Effects of the increase in neuronal fatty acids availability on food intake and satiety in mice

Rationale: Neurons detect free fatty acids (FFAs) availability and use this nutritional status to modulate feeding and control body weight. Objectives: The work is designed to characterize the impact on feeding behavior of either oleic acid (OA) administration (experiment 1) or the inhibition (experiment 2) of the enzyme carnitine palmitoyltransferase-1 (CPT-1). The structure of feeding behavior and satiation time course were examined through the behavioral satiety sequence (BSS) paradigm. Methods: Adult male mice were initially habituated to a palatable diet, then subjected to intracerebroventricular (i.c.v.) infusion of different doses of OA or the CPT-1 inhibitor ST1326. Food intake at different time points, duration, and frequencies of feeding and non-feeding-related behaviors were continuously monitored over 40 min and satiety development profiled according to BSS. Results: Intra-i.c.v. infusion of oleic acid (300 nM) and ST1326 (50 and 75 pM) suppressed food intake. As indicated by the earlier leftward shifting of the normal transition from eating to resting, both strategies similarly accelerated the onset of satiety. The premature onset of satiety resulted in a dose-related fashion with 50 pM of ST1326 producing a marked premature onset than the lower dose. However, at the highest dose injected, the inhibition of CPT-1 disrupted the BSS profile. Conclusions: The increased neuronal availability of FFAs mediates a significant anorectic response which is mirrored by an early occurrence of satiety onset. Besides supporting the role of central nutrient sensing in feeding, the present data demonstrate that the modulation of satiety enhancement can produce appetite suppressant effects within narrow range of neuronal FFAs availability.