Inhibition of protein synthesis and intestinal absorptive cell ultrastructure in cycloheximide or puromycin-treated rats

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Actidione-cycloheximide et voie d'absorption intestinale des lipides chez le rat

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Fatty acid regulation of fatty acid-binding protein expression in the small intestine

International audienceThe effects of dietary oil intake and fatty acid infusions on the expression of intestinal and liver fatty acid-binding proteins (I-FABP and L-FABP, respectively) were investigated in the small intestine of mice. A daily force-feeding for 7 days with 0.2 ml sunflower oil specifically increased L-FABP mRNA and protein levels in duodenum and proximal jejunum. This upregulation was mediated in time- and dose-dependent manners by a minute quantity of linoleic acid, the main fatty acid found in sunflower oil. The L-FABP induction was only found with long-chain fatty acids, with the nonmetabolizable, substituted fatty acid alpha-bromopalmitate being far more active. A hormonally mediated effect is unlikely because long-chain fatty acids induced L-FABP mRNA in the Caco-2 cell line cultured in serum-free medium. Therefore, long-chain fatty acids are strong inducers of L-FABP gene expression in the small intestine. In contrast to data found in the rat, I-FABP gene expression appears to be unaffected by a lipid-enriched diet in the mouse

Chronic high-fat diet affects intestinal fat absorption and postprandial triglyceride levels in the mouse

International audienceThe effects of chronic fat overconsumption on intestinal physiology and lipid metabolism remain elusive. It is unknown whether a fat-mediated adaptation to lipid absorption takes place. To address this issue, mice fed a high-fat diet (40%, w/w) were refed or not a control diet (3%, w/w) for 3 additive weeks. Despite daily lipid intake 7.7-fold higher than in controls, fecal lipid output remained unchanged in mice fed the triglyceride (TG)-rich diet. In situ isolated jejunal loops revealed greater [1-(14)C]linoleic acid uptake without TG accumulation in mucosa, suggesting an increase in lipid absorption capacity. Induction both in intestinal mitotic index and in the expression of genes involved in fatty acid uptake, trafficking, and lipoprotein synthesis was found in high-fat diet mice. These changes were lipid-mediated, in that they were fully abolished in mice refed the control diet. A lipid load test performed in the presence or absence of the LPL inhibitor tyloxapol showed a sustained blood TG clearance in fat-fed mice likely attributable to intestinal modulation of LPL regulators (apolipoproteins C-II and C-III). These data demonstrate that a chronic high-fat diet greatly affects intestinal physiology and body lipid use in the mouse

Hyperinsulinaemia triggered by dietary conjugated linoleic acid is associated with a decrease in leptin and adiponectin plasma levels and pancreatic beta cell hyperplasia in the mouse

International audienceDietary supplementation with conjugated linoleic acids (CLA) has a fat-reducing effect in various species, but induces severe hyperinsulinaemia and hepatic steatosis in the mouse. This study aimed to determine the causes of the deleterious effects of CLA on insulin homeostasis. The chronology of adipose and liver weight, hepatic triglyceride accumulation and selected blood parameters, including lipids, insulin, leptin and adiponectin, was determined in C57BL/6J female mice fed a 1% isomeric mixture of CLA for various periods of time ranging from 2 to 28 days. Insulin secretion was measured in 1-h static incubations of pancreatic islets, and pancreas morphometric parameters were determined in mice fed CLA for 28 days. Plasma levels of leptin and adiponectin sharply decreased after 2 days of CLA feeding, although adipose tissue mass only decreased after day 6. Hyperinsulinaemia developed at day 6 and consistently worsened up to day 28, in parallel with increases in hepatic lipid content. Islets from CLA-fed mice displayed three- to four-fold increased rates of glucose-stimulated insulin secretion, both in the absence and presence of isobutyl methylxanthine or carbachol. The increased insulin-releasing capacity of islets from CLA-fed mice was explained by an increase in beta cell mass and number. The data suggest that CLA supplementation induces a profound reduction of leptinaemia and adiponectinaemia, followed by hyperinsulinaemia due to the increased secretory capacity of pancreatic islets, leading, in turn, to liver steatosis. These observations cast doubt on the safety of dietary supplements containing CLA

Varia

Le langage, l’espace public, la méthode, thèmes prégnants de ce numéro varia. La comparaison des classiques confucéens et des cosmogonies périphériques, telle celle des Hani dans la province du Yunnan, soulève d’abord la question des influences réciproques entre différentes constructions mythologiques que l’Empire du Milieu a mises en contact. L’analyse rhétorique vient ensuite éclairer les enjeux de la concurrence au salut des âmes que se livrent les voix catholiques, protestantes et musulmanes dans la Haute-Volta coloniale (aujourd’hui Burkina Faso). Les mots mêmes sont des êtres qui font agir au-delà du sens qu’ils véhiculent comme le rappelle l’examen d’un débat scolastique dans la chrétienté médiévale. Enfin, l’attention portée aux gestes, comme c’est le cas pour l’étude de certaines salutations cérémonielles au Brésil, met à jour leur force de lien. Dans une perspective de science politique, sont ensuite décrits le rôle joué par la philanthropie bouddhiste dans l’action sociale de la Chine contemporaine ainsi qu’en Italie l’émergence d’un islam national s’ancrant dans les collectivités locales. Deux réflexions de nature méthodologique et épistémologique ferment la marche : l’une sur la mesure quantitative des pratiques religieuses en Suisse; l’autre sur les limites de l’analogie religieuse dans l’approche de la célébrité publique. Un petit dossier thématique s’adjoint à cette livraison par un retour sur Thérèse de Lisieux comme figure littéraire (Theresiana). La jeune sainte carmélite fut-elle en effet une écrivaine, progressivement enfouie par le procès de sa sanctification ? Cette forte hypothèse, développée par Claude Langlois dans de nombreux ouvrages, est ici présentée, discutée et accompagnée par d’autres approches d’une expérience d’écriture féminine conventuelle à l’époque du Modernisme catholique

Luminal Lipid Regulates CD36 Levels and Downstream Signaling to Stimulate Chylomicron Synthesis

International audienceThe 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 only when the diet contains lipids. This drop is significant 1 h after a lipid supply and associates with ubiquitination of CD36. Using CHO cells expressing CD36, it is shown that the digestion products LCFA and diglycerides trigger CD36 ubiquitination. In vivo treatment with the proteasome inhibitor MG132 prevents the lipid-mediated degradation of CD36. In vivo and ex vivo, CD36 is shown to be required for lipid activation of ERK1/2, which associates with an increase of the key chylomicron synthesis proteins, apolipoprotein B48 and microsomal triglyceride transfer protein. Therefore, intestinal CD36, possibly through ERK1/2-mediated signaling, is involved in the adaptation of enterocyte metabolism to the postprandial lipid challenge by promoting the production of large triglyceride-rich lipoproteins that are rapidly cleared in the blood. This suggests that CD36 may be a therapeutic target for reducing the postprandial hypertriglyceridemia and associated cardiovascular risks

CD36 Displays Features of a Lipid-Sensor Involved in Chylomicron Processing in the Rodent Small Intestine

International audienceThe 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 when the diet contained lipids. This drop was significant 1 h after a lipid supply and was associated with an ubiquitination of CD36 as reported during the ligand receptor desensitization process. Using CHO cells expressing CD36, it is shown that the digestion products, LCFA and diglycerides, triggered the CD36 ubiquitination. In vivo treatment with the proteasome inhibitor MG132 prevented the lipid-mediated degradation of CD36 and the up-regulation of L-FABP, a key gene implicated in the formation and secretion of large chylomicrons. Since the L-FABP up-regulation by lipids remained abolished in CD36-null mice with and without MG132, CD36 degradation appears to be linked to the chylomicron formation.Therefore, intestinal CD36 displays features of a lipid sensor involving in the adaptation of enterocyte metabolism to the post-prandial lipid challenge by producing large triglyceride-rich lipoproteins rapidly cleared in blood. This finding raises the possibility of alternative therapeutic approaches to reduce the post-prandial hypertriglyceridemia and prevent cardiovascular risks

Intestinal CD36. A lipid-sensor involved in the processing of chylomicrons in rodents

International audienceCD36 is a multifunctional glycoprotein which binds nanomolar concentrations of long-chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. Despite of its implication in oleoylethanolamide (OEA) and chylomicron synthesis, CD36 function in small intestine remains incompletely understood. Our in vivo data demonstrated that CD36 gene deletion in mice did not affect intestinal LCFA uptake. CD36 protein disappeared early from the luminal side of intestinal villi during the post-prandial period but only when the diet contained lipids. This drop was significant 1 h after a lipid supply and was associated with ubiquitination of CD36. Using CHO cells expressing CD36, it was shown that the digestion products, LCFA and diglycerides, trigger CD36 ubiquitination. In vivo treatment with a proteasome inhibitor prevented the lipid-mediated degradation of CD36. In vivo and ex vivo, CD36 was required for dietary-lipid activation of ERK1/2 which is associated ex vivo with an increase of ApoB48 and MTP, proteins involved in chylomicron formation. Therefore, intestinal CD36 through ERK1/2 mediated signaling displays features of a lipid sensor involved in the adaptation of intestinal metabolism to the postprandial lipid challenge by promoting the production of large chylomicrons rapidly cleared in the blood. Supported by: National Institute of Health and Medical Research (INSERM) and the National Institute of Agronomic Research (INRA) and by grants from the Research Program in Human Nutrition SensoFAT, French National