Physiological Roles of circulating ghrelin on food intake and energy homeostasis

循环生长素释放肽对食物摄入和能量稳态的生理作用

• 批准号: 23791055
• 负责人: ARIYASU Hiroyuki
• 金额: $ 2.75万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791055/
• 关键词: 成長ホルモン; グレリン; 遺伝子改変動物; 摂食; エネルギー代謝; 内分泌代謝学

Ghrelin has a potent orexigenic effect and induces adiposity when administered exogenously. Because plasma ghrelin levels rise before meals, ghrelin has been thought to play a crucial role in the regulation of appetite. By contrast, mice deficient in the production of ghrelin or its receptor, GHS-R, do not eat less, throwing into question the role of ghrelin in the regulation of energy homeostasis. Since these mice lack ghrelin or GHS-R from conception, one cannot rule out the possibility that compensatory mechanisms may have arisen during development. In this study, we used a transgenic mouse that expresses human diphtheria toxin (DT) receptor cDNA under control of the ghrelin promoter (GPDTR-Tg mice). As we previously reported, an injection of DT into this mouse ablates ghrelin-secreting cells in the stomach but not in the hypothalamus, resulting in a reduction in circulating ghrelin levels. We used this model system to evaluate the physiological roles of circulating ghrelin in the regulation of food intake. The meal patterns, diurnal and nocturnal meal sizes, and the cumulative food intake of DT-treated GPDTR-Tg mice were not affected, though circulating ghrelin levels were markedly decreased even after fasting. These mice also displayed normal responses to starvation, but increased their use of fat and exhibited slower weight gain when maintained on a high fat diet. Together, these data suggested that circulating ghrelin does not play a crucial role in feeding behavior, but rather is involved in maintaining body weight.

生长素释放肽具有有效的促食欲作用，外源给药时可诱导肥胖。由于血浆胃饥饿素水平在餐前升高，胃饥饿素被认为在调节食欲方面发挥着至关重要的作用。相比之下，缺乏生长素释放肽或其受体 GHS-R 产生的小鼠的食量并没有减少，这使得生长素释放肽在能量稳态调节中的作用受到质疑。由于这些小鼠从受孕时就缺乏生长素释放肽或 GHS-R，因此不能排除在发育过程中可能出现补偿机制的可能性。在本研究中，我们使用了在生长素释放肽启动子控制下表达人白喉毒素 (DT) 受体 cDNA 的转基因小鼠（GPDTR-Tg 小鼠）。正如我们之前报道的，向该小鼠注射DT会消除胃中的生长素释放肽分泌细胞，但不会消除下丘脑的生长素释放肽细胞，从而导致循环生长素释放肽水平降低。我们使用这个模型系统来评估循环饥饿素在食物摄入调节中的生理作用。 DT处理的GPDTR-Tg小鼠的膳食模式、白天和夜间的膳食量以及累积食物摄入量没有受到影响，但即使在禁食后，循环胃饥饿素水平也显着降低。这些小鼠也表现出对饥饿的正常反应，但在维持高脂肪饮食时增加了脂肪的使用并表现出较慢的体重增加。总之，这些数据表明循环中的生长素释放肽在进食行为中并不起关键作用，而是参与维持体重。

项目成果

Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo

• DOI: 10.1152/ajpendo.00341.2011
• 发表时间: 2012-02-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
• 影响因子: 5.1
• 作者: Bando, Mika;Iwakura, Hiroshi;Akamizu, Takashi
• 通讯作者: Akamizu, Takashi

後天的グレリン分泌低下マウスを用いたグレリン生理的役割の検討

使用获得性胃饥饿素分泌减少的小鼠检查胃饥饿素的生理作用

• 发表时间: 2011
• 作者: 有安宏之;岩倉浩;赤水尚史;山田豪;中尾一和;寒川賢治
• 通讯作者: 寒川賢治

Akamizu T, Sakura N, Shigematsu Y, Tajima G, Ohtake A, Hosoda H, Iwakura H, Ariyasu H, Kangawa K.

赤水 T、樱花 N、重松 Y、田岛 G、大竹 A、细田 H、岩仓 H、Ariyasu H、Kangawa K。

• 发表时间: 2012
• 期刊: Eur J Endocrinol
• 影响因子: 5.8
• 作者: 園山拓洋;曽根正勝;本田恭子;田浦大輔;小嶋勝利;犬塚恵;金本巨哲;田村尚久;中尾一和;酒井 建;酒井 建;酒井 建;青谷大介;青谷大介;日下部 徹;園山 拓洋;青谷大介;片岡祥子;青谷大介;阿部 恵;M. Aizawa-Abe;D.Aotani;酒井 建;海老原健;酒井 建;海老原千尋;酒井 建;酒井 建;青谷大介;青谷大介;Analysis of plasma ghrelin in patients with medium-chain acyl-CoA dehydrogenase deficiency and glutaric aciduria type II.
• 通讯作者: Analysis of plasma ghrelin in patients with medium-chain acyl-CoA dehydrogenase deficiency and glutaric aciduria type II.

摂食・エネルギー代謝におけるグレリン/GHS-R系の役割の検討

检测 ghrelin/GHS-R 系统在摄食和能量代谢中的作用

• 发表时间: 2012
• 作者: Iwakura H;Ariyasu H;Hosoda H;Yamada G;Hosoda K;Nakao K;Kangawa K;Akamizu T.;有安宏之
• 通讯作者: 有安宏之