Nesfatin-1(30-59) but not the N- and C-terminal fragments, nesfatin-1(1-29) and nesfatin-1(60-82) injected intracerebroventricularly decreases dark phase food intake by increasing inter-meal intervals in mice

作者：Stengel Andreas; Goebel Stengel Miriam; Wang Lixin; Kato Ikuo; Mori Masatomo; Tache Yvette^*

来源：Peptides, 2012, 35(2): 143-148.

DOI：10.1016/j.peptides.2012.03.015

• Food intake
• Meal pattern
• Mouse
• Nesfatin-1 fragments
• Satiation
• Satiety

Nesfatin-1 is an 82 amino acid N-terminal fragment of nucleobindin2 that was consistently shown to reduce dark phase food intake upon brain injection in rodents. We recently reported that nesfatin-1(1-82) injected intracerebroyentricularly (icy) reduces dark phase feeding in mice. Moreover, intraperitoneal injection of mid-fragment nesfatin-1 (nesfatin-1(30-59)) mimics the food intake-reducing effects of nesfatin-1(1-82), whereas N-terminal (nesfatin-1(1-29)) and C-terminal fragments (nesfatin-1(60-82)) did not. We therefore characterized the structure-activity relationship of nesfatin-1 injected icy to influence the dark phase meal pattern in mice. Mouse nesfatin-1(1-29), nesfatin-1(30-59), nesfatin-1(60-82) or vehicle was injected icy in freely fed C57Bl/6 mice immediately before the dark phase and food intake was monitored using an automated episodic feeding monitoring system. Nesfatin-1(30-59) (0.1, 0.3, 0.9 nmol/mouse) induced a dose-related reduction of 4-h food intake by 28%, 49% and 49% respectively resulting in a 23% decreased cumulative 24-h food intake compared to vehicle at the 0.3 nmol/mouse dose (p %26lt; 0.05). The peak reduction occurred during the 3rd (-96%) and 4th hour (-91%) post injection and was associated with a reduced meal frequency (0-4 h: -47%) and prolonged inter-meal intervals (3.1-times) compared to vehicle (p %26lt; 0.05), whereas meal size was not altered. In contrast, neither nesfatin-1(1-29) nor nesfatin-1(60-82) reduced dark phase food intake at equimolar doses although nesfatin-1(60-82) prolonged inter-meal intervals (1.7-times, p %26lt; 0.05). Nesfatin-1(30-59) is the active core of nesfatin-1(1-82) to induce satiety indicated by a reduced meal number during the first 4 h post injection. The delayed onset may be indicative of time required to modulate other hypothalamic and medullary networks regulating nocturnal feeding as established for nesfatin-1. Published by Elsevier Inc.

• 出版日期2012-6