Journal
PEPTIDES
Volume 32, Issue 1, Pages 36-43Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2010.09.027
Keywords
Food intake; Hypothalamus; Meal pattern; Mouse; Nesfatin-1; Satiation; Satiety
Funding
- Veterans Administration [R01 NIH DK-33061, DK-41301]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK041301, R01DK033061] Funding Source: NIH RePORTER
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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 (icy) and peripheral (intraperitoneal, ip, subcutaneous, sc) injection of nesfatin-1 on dark phase ingestive behavior using an automated feeding monitoring system and co-localized NUCB2/nesfatin-1 immunoreactivity in the associated brain areas. Nesfatin-1 (0.3, 1 or 3 mu g/mouse, icy) caused a dose-related reduction of 4-h dark phase food intake by 13%, 27%, and 46% respectively. Nesfatin-1 (3 mu g/mouse, icy) action had a 2-h delayed onset, 82% peak inhibition occurring at 3-4 h post-injection and was long lasting (30% reduction for 12 h period post-injection). Nesfatin-1 (3 mu g/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). NUCB2/nesfatin-1-immunopositive neurons were found in hypothalamic (supraoptic, paraventricular, arcuate, dorsomedial, lateral) and brainstem (dorsal vagal complex) feeding regulatory nuclei. When injected peripherally, neither food intake nor feeding microstructure parameters were altered. These results demonstrate that NUCB2/nesfatin-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. (C) 2010 Elsevier Inc. All rights reserved.
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