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

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• 作者：Andreas Stengel^a ; ^b ; Miriam Goebel-Stengel^a ; ^c ; Lixin Wang^a ; Ikuo Kato^d ; Masatomo Mori^e ; Yvette Taché ; ^a ; ^{ytache@mednet.ucla.edu}
• 关键词：Food intake ; Meal pattern ; Mouse ; Nesfatin-1 fragments ; Satiation ; Satiety
• 刊名：Peptides
• 出版年：2012
• 期刊代码：59_01969781
• 类别：neu
• 出版时间：June, 2012
• 卷：35
• 期：2
• 页码：143-148
• 文件大小：382 K

摘要

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 intracerebroventricularly (icv) 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 icv 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 icv 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 < 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: 鈭?7%) and prolonged inter-meal intervals (3.1-times) compared to vehicle (p < 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 < 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.