Administration of physiologic plasma lipid reduces food intake in rats and mice

Gillum MP et al. (2008) N-acylphosphatidylethanolamine, a gut- derived circulating factor induced by fat ingestion, inhibits food intake. Cell 135: 813–824

Regulation of the intake of dietary fat, the macronutrient that most promotes obesity, is a primary target of research into obesity. Gillum et al. found that fasted rats fed a high-fat diet display significantly increased plasma concentrations of N-acylphosphatidylethanolamines (NAPEs), and that intraduodenal infusion of a lipid—but not of dextrin or casein—induced a significant increase in lymph concentrations of NAPEs.

Intraperitoneal injection of the most abundant NAPE, C16:0, caused a dose-dependent decrease in food intake in mice. In rats, intraperitoneal infusion of 100 mg/kg of C16:0 NAPE led to a significant reduction of food intake, but did not cause conditioned taste aversion. Importantly, the 7 h profiles of the total plasma concentration of NAPEs in rats were similar following intraduodenal lipid infusion or injection of 100 mg/kg C16:0 NAPE. Data suggest that the appetite-reducing effect of C16:0 NAPEs is mediated by targets in the central nervous system: both intravenously administered, radiolabeled C16:0 NAPE, which became concentrated in the hypothalamus, and intracerebroventricular infusion of C16:0 NAPE (at far lower doses than those used in intraperitoneal injection) led to significant reductions in food intake.

Although postprandial increases in plasma concentration of NAPEs stopped in rats that were fed a high-fat diet for 35 days, exogenous administration of C16:0 NAPE still suppressed their food intake. By contrast, the appetite-reducing properties of leptin are quickly diminished by obesity. This property suggests that NAPEs should be investigated as physiologic therapeutics.