Central nesfatin-1 reduces the nocturnal food intake in mice by reducing meal size and increasing inter-meal intervals

摘要

Nesfatin-1 is well established to reduce food intake upon brain injection in rats, while in mice its anorexigenic action and brain expression are largely unexplored. We characterized the influence of intracerebroventricular (icv) and peripheral (intraperitoneal, ip, subcutaneous, sc) injection of nesfatin-1 on dark phase ingestive behavior using an automated feeding monitoring system and mapped NUCB2esfatin-1 immunoreactivity in the mouse brain. Nesfatin-1 (0.3, 1 or 3 μg/mouse, icv) caused a dose-related reduction of 4-h dark phase food intake by 13%, 27%, and 46% respectively. Nesfatin-1 (3 μg/mouse, icv) action had a 2-h delayed onset, 82% peak inhibition occurring at 3-4 h post injection and was long lasting (30% reduction for 12h period post injection). Nesfatin-1 (3 μg/mouse, icv)-treated mice had a 46% lower meal frequency associated with 2-times longer inter-meal intervals and a 35% reduction in meal size compared to vehicle during the 1-4 h post injection (p<0.05). NUCB2esfatin-1-immunopositive neurons were found in hypothalamic (supraoptic, paraventricular, arcuate, lateral) and brainstem (dorsal vagal complex) feeding-regulatory nuclei. When injected peripherally, neither food intake nor any feeding microstructure parameters were altered. These results demonstrate that NUCB2esfatin-1 is prominently expressed in mouse hypothalamus and medulla and acts in the brain to curtail the dark phase feeding by inducing satiation and satiety indicated by reduced meal size and prolonged inter-meal intervals respectively. The lack of nesfatin-1 effect when injected peripherally at a 23-times higher dose indicates a primarily central site of the anorexigenic action for nesfatin-1 in mice.