Modulation of meal pattern in the rat by the anorexic lipid mediator oleoylethanolamide

Oleoylethanolamide (CEA) is a structural analog of the endogenous cannabinoid anandamide, which does not activate cannabinoid receptors. The biosynthesis of OEA in rat small intestine is increased by feeding and reduced by fasting. Moreover, OEA decreases food intake in food-deprived rats via a mechanism that requires intact sensory fibers (Rodriguez de Fonseca, 200 1). These results suggest that OEA may contribute to the peripheral regulation of feeding. In the present study, we have investigated the effects of systemic OFA administration (1-20 mg/kg, intraperitoneal) on meal pattern in free-feeding and food-deprived rats. In free-feeding animals, OEA delayed feeding onset in a dose-dependent manner, but had no effect on meal size or postmeal interval In food-deprived animals, OEA both delayed feeding onset and reduced meal size. The selective effects of OEA in free-feeding rats are strikingly different from those of the serotonergic anonexiant d-fenfluramine (which delayed feeding and reduced meal size) and the intestinal peptide cholecystokinin (which reduced meal size). These results suggest that OEA may participate in the regulation of satiety and may provide a chemical scaffold for the design of novel appetite-suppressing medications

Control of food intake and energy expenditure by amylin-therapeutic implications

Amylin is a pancreatic B-cell hormone that plays an important role in the control of nutrient fluxes because it reduces food intake, slows gastric emptying, and reduces postprandial glucagon secretion. These actions seem to depend on a direct effect on the area postrema (AP). Subsequent to area AP activation, the amylin signal is conveyed to the forebrain via distinct relay stations. Within the lateral hypothalamic area, amylin diminishes the expression of orexigenic neuropeptides. Recent studies suggest that amylin may also play a role as a long term, adiposity signal. Similar to leptin or insulin, an infusion of amylin into the brain resulted in lower body weight gain than in controls, irrespective of the starting body weight. Interestingly, preliminary data also suggest that rats fed an energy-dense diet develop resistance to central amylin. In addition to amylin's action to control meal termination and to act as a potential adiposity signal, amylin and its agonist salmon calcitonin have recently been shown to increase energy expenditure under certain conditions. In summary, amylin may be an interesting target as a body weight lowering drug. In fact, recent studies provide evidence that amylin, especially when combined with other anorectic hormones (for example, peptide YY and leptin) has beneficial long-term effects on body weight

Exogenous peptide YY3-36 and Exendin-4 further decrease food intake, whereas octreotide increases food intake in rats after Roux-en-Y gastric bypass

Background:Patients show an elevated postprandial satiety gut hormone release after Roux-en-Y Gastric bypass (gastric bypass). The altered gut hormone response appears to have a prominent role in the reduction of appetite and body weight (BW) after gastric bypass. Patients with insufficient BW loss after gastric bypass have an attenuated postprandial gut hormone response in comparison with patients who lost an adequate amount of BW. The effects of additional gut hormone administration after gastric bypass are unknown.Methods:The effects of peripheral administration of peptide YY3-36 (PYY3-36; 300 nmol kg(-1)), glucagon-like peptide-1 (GLP-1) analogue Exendin-4 (20 nmol kg(-1)) and somatostatin analogue octreotide (10 μg kg(-1)) on feeding and BW were evaluated in rats after gastric bypass.Results:Gastric bypass rats weighed (P<0.01) and ate less on postoperative day 5 (P<0.001) and thereafter, whereas postprandial plasma PYY and GLP-1 levels were higher compared with sham-operated controls (P<0.001). Administration of both PYY3-36 and Exendin-4 led to a further decrease in food intake in bypass rats compared with saline treatment (P=0.02 and P<0.0001, respectively). Similar reduction in food intake was observed in sham rats (P=0.02 and P<0.001, respectively). Exendin-4 treatment resulted in a significant BW loss in bypass (P=0.03) and sham rats (P=0.04). Subsequent treatment with octreotide led to an increase in food intake in bypass (P=0.007), but not in sham rats (P=0.87).Conclusion:Peripheral administration of PYY3-36 and Exendin-4 reduces short-term food intake, whereas octreotide increases short-term food intake in rats after gastric bypass. The endogenous gut hormone response after gastric bypass can thus potentially be further enhanced by additional exogenous therapy with pharmacological doses of gut hormones in patients with insufficient weight loss or weight regain after surgery.International Journal of Obesity advance online publication, 21 June 2011; doi:10.1038/ijo.2011.126