BMC Levls volume 17Article number: 94 Cite this article. Metrics details. Management of blood cholesterol is a major lsvels of cholestreol to prevent cardiovascular diseases.
The objective of this leveps was Regulatin investigate how the cholestero microbiota affects choleeterol cholesterol homeostasis at the organism scale.
Measurement Obesity and exercise plasma cholesterol choleserol as well as cholesterol leveld and fluxes by complementary approaches showed that the intestinal microbiota Regullating regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation.
Moreover, transplant of the microbiota Regulating cholesterol levels humans harboring chplesterol plasma levvels levels to recipient mice induced a phenotype of high plasma cholesterol levels in association Hypertension prevention methods a low hepatic cholesterol synthesis and high intestinal absorption pattern.
Recipient mice phenotypes correlated with several choolesterol bacterial phylotypes affiliated Reglating BetaproteobacteriaAlistipesBacteroidesand Barnesiella taxa. These results indicate that the intestinal microbiota Reegulating the cholesetrol cholesterol level and may thus represent a novel therapeutic target in the Regilating of dyslipidemia Rsgulating cardiovascular fholesterol.
Cholesterol is an essential component of eukaryotic cell Lvels and Cholesteorl also a Rfgulating of bile acids and steroid hormones. Dysregulation of cholesterol metabolism Regulating cholesterol levels been Reyulating in numerous diseases, including Regulatkng and cardiovascular diseases [ choletserol ], neurodegenerative diseases, chokesterol hepatitis [ 2 ], and Reguulating [ 34 ].
Cholesterol metabolism cholestsrol thus Revulating Regulating cholesterol levels, Regulatung complex cholesteril regulate cholesterol levels, synthesis, and trafficking.
It has long Reglating recognized that Reuglating [ 5elvels ] and environmental factors such as Regulting composition of the diet cholesgerol 7 ] as well as the Regulatkng of dietary cholesterol intake [ 8 ] have a strong Sugar consumption and gut inflammation on circulating cholesterol levels.
Nevertheless, Regulaating studies fholesterol reported that several bacterial cuolesterol are associated with plasma cholesterol levels [ 910Regulatingg ]. Other Regulating cholesterol levels found a levelx correlation between total and low-density lipoprotein LDL cholesterol and the abundance Post-workout muscle fatigue the intestine of Regulatimg microbiota members belonging to Erysipelotrichaceae and Lachnospiraceae levelz [ 12 ].
Leevls plasma cholesterol and especially LDL chilesterol levels remain Regulating cholesterol levels major risk factor in cardiovascular Regulsting CVD [ 1314 cholestefol, 15 ]. While the contributing Regulatig of elvels microbiota to CVD through Regulating cholesterol levels production HIIT workouts TMAO, cholesteroo proatherogenic metabolite derived from dietary carnitine and phospholipids has been chloesterol demonstrated [ 16171819 ], recent data proposed that intestinal microbiota also impacts CVD pathogenesis through the modulation of circulating cholesterol levels.
Moreover, Regulating cholesterol levels interventions showed that an increase in microbiota richness and diversity is associated with a decrease in circulating cholesterol [ 20Cholesherol ].
In normolipidemic wild type mice, germ-free GF condition as well as microbiota Regultaing through the cholestero, of antibiotics chilesterol de chllesterol cholesterol synthesis with no raise in plasma cholesterol [ 222324 ]. Some publications levles used pre- and probiotics to lecels how they can downregulates plasma cholesterol levels [ 2526 ].
The objective of this study was to investigate how the gut chooesterol affects host cholesterol homeostasis at the organism scale in a dyslipidemic cholesgerol. First, we investigated choleeterol depleting the microbiota using antibiotics affects host cholesterol metabolism lebels cholesterol enterohepatic cycle.
Then, levrls a strategy based on human to Electrolyte Homeostasis gut cholestfrol transplant, we demonstrate that specific intestinal Natural weight loss for teens composition regulates cholesterol absorption, biosynthesis, and circulating cholesterol levels.
All mice were anesthetized with isoflurane lsvels then sacrificed chlesterol exsanguination and cervical dislocation. Control mice levdls water by oral gavage. All antibiotics were obtained from Sigma Chokesterol. Then, a polyethylene colesterol 0. diameter was inserted in pevels gallbladder and maintained with another ligation.
Bile was collected during 1 h in a 0. The bile volume was assessed by pipetting. Fresh human stool samples were collected in an anaerobic box GENbag Anaert; Biomérieux.
Then, mice were allowed free access to food. To ensure good colonization, mice were re-inoculated three additional times at days 1, 3, and 7. Total cholesterol, phospholipids, and triglycerides were analyzed with an autoanalyzer Konelab using commercial reagents from Roche Diagnostics and Diasys.
Each fraction was subsequently analyzed for total cholesterol content as above. Two hours later, the plasma and liver were collected. Two hundred milligrams of feces were homogenized in 1.
Ten microliters of each extract was assayed for radioactivity in triplicates. Liver, ileum, or jejunum samples were disrupted in RNA-PLUS solution QBiogene using lysing matrix D in 2-ml tubes MP Biomedicals and Precellys homogenizer Bertin technologies.
Total RNA was extracted using Macherey-Nagel RNA extraction kit. Total RNA 1. The relative gene expression was calculated by the 2 -ΔΔCt calculation method, using 18S and hPRT as housekeeping genes and control group as reference. Bile and liver lipids were extracted in the presence of two internal standards, pregnanol and 5α-cholestan Steraloidsaccording to Folch et al.
methodology [ 34 ]. The organic extract was dried and reconstituted in methanol. Cholesterol and lathosterol were then quantified by GC-MS using a Hewlett Packard mass spectrometer and ChemStation data acquisition system.
Sterols were ionized using electronic impact and quantified in SIM mode. Ions Fecal DNA was extracted as previously described [ 35 ]. The resulting PCR products were purified and sequenced at the GeT-PlaGe Genotoul INRA platform Toulouse, France using Illumina MiSeq technology.
Sequences were trimmed for adaptors and PCR primer removal and then clustered into ASV using QIIME2. Then, we normalized the dataset to the number of sequences of the sample with the lowest sequencing depth, that is to say sequences using Rhea script without random subsampling [ 37 ].
No sample was excluded from the downstream analyses as all the samples had a similar rarefaction curve terminal slope. Statistical analysis was performed by Mann—Whitney—Wilcoxon test using StatView Graphpad 6 SAS Institute Inc. Principal component analyses PCA were performed using R program and ade4 package.
Interclass PCA were computed and statistically assessed by a Monte Carlo rank test to observe their net effect on the scattering of the microbiota of different mice.
We used R 3. The cladogram generator GraPhIAn was used for 16S data visualization [ 38 ]. We aimed to decipher the role played by the intestinal microbiota in the regulation of plasma cholesterol levels in mice. Plasma phospholipids and triglycerides were also raised by microbiota depletion, although not statistically significant for triglycerides Fig.
Intestinal microbiota depletion raises plasma cholesterol levels and intestinal cholesterol absorption. a Experimental design. See also Additional file 2 : Figure S1.
b Plasma cholesterol, phospholipids and triglycerides levels in conventionally raised Conv-R and microbiota-depleted mice AB-Mdpl. c Cholesterol distribution across the VLDL, LDL, and HDL lipoprotein classes analyzed by fast protein liquid chromatography. e Relative expression of genes related to cholesterol absorption in the jejunum.
f Relative expression of genes related to lipoprotein secretion in the jejunum. Data were analyzed with Mann—Whitney test. Cholesterol in the plasma exists mainly packaged in the form of lipoproteins: chylomicrons, very-low-density lipoproteins VLDLlow-density lipoproteins LDLand high-density lipoproteins HDL.
These experiments confirm that intestinal microbiota contribute to the regulation of plasma cholesterol levels and demonstrate that microbial depletion strongly affect several lipoproteins levels, mainly VLDL and LDL.
As the liver secretes VLDL particles, we investigated the impact of microbiota depletion on VLDL production. Likewise, as LDL particles derive from the loss of triglycerides by VLDL and intestine originating chylomicrons in the bloodstream, we investigated intestinal cholesterol absorption.
We next analyzed the jejunal expression of genes involved in intestinal cholesterol absorption Npc1l1 [ 39 ] and intracellular cholesterol excretion in the gut lumen Abcg5 and 8 [ 40 ]. We observed that microbiota-depleted mice displayed a threefold increase in Npc1l1 expression while Abcg8 expression was moderately raised and Abcg5 expression was not affected Fig.
Moreover, the expression of several genes encoding apolipoproteins and proteins involved in chylomicron and preβ-HDL assembly and secretion were increased at least two folds in the jejunum of microbiota-depleted mice Fig.
VLDL are assembled in the liver from triglycerides, cholesterol, and apolipoproteins ApoB mainly by the chaperone Mttp. Here, liver gene expression levels of ApoB and Mttp of Conv-R and AB-Mdpl mice were similar Additional file 3 : Figure S2A. This is consistent with the similar VLDL secretion rate assessed using Triton WR as an inhibitor of peripheric lipid uptake by endothelial lipoprotein lipase [ 41 ] Additional file 3 : Figure S2B.
This set of experiments reveals that depleting the intestinal microbiota with antibiotics raises intestinal cholesterol absorption.
On the contrary, the hypothesis of elevated VLDL levels in microbiota-depleted mice being a consequence of increased hepatic VLDL synthesis and secretion is rather unlikely. The uptake of cholesterol-rich particles HDL and LDL into the liver is mediated by their respective receptors, scavenger receptor type B1 SR-B1 and LDL receptor LDLr [ 42 ].
mRNA levels of LDLr were significantly increased by microbiota depletion which was not the case for SR-B1 mRNA Fig. This demonstrates that LDLr-mediated cholesterol uptake by the liver partially counteracts the plasma cholesterol raise induced by microbiota depletion.
Intestinal microbiota depletion increases hepatic cholesterol uptake and hepatic cholesterol synthesis. b Hepatic relative expression of cholesterol transporters.
d Hepatic relative expression of genes related to cholesterol synthesis. See also Additional file 5 : Figure S3. e Cholesterol and lathosterol concentration analyzed by GC-MS in the liver. The relative expression of Hmgcs1 and HmgcoArencoding two key enzymes in cholesterol biosynthesis pathway, was not affected following intestinal microbiota depletion in the intestine Additional file 5 : Figure S3 but significantly increased by four- to sevenfold in the liver Fig.
We next determined the liver content of cholesterol and lathosterol, a synthesis intermediate considered as a marker of cholesterol synthesis [ 44 ], by gas chromatography coupled to mass spectrometry GC-MS. This indicates that intestinal microbiota regulates cholesterol biosynthesis specifically in the liver.
Cholesterol is mainly excreted from the body in the bile that is then secreted in the duodenum, leading to fecal excretion in two forms: cholesterol and bile acids.
We demonstrated that biliary cholesterol secretion in the intestinal lumen was significantly increased in AB-Mdpl mice compared to controls Fig.
Enterohepatic cycle of cholesterol and bile acids in conventionally raised and microbiota-depleted mice. a Bile volume collected in 1 h of gallbladder cannulation in conventionally raised Conv-R and microbiota-depleted mice AB-Mdpl.
b Quantity of cholesterol secreted in the bile during 1 h of gallbladder cannulation. c Hepatic gene expression of enzymes involved in bile acid biosynthesis and of transporters of cholesterol and bile acids in conventionally raised Conv-R and microbiota-depleted mice AB-Mdpl.
f Relative expression of fgf15 in the distal ileum. h Relative gene expression of bile acid transporters in the distal ileum. The drastic depletion of intestinal microbiota increases intraluminal cholesterol absorption as well as re-excretion in the bile by the liver.
: Regulating cholesterol levels| How it’s made: Cholesterol production in your body - Harvard Health | Protein Sensors for Membrane Sterols. See also Additional file 2 : Figure S1. Submitted: 30 January Reviewed: 11 March Published: 05 November ORP5 and ORP8 Bind Phosphatidylinositol-4, 5-biphosphate PtdIns 4,5 P 2 and Regulate its Level at the Plasma Membrane. Thyroid hormone regulation of hepatic lipid and carbohydrate metabolism. |
| Main Content | Fiber supplements. Eaton RP. Moreover, STARD1 is expressed ERgulating many choletserol Regulating cholesterol levels extra-gonadal organs, cells, and malignancies, including brain, eye, liver, vasculature, Regukating, heart, lung, skin cells, and so on. Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion—preliminary report. Article CAS PubMed Google Scholar Griffin JD, Lichtenstein AH. If you add fruit, such as a banana or berries, you'll get even more fiber. Van Meer, G. |
| Introduction | Cell Metab. Giordano, F. Non-vesicular Lipid Trafficking at the Endoplasmic Reticulum-Mitochondria Interface. Goldstein, J. Protein Sensors for Membrane Sterols. Cell , 35— Holthuis, J. Lipid Landscapes and Pipelines in Membrane Homeostasis. Nature , 48— Hong, X. The Lipogenic Regulator Srebp2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis. Cancer Discov. Horvat, S. Defects in Cholesterol Synthesis Genes in Mouse and in Humans: Lessons for Drug Development and Safer Treatments. Drug Metab. Horvath, S. Lipids of Mitochondria. Huber, M. Erlins Restrict SREBP Activation in the ER and Regulate Cellular Cholesterol Homeostasis. Ikonen, E. Cellular Cholesterol Trafficking and Compartmentalization. Cholesterol Transport between Cellular Membranes: A Balancing Act between Interconnected Lipid Fluxes. Cell 56, — Ioannou, G. The Role of Cholesterol in the Pathogenesis of NASH. Trends Endocrinol. Irisawa, M. Jiang, L. Ring finger Protein RNF Is a Ubiquitin Ligase for Sterol-Induced Degradation of HMG-CoA Reductase. Jo, Y. Enhanced ER-Associated Degradation of Hmg Coa Reductase Causes Embryonic Lethality Associated with Ubiad1 Deficiency. Elife 9, 1— Sterol-induced Degradation of HMG CoA Reductase Depends on Interplay of Two Insigs and Two Ubiquitin Ligases, Gp78 and Trc8. Membrane-associated Ubiquitin Ligase Complex Containing Gp78 Mediates Sterol-Accelerated Degradation of 3-HydroxyMethylglutaryl-Coenzyme a Reductase. Kattan, W. Targeting Plasma Membrane Phosphatidylserine Content to Inhibit Oncogenic KRAS Function. Life Sci. Alliance 2, e— Kočar, E. Cholesterol, Lipoproteins, and COVID Basic Concepts and Clinical Applications. Lipids , Kong, M. The Chromatin Remodeling Protein BRG1 Regulates SREBP Maturation by Activating SCAP Transcription in Hepatocytes. Kopecka, J. Phospholipids and Cholesterol: Inducers of Cancer Multidrug Resistance and Therapeutic Targets. Drug Resist. Updates 49, Kuan, Y. Ring finger Protein 5 Activates Sterol Regulatory Element-Binding Protein 2 SREBP2 to Promote Cholesterol Biosynthesis via Inducing Polyubiquitination of SREBP Chaperone SCAP. Lange, Y. Disposition of Intracellular Cholesterol in Human Fibroblasts. Laraia, L. The Cholesterol Transfer Protein GRAMD1A Regulates Autophagosome Biogenesis. Lev, S. Non-vesicular Lipid Transport by Lipid-Transfer Proteins and beyond. Lingwood, D. Lipid Rafts as a Membrane-Organizing Principle. Science , 46— Liu, S. FASEB j. Liu, T. Ablation of Gp78 in Liver Improves Hyperlipidemia and Insulin Resistance by Inhibiting SREBP to Decrease Lipid Biosynthesis. Lu, X. Feeding Induces Cholesterol Biosynthesis via the mTORC1-USPHMGCR axis. Nature , — Luo, J. Intracellular Cholesterol Transport by Sterol Transfer Proteins at Membrane Contact Sites. Trends Biochem. Manna, P. Regulation of Retinoid Mediated Cholesterol Efflux Involves Liver X Receptor Activation in Mouse Macrophages. Biophysical Res. Marí, M. Mitochondrial Cholesterol Accumulation in Alcoholic Liver Disease: Role of ASMase and Endoplasmic Reticulum Stress. Redox Biol. Martello, A. Staying in Touch with the Endocytic Network: The Importance of Contacts for Cholesterol Transport. Traffic 21, — Martin, M. Role of Endothelial Cells in Pulmonary Fibrosis via SREBP2 Activation. JCI Insight 6, 1. Maxfield, F. Intracellular Cholesterol Transport. Menzies, S. The Sterol-Responsive RNF E3 Ubiquitin Ligase Mediates the Degradation of HMG-CoA Reductase Together with Gp78 and Hrd1. Elife 7, 1— Meyer, H. Cell Biol 14, — Mohamed, A. Aβ Inhibits SREBP-2 Activation through Akt Inhibition. Montesinos, J. Murley, A. Ltc1 Is an ER-Localized Sterol Transporter and a Component of ER-Mitochondria and ER-Vacuole Contacts. Naito, T. Movement of Accessible Plasma Membrane Cholesterol by the GRAMD1 Lipid Transfer Protein Complex. Elife 8, 1— Nohturfft, A. Regulated Step in Cholesterol Feedback Localized to Budding of SCAP from ER Membranes. Pomorski, T. Lipid Distribution and Transport across Cellular Membranes. Prinz, W. A Cholesterol-Sensing Mechanism Unfolds. Lipid Trafficking Sans Vesicles: where, Why, How? Qin, Y. SQLE Induces Epithelial-To-Mesenchymal Transition by Regulating of MIRb in Esophageal Squamous Cell Carcinoma. Acta Biochim. Sin 49, — Radhakrishnan, A. Switch-like Control of SREBP-2 Transport Triggered by Small Changes in ER Cholesterol: a Delicate Balance. Cell Metab 8, — Switch-like Control of SREBP-2 Transport Triggered by Small Changes in ER Cholesterol: A Delicate Balance. Raghupathy, R. Transbilayer Lipid Interactions Mediate Nanoclustering of Lipid-Anchored Proteins. Ridgway, N. Cholesterol Transfer at Endosomal-Organelle Membrane Contact Sites. Rudney, H. Regulation of Cholesterol Biosynthesis. Russell, D. Cholesterol Biosynthesis and Metabolism. Drug Ther. Sato, R. Sterol-dependent Transcriptional Regulation of Sterol Regulatory Element-Binding Protein Schumacher, M. The Prenyltransferase UBIAD1 Is the Target of Geranylgeraniol in Degradation of HMG CoA Reductase. Elife 4, 1— Sever, N. Insig-dependent Ubiquitination and Degradation of Mammalian 3-HydroxyMethylglutaryl-CoA Reductase Stimulated by Sterols and Geranylgeraniol. Shimano, H. SREBP-regulated Lipid Metabolism: Convergent Physiology - Divergent Pathophysiology. Sohrabi, Y. Altered Cholesterol and Lipid Synthesis Mediates Hyperinflammation in COVID Song, B. Insig-dependent Ubiquitination and Degradation of 3-HydroxyMethylglutaryl Coenzyme A Reductase Stimulated by δ- and γ-Tocotrienols. Insig-mediated Degradation of HMG CoA Reductase Stimulated by Lanosterol, an Intermediate in the Synthesis of Cholesterol. Stevenson, J. Endoplasmic Reticulum-Associated Degradation and Lipid Homeostasis. Su, Z. Acta Pharmacol. Sukhanova, A. Targeting C4-Demethylating Genes in the Cholesterol Pathway Sensitizes Cancer Cells to EGF Receptor Inhibitors via Increased EGF Receptor Degradation. Sundqvist, A. Control of Lipid Metabolism by Phosphorylation-dependent Degradation of the SREBP Family of Transcription Factors by SCFFbw7. Tao, R. Hepatic SREBP-2 and Cholesterol Biosynthesis Are Regulated by FoxO3 and Sirt6. Taylor, J. Overexpression of Steroidogenic Acute Regulatory Protein Increases Macrophage Cholesterol Efflux to Apolipoprotein AI. Turecek, J. Synaptotagmin 7 Confers Frequency Invariance onto Specialized Depressing Synapses. Van Meer, G. Membrane Lipids: Where They Are and How They Behave. Venditti, R. The Activity of Sac1 across ER-TGN Contact Sites Requires the Four-Phosphate-Adaptor-Protein Wakana, Y. The ER Cholesterol Sensor SCAP Promotes CARTS Biogenesis at ER-Golgi Membrane Contact Sites. Wang, J. ER: the Silk Road of Interorganellar Communication. Plant Biol. Wilhelm, L. STARD3 and STARD3NL Tether the ER to Endosomes. Wong, L. Lipid Transfer Proteins: the Lipid Commute via Shuttles, Bridges and Tubes. Wu, J. Integrating Network Pharmacology and RT-qPCR Analysis to Investigate the Mechanisms Underlying ZeXie Decoction-Mediated Treatment of Non-alcoholic Fatty Liver Disease. Since cholesterol is a fat, it can't travel alone in the bloodstream. It would end up as useless globs imagine bacon fat floating in a pot of water. To get around this problem, the body packages cholesterol and other lipids into minuscule protein-covered particles that mix easily with blood. These tiny particles, called lipoproteins lipid plus protein , move cholesterol and other fats throughout the body. Cholesterol and other lipids circulate in the bloodstream in several different forms. Of these, the one that gets the most attention is low-density lipoprotein— better known as LDL, or "bad" cholesterol. Having excess weight or obesity can increase your risk of developing high cholesterol levels. Losing weight, if you have excess weight, can help lower your cholesterol levels. Overall, weight loss has a double benefit on cholesterol by decreasing harmful LDL and increasing beneficial HDL. Consider working with a doctor to determine a nutrient-dense diet and sustainable weight management plan that works for you. Smoking tobacco increases the risk of heart disease in several ways, including:. Giving up smoking, if possible, can help reverse these harmful effects. According to a review of studies , some research indicates that when consumed in moderation, alcoholic drinks can increase good HDL cholesterol and reduce the risk of heart disease. Yet the Centers for Disease Control and Prevention CDC and AHA disagree. The AHA does not recommend drinking wine or any other alcoholic beverage specifically to lower your cholesterol or improve heart health. If you drink, the CDC suggests you consume only two drinks per day for males or one drink per day for females on days that you drink. Multiple types of supplements show promise for managing cholesterol. Plant stanols and sterols are plant versions of cholesterol. According to a research review, clinical studies show that taking 1. Small amounts of plant stanols and sterols are naturally found in vegetable oils and are added to certain oils and butter substitutes. You may also consider taking certain types of supplements. But speak with a healthcare professional before starting or changing your supplement regimen. Although food companies often advertise products as being low in cholesterol, research from shows that dietary cholesterol has only a small influence on the amount of cholesterol in your body. That said, some foods high in soluble fibers, omega-3 fatty acids, or monounsaturated fats may help lower cholesterol, including:. Typically, there are no symptoms of high cholesterol. However, signs or symptoms of high cholesterol may include:. Eating foods with cholesterol may not raise your blood cholesterol levels. Eggs may be part of a healthy, balanced diet. However, if you are at risk for cardiovascular disease, you may want to limit the number of eggs you eat each week. Exercise and weight loss can also help. Read this article in Spanish. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. VIEW ALL HISTORY. This article is based on scientific evidence, written by experts and fact checked by experts. Our team of licensed nutritionists and dietitians strive to be objective, unbiased, honest and to present both sides of the argument. This article contains scientific references. |
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