Effects of central administration of distinct fatty acids on hypothalamic neuropeptide expression and energy metabolism

Objective: To investigate the differential effects of acute central administration of distinct fatty acids (FA) on food intake, body weight and energy metabolism. Design: Male Sprague–Dawley rats were treated with bolus intracerebroventricular injections of control hydroxypropyl-β-cyclodextrin (HPB) or HPB complexed with 30 nmol of saturated palmitic acid (PA), monounsaturated oleic acid (OA) or polyunsaturated ω-3 docosahexaenoic acid (DHA). Food intake, body weight, neuropeptide expression and various serum parameters were assessed. Results: When compared with controls, rats injected with either OA or DHA had significantly reduced food intake and body weight for 48h following injections. No significant changes in food intake or body weight were observed in the PA group. In conjunction with reduced food intake, hypothalamic anorexigenic pro-opiomelanocortin (POMC) gene expression was significantly augmented in the OA and DHA groups, with essentially no changes observed in the PA group. Changes in serum measures of energy metabolism also changed coinciding with the observed differences in food intake. Moreover, central administration of SHU9119, a melanocortin-4-rececptor (MC4R) antagonist, completely abolished the anorexigenic actions of OA, suggesting a role for OA-induced augmentation of hypothalamic POMC expression in mediating its central inhibition of food intake. Conclusions: The hypothalamus differentially senses FA and, specifically, that OA and DHA, but not PA, reduce food intake and body weight, which may be mediated through POMC/MC4R signaling.