GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice.

IF 7.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
PLoS Biology Pub Date : 2023-08-18 eCollection Date: 2023-08-01 DOI:10.1371/journal.pbio.3002252
Youjin Oh, Eun-Seon Yoo, Sang Hyeon Ju, Eunha Kim, Seulgi Lee, Seyun Kim, Kevin Wickman, Jong-Woo Sohn
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引用次数: 1

Abstract

It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function. Here, we found that the G protein-gated inwardly rectifying K+ (GIRK) channels are key to stabilize NPY/AgRP neurons and that NPY/AgRP neuron-selective deletion of the GIRK2 subunit results in a persistently increased excitability of the NPY/AgRP neurons. Interestingly, increased body weight and adiposity observed in the NPY/AgRP neuron-selective GIRK2 knockout mice were due to decreased sympathetic activity and EE, while food intake remained unchanged. The conditional knockout mice also showed compromised adaptation to coldness. In summary, our study identified GIRK2 as a key determinant of NPY/AgRP neuronal excitability and driver of EE in physiological and stress conditions.

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AgRP神经元表达的GIRK2钾通道可降低小鼠的肥胖和体重。
众所周知,神经肽Y(NPY)/食欲相关肽(AgRP)神经元增加食欲并降低产热。先前的研究表明,NPY/AgRP神经元活动的光遗传学和/或化学遗传学操作会改变食物摄入和/或能量消耗(EE)。然而,对调节NPY/AgRP神经元兴奋性以影响长期代谢功能的内在分子知之甚少。在这里,我们发现G蛋白门控的内向整流K+(GIRK)通道是稳定NPY/AgRP神经元的关键,并且NPY/AgRP-神经元选择性缺失GIRK2亚基导致NPY/AgRP-神经元的兴奋性持续增加。有趣的是,在NPY/AgRP神经元选择性GIRK2敲除小鼠中观察到的体重和肥胖增加是由于交感神经活性和EE降低,而食物摄入保持不变。条件敲除小鼠对寒冷的适应能力也有所下降。总之,我们的研究确定GIRK2是NPY/AgRP神经元兴奋性的关键决定因素,也是生理和应激条件下EE的驱动因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
PLoS Biology
PLoS Biology 生物-生化与分子生物学
CiteScore
14.40
自引率
2.00%
发文量
359
审稿时长
3 months
期刊介绍: PLOS Biology is an open-access, peer-reviewed general biology journal published by PLOS, a nonprofit organization of scientists and physicians dedicated to making the world's scientific and medical literature freely accessible. The journal publishes new articles online weekly, with issues compiled and published monthly. ISSN Numbers: eISSN: 1545-7885 ISSN: 1544-9173
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