Analysis of leptin-induced anorexia : Involvement of serotonin and nitric oxide

瘦素引起的厌食症分析：血清素和一氧化氮的参与

• 批准号: 14570093
• 负责人: YAMADA Jun
• 金额: $ 1.92万
• 依托单位: Kobe Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570093/
• 关键词: leptin; serotonin; nitric oxide; food intake; anorexia; insulin

Leptin is an adipocytokine, released from adipose tissue. Leptin is a strong anorectic factor by acting the hypothalamus which control food intake. It is well known that mice deficient of leptin display a marked hyperphagia and obesity. However, mechanism of leptin-induced hypophagia is not yet clarified. In this research, the involvement of serotonin(5-HT) and nitric oxide(NO) in anorexia elicited by leptin in mice. The 5-HT depleter significantly suppressed leptin-induced hypophagia. The 5-HT2B/2C receptor antagonist also reduced anorexia induced by leptin. Therefore, the 5-HT2B/2C receptor activation is involved in leptin-induced hypophagia. We found that leptin did not change brain NOx levels in staraved mice, although leptin inhibited food intake. The serum leptin levels were elevated by pretreatment with the 5-HT precursor, 5-hydroxytryptophan(5-HTP). Hyperleptinemia by 5-HTP is antagonized by streptozotocin which deplets insulin. Furthermore, increases in serum leptin levels induced by 5-HTP are inhibited by the NO synthesis inhibitor. These results suggest that leptin secretion may be controlled by 5-HT and NO and that 5-HT and NO play a significant role in leptin-induced anorexia.

瘦素是一种脂肪细胞因子，由脂肪组织释放。瘦素是通过作用于控制摄食的下丘脑而产生的一种强厌食因子。众所周知，缺乏瘦素的小鼠表现出明显的暴食和肥胖。然而，瘦素诱导的摄食减少的机制尚未阐明。本研究探讨了5-羟色胺（5-HT）和一氧化氮（NO）在瘦素诱导的小鼠厌食中的作用。5-HT耗竭剂显著抑制瘦素诱导的食欲减退。5-HT 2B/2C受体拮抗剂也可减少瘦素诱导的厌食。因此，5-HT 2B/2C受体激活参与瘦素诱导的摄食减少。我们发现，瘦素并没有改变大脑中的氮氧化物水平在饥饿的小鼠，虽然瘦素抑制食物的摄入。5-HT前体5-羟色氨酸（5-HTP）预处理可升高血清瘦素水平。5-HTP引起的高瘦素血症可被消耗胰岛素的链脲佐菌素拮抗。此外，5-HTP诱导的血清瘦素水平的增加被NO合成抑制剂抑制。提示瘦素的分泌可能受5-HT和NO的调控，5-HT和NO在瘦素诱导的厌食中起重要作用。

项目成果

J.Yamada, Y.Sugimoto, M.Ujikawa, T.Yagura, H.Goko: "Hyperleptinemia Elicited by the 5-HT Precursor, 5-Hydroxytryptophan in Mice : Involvement of Insulin"Life Sciences. 73・18. 2335-2344 (2003)

J.Yamada、Y.Sugimoto、M.Ujikawa、T.Yagura、H.Goko：“小鼠体内 5-HT 前体 5-羟基色氨酸引起的高瘦素血症：胰岛素的参与”生命科学 73・18。 (2003)

Effects of insulin and adrenalectomy on elevation of serum leptin levels induced by 5-hydroxytryptophan in mice

胰岛素和肾上腺切除术对5-羟色氨酸引起的小鼠血清瘦素水平升高的影响

• 发表时间: 2003
• 期刊: Biological and Pharmaceutical Bulletin 26
• 作者: Yoon JH;Toshihide Fujii;Yumi Sugimoto
• 通讯作者: Yumi Sugimoto

Leptin inhibits food intake without affecting brain NOx levels in food-deprived mice

瘦素抑制食物摄入而不影响食物匮乏小鼠的脑部氮氧化物水平

• 发表时间: 2003
• 期刊: Biological and Pharmaceutical Bulletin 26
• 作者: Toshihide FUJII;Yumi Sugimoto
• 通讯作者: Yumi Sugimoto

Hyperleptinemia elicited by the 5-HT precursor, 5-hydroxytryptophan in mice : Involvement of insulin

小鼠体内 5-HT 前体 5-羟色氨酸引起的高瘦素血症：胰岛素的参与

• 发表时间: 2003
• 期刊: Life Sciences 73
• 作者: Toshihide FUJII;Jun Yamada
• 通讯作者: Jun Yamada

Role of serotonergic mechanisms in leptin-induced suppression of milk intake in mice

血清素能机制在瘦素诱导的小鼠牛奶摄入抑制中的作用

• 发表时间: 2003
• 期刊: Neuroscience Letters 348
• 作者: Jun Yamada