0000000000013866
AUTHOR
Hélène Poirier
CD36 as a lipid sensor
International audience; CD36 is a multifunctional protein homologous to the class B scavenger receptor SR-B1 mainly found in tissues with a sustained lipid metabolism and in several hematopoieic cells. CD36 is thought to be involved in various physiological and pathological processes like angiogenesis, thrombosis, atherogenesis, Alzheimer's disease or malaria. An additive emerging function for CD36 is a role as a lipid sensor. Location of CD36 and orthologue molecules in plasma membrane of cells in contact with the external environment (e.g. gustatory, intestinal or olfactory epithelia) allows the binding of exogenous-derived ligands including dietary lipids, diglycerides from bacterial wal…
CLA-Enriched Diet Containing t10,c12-CLA Alters Bile Acid Homeostasis and Increases the Risk of Cholelithiasis in Mice
International audience; Mice fed a mixture of CLA containing t10,c12-CLA lose fat mass and develop hyperinsulinemia and hepatic steatosis due to an accumulation of TG and cholesterol. Because cholesterol is the precursor in bile acid (BA) synthesis, we investigated whether t10,c12-CLA alters BA metabolism. In Expt. 1, female C57Bl/6J mice were fed a standard diet for 28 d supplemented with a CLA mixture (1 g/100 g) or not (controls). In Expt. 2, the feeding period was reduced to 4, 6, and 10 d. In Expt. 3, mice were fed a diet supplemented with linoleic acid, c9,t11-CLA, or t10,c12-CLA (0.4 g/100 g) for 28 d. In Expt. 1, the BA pool size was greater in CLA-fed mice than in controls and the …
CLA, “new nutrients”?
International audience; Conjugated linoleic acid (CLA) refers to a class of positional and geometric dienoic isomers of linoleic acid. Chronic dietary supplementation with commercial isomeric mixtures sold as dietary supplements leads to a drop in fat mass in various species. The t10,c12-CLA isomer is responsible for this antiobesity effect.The reduction of fat mass is especially dramatic in the mouse, in which it is associated with a severe hyperinsulinemia, an insulin resistance and a massive liver steatosis. The origin of these adverse side effects and the putative chronology of events leading to CLA-mediated lipoatrophic syndrome are presented and discussed in this review. In Human, the…
P059 Le lipido-récepteur intestinal CD36 et sa cascade de signalisation ERK1/2 dépendante contrôle la synthèse des chylomicrons
International audience; Introduction et but de l’étude. – L’intestin est capable d’adapter sa capacité d’absorption à la teneur en lipide du régime. Cette adaptation implique un système de détection des lipides au niveau entérocytaire. Le CD36, qui est une glycoprotéine transmembranaire liant avec une forte affinité les acides gras à longue chaîne (AGLC), pourrait jouer ce rôle. En effet, ex vivo, la présence d’AGLC est associée à une activation de la voie ERK1/2 et conduit à l’induction de protéines clés du métabolisme intestinal des lipides : l’ApoB48 et la MTP. Cette régulation est CD36 dépendante (Tran et al. 2011). De plus, la déficience de CD36 est associée chez l’Homme et l’animal à …
Induction of the fatty acid transport protein 1 and acyl-CoA synthase genes by dimer-selective rexinoids suggests that the peroxisome proliferator-activated receptor-retinoid X receptor heterodimer is their molecular target
The intracellular fatty acid content of insulin-sensitive target tissues determines in part their insulin sensitivity. Uptake of fatty acids into cells is a controlled process determined in part by a regulated import/export system that is controlled at least by two key groups of proteins, i.e. the fatty acid transport protein (FATP) and acyl-CoA synthetase (ACS), which facilitate, respectively, the transport of fatty acids across the cell membrane and catalyze their esterification to prevent their efflux. Previously it was shown that the expression of the FATP-1 and ACS genes was controlled by insulin and by peroxisome proliferator-activated receptor (PPAR) agonists in liver or in adipose t…
CD36 Displays Features of a Lipid-Sensor Involved in Chylomicron Processing in the Rodent Small Intestine
International audience; The membrane glycoprotein CD36 binds nanomolar concentrations of long-chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms.In this report, we provide novel insights into the potential underlying mechanisms. Our in vivo data demonstrated that CD36 gene deletion in mice did not affect LCFA uptake and their subsequent esterification into triglycerides by the intestinal mucosa at micellar LCFA concentrations prevailing in the intestine. In rodents, CD36 protein early disappeared from the luminal side of intestinal villi during the post-prandial period but only whe…
Link between Intestinal CD36 Ligand Binding and Satiety Induced by a High Protein Diet in Mice
International audience; CD36 is a ubiquitous membrane glycoprotein that binds long-chain fatty acids. The presence of a functional CD36 is required for the induction of satiety by a lipid load and its role as a lipid receptor driving cellular signal has recently been demonstrated. Our project aimed to further explore the role of intestinal CD36 in the regulation of food intake. Duodenal infusions of vehicle or sulfo-N-succinimidyl-oleate (SSO) was performed prior to acute infusions of saline or Intralipid (IL) in mice. Infusion of minute quantities of IL induced a decrease in food intake (FI) compared to saline. Infusion of SSO had the same effect but no additive inhibitory effect was obser…
Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissue.
Conjugated linoleic acids (CLAs) are conjugated dienoic isomers of linoleic acid. Many people supplement their diets with CLAs to attempt weight loss, and the trans-10,cis-12 isomer (t10,c12-CLA) of CLA reduces adiposity in animal models and humans. However, CLA treatment in mice causes insulin resistance that has been attributed to the lipoatrophic state, which is associated with hyperinsulinemia and hepatic steatosis. Here, we investigated the effect of t10,c12-CLA on adipose tissue inflammation, another factor promoting insulin resistance. We confirmed that t10,c12-CLA daily gavage performed in mice reduces white adipose tissue (WAT) mass and adiponectin and leptin serum levels and provo…
O04 Le sensing intestinal des lipides alimentaires médié par CD36 est-il altéré en cas de syndrome métabolique ?
International audience; [Pas de résumé]
Mécanisme d’absorption intestinale des acides gras à longue chaîne : rôle émergent du CD36
International audience; Excessive lipid intake, associated with a qualitative imbalance, favors the development of obesity and associated diseases. Among the organs involved in lipid homeostasis, the small intestine remains the most poorly known although it is responsible for the lipid bioavailability and largely contributes to the regulation of postprandial hypertriglyceridemia. The mechanism of long chain fatty acid (LCFA) intestinal absorption is not totally elucidated. The synthesis of recent literature indicates that the intestine is able to adapt its absorption capacity to the fat content of the diet. This adaptation takes place through a fat-coordinated induction of LBP and apolipopr…
Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model
International audience; The metabolic syndrome (MetS) greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL) in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD). By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertrigl…
Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36. : Obesity decreases the fat preference
International audience; A relationship between orosensory detection of dietary lipids, regulation of fat intake, and body mass index was recently suggested. However, involved mechanisms are poorly understood. Moreover, whether obesity can directly modulate preference for fatty foods remains unknown. To address this question, exploration of the oral lipid sensing system was undertaken in diet-induced obese (DIO) mice. By using a combination of biochemical, physiological, and behavioral approaches, we found that i) the attraction for lipids is decreased in obese mice, ii) this behavioral change has an orosensory origin, iii) it is reversed in calorie-restricted DIO mice, revealing an inverse …
9-cis-Retinoic acid enhances fatty acid-induced expression of the liver fatty acid-binding protein gene
The role of retinoic acids (RA) on liver fatty acid- binding protein (L-FABP) expression was investigated in the well differentiated FAO rat hepatoma cell line. 9-cis-Retinoic acid (9-ci's-RA) specifically enhanced L-FABP mRNA levels in a time- and dose-dependent manner. The higher induction was found 6 h after addition of 10 -6 M 9-CK-RA in the medium. RA also enhanced further both L-FABP mRNA levels and cytosolic L-FABP protein content induced by oleic acid. The retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR), which are known to be activated, respectively, by 9-c/s-RA and long chain fatty acid (LCFA), co-operated to bind specifically the peroxisome prol…
Obesogen effects after perinatal exposure of 4,4′-sulfonyldiphenol (Bisphenol S) in C57BL/6 mice
International audience; Bisphenol A were removed from consumer products and replaced by chemical substitutes such as Bisphenol S (BPS). Based on their structural similarity, BPS may be obesogen like Bisphenol A in mice. Our objective was to determine the impact of BPS on lipid homeostasis in C57B1/6 mice after perinatal and chronic exposure. Pregnant mice were exposed to BPS via the drinking water (0.2; 1.5; 50 mu g/kg bw/d). Treatment began at gestational day 0 and continued in offspring up to 23-weeks old. Then, offspring mice were fed with a standard or high fat diet. The body weight, food consumption, fat mass and energy expenditure were measured. A lipid load test was performed to chec…
From fatty-acid sensing to chylomicron synthesis: Role of intestinal lipid-binding proteins
International audience; Today, it is well established that the development of obesity and associated diseases results, in part, from excessive lipid intake associated with a qualitative imbalance. Among the organs involved in lipid homeostasis, the small intestine is the least studied even though it determines lipid bioavailability and largely contributes to the regulation of postprandial hyperlipemia (triacylglycerols (TG) and free fatty acids (FFA)). Several Lipid-Binding Proteins (LBP) are expressed in the small intestine. Their supposed intestinal functions were initially based on what was reported in other tissues, and took no account of the physiological specificity of the small intes…
Luminal Lipid Regulates CD36 Levels and Downstream Signaling to Stimulate Chylomicron Synthesis
International audience; The membrane glycoprotein CD36 binds nanomolar concentrations of long chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into some of the underlying mechanisms. Our in vivo data demonstrate that CD36 gene deletion in mice does not affect LCFA uptake and subsequent esterification into triglycerides by the intestinal mucosa exposed to the micellar LCFA concentrations prevailing in the intestine. In rodents, the CD36 protein disappears early from the luminal side of intestinal villi during the postprandial period, but …