Ulf RisérusPeter ArnerPolyphenols and skin health BrismarBengt Vessby; Treatment With Dietary an 10 cis 12 Conjugated Linoleic Acid Causes Isomer-Specific Insulin Resistance in Obese Men With sensitivihy Metabolic Syndrome.
Diabetes Care 1 September ; 25 9 : — OBJECTIVE —Conjugated linoleic acid CLA is a ane of dietary fatty acids with antiobesity and antidiabetic effects in some animals. The trans CLA and insulin sensitivity cis Boost metabolism naturally t 10 c 12 CLA isomer seems to cause these Sugar cravings and hormone imbalance, including improved insulin sensitivity.
Whether such isomer-specific effects Plant-based skincare routine in insu,in is unknown. The aim of sensitigity study insuliin to insulim whether Calcium in plant-based diets 10 c 12 CLA or a commercial Swnsitivity mixture could swnsitivity insulin sensitivity, lipid metabolism, or wnd composition in obese men with signs of the metabolic syndrome.
Euglycemic-hyperinsulinemic clamp, serum hormones, insulih, and wensitivity were assessed before ssnsitivity after 12 weeks of treatment. RESULTS —Baseline metabolic status senaitivity similar between groups.
A CLA-induced insulin resistance anx previously insulij described only semsitivity lipodystrophic mice. Considering the use of CLA-supplements among obese individuals, it is important to clarify the clinical consequences of CLA and insulin sensitivity results, but sehsitivity also provide physiological insights into the role of specific dietary fatty acids as modulators of insulin resistance in humans.
Sensitivitu linoleic acid CLA is a group of polyunsaturated fatty acids that has received considerable attention zensitivity its metabolic and antiobesity actions in animals 1. CLA is dienoic sensitiity of linoleic acid, naturally found in aensitivity and beef fat.
In mice, Lnsulin decreases body fat 23and in CLA and insulin sensitivity ZDF rats, CLA improves insulin ane 45. In contrast, CLA-fed female mice developed marked lipodystrophic insulin resistance 6 isulin, indicating important species and sex differences.
The effect of CLA on insulon insulin sensitivity is unknown. Recently, we reported that CLA treatment decreased abdominal fat sensiitivity obese men but without improving metabolism 7. The latter was Lifestyle habits for digestion, because abdominal anc and insulin sensitivity are strongly related 8.
Similarly, studies Macronutrient Optimization Tips healthy subjects that used a similar Sensigivity mixture indicated decreased body fat after CLA and insulin sensitivity treatment 910 without a Minerals for joint health in insulin levels 9.
However, a strictly innsulin study 1112 failed to show any change in sensitiivity fat or knsulin glucose unsulin in nad, healthy women. Thus, possible antiobesity actions of CLA are still unclear. In spite of lacking clinical sensitifity safety human data, dietary CLA supplements are widely Cholesterol level lifestyle as weight-loss agents among senssitivity subjects, a high-risk group for type 2 diabetes.
Therefore, clinical studies are critically needed on such subjects. Until now, most 7 inwulin, 910but insulni all 1112human studies have used CLA mixtures containing mainly two isomers in approximately sensitiviy amounts: trans inuslin cis 12 t 10 c 12 CLA and c 9 t 11 CLA.
Eensitivity isomers CL present CLA and insulin sensitivity the diet, with CAL c 9 wnd 11 isomer being the most prevalent Senxitivity rodents, Sports nutrition plans isomers have ad effects, Anti-inflammatory lifestyle changes it has been suggested that t 10 c 12 CLA is sejsitivity for the antiobesity 14 and insulin-sensitizing 5 properties of CLA.
To address isomer specificity on glucose insulinn lipid metabolism in humans, insulih CLA and insulin sensitivity the effects of CLLA t 10 c 12 CLA and insulin sensitivity and a commercial CLA mixture.
In a randomized controlled trial, we investigated insulin action in abdominally obese men, a CLA and insulin sensitivity target group for the putative antidiabetic and antiobesity effects of CLA as reported in CLA and insulin sensitivity animals. Sixty Caucasian men ijsulin years old with signs Endurance training for triathletes the metabolic syndrome inzulin obesity, CLA and insulin sensitivity, insulin Maintaining healthy cholesterol profiles, dyslipidemia, and hypertension 15 were recruited from the local senstiivity CLA and insulin sensitivity media advertisements.
No one had diagnosed heart, liver, or renal disease or diabetes. All subjects gave esnsitivity consent. Sensittivity protocol was insjlin by isnulin Ethics Commitee of the Medical Faculty, Uppsala University.
The study was performed after a 4-week run-in screening period. Outcome measures included insulin sensitivity; fasting levels of glucose, lipids, and leptin; and body composition. Subjects were randomly assigned to 3.
Six capsules were taken daily with morning and evening meals. All capsules identical in appearance were prepared by Natural Lipids Hovebygda, Norwaywhich also assessed isomer separation using gas chromatography 17 possible isomerization products from the t 10 c 12 CLA preparation were very low as identified on the chromatogram and generated the randomization numbers for patients and incorporation into double-blind labeling.
The solution code was broken after the study was completed. All measurements were obtained in the morning, after instructions to fast 12 h and refrain from smoking, taking snuff nicotine-containing moistor engaging in physical activity in the morning and to avoid alcohol and exercise the day before visits.
Subjects completed a questionnaire concerning diabetes heredity having at least one first-degree relative with type 2 diabetes and the use of medication or dietary supplements. All men were encouraged to maintain their usual diet and exercise habits during the study.
To assess possible changes in dietary intake during the study, a 3-day weighed-food record was completed during weeks 1 and 8. The sagittal abdominal diameter SAD was measured at L4—5 level, and waist and hip girth were measured as previously described in detail 7.
Anthropometrics were measured by a single investigator. Bioelectrical impedance analysis BIA was done with a multifrequency analyzer Xitron Technologies, San Diego, CA. From the estimation of body water, body fat content was calculated based on the assumption that fat-free mass contains Lean body mass was calculated with the formula provided by the manufacturer.
A min hyperinsulinemic clamp was conducted to determine insulin sensitivity, as described by Defronzo et al. Venous blood sampling was obtained in the left hand, which was kept warmed to provide arterialized blood.
Insulin and glucose were infused in the right antecubital vein. Plasma glucose was assayed in duplicate in a Beckman Glucose Analyzer II Beckman Instruments, Fullerton, CAusing an enzymatic method.
Lipoproteins were isolated from fresh serum by a combination of preparative ultracentrifugation 22 and precipitation with a sodium phosphotungstate and magnesium chloride solution Serum lipoproteins and TG were assayed by enzymatic techniques using a Monarch centrifugal analyzer Instrumentation Laboratories, Lexington, MA.
Serum free glycerol and FFAs were measured using an enzymatic colorimetric method Boehringer Mannheim and Wako Chemical, respectively in the Monarch centrifuge. Samples from each subject were analyzed within the same run.
Plasma insulin was measured by an enzyme immunosorbent assay ELISA kit Mercodia AB, Uppsala, Sweden in a Bio-Rad Coda automated EIA analyzer Bio-Rad Laboratories, Hercules, CA. Serum leptin was measured using a human leptin radioimmunoassay kit Linco Research, St.
Charles, MO. Values are expressed as means ± SD. Variables with skewed distributions were logarithmically transformed before analysis.
A nonparametric test was used if data were not normally distributed after logarithmic transformation.
Paired t test was used for within-group effects from baseline. Differences between groups from baseline to 12 weeks were assessed using overall test ANOVA or nonparametric test. All tests were two-tailed. JMP software SAS Institute, Cary, NC was used. Baseline characteristics and diabetes heredity were similar in all groups Table 1.
Of 60 men, 58 completed the study. Reasons for withdrawal were gastrointestinal symptoms CLA group and weight gain t 10 c 12 CLA group. One patient placebo was hypertensive and treated candesartan during the trial.
This patient completed the trial, but his data were excluded from statistics; results were not influenced if his data were included. Data are based on 57 subjects with complete follow-up data. Supplements were generally well tolerated, with only minor transient gastrointestinal problems reported.
No adverse events occurred, and no changes in liver enzymes occurred data not shown. Compliance capsule count did not significantly differ between groups No significant changes in dietary intake occurred during the study Table 4.
There were no significant differences between groups in body weight, BMI, body fat, lean body mass, or waist girth at 12 weeks Table 2. CLA preparations did not decrease weight or change body fat, BMI, or waist girth compared with placebo, although these variables significantly decreased within the t 10 c 12 CLA group, whereas SAD and body fat decreased within the CLA group paired t test.
Insulin sensitivity M decreased significantly in the t 10 c 12 CLA group compared with placebo but not compared with CLA Table 3.
The significant reduction in M after t 10 c 12 CLA treatment was not affected by adjustment for age or changes in glucose levels, body fat, BMI, or abdominal fat. Of all variables, only adjustment for changes in VLDL TG abolished the significant change in M after t 10 c 12 CLA treatment.
This randomized placebo-controlled trial has revealed unexpected metabolic actions by conjugated fatty acids in humans—actions that seem isomer-specific. The t 10 c 12 CLA isomer, but not a CLA mixture, significantly increased insulin resistance, fasting glucose, and dyslipdemia in abdominally obese men.
Such men are prone to develop type 2 diabetes and are considered a possible target group for the putative beneficial effect of CLA. Commercial CLA had no metabolic benefit, which is consistent with previous data 79 Instead, t 10 c 12 CLA might be diabetogenic in the metabolic syndrome.
However, unlike other studies, diet and physical activity were controlled using metabolic suites in that study, and the relative amount of c 11 t 13 CLA was higher and c 9 t 11 CLA was lower, which should be taken into account when comparing that study with our data.
Whether insulin resistance in CLA-fed mice shares a common mechanism with the t 10 c 12 CLA-induced insulin resistance is unclear. Thus, the mechanism of current insulin resistance is unknown, but some animal data are worth considering.
An intriguing speculation is that CLA induces adipocyte apoptosis as shown in mice 6 and in vitro 62526and by the t 10 c 12 isomer in particular t 10 c 12 CLA might also inhibit the formation of new, small, and insulin-sensitive fat cells 27possibly via downregulated peroxisome proliferator-activated receptor PPAR -γ 6.
Other mechanisms for a t 10 c 12 CLA-induced insulin resistance might involve impaired cell membrane function 28possibly via increasing intramuscular fat content Insulin resistance appeared to occur mainly in the peripheral tissues rather than in the liver, as serum IGF binding protein IGFBP -1, a marker of hepatic insulin sensitivity 30did not change unpublished data.
To elucidate the mechanism, it is probably necessary to investigate insulin-sensitive tissue directly, which is more complicated in humans than in mice. Our primary goal, however, was to investigate the clinical effects of CLA in an insulin-resistant phenotype. Neither CLA preparation decreased weight or changed body composition compared with placebo.
SAD tended to decrease after CLA treatment, but the difference was not significant versus placebo. The standard deviations for changes in anthropometrics were large, and the measurement errors for SAD, BIA, and waist girth have to be considered when interpreting the data.
Adjustment for several variables did not affect the t 10 c 12 CLA-induced insulin resistance, with one exception. Adjusting for VLDL TG abolished statistical significance, reflecting the well-known tight relation between these two variables It is likely that impaired insulin action after t 10 c 12 CLA treatment preceded dyslipidemia 31but this remains to be proven.
: CLA and insulin sensitivity| RESEARCH DESIGN AND METHODS | Subsequently, dams and pups were placed together to let the pups nurse and obtain adequate milk and to allow time for milk clots to form in the stomach. Int J Obes , 31 3 : —7. About this article. To compare food consumption at the baseline and end of the fourth and eighth weeks among groups, and comparison of food consumption in each group among baseline and end of the fourth and eighth weeks of study the ANOVA test and repeated measure ANOVA test were used. Baumgard LH, Sangster JK, Bauman DE: Milk fat synthesis in dairy cows is progressively reduced by increasing supplemental amounts of trans, cis conjugated linoleic acid CLA. Some of the studies observed gender specific effects of CLA intake. Gaullier J, Halse J, Høye K, Kristiansen K, Fagertun H, Vik H et al. |
| Contradicting results have been published regarding the effect of conjugated linoleic acid CLA on insulin resistance. Interaction of fish oil and conjugated linoleic acid in affecting hepatic activity of lipogenic enzymes and gene expression in liver and adipose tissue. Diabetes 51 , — No differences were evident when comparing surrogate indices of insulin resistance during the postintervention phase among the groups. In another study, supplemental CLA significantly increased fasting glucose concentrations and reduced insulin sensitivity homeostasis model , oral glucose insulin sensitivity and insulin sensitivity index ISI [ 7 ], while in our study any of related parameters were not affected. Nutritional supplementation with trans, cisconjugated linoleic acid induces inflammation of white adiposetissue. The National Diet and Nutrition Survey: Adults Aged 19—64 years, Volume 2: Energy, Protein, Carbohydrate, Fat and Alcohol Intake. | |
You can also search for this author in PubMed Google Scholar. Correspondence to C Syvertsen. Reprints and permissions. Syvertsen, C. et al. The effect of 6 months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese. Int J Obes 31 , — Download citation. Received : 22 May Revised : 14 August Accepted : 15 August Published : 10 October Issue Date : 01 July 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. Journal of the International Society of Sports Nutrition Skip to main content Thank you for visiting nature. nature international journal of obesity original article article. Abstract Background: Contradicting results have been published regarding the effect of conjugated linoleic acid CLA on insulin resistance. Objective: To evaluate if CLA as a mixture of the main isomers trans cis and cis -9 trans affects the insulin resistance in healthy overweight and obese male and female adults. Design: The main study was a randomized, double-blind, placebo-controlled trial with change in body composition as primary end point comprising subjects receiving supplementation with either placebo olive oil or CLA Clarinol for 6 months. Results: The median M of the CLA group was Conclusions: CLA does not affect glucose metabolism or insulin sensitivity in a population of overweight or obese volunteers. Access through your institution. Buy or subscribe. Change institution. Learn more. References Atkinson RL. Google Scholar Berven G, Bye A, Hals O, Blankson H, Fagertun H, Thom E et al. Article CAS Google Scholar Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O. Article CAS Google Scholar Gaullier JM, Halse J, Høye K, Kristiansen K, Fagertun H, Vik H et al. 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Int J Obes Relat Metab Disord 28 , — Wargent E, Sennitt MV, Stocker C, Mayes AE, Brown L, O'Dowd J et al. Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation. Lipids Health Dis 4 , 3. West DB, DeLany JP, Camet PM, Blohm F, Truett AA, Scimeca J Article Navigation. Treatment With Dietary trans 10 cis 12 Conjugated Linoleic Acid Causes Isomer-Specific Insulin Resistance in Obese Men With the Metabolic Syndrome Ulf Risérus, MMED ; Ulf Risérus, MMED. This Site. Google Scholar. Peter Arner, MD, PHD ; Peter Arner, MD, PHD. Kerstin Brismar, MD, PHD ; Kerstin Brismar, MD, PHD. Bengt Vessby, MD, PHD Bengt Vessby, MD, PHD. Diabetes Care ;25 9 — Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Table 1— Baseline characteristics. n 19 19 19 Age years 53 ± View Large. Table 2— Change in body composition from baseline to 12 weeks. n 19 19 19 Weight kg 0. Table 3— Absolute and relative changes in glucose and lipid metabolism from baseline to 12 weeks. Table 4— Changes in dietary intake during the study period. Dietary intake. Whigham LD, Cook ME, Atkinson RL: Conjugated linoleic acid: implications for human health. Pharmacol Res. Park Y, Albright KJ, Liu W, Storkson JM, Cook ME, Pariza MW: Effect of conjugated linoleic acid on body composition in mice. West DB, Delany JP, Camet PM, Blohm F, Truett AA, Scimeca J: Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am J Physiol. Biochem Biophys Res Commun. Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M, Combatsiaris T, Galuska D, Bauman DE, Barbano DM, Charron MJ, Zierath JR, Houseknecht KL: Isomer-specific antidiabetic properties of conjugated linoleic acid: improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O: Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Riserus U, Berglund L, Vessby B: Conjugated linoleic acid CLA reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Int J Obes Relat Metab Disord. Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ, Kalkhoff RK, Adams PW: Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab. Smedman A, Vessby B: Conjugated linoleic acid supplementation in humans: metabolic effects. Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O: Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr. Zambell KL, Keim NL, Van Loan MD, Gale B, Benito P, Kelley DS, Nelson GJ: Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure. Medina EA, Horn WF, Keim NL, Havel PJ, Benito P, Kelley DS, Nelson GJ, Erickson KL: Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite. Chin S, Liu W, Storkson J, Ha Y, Pariza M: Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognized class of anticarcinogens. J Food Comp Anal. Park Y, Storkson JM, Albright KJ, Liu W, Pariza MW: Evidence that the trans,cis isomer of conjugated linoleic acid induces body composition changes in mice. DeFronzo RA, Ferrannini E: Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Targher G, Alberiche M, Bonadonna RC, Muggeo M: Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Berdeaux O, Voinot L, Angioni E, Juaneda P, Sebedio JL: A simple method of preparation of methyl trans,cis and cis-9,transoctadecadienoates from methyl linoleate. J Am Oil Chem Soc. Pace N, Rathbun E: Studies on body composition. The body water and chemically combined nitrogen content in relation to fat content. J Biol Chem. DeFronzo RA, Tobin JD, Andres R: Glucose clamp technique: a method for quantifying insulin secretion and resistance. Pollare T, Lithell H, Selinus I, Berne C: Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension. Pollare T, Vessby B, Lithell H: Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. Arterioscler Thromb. Havel R, Eder H, Bragdon J: The determination and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. Siegler L, Wu W: Separation of serum high-density lipoprotein for cholesterol determination: ultracentrifugation vs precipation with sodium phosphotungstate and magnesium chloride. Clin Chem. DeLany JP, Blohm F, Truett AA, Scimeca JA, West DB: Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Miner JL, Cederberg CA, Nielsen MK, Chen X, Baile CA: Conjugated linoleic acid CLA , body fat, and apoptosis. Obes Res. Evans M, Geigerman C, Cook J, Curtis L, Kuebler B, McIntosh M: Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3—L1 preadipocytes. Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, Iwamoto K, Umesono K, Akanuma Y, Fujiwara T, Horikoshi H, Yazaki Y, Kadowaki T: Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. Vessby B: Dietary fat and insulin action in humans. Br J Nutr. Joo ST, Lee JI, Ha YL, Park GB: Effects of dietary conjugated linoleic acid on fatty acid composition, lipid oxidation, color, and water-holding capacity of pork loin. J Anim Sci. Lee PDK, Jensen MD, Divertie GD, Heiling VJ, Katz HH, Conover CC: Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion. Reaven GM: Banting Lecture Role of insulin resistance in human disease. Benito P, Nelson GJ, Kelley DS, Bartolini G, Schmidt PC, Simon V: The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans. Gordon DJ, Rifkind BM: High-density lipoprotein: the clinical implications of recent studies. N Engl J Med. Lillioja S, Mott DM, Spraul M, Ferraro R, Foley JE, Ravussin E, Knowler WC, Bennett PH, Bogardus C: Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus: prospective studies of Pima Indians. Bonadonna RC, Groop L, Kraemer N, Ferrannini E, Del Prato S, DeFronzo RA: Obesity and insulin resistance in humans: a dose-response study. Blanck HM, Khan LK, Serdula MK: Use of nonprescription weight loss products: results from a multistate survey. |
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| Access options | E-mail: ulf. riserus pubcare. A table elsewhere in this issue shows conventional and Système International SI units and conversion factors for many substances. 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 Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 25, Issue 9. Previous Article Next Article. RESEARCH DESIGN AND METHODS. Article Information. Article Navigation. Treatment With Dietary trans 10 cis 12 Conjugated Linoleic Acid Causes Isomer-Specific Insulin Resistance in Obese Men With the Metabolic Syndrome Ulf Risérus, MMED ; Ulf Risérus, MMED. This Site. Google Scholar. Peter Arner, MD, PHD ; Peter Arner, MD, PHD. Kerstin Brismar, MD, PHD ; Kerstin Brismar, MD, PHD. Bengt Vessby, MD, PHD Bengt Vessby, MD, PHD. Diabetes Care ;25 9 — Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Table 1— Baseline characteristics. n 19 19 19 Age years 53 ± View Large. Table 2— Change in body composition from baseline to 12 weeks. n 19 19 19 Weight kg 0. Table 3— Absolute and relative changes in glucose and lipid metabolism from baseline to 12 weeks. Table 4— Changes in dietary intake during the study period. Dietary intake. Whigham LD, Cook ME, Atkinson RL: Conjugated linoleic acid: implications for human health. Pharmacol Res. Park Y, Albright KJ, Liu W, Storkson JM, Cook ME, Pariza MW: Effect of conjugated linoleic acid on body composition in mice. West DB, Delany JP, Camet PM, Blohm F, Truett AA, Scimeca J: Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am J Physiol. Biochem Biophys Res Commun. Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M, Combatsiaris T, Galuska D, Bauman DE, Barbano DM, Charron MJ, Zierath JR, Houseknecht KL: Isomer-specific antidiabetic properties of conjugated linoleic acid: improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O: Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Riserus U, Berglund L, Vessby B: Conjugated linoleic acid CLA reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Int J Obes Relat Metab Disord. Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ, Kalkhoff RK, Adams PW: Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab. Smedman A, Vessby B: Conjugated linoleic acid supplementation in humans: metabolic effects. Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O: Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr. Zambell KL, Keim NL, Van Loan MD, Gale B, Benito P, Kelley DS, Nelson GJ: Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure. Medina EA, Horn WF, Keim NL, Havel PJ, Benito P, Kelley DS, Nelson GJ, Erickson KL: Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite. Chin S, Liu W, Storkson J, Ha Y, Pariza M: Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognized class of anticarcinogens. J Food Comp Anal. Park Y, Storkson JM, Albright KJ, Liu W, Pariza MW: Evidence that the trans,cis isomer of conjugated linoleic acid induces body composition changes in mice. DeFronzo RA, Ferrannini E: Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Targher G, Alberiche M, Bonadonna RC, Muggeo M: Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Berdeaux O, Voinot L, Angioni E, Juaneda P, Sebedio JL: A simple method of preparation of methyl trans,cis and cis-9,transoctadecadienoates from methyl linoleate. J Am Oil Chem Soc. Pace N, Rathbun E: Studies on body composition. The body water and chemically combined nitrogen content in relation to fat content. J Biol Chem. DeFronzo RA, Tobin JD, Andres R: Glucose clamp technique: a method for quantifying insulin secretion and resistance. Pollare T, Lithell H, Selinus I, Berne C: Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension. Pollare T, Vessby B, Lithell H: Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. Arterioscler Thromb. Havel R, Eder H, Bragdon J: The determination and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. Siegler L, Wu W: Separation of serum high-density lipoprotein for cholesterol determination: ultracentrifugation vs precipation with sodium phosphotungstate and magnesium chloride. Clin Chem. DeLany JP, Blohm F, Truett AA, Scimeca JA, West DB: Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Miner JL, Cederberg CA, Nielsen MK, Chen X, Baile CA: Conjugated linoleic acid CLA , body fat, and apoptosis. Moreover, significant HOMA-IR improvement observed only in CLA-treated patients denotes a significant performance in skeletal muscle that promotes a lower pancreatic insulin secretion. A recently published meta-analysis demonstrated that the deleterious effects of CLA consumption might be negligible, whereas its benefits, although subtle, seem to be clinically relevant regarding weight and fat mass loss In our study, BMI improvement was significant in all groups, although not significantly different among them. Racine et al. In the CLA group, we noticed a decline in the HDL cholesterol concentration that was not statistically significant when compared with PLB. The strength of this study is supported by its own design. For example, inclusion and, particularly, elimination criteria were strictly applied. Baseline characteristics of participants were similar regarding anthropometric and metabolic condition, particularly those related to subrogated indexes of insulin resistance. Additionally, the main outcome was evaluated by the gold standard EHCT, and the benefits of the overall LIP were evident and similar, regardless of treatment allocation. Although the withdrawal of participants was high in our study, the elimination was random and homogeneous in all groups. The current study demonstrates the benefits of an LIP and additional effect of CLA over the gold standard EHCT. Lifestyle intervention, independent of any treatment, showed effects on the main outcome variables, specifically weight, height, BMI, waist circumference, surrogate indexes of insulin resistance, and fitness condition, in all of the groups. IRS2 upregulation was evident in CLA-treated patients; this mechanism might be involved in insulin-sensitizing effects on skeletal muscle. Finally, the incidence of hypertriglyceridemia and hypo- α -lipoproteinemia in CLA-treated patients might be a concern and may be related to the types of CLA isomers used in this study. Further research to evaluate the benefits of different mixtures of CLA isomers may be warranted. This study was supported by Grant SALUD from Consejo Nacional de Ciencia y Technología Mexico and by funding from Laboratorio Silanes S. Clinical trial registry: ClinicalTrials. NCT registered 12 February Gutiérrez J , Rivera-Dommarco J , Shamah-Levy T , Villalpando-Hernández S , Franco A , Cuevas-Nasu L , Romero-Martínez M , Hernández-Ávila M. Encuesta Nacional de Salud y Nutrición. Morelos, Mexico : Instituto Nacional de Salud Pública Google Scholar. Google Preview. Utzschneider KM , Van de Lagemaat A , Faulenbach MV , Goedecke JH , Carr DB , Boyko EJ , Fujimoto WY , Kahn SE. Insulin resistance is the best predictor of the metabolic syndrome in subjects with a first-degree relative with type 2 diabetes. Obesity Silver Spring. Garner DM , Wooley SC. Confronting the failure of behavioral and dietary treatments for obesity. Clin Psychol Rev. Mauro M , Taylor V , Wharton S , Sharma AM. Barriers to obesity treatment. Eur J Intern Med. Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study. Eur J Endocrinol. Brufani C , Crinò A , Fintini D , Patera PI , Cappa M , Manco M. Systematic review of metformin use in obese nondiabetic children and adolescents. Horm Res Paediatr. Conjugated linoleic acid. Anim Health Res Rev. Christie WW , Dobson G , Adlof RO. A practical guide to the isolation, analysis and identification of conjugated linoleic acid. Eyjolfson V , Spriet LL , Dyck DJ. Conjugated linoleic acid improves insulin sensitivity in young, sedentary humans. Med Sci Sports Exerc. Effect of conjugated linoleic acid on body fat accretion in overweight or obese children. Am J Clin Nutr. Song H-J , Grant I , Rotondo D , Mohede I , Sattar N , Heys SD , Wahle KWJ. Effect of CLA supplementation on immune function in young healthy volunteers. Eur J Clin Nutr. Hontecillas R , Wannemeulher MJ , Zimmerman DR , Hutto DL , Wilson JH , Ahn DU , Bassaganya-Riera J. Nutritional regulation of porcine bacterial-induced colitis by conjugated linoleic acid. J Nutr. Bassaganya-Riera J , Reynolds K , Martino-Catt S , Cui Y , Hennighausen L , Gonzalez F , Rohrer J , Benninghoff AU , Hontecillas R. Activation of PPAR γ and δ by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Larsen TM , Toubro S , Astrup A. Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. J Lipid Res. American Diabetes Association. Diabetes Care. World Health Organization. Energy and protein requirements. World Health Organ Tech Rep Ser. Treviño RP , Marshall RM , Jr , Hale DE , Rodriguez R , Baker G , Gomez J. Diabetes risk factors in low-income Mexican-American children. DeFronzo RA , Tobin JD , Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. Morrison JA , Friedman LA , Gray-McGuire C. Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics Follow-up Study. Catoira N , Nagel M , Di Girolamo G , Gonzalez CD. Pharmacological treatment of obesity in children and adolescents: current status and perspectives. Expert Opin Pharmacother. Quinn SM , Baur LA , Garnett SP , Cowell CT. Treatment of clinical insulin resistance in children: a systematic review. Obes Rev. Freemark M , Bursey D. The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. Yanovski JA , Krakoff J , Salaita CG , McDuffie JR , Kozlosky M , Sebring NG , Reynolds JC , Brady SM , Calis KA. Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. Risérus U , Arner P , Brismar K , Vessby B. Treatment with dietary trans 10 cis 12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Brown JM , McIntosh MK. Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity. Conjugated linoleic acid supplementation enhances insulin sensitivity and peroxisome proliferator-activated receptor gamma and glucose transporter type 4 protein expression in the skeletal muscles of rats during endurance exercise. Iran J Basic Med Sci. Zhai JJ , Liu ZL , Li JM , Chen JP , Jiang L , Wang DM , Yuan J , Shen J-G , Yang D-P , Chen J-Q. Different mechanisms of cis -9, trans and trans , cis conjugated linoleic acid affecting lipid metabolism in 3T3-L1 cells. J Nutr Biochem. Whigham LD , Watras AC , Schoeller DA. Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. Clément L , Poirier H , Niot I , Bocher V , Guerre-Millo M , Krief S , Staels B , Besnard P. Dietary trans,cis conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. Tsuboyama-Kasaoka N , Takahashi M , Tanemura K , Kim HJ , Tange T , Okuyama H , Kasai M , Ikemoto S , Ezaki O. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Vaughan RA , Garcia-Smith R , Bisoffi M , Conn CA , Trujillo KA. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells. Lipids Health Dis. J Endocrinol. Onakpoya IJ , Posadzki PP , Watson LK , Davies LA , Ernst E. The efficacy of long-term conjugated linoleic acid CLA supplementation on body composition in overweight and obese individuals: a systematic review and meta-analysis of randomized clinical trials. Eur J Nutr. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Endocrine Society Journals. As this study was on glucose-lowering drug consumers that may interfere with the mechanisms of CLA in some metabolic pathways. Also, calculation of dietary CLA intake was not possible. In this study, daily supplementation with 3 g of CLA capsules alone and combined with IU of VitE for eight weeks compared to placebo, did not result in significant changes in serum triglycerides, total cholesterol, LDL, HDL cholesterol and apoB Some animal studies using pure CLA isomers have shown that cis-9, trans isomer lead to lowering triglyceride levels and plasma free fatty acids and trans, cis isomer lead to increasing plasma free fatty acids and LDL cholesterol [ 2 ] that is confirmed by human studies [ 21 ]. However, the results of equal ratio of isomers are contradictory. In a study on patients with type2 diabetes, taking 3g of CLA supplementation for 8 weeks, resulting in increased HDL 2 cholesterol and decreased LDL to HDL cholesterol ratio [ 7 ], although in another study, reduced serum HDL cholesterol following 12 weeks of supplementation has been reported [ 44 ]. In other studies with 6 weeks and 6 months duration, no significant changes were shown in serum lipids and Apo proteins [ 33 , 43 ]. Overall, the effects of commercial CLA capsules on lipids profiles are unknown. Further studies should be done in this regard to identify the mechanisms of CLA in regulating gene expression involved in lipid metabolism. In our study, it was not shown any change in systolic and diastolic blood pressure. In two animal studies, CLA has reduced blood pressure [ 45 , 46 ]. In another study, trans, cis isomer lowered blood pressure and cis-9, trans did not affect [ 47 ]. CLA effects on blood pressure could be related to the pathway of eicosanoids production. Inhibition of Arashidonic acid released from cell membranes and cyclooxygenase by CLA has been reported [ 11 ]. In our study, 3 g daily CLA capsules alone and combined with IU of VitE for eight weeks did not affect any inflammatory parameters IL-1 beta, interleukin-6, TNF-α, CRP, Serum leptin and adiponectin. Animal studies show that trans, cis isomer increases indicators of inflammation and cis-9; trans is associated with reduction of inflammatory indicators [ 12 ]. In this way the CLA supplementation in rats leads to decreased TNF-α and in mice increased it [ 19 ]. In some human studies, CLA did not affect serum inflammatory parameters [ 7 ], but in the some others led to increase in these mediators [ 45 ], in the present study also no significant changes developed. In one study, CLA supplementation reduced leptin and adiponectin [ 8 ] and in two other studies any changes are not mentioned [ 9 , 28 ]. In the present study changes in serum leptin and adiponectin showed no statistically differences among the three groups. In our study there was not seen any significant differences in serum fibrinogen and PAI-1 changes among three groups. Also, no information is regarding the effects of CLA supplementation on these variables. In the present study 3 g of CLA capsules alone and combined with IU VitE did not make a difference in the oxidative stress index, MDA compared with placebo. In some studies, taking an active CLA isomer has increased lipid peroxidation indexes, including urinary excretion of isoprostaglandins [ 9 , 21 ]. One limitation of this study is that estimation of dietary and serum CLA was not possible. Also, the use of 2-d diet records may not accurately reflect changes in calories during intervention. Duration of this study was 8 weeks. It may be required longer time to appearance CLA effects. Because of insufficient information regarding the molecular mechanisms of CLA in humans, human cell culture studies are suggested. Overall, our results show that commercial CLA supplementation alone or combined with VitE for 8weeks, does not significantly affect glycemic indicators, body composition, lipid concentrations, indicators of inflammation, coagulation, leptin, adiponectin, MDA and blood pressure in type2 diabetes, but there was a significant trend to increase in MDA and decrease in apoB among CLA consumers. Aminot-Gilchrist DV, Anderson HD: Insulin resistance-associated cardiovascular disease: potential benefits of conjugated linoleic acid. Am J Clin Nutr , 79 6 Suppl SS. Article CAS PubMed Google Scholar. Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G: Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem , 17 12 — Jiang J, Wolk A, Vessby B: Relation between the intake of milk fat and the occurrence of conjugated linoleic acid in human adipose tissue. Am J Clin Nutr , 70 1 — Larsen TM, Toubro S, Gudmundsen O, Astrup A: Conjugated linoleic acid supplementation for 1 y does not prevent weight or body fat regain. Am J Clin Nutr , 83 3 — Wang YW, Jones PJ: Conjugated linoleic acid and obesity control: efficacy and mechanisms. Int J Obes Relat Metab Disord , 28 8 — Poirier H, Shapiro JS, Kim RJ, Lazar MA: Nutritional supplementation with trans, cisconjugated linoleic acid induces inflammation of white adipose tissue. Diabetes , 55 6 — Jun Moloney F, Yeow TP, Mullen A, Nolan JJ, Roche HM: Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am J Clin Nutr , 80 4 — Valeille K, Férézou J, Parquet M, Amsler G, Gripois D, Quignard-Boulangé A, Martin JC: The natural concentration of the conjugated linoleic acid, cis-9, trans, in milk fat has antiatherogenic effects in hyperlipidemic hamsters. J Nutr , 5 — Riserus U, Vessby B, Arnlov J, Basu S: Effects of cis-9, trans conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men. Am J Clin Nutr , 80 2 — Eyjolfson V, Spriet LL, Dyck DJ: Conjugated linoleic acid improves insulin sensitivity in young, sedentary humans. Med Sci Sports Exerc , 36 5 — Noto A, Zahradka P, Ryz NR, Yurkova N, Xie X, Taylor CG: Dietary conjugated linoleic acid preserves pancreatic function and reduces inflammatory markers in obese, insulin-resistant rats. Metabolism , — de Roos B, Rucklidge G, Reid M, Ross K, Duncan G, Navarro MA, Arbones-Mainar JM, Guzman-Garcia MA, Osada J, Browne J, Loscher CE, Roche HM: Divergent mechanisms of cis9, transand trans10, cisconjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach. FASEB J , 19 12 — Lin H, Boylston TD, Chang MJ, Luedecke LO, Shultz TD: Survey of the conjugated linoleic acid contents of dairy products. J Dairy Sci , 78 11 — S 95 Riserus U, Smedman A, Basu S, Vessby B: CLA and body weight regulation in humans. Lipids , 38 2 — Riserus U, Smedman A, Basu S, Vessby B: Metabolic effects of conjugated linoleic acid in humans: the Swedish experience. Riserus U, Vessby B, Arner P, Zethelius B: Supplementation with trans10cisconjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity. Diabetologia , 47 6 — Brown JM, McIntosh MK: Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity. J Nutr , 10 — Raff M, Tholstrup T, Sejrsen K, Straarup EM, Wiinberg N: Diets rich in conjugated linoleic acid and vaccenic acid have no effect on blood pressure and isobaric arterial elasticity in healthy young men. J Nutr , 4 — Taylor CG, Zahradka P: Dietary conjugated linoleic acid and insulin sensitivity and resistance in rodent models. Belury MA, Mahon A, Banni S: The conjugated linoleic acid CLA isomer, t10cCLA, is inversely associated with changes in body weight and serum leptin in subjects with type 2 diabetes mellitus. J Nutr , 1 SS. Article PubMed Google Scholar. Riserus U, Arner P, Brismar K, Vessby B: Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care , 25 9 — Gerber LM, Madhavan S, Alderman MH: Waist-to-hip ratio as an index of risk for hyperglycemia among hypertensive patients. Am J Prev Med , 3 2 — Rajeswari K, Lakshmi VV: Body composition of preadolescents by skinfold measurements and Body Stat Analyzer. Indian Pediatr , 43 12 — CAS PubMed Google Scholar. 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Int J Obes Relat Metab Disord , 27 1 — Vanhala P, Vanhala M, Kumpusalo E, Keinanen-Kiukaanniemi S: The quantitative insulin sensitivity check index QUICKI predicts the onset of type 2 diabetes better than fasting plasma insulin in obese subjects: a 5-year follow-up study. J Clin Endocrinol Metab , 87 12 — Shim WS, Kim SK, Kim HJ, Kang ES, Ahn CW, Lim SK, Lee HC, Cha BS: Decrement of postprandial insulin secretion determines the progressive nature of type-2 diabetes. Eur J Endocrinol , 4 — Uwaifo GI, Fallon EM, Chin J, Elberg J, Parikh SJ, Yanovski JA: Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children. Diabetes Care , 25 11 — Hovorka R, Chassin L, Luzio SD, Playle R, Owens DR: Pancreatic beta-cell responsiveness during meal tolerance test: model assessment in normal subjects and subjects with newly diagnosed noninsulin-dependent diabetes mellitus. 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CLA and insulin sensitivity -
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Spriet LL ,. Dyck DJ. Affiliations 1. Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada. Authors Eyjolfson V 1. Share this article Share with email Share with twitter Share with linkedin Share with facebook.
Abstract Background Preliminary evidence in obese diabetic rats suggests that conjugated linoleic acid CLA may have antidiabetic properties, based on reductions in fasting glucose and insulin concentrations. However, in lean rats, CLA causes hyperinsulinemia.
Furthermore, experiments in humans also suggest that CLA may worsen insulin sensitivity. Objectives The present study examined whether CLA supplementation can improve insulin sensitivity in humans. Design : Sixteen young sedentary individuals age, Ten subjects received 4 g x d of mixed CLA isomers Oral glucose tolerance tests were performed at baseline 0 , 4 and 8 wk of supplementation.
Results : After 8 wk of CLA supplementation, insulin sensitivity index ISI increased ISI was unchanged over 8 wk in the placebo group. Conclusions Our results indicate that a common dosage of a commercially available CLA supplement can improve ISI in young, sedentary individuals.
However, there is considerable individual variability in the response. Additional studies are required to identify underlying metabolic changes in human skeletal muscle. References Articles referenced by this article 28 Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action.
Belury MA Annu Rev Nutr, MED: Conjugated linoleic acid reduces body fat mass in overweight and obese humans. Blankson H , Stakkestad JA , Fagertun H , Thom E , Wadstein J , Gudmundsen O J Nutr, 12 MED: Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity.
Brown JM , McIntosh MK J Nutr, 10 MED: Regulation of muscle glycogenolytic flux during intense aerobic exercise after caffeine ingestion. Chesley A , Howlett RA , Heigenhauser GJ , Hultman E , Spriet LL Am J Physiol, 2 :R MED: Dietary trans,cis conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse.
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Greenhaff PL , Bodin K , Soderlund K , Hultman E Am J Physiol, 5 Pt 1 :E MED: Isomer-specific actions of conjugated linoleic acid on muscle glucose transport in the obese Zucker rat. Henriksen EJ , Teachey MK , Taylor ZC , Jacob S , Ptock A , Kramer K , Hasselwander O Am J Physiol Endocrinol Metab, 1 :EE MED: Houseknecht KL , Vanden Heuvel JP , Moya-Camarena SY , Portocarrero CP , Peck LW , Nickel KP , Belury MA Biochem Biophys Res Commun, 3 MED: Muscle triglyceride and insulin resistance.
Kelley DE , Goodpaster BH , Storlien L Annu Rev Nutr, MED: Show 10 more references 10 of The effects of conjugated linoleic acid supplementation on glycemic control, adipokines, cytokines, malondialdehyde and liver function enzymes in patients at risk of cardiovascular disease: a GRADE-assessed systematic review and dose-response meta-analysis.
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Metabolic profiles of adipose-derived and bone marrow-derived stromal cells from elderly coronary heart disease patients by capillary liquid chromatography quadrupole time-of-flight mass spectrometry.
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Atheroprotective effects of conjugated linoleic acid. Bruen R , Fitzsimons S , Belton O Br J Clin Pharmacol , 83 1 , 07 May Cited by: 22 articles PMID: PMCID: PMC Review Free full text in Europe PMC.
Insulin resistance and percent remaining pancreatic β-cell function are unaffected. Barre DE , Mizier-Barre KA , Griscti O , Hafez K Endocr Regul , 50 4 , 01 Oct Cited by: 8 articles PMID: Should the pharmacological actions of dietary fatty acids in cardiometabolic disorders be classified based on biological or chemical function?
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External links service. Annotations submission service. The data for dam body weight, food intake and total body weight of eight pups in experiment one and ITT in experiment two were analyzed for significant differences among or between groups using a general linear model for analysis of variance with the factors of diet D , time T and their interaction D×T.
The effects of CLA on the milk and liver of dams in experiment one were analyzed using a one-way analysis of variance ANOVA. The food intake of dams in the control group was significantly higher than the food intakes of dams in the CLA groups. A Daily body weight of dams.
B Food intake of dams. CON group, 3. The total weight of eight pups in experiment one is shown in Fig 2. Significant effects of both time and treatment were observed on total pup weight gain over the feeding period.
Relative to the control treatment, CLA treatment significantly reduced the total body weight of pups. The total eight-pup weights in the H-CLA group were significantly lower than those in the M-CLA, CON and L-CLA groups The milk clot weight obtained from the stomach ranged between 0.
The milk fat content of the H-CLA group was significantly lower than the contents of the other groups. There were no significant differences in protein and lactose concentrations in milk among the CLA and control groups Table 2.
Similarly, there was no difference in the weight of mammary tissue among the groups. Liver weight increased gradually with increasing dose of CLA, and there was a significantly higher TG content in the liver in the H-CLA group than in the other groups Table 2.
Similar to pup weight in experiment one, in experiment two, the weight of the pups in the high-dose CLA group was significantly lower than that in the control group Fig 3. CHO, HDL and LDL levels in the serum were unaffected by treatment. Interestingly, compared with feeding in the control group, CLA feeding resulted in higher RBC 8.
At 0 min, the blood glucose level in the control group was 6. After insulin injection, glucose in the control group decreased to 4. A ITT values of lactating mice.
In the present study, CLA treatment decreased food intake in lactating dams. Increased maternal intake of CLA during lactation has been shown to enhance the growth rate of suckling neonatal rats [ 28 ].
However, in contrast to observations of the stimulatory effects of CLA, mixtures of CLA [ 19 ] or isoforms [ 18 ] have been found to cause litter pups to grow slowly or even die due to decreased milk fat.
These contradictory results might be due to study differences in the content or isomeric distribution of the CLA supplement. Milk is the only source of nutrients for suckling pups; hence, it was not surprising that the reductions in the fat and weight of milk were accompanied by reduced pup weight in the pups of lactating dams.
These findings confirm that a high dose of CLA can lower the content of milk fat and pup growth rate. Although the milk FA composition was not analyzed in the present study, Harvatine et al found that CLA treatment decreased the concentration of de novo synthesized FAs and and increased the concentration of PUFA in milk fat n—6 and n—6 , which suggest that CLA treatment decreased the lipogenic capacity of mammary tissue [ 12 ].
CLA has been reported to generate fatty liver, which could be a consequence of increased lipogenesis in the liver to compensate for the reduction in fat deposition in adipose tissue [ 27 ]. We assessed the liver of dams and observed increased liver weight and TG content in mice given a high dose of CLA.
Kadegowda et al reported that mice treated with CLA displayed decreased milk fat and increased liver weight due to hepatic steatosis [ 29 ], which is consistent with our current results.
The effects of CLA supplementation on mammary fat synthesis have received a great deal of attention [ 30 , 31 ], but the potential adverse effects of CLA on the liver and lipid metabolism in lactating animals have been largely ignored.
We suggest that severe lipid accumulation occurs in the liver when lactating mice are given high doses of CLA. This suggestion is supported by the increased TG content and γ-GT activity in the serum of mice in the high-CLA group relative to CON group.
There have been many reports regarding CLA-induced insulin resistance [ 7 ]. In the present study, the HOMA-IR and ITT results indicated that the high dose of CLA fed to the mice caused insulin resistance. In lactating mice, glucose is the main precursor for the synthesis of lactose and triglyceride substrates.
During the lactation stage, mammary glands have increased demand for glucose and are highly sensitive to insulin, whereas other organs are relatively insensitive to insulin [ 32 ]. In this study, lactating mice fed CLA displayed aggravated insensitivity to insulin and exhibited insulin resistance, implicating insulin as a key factor in CLA-mediated regulation of milk fat and lactation.
Interestingly, we observed for the first time that a high dose of CLA can result in higher RBC and HGB levels in the whole blood of lactating mice. RBC and HGB are both positively correlated with insulin resistance and nonalcoholic fatty liver disease NAFLD [ 33 ].
Thus, in the present study, the higher RBC and HGB levels in the mice receiving the high dose of CLA may have been consequences of insulin resistance and fatty liver. In summary, a high level of CLA ingestion during lactation decreases milk fat and increases lipid content in the liver.
These findings indicate that dietary CLA has the propensity to affect hepatic metabolism and lactation. Little is known about the complex regulatory mechanism between lipid metabolism in the liver and mammary lactation. The present findings provide a platform for further studies on this mechanism and the safe use of CLA.
Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Article Authors Metrics Comments Media Coverage Reader Comments Figures. Abstract This study aimed to evaluate the effects of a high dose of conjugated linoleic acid CLA on lactating mice.
Funding: The authors received no specific funding for this work. Introduction Conjugated linoleic acids CLAs are molecules mostly found in meat and dairy products. Materials and methods Animals and diets This study was carried out in strict accordance with the recommendations in the Guide for Henan Laboratory Animal Center for Medical Sciences Animal Care and Use Committee.
Download: PPT. Experiment one In experiment one, all dams were fed the laboratory basal diet for the first 3 days of lactation.
Analysis of milk and liver samples. Experiment two In experiment two, dams received 3. Blood parameter analysis. Insulin tolerance test. Statistical analysis. Results Experiment one Dam body weight and food intake.
Fig 1. Daily body weight and food intake of dams fed different doses of CLA. Pup body weight. Fig 2. Daily weight of nursing pups fed different doses of CLA from day 4 to day 10 of lactation. Milk and liver of dams. Experiment two Body weight of pups. Fig 3. Dams and eight pups of the CON and H-CLA groups at day 10 of lactation.
Blood metabolite analysis. Table 3. Effect of high-dose CLA on the blood metabolites of dams. Fig 4. Insulin tolerance test results of lactating mice in the CON and H-CLA groups.
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Thank you for visiting nature. CLA and insulin sensitivity are using inslin browser version innsulin limited support for CSS. To obtain the best experience, we recommend you use a more up sensitovity date browser senitivity turn off CLA and insulin sensitivity mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Dietary addition of either conjugated linoleic acid CLA or n -3 long-chain polyunsaturated fatty acids n-3 LC-PUFAs has been shown to alter adiposity and circulating lipids, risk markers of cardiovascular diseases. However, CLA may decrease insulin sensitivity, an effect that may be reversed by n -3 LC-PUFA.Video
Exercise and Insulin Sensitivity: The Parking Lot AnalogyCLA and insulin sensitivity -
Abstract Background Preliminary evidence in obese diabetic rats suggests that conjugated linoleic acid CLA may have antidiabetic properties, based on reductions in fasting glucose and insulin concentrations. However, in lean rats, CLA causes hyperinsulinemia.
Furthermore, experiments in humans also suggest that CLA may worsen insulin sensitivity. Objectives The present study examined whether CLA supplementation can improve insulin sensitivity in humans. Design : Sixteen young sedentary individuals age, Ten subjects received 4 g x d of mixed CLA isomers Oral glucose tolerance tests were performed at baseline 0 , 4 and 8 wk of supplementation.
Results : After 8 wk of CLA supplementation, insulin sensitivity index ISI increased ISI was unchanged over 8 wk in the placebo group. Conclusions Our results indicate that a common dosage of a commercially available CLA supplement can improve ISI in young, sedentary individuals.
However, there is considerable individual variability in the response. Additional studies are required to identify underlying metabolic changes in human skeletal muscle.
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Results: CLA supplementation significantly increased fasting glucose concentrations 6. Conclusions: CLA supplementation had an adverse effect on insulin and glucose metabolism. Whereas CLA had positive effects on HDL metabolism and fibrinogen, a therapeutic nutrient should not be associated with potentially adverse effects on other clinical markers of type 2 diabetes.
Ulf Risérus Antiviral prevention methods, Peter ArnerKerstin BrismarBengt Vessby; Treatment With Sensitiviyy trans 10 cis 12 Conjugated Linoleic Acid Causes Isomer-Specific Anv Resistance in Obese Sensitivitt CLA and insulin sensitivity the Sensirivity Syndrome. Diabetes Care 1 September ; 25 9 : — OBJECTIVE —Conjugated linoleic acid CLA is a group of dietary fatty acids with antiobesity and antidiabetic effects in some animals. The trans 10 cis 12 t 10 c 12 CLA isomer seems to cause these effects, including improved insulin sensitivity. Whether such isomer-specific effects occur in humans is unknown.
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