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

Abstract

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 hydroxypropylb-cyclodextrin (HPB) or HPB complexed with 30 nmol of saturated palmitic acid (PA), monounsaturated oleic acid (OA) or polyunsaturated o-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 48 h 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.

Glucose Regulates Hypothalamic Long-chain Fatty Acid Metabolism via AMP-activated Kinase (AMPK) in Neurons and Astrocytes

“…Third, our results provide a metabolic basis for the different effect of centrally administered LCFA on feeding (68,69). Indeed, oleate but not palmitate has an anorectic action making it tempting to speculate that such differences could be related to the difference between palmitate and oleate metabolism observed in our study.…”

Hypothalamic Integration of Metabolic, Endocrine, and Circadian Signals in Fish: Involvement in the Control of Food Intake

“…The 18 carbon monounsaturated fatty acid oleate (C18:1 n-9) is the most studied LCFA in mammals involved in the activation of fatty acid sensing systems (López et al, 2007; Blouet and Schwartz, 2010; Duca and Yue, 2014). Fatty acid unsaturation appears to be important since the saturated fatty acid palmitate (C16:0) does not activate hypothalamic fatty acid sensing systems (Ross et al, 2010; Schwinkendorf et al, 2011; Greco et al, 2014). Moreover, the presence of more than one double bond, such as for linoleate (C18:2 n-6) or docosahexanoate (C22:6 n-3), does not activate fatty acid sensing systems in mammals (Gomez-Pinilla and Ying, 2010; Ross et al, 2010; Schwinkendorf et al, 2011; Greco et al, 2014).…”

Nutrient Sensing Systems in Fish: Impact on Food Intake Regulation and Energy Homeostasis

“…The ability of other classes of LCFA differing in the length of their acyl chain and/or in their degree of unsaturation to elicit the activation of these systems has been scarcely assessed to date. The available studies in mammals indicate that neither saturated fatty acids like palmitate (C16:0) nor the presence of two (such as in linoleate, C18:2 n-6) or three (such as in docosahexanoate, C22:6 n-3) double bonds activate fatty acid sensing systems (Gomez-Pinilla and Ying, 2010; Ross et al, 2010; Schwinkendorf et al, 2011; Greco et al, 2014). …”