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Hypothalamic GABRA5-positive neurons control obesity via astrocytic GABA

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Title
Hypothalamic GABRA5-positive neurons control obesity via astrocytic GABA
Author(s)
Moonsun Sa; Yoo, Eun-Seon; Wuhyun Koh; Mingu Gordon Park; Jang, Hyun-Jun; Yang, Yong Ryoul; Mridula Bhalla; Jae-Hun Lee; Jiwoon Lim; Woojin Won; Jea Kwon; Joon-Ho Kwon; Yejin Seong; Kim, Byungeun; Heeyoung An; Lee, Seung Eun; Park, Ki Duk; Suh, Pann-Ghill; Sohn, Jong-Woo; C. Justin Lee
Publication Date
2023-08
Journal
Nature Metabolism, v.5, no.9, pp.1506 - 1525
Publisher
Nature Research
Abstract
The lateral hypothalamic area (LHA) regulates food intake and energy balance. Although LHA neurons innervate adipose tissues, the identity of neurons that regulate fat is undefined. Here we show that GABRA5-positive neurons in LHA (GABRA5LHA) polysynaptically project to brown and white adipose tissues in the periphery. GABRA5LHA are a distinct subpopulation of GABAergic neurons and show decreased pacemaker firing in diet-induced obesity mouse models in males. Chemogenetic inhibition of GABRA5LHA suppresses fat thermogenesis and increases weight gain, whereas gene silencing of GABRA5 in LHA decreases weight gain. In the diet-induced obesity mouse model, GABRA5LHA are tonically inhibited by nearby reactive astrocytes releasing GABA, which is synthesized by monoamine oxidase B (Maob). Gene silencing of astrocytic Maob in LHA facilitates fat thermogenesis and reduces weight gain significantly without affecting food intake, which is recapitulated by administration of a Maob inhibitor, KDS2010. We propose that firing of GABRA5LHA suppresses fat accumulation and selective inhibition of astrocytic GABA is a molecular target for treating obesity. © 2023, The Author(s), under exclusive licence to Springer Nature Limited.
URI
https://pr.ibs.re.kr/handle/8788114/14299
DOI
10.1038/s42255-023-00877-w
ISSN
2522-5812
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
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