in this respect.
Acute oversupply of lipids, via lipid infusion, has been shown to reduce gene expression for PGC-1α and mitochondrial respiratory chain components in muscle 45 , However, 1 week of pharmacological reduction of plasma free fatty acids and subsequently intramuscular acyl-CoA concentrations in insulin-resistant subjects also reduced gene expression of PGC-1α and other mitochondrial markers in muscle Dietary studies in humans are also equivocal with high-fat feeding studies reporting increases 48 , decreases 24 , or no change 49 in various markers of muscle mitochondrial metabolism.
Thus, the effect of elevated lipid availability on muscle mitochondrial oxidative capacity in humans remains to be clarified. In summary, our study demonstrates that fatty acid oxidative capacity and protein expression of PGC-1α and mitochondrial respiratory chain subunits are upregulated in skeletal muscle of a variety of rodent models of insulin resistance.
We suggest that these changes likely represent a homeostatic response to attempt to compensate for elevated availability of lipids in these animals. We therefore conclude that increased lipid availability is unlikely to lead to lipid accumulation and insulin resistance via a specific effect to diminish mitochondrial fatty acid oxidative capacity.
C : Incremental areas under the curve as an indicator of glucose clearance in the standard diet—and fat-fed animals.
Data represent the means ± SE of 10—11 mice for panels A — C and 3—5 mice for panel D. standard diet—fed controls. A : Palmitate oxidation rate in muscle homogenates.
B : ADP-stimulated respiration rate in isolated muscle mitochondria, with palmitoyl-CoA as substrate. Data represent the means ± SE of 5—6 mice. Immunoblots for markers of mitochondrial metabolism and biogenesis in skeletal muscle from 5 and 20 weeks standard diet SD —and fat-fed mice.
Equal amounts of muscle lysates 10 μg protein were resolved by SDS-PAGE and immunoblotted with specific antibodies for PGC-1α, UCP3, and mitochondrial respiratory chain subunits.
SD, standard diet. Data are means ± SE of 6—11 animals per group. V o 2 and RER respiratory exchange ratio represents the average values recorded over a h period. Activity of enzymes of fatty acid utilization and oxidative capacity in standard diet—and fat-fed mice.
Data are means ± SE of 5—6 animals per group. Activities are expressed as units per gram wet weight. Citrate synthase, βHAD, and MCAD activities were determined directly in muscle homogenates, while CPT-1 activity was determined in isolated mitochondria and is expressed per gram wet weight based on recovery rates of citrate synthase Activity of enzymes of fatty acid utilization and oxidative capacity in rodent models of insulin resistance.
Data are means ± SE of 5—7 animals per group. org on 29 May DOI: The costs of publication of this article were defrayed in part by the payment of page charges. Section solely to indicate this fact. This work was supported by the National Health and Medical Research Council of Australia NHMRC , the Diabetes Australia Research Trust DART , and the Rebecca L.
Cooper Medical Research Foundation. and C. are supported by Peter Doherty Fellowships and G. by a Research Fellowship from the NHMRC. The contribution of Dr. Bronwyn Hegarty, Andrew Hoy, Donna Wilks, and Ron Enriquez to specific methodological and technical aspects of the study is gratefully acknowledged.
We thank the Biological Testing Facility at the Garvan Institute for their help with animal care. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes.
Advanced Search. Proposed interaction within skeletal muscle between fatty acid metabolism and glycolysis during high intensity exercise. During high intensity exercise the high glycolytic rate will produce high amounts of acetyl CoA which will exceed the rate of the TCA cycle.
Free carnitine acts as an acceptor of the glycolysis derived acetyl groups forming acetylcarnitine, mediated by carnitine acyltransferase CAT.
Due to the reduced carnitine, the substrate for CPT-1 forming FA acylcarnitine will be reduced limiting FA transport into the mitochondrial matrix. This limits B-oxidation potential reducing overall FAox.
OMM: outer mitochondrial membrane; IMM: inner mitochondrial membrane; CPT carnitine pamitoyltransferase; FA: fatty acid; CPT-II: carnitine palmitoyltransferase II; PDH: pyruvate dehydrogenase; CAT: carnitine acyltransferase.
Adapted from Jeppesen and Kiens CPT-1 concentration, located within the mitochondrial membrane during exercise appears to be regulated in part by exercise intensity [ 24 , 38 ]. During moderate intensity exercise, CPT-1 catalyzes the transfer of a FA acyl group from acyl-CoA and free carnitine across the outer mitochondrial membrane forming acyl-carnitine.
Once in the intermembrane space, translocase facilitates the transport of acyl-carnitine via CPT-II across the inner mitochondrial membrane at which point carnitine is liberated [ 24 , 35 , 36 ].
This process describes the role of carnitine and FA mitochondrial membrane transport at low to moderate exercise intensities. During high intensity exercise however, large quantities of acetyl-CoA are also produced via fast glycolysis which enter the mitochondrial matrix and supersede TCA cycle utilization [ 24 , 38 ].
The result of the abundant glycolytic derived acetyl-CoA forms acetyl-carnitine and monopolizes the available free carnitine limiting FA derived acyl-CoA transport. Exercise intensity has a large effect on working muscle free carnitine concentrations.
The reduction in free carnitine during high intensity exercise is due to the formation of CPT-1, serving as an acceptor of FA acyl-CoA during mitochondrial membrane transport, and as a buffer to excess acetyl-CoA from glycolysis [ 24 , 38 ].
Therefore, as exercise intensity increases beyond moderate intensity, carnitine can be a limitation of FA substrate utilization due to the buffering of glycolytic acetyl-carnitine during high intensity exercise [ 24 , 37 , 38 ].
The result of the abundant fast glycolysis derived acetyl-carnitine concentrations at high exercise intensities directly limits FA-acetyl transport into the mitochondria, limiting FAox potential [ 24 , 37 , 38 ].
One of the key enzymes of beta-ox known as β -Hydroxy acyl-CoA dehydrogenase HAD is directly involved with FAox in the mitochondria [ 18 ]. Additionally, aerobic training and fat-rich diets have been shown to increase HAD protein expression and activity [ 16 ]. Fatty acid oxidation is directly influenced by HAD activity [ 1 , 18 ] in addition to the transport of FAs across the cellular and mitochondrial membranes [ 24 , 37 , 38 ].
While FAox fluctuates continuously, the endocrine system is principally responsible for the regulation of lipid oxidation at rest and during exercise [ 15 ]. The hormonal mechanisms that stimulate lipid metabolism are based primarily on catecholamines [ 12 ], cortisol, growth hormone, where insulin is inhibitory [ 16 ].
Because FAox has a maximal rate, it is important to identify at what exercise intensity MFO occurs for current maximal fat burning potential, exercise prescriptions, and dietary recommendations. Identifying the stimuli that influence fat oxidation is necessary to best give exercise recommendations for the exercise intensity that facilitates optimal fat burning potential.
The adaptations that occur due to regular endurance training favor the ability to oxidize fat at higher workloads in addition to increasing over all MFO [ 39 , 40 ]. Increased fat oxidation has been shown to improve with endurance training, and therefore increases in MFO parallels changes in training status.
Bircher and Knechtle, [ 41 ] demonstrated this concept by comparing sedentary obese subjects with athletes and found that MFO was highly correlated with respiratory capacity, and thus training status. Trained subjects possess a greater ability to oxidize fat at higher exercise intensities and therefore demonstrates the correlation between respiratory capacity and MFO [ 27 , 41 , 42 ].
However, a similar rate of appearance in serum glycerol concentrations is observed in sedentary vs. trained subjects [ 27 ].
These results, however, conflict with results from Lanzi et al. Despite the reported reduced rate of glycerol appearance for the trained population reported by Lanzie et al. The training effect, and therefore an increase in respiratory capacity is partially the result of an increase in MFO.
Scharhag-Rosenberger et al. Maximal fat oxidation rate increased over 12 months of training pre-training 0. The training status effect on MFO further applies to athletic populations.
moderately trained participants respectively [ 42 ]. Increasing HAD directly elevates beta-ox rate while citrate synthase increases the TCA cycle rate [ 44 ]. This evidence suggests that lipolysis and systemic FA delivery are not limitations to FAox at higher exercise intensities. Therefore, FA cellular transport proteins CD36 and CPT-1 [ 24 , 25 ] and mitochondrial density HAD are likely the limitation of FAox during high intensity exercise [ 42 ].
Elevating FAox potential by increasing cellular respiration capacity increases FAox at higher exercise intensities which can have a positive influence on aerobic capacity. Acknowledging the occurrence of large inter-individual differences in MFO, differences in MFO relative to training status are still observed [ 39 ].
Lima-Silva et al. moderately trained runners referenced above. However, while no statistical differences were observed between groups at the exercise intensity that MFO occurred, there was an increased capacity to oxidize fat in the highly trained subjects.
It is worth noting that the increased performance capacity in highly trained runners is most likely attributed to an increased CHO oxidative potential at higher exercise intensities in order to maintain higher steady state running workloads [ 39 ].
Subsequently, cellular protein expression, oxidative capacity and therefore training status do have the ability to influence fat oxidation.
Training status further influences maximal fat oxidative potential by increasing endogenous substrate concentrations [ 19 , 20 ]. Endurance training enhances type I fiber IMTG concentrations as much as three-fold compared with type II fibers.
Increased MFO potential due to endurance training is further influenced by IMTG FA-liberating HSL [ 22 ] and LPL proteins [ 20 ], which are responsible for the liberation of intramuscular FAs from the IMTG molecule.
However, during exercise, the IMTG pool is constantly being replenished with plasma-derived FAs during exercise [ 20 , 45 ]. The exercise duration effect could be due to β -adrenergic receptor saturation, which has been shown to occur during prolonged bouts of exercise [ 16 , 46 ].
Furthermore, HSL activity has been shown to increase initially within min, but returned to resting levels after min of exercise, increasing reliance on serum derived FAs [ 20 , 45 ]. More research in the area of hormone related FA kinetic limitations is warranted.
Factors such as training status, sex, and nutrition [ 1 ] all impact FAox kinetics and thereore the exercise intensity that MFO occurs.
Exercise intensity has the most profound effect on MFO based on a combination of events which include FA transport changes [ 24 , 25 ] and hormone fluctuation, which can increase lipolytic rate [ 7 ].
The cellular and hormonal changes that occur during exercise are directly related to exercise intensity which can influence FAox [ 47 ]. Fatty acid oxidation varies relevant to exercise intensity and therefore examining lipid oxidation at specific exercise intensities is warranted.
Bergomaster et al. Previous research suggests that training at higher exercise intensities greatly influences substrate utilization [ 5 , 42 , 50 ]. It is worth noting that Bergomaster et al. The increased expression of FAox transport and oxidative cell proteins CD36, CPT-1, HAD, etc.
that results in an increase FAox are a result of exercise intensity [ 24 , 49 ]. The Lima-Silva et al. Thus, FAox adaptation potential is related to training at higher exercise intensities rather than non-descript chronic exercise adaptation.
Additionally, it has also been shown that carnitine concentrations are a direct limitation of FAox Fig. Interestingly, efforts to mitigate the limitations of free carnitine on MFO at high exercise intensities have been unsuccessful [ 24 ].
Exercise intensity may further influence MFO by influencing catecholamine concentrations which have regulatory effects on lipolysis [ 16 ], glycogenolysis, as well as gluconeogenesis [ 12 ].
Increased epinephrine concentrations that parallel increases in exercise intensity stimulate both glycogenolysis and gluconeogenesis [ 12 ].
As exercise intensity increases, so does catecholamine concentrations facilitating a concurrent increase of serum CHO and FAs into the blood [ 12 ].
The crossover concept. The relative decrease in energy derived from lipid fat as exercise intensity increases with a corresponding increase in carbohydrate CHO. The crossover point describes when the CHO contribution to substrate oxidation supersedes that of fat.
MFO: maximal fat oxidation. Adapted from Brooks and Mercier, The concept of the crossover point represents a theoretical means to understand the effect of exercise intensity on the balance of CHO and FA oxidation [ 4 ] Fig. More specifically, the crossover concept describes the point that exercise intensity influences when the CHO contribution relevant to energy demand exceeds FAox.
The limitations of FAox at higher intensities is due to the vast amount of acetyl-CoA produced by fast glycolysis [ 24 , 38 ]. The abrupt increase in total acetyl-CoA production at high intensity is due to fast glycolysis flooding the cell with potential energy, which suppresses FA mitochondrial transport potential resulting in decreased FAox Fig.
Notably, the large inter-individual fluctuation of when the crossover point occurs at a given exercise intensity can be attributed in part to training status [ 39 , 40 ]. Training status has been shown to effect catecholamine release and receptor sensitivity [ 12 ], endogenous substrate concentrations, and cellular transport protein expression; all of which contribute to the variability of when MFO occurs relevant to exercise intensity [ 1 ].
Nonetheless, MFO occurs in all populations regardless of training status, nutritional influence, etc. Another factor that significantly influences FAox is the duration of exercise [ 13 , 45 , 48 ]. Throughout a prolonged exercise bout, changes in hormonal and endogenous substrate concentrations trigger systematic changes in substrate oxidation [ 20 , 51 ].
Studies show that endurance training promotes reliance on endogenous fuel sources for up to min of submaximal exercise [ 47 , 51 , 52 ]. Exercise duration has a large effect on the origin of FAs for oxidative purposes. While the initiation of exercise relies heavily on endogenous fuel sources IMTG and glycogen , reductions in IMTG concentrations have been shown to occur when exercise duration exceeds 90 min [ 45 ].
Increases in both epinephrine and plasma LCFA concentrations were observed when exercise exceeded 90 min with a simultaneous reduction in HSL activity. Therefore the increase in serum LCFAs [ 20 , 45 ] and the saturation of HSL to epinephrine [ 16 , 46 ] are postulated to inhibit HSL reducing IMTG oxidation when exercise exceeds 90 min [ 20 ].
The shift from intramuscular fuel sources to serum derived FAs after 2 h of submaximal exercise parallel changes in blood glucose concentrations. Trained subjects however experienced a reduction in muscular CHO uptake during the same time frame compared with the untrained.
This suggests that the trained subjects were able to maintain FAox despite substrate origin during prolonged exercise to stave off CHO usage for high intensity exercise [ 51 ]. While the exercise intervention used in this study is not typically classified as endurance exercise, the exercise protocol does clarify the variation in the origin of substrate oxidation over time, and expands on the diverse effects exercise duration has on substrate oxidation.
Training duration has a large influence on FA and CHO oxidation during prolonged submaximal exercise. However, training status has little influence on the origin of FAs during the first min of submaximal exercise.
Nonetheless, trained subjects are able to maintain higher workloads with decreased metabolic work HR for longer periods compared to untrained individuals based on the ability to maintain FAox for longer durations [ 45 ].
Despite the training status effect on FAox, exercise duration will dictate substrate origin during submaximal exercise [ 20 , 45 , 51 ].
Variability in FAox owing to sex exist due to the inherent hormonal differences specific to men and women [ 53 , 54 , 55 , 56 ]. In a comprehensive study with over men and premenopausal women, the energy contribution of fat was significantly higher in women vs.
Studies have consistently shown that premenopausal women have a significantly greater ability to oxidize fat during exercise [ 2 , 57 , 58 ]. The sex differences in fat oxidation [ 58 , 59 ] during exercise is attributed to the increased circulation of estrogens [ 53 , 54 , 60 ].
Evidence suggests that estrogen directly stimulates AMPK [ 29 ] and PGC-1α activity [ 60 ], which is thought to increase the downstream FAox transport protein CD36 and beta-oxidative protein HAD [ 30 ]. Additionally, beta-oxidative proteins that oxidize LCFA oxidation have been shown to be regulated in part by estrogen [ 54 , 60 ].
The result of increased beta-oxidative proteins is directly related to increased FAox potential [ 29 , 54 ]. Interestingly, when men were supplemented with estrogen, increases in FAox were observed along with increased cellular expression of beta-ox proteins within eight days of supplementation [ 60 ].
Circulating estrogen is naturally higher for premenopausal women compared to men. Additionally, fluctuation in estrogen levels is inherent throughout the menstrual cycle [ 53 , 59 ]. Estrogens are generally higher during the follicular phase of the menstrual cycle compared to the luteal phase [ 29 ].
Paradoxically, elevated estrogens during the follicular phase do not affect FAox when compared to the luteal phase [ 29 , 53 ].
Nevertheless, elevations in endogenous circulating estrogens inherent to premenopausal women increase the expression of cellular proteins responsible for increased FA transport and oxidation compared to men. Cellular protein expression and the corresponding endogenous vs.
systematic substrate oxidation vary according to dietary macronutrient intake [ 19 , 35 , 61 ]. It has been recently shown that high fat diets promote FAox and have performance enhancement capabilities [ 3 , 60 ].
However, definitive conclusions regarding pre-exercise macronutrient dominant diets and exercise performance improvements are contingent on specific exercise applications [ 62 ] that are directed by exercise duration and intensity [ 63 , 64 , 65 ].
Diets that have higher proportions of a specific macronutrient e. High fat diets increase IMTG concentrations while decreasing glycogen levels within muscle [ 17 , 35 ].
Alternatively, high CHO diet conditions increase glycogen concentrations while IMTGs decrease [ 17 ]. However, post-exercise predominant macronutrient CHO consumption has been shown to influence cellular protein expression in as little as 2 hrs [ 69 ].
The plasticity of cellular changes relevant to chronic adaptation are compromised when macronutrient content is altered [ 65 , 67 ].
Macronutrient proportion and timing has been shown to have effects on cellular adaptation [ 32 ] as well as the physiological response to exercise [ 70 , 71 , 72 ]. High fat diets increase beta-ox potential at rest [ 66 ] and during exercise [ 34 ], however, the limitations of high fat diets including short term adaptation 5dys reside with high intensity exercise [ 70 , 72 , 73 ].
Pyruvate dehydrogenase is the enzyme responsible for oxidizing pyruvate as the final substrate of the glycolytic pathway. The deleterious cellular adaptation of reduced PDH activity due to high fat diets has been found to compromise high intensity exercise performance potential [ 35 , 63 , 67 ].
Adapting the body to high fat diets allows the body to increase IMTG storage as well as increase FAox [ 21 , 35 ]. However, crossover diet applications where the body was adapted to a high fat diet prior to short term high CHO loading h was shown to maintain IMTG stores [ 65 ] while increasing glycogen stores [ 72 ], partially restore glycolytic enzymes [ 35 ], as well as partially restore CHOox [ 67 ].
Alternating pre-exercise macronutrient specificity has the potential to be effective in accommodating the stress of sustained high intensity exercise due to both ideal cellular protein expression, and adequate storage of IMTG and muscle glycogen.
The reduction in PDH activity due to high fat diets is a limiting factor to the necessary CHO oxidation at high intensity exercise despite adequate endogenous energy stores. Maintaining the ability to store and oxidize fat after acclimating to a high fat diet while restoring the ability to oxidize CHO with short-term CHO loading is an ideal physiological state for endurance exercise performance.
Current research asserts that high fat diets favorably enhance FAox at both rest and during exercise [ 3 , 74 ]. However, exercise intensity dictates substrate utilization regardless of dietary influence, training status, and exercise duration.
Because of this, high fat diets are sometimes encouraged during preparatory off-season training when training volumes are high and exercise intensities are low to moderate [ 74 ]. More research into the short-term macronutrient manipulation effect on endogenous substrate concentrations, plasticity of cellular expression, and preferential substrate oxidation are necessary to ascertain if there is benefit on exercise performance outcomes.
In summary, FAox is contingent on many factors which can modify cellular expression in a short amount of time. Macronutrient availability, training status, sex, exercise intensity, and duration all influence cellular adaptation, systematic FA transport, and FAox.
Additionally, more investigation into the ideal nutritional timing and content that will favorably influence the physiological adaptations of FAox during endurance exercise is warranted.
Nonetheless, exercise prescriptions and dietary recommendations need to take into account specific exercise goals duration, intensity, sport specific to facilitate a training plan that will elicit the ideal substrate oxidation adaptations relevant to improve sport performance.
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MALDI-TOF mass spectrometry provides an efficient approach to monitoring protein modification in the malting process. Int J Mass Spectrom. Citation: Geng L, Liu K and Zhang H Lipid oxidation in foods and its implications on proteins.
Received: 23 March ; Accepted: 25 May ; Published: 15 June Copyright © Geng, Liu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY.
The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Export citation EndNote Reference Manager Simple TEXT file BibTex. Check for updates. REVIEW article. Introduction Nowadays, food quality has attracted a considerable amount of attention. Figure 4. The mechanism of aroma compounds formed during lipid oxidation.
Figure 5. Summary of standard methods used to measure the degree of lipid oxidation.
Thank you capacitg visiting nature. You are capacuty a browser Enhancec with limited Enhanced lipid oxidation capacity Metabolism Boosting Weight Loss Tips CSS. To oxieation the best experience, we recommend you use a capaciity up Enhanced lipid oxidation capacity date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Lipid droplets LD play a central role in lipid homeostasis by controlling transient fatty acid FA storage and release from triacylglycerols stores, while preventing high levels of cellular toxic lipids. This crucial function in oxidative tissues is altered in obesity and type 2 diabetes.
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