POMC神经元表达的g12家族蛋白调控关键代谢功能

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-07-11 DOI:10.1126/sciadv.adu1670

Dhanush Haspula, Zhenzhong Cui, Srinivas Pittala, Yinghong Cui, Huiyan Lu, Yan Xiong, Jian Jin, Oksana Gavrilova, Eunsang Hwang, Jason Ajwani, Bryan Portillo, Kevin W. Williams, Asuka Inoue, Jürgen Wess

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引用次数: 0

摘要

Proopiomelanocortin （POMC）神经元在维持葡萄糖和能量稳态中起关键作用。POMC神经元表达许多异三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）偶联受体，这些受体与不同功能类别的G蛋白相连。g12 /13在调节中央POMC神经元功能中的潜在作用尚不清楚。为了解决这个问题，我们使用化学遗传学方法选择性地刺激POMC神经元中的g12 /13信号。我们发现，受体介导的POMC神经元中g12 /13信号的激活可显著改善瘦小鼠和肥胖小鼠的葡萄糖稳态。刺激POMC神经元中的g12 /13信号也增强了瘦素的生理作用。对G 12/13基因敲除小鼠的研究表明，POMC神经元中的G 12/13信号介导氯卡色林的有益代谢作用，氯卡色林是一种选择性激活5-羟色胺5-羟色胺2C受体的食欲抑制药物。这些发现表明，POMC神经元表达的G 12/13偶联受体是高级抗糖尿病和食欲抑制药物的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

G proteins of the G12 family expressed by POMC neurons regulate key metabolic functions

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G proteins of the G12 family expressed by POMC neurons regulate key metabolic functions

Proopiomelanocortin (POMC) neurons play a key role in maintaining glucose and energy homeostasis. POMC neurons express many heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors that are linked to different functional classes of G proteins. The potential role of G_12/13 in regulating the function of central POMC neurons remains unknown. To address this question, we used a chemogenetic approach to selectively stimulate G_12/13 signaling in POMC neurons. We found that receptor-mediated activation of G_12/13 signaling in POMC neurons caused notable improvements in glucose homeostasis in lean and obese mice. Stimulation of G_12/13 signaling in POMC neurons also enhanced the physiological actions of leptin. Studies with G_12/13 knockout mice showed that G_12/13 signaling in POMC neurons mediated the beneficial metabolic effects of lorcaserin, an appetite-suppressant drug that selectively activates serotonin 5-HT_2C receptors. These findings indicate that G_12/13-coupled receptors expressed by POMC neurons represent potential targets for advanced classes of antidiabetic and appetite-suppressant drugs.

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.