Acute activation of cannabinoid receptors by anandamide reduces gastrointestinal motility and improves postprandial glycemia in mice.

International audienceThe endocannabinoid system (ECS) is associated with an alteration of glucose homeostasis dependent on cannabinoid receptor-1 (CB1R) activation. However, very little information is available concerning the consequences of ECS activation on intestinal glucose absorption. Mice were injected intraperitoneally with anandamide, an endocannabinoid binding both CB1R and CB2R. We measured plasma glucose and xylose appearance after oral loading, gastrointestinal motility, and glucose transepithelial transport using the everted sac method. Anandamide improved hyperglycemia after oral glucose charge whereas glucose clearance and insulin sensitivity were impaired, pointing out some gastrointestinal events. Plasma xylose appearance was delayed in association with a strong decrease in gastrointestinal transit, while anandamide did not alter transporter-mediated glucose absorption. Interestingly, transit was nearly normalized by coinjection of SR141716 and AM630 (CB1R and CB2R antagonist, respectively), and AM630 also reduced the delay of plasma glucose appearance induced by anandamide. When gastric emptying was bypassed by direct glucose administration in the duodenum, anandamide still reduced plasma glucose appearance in wild-type but not in CB1R(-/-) mice. In conclusion, our findings demonstrated that acute activation of intestinal ECS reduced postprandial glycemia independently on intestinal glucose transport but rather inhibiting gastric emptying and small intestine motility and strongly suggest the involvement of both CB1R and CB2R

Effets de l’acide trans-10, cis-12 linoléique sur le métabolisme des lipides dans le foie chez la souris C57BL/6

A 4-week diet containing 1% of the conjugated trans-10,cis-12 linoleic acid (CLA2) induces, in C57BL/6 mice, a lipodystrophy, a liver steatosis and a reduction of plasma triglycerides. We demonstrate that, first, hepatic lipid accumulation is not due to an in vivo alteration of lipoprotein production. Fates of CLA2 relative to ß-oxidation reactions are then studied in mitochondrial fractions isolated from liver of control animals and the data indicate not only that the CLA is poorly oxidised but also that it modifies the oxidation of usual fatty acids. We also demonstrate that oxidation capacities are increased by CLA2 treatment concomitantly to carnitine palmitoyltransferase I (CPT I) activity. Besides, the increases in acetyl-CoA carboxylase activity and malonyl-CoA concentration in the liver of CLA2 treated mice provide evidence of a high rate of lipogenesis. The increased CPT I sensibility to malonyl-CoA inhibition due to the treatment suggests that the whole fatty acid ß-oxidation is finally reduced in vivo. The mechanisms implicated in the setup of the hepatic steatosis and in the reduction of the lipaemia despite the increased VLDL secretion are discussed

L’activation du système endocannabinoide dans le tissu adipeux altère l’action anti-lipolytique de l’insuline

International audienc

Changes in membrane lipid composition in ethanol- and acid-adapted Oenococcus oeni cells: characterization of the cfa gene by heterologous complementation

International audienceCyclopropane fatty acid (CFA) synthesis was investigated in Oenococcus oeni. The data obtained demonstrated that acid-grown cells or cells harvested in the stationary growth phase showed changes in fatty acid composition similar to those of ethanol-grown cells. An increase of the CFA content and a decrease of the oleic acid content were observed. The biosynthesis of CFAs from unsaturated fatty acid phospholipids is catalysed by CFA synthases. Quantitative real-time-PCR experiments were performed on the cfa gene of O. oeni, which encodes a putative CFA synthase. The level of cfa transcripts increased when cells were harvested in stationary phase and when cells were grown in the presence of ethanol or at low pH, suggesting transcriptional regulation of the cfa gene under different stress conditions. In contrast to Escherichia coli, only one functional promoter was identified upstream of the cfa gene of O. oeni. The function of the cfa gene was confirmed by complementation of a cfa-deficient E. coli strain. Nevertheless, the complementation remained partial because the conversion percentage of unsaturated fatty acids into CFA of the complemented strain was much lower than that of the wild-type strain. Moreover, a prevalence of cycC19 : 0 was observed in the membrane of the complemented strain. This could be due to a specific affinity of the CFA synthase from O. oeni. In spite of this partial complementation, the complemented strain of E. coli totally recovered its viability after ethanol shock (10 %, v/v) whereas its viability was only partly recovered after an acid shock at pH 3.0

Effect of short and long-term treatments by a low level of dietary L-carnitine on parameters related to fatty acid oxidation in Wistar rat

International audienceThis study was designed to examine whether short- and long-term treatments by a low level of dietary l-carnitine are capable of altering enzyme activities related to fatty acid oxidation in normal Wistar rats. Under controlled feeding, ten days of treatment changed neither body weights nor liver and gastrocnemius weights, but succeeded in reducing the weight of peri-epididymal adipose tissues. Triacylglycerol contents were lowered in liver and ketone body concentrations were found slightly more elevated in blood. In the liver, mitochondrial carnitine palmitoyltransferase I (CPT I) exhibited a slightly higher specific activity and a lower sensitivity to malonyl-CoA inhibition, while peroxisomal fatty acid oxidizing system (PFAOS) was found to be less active. Carnitine supplied for one month reduced the mass of the periepididymal fat tissue, but not those of the other studied organs, and produced a slight but non-significant gain in body weight after ten days of treatment. In the liver, CPTI characteristics were comparable in control and treated groups, while PFAOS activity was less in rats receiving carnitine. Data show that l-carnitine at a low level in the diet exerted two paradoxical effects before and after ten days of treatment. Results are discussed in regard to fatty acid oxidation in mitochondria and peroxisomes, and to the possible altered acyl-CoA/acylcarnitine ratio with increased concentrations of l-carnitine in the liver