n-oleoylethanolamine and Weight-Gain

The endocannabinoid system is dysregulated during obesity in tissues involved in the control of food intake and energy metabolism. We examined the effect of chronic exercise on the tissue levels of endocannabinoids (eCBs) and on the expression of genes coding for cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) (Cnr1 and Cnr2, respectively) in the subcutaneous (SAT) and visceral adipose tissues and in the soleus and extensor digitorim longus (EDL) muscles, in rats fed with standard or high-fat diet. Twenty-eight male Wistar rats were placed on high-fat diet or standard diet (HFD and Ctl groups, respectively) during 12 weeks whereafter half of each group was submitted to an exercise training period of 12 weeks (HFD + training and Ctl + training). Tissue levels of eCBs were measured by LC-MS while expressions of genes coding for CB1 and CB2 receptors were investigated by qPCR. High-fat diet induced an increase in anandamide (AEA) levels in soleus and EDL (p < 0.02). In soleus of the HFD group, these changes were accompanied by elevated Cnr1 messenger RNA (mRNA) levels (p < 0.05). In EDL, exercise training allowed to reduce significantly this diet-induced AEA increase (p < 0.005). 2-Arachidonoylglycerol (2-AG) levels were decreased and increased by high-fat diet in SAT and EDL, respectively (p < 0.04), but not affected by exercise training. Unlike the HFD + training group, 2-AG levels in soleus were also decreased in the HFD group compared to Ctl (p < 0.04). The levels of eCBs and Cnr1 expression are altered in a tissue-specific manner following a high-fat diet, and chronic exercise reverses some of these alterations.

Topics: Amides; Animals; Arachidonic Acids; Body Composition; Diet, High-Fat; Endocannabinoids; Ethanolamines; Gene Expression Regulation; Glycerides; Hyperglycemia; Intra-Abdominal Fat; Male; Motor Activity; Muscle, Skeletal; Obesity; Oleic Acids; Organ Specificity; Palmitic Acids; Polyunsaturated Alkamides; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Subcutaneous Fat, Abdominal; TRPV Cation Channels; Weight Gain

Obesity prevalence in developed countries has promoted the need to identify the mechanisms involved in control of feeding and energy balance. We have tested the hypothesis that different fats present in diet composition may contribute in body weight gain and body indexes by regulation of oxytocin gene (oxt) expression in hypothalamus and Oleylethanolamide (OEA) levels in plasma. Sprague-Dawley rats were fed two high fat diets, based on corn (HCO) and extra virgin olive oil (HOO) and results were compared to a low fat diet (LF). LC-MS/MS analysis showed an increasing trend of OEA plasma levels in HOO group, although no significant differences were found. However, body weight gain of LF and HOO were similar and significantly lower than HCO. HCO rats also had higher Lee index than HOO. Rats fed HOO diet showed higher levels of hypothalamic oxt mRNA expression, which could indicate that oxytocin may be modulated by dietary lipids.

Topics: Animals; Body Mass Index; Body Weight; Chromatography, High Pressure Liquid; Chromatography, Liquid; Corn Oil; Diet, Fat-Restricted; Diet, High-Fat; Dietary Fats; Male; Obesity; Oleic Acids; Olive Oil; Oxytocin; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tandem Mass Spectrometry; Weight Gain

Oleoylethanolamide (OEA) has been previously reported to regulate food intake and body weight gain when administered intraperitoneally. Nevertheless, little information is available with regard to oral administration. To assess whether oral OEA can also exert a similar effect on body fat, we fed C3H mice a high-fat diet supplemented with either 10 or 100 mg/kg body weight OEA for 4 weeks. OEA supplementation significantly lowered food intake over the 4 weeks and decreased adipose tissue mass. Plasma triglyceride levels were also significantly decreased by OEA treatment. In order to identify the potential molecular targets of OEA action, we screened the expression levels of 44 genes related to body fat mass and food intake in peripheral tissues. Adipose tissue fatty acid amide hydrolase (FAAH), intestinal fatty acid transporter/cluster of differentiation 36 and the OEA receptor G-protein-coupled receptor 119 (GPR119) were among the most OEA-responsive genes. They were also associated with reduced body fat pads regardless of the dose. Adipose FAAH was found to be primarily associated with a decrease in food intake. Our data suggest that the anti-obesity activity of OEA partially relies on modulation of the FAAH pathway in adipose tissue. Another mechanism might involve modulation of the newly discovered GPR119 OEA signaling pathway in the proximal intestine. In conclusion, our study indicates that oral administration of OEA can effectively decrease obesity in the mouse model and that modulation of the endocannabinoid fatty acid ethanolamide pathway seems to play an important role both in adipose tissue and in small intestine.

Topics: Adipose Tissue; Animals; Diet; Endocannabinoids; Feeding Behavior; Gene Expression Profiling; Male; Mice; Mice, Inbred C3H; Oleic Acids; Triglycerides; Weight Gain