肥満研究の新たなブレークスルーにより、好きなだけ食べながら脂肪を落とすことが可能に(A new breakthrough in obesity research allows you to lose fat while eating all you want)

アストロサイトが、エネルギー消費を制御する脳の神経細胞群を制御していることを発見した。 Researchers discover that astrocytes control a cluster of neurons in the brain that regulates energy expenditure

2023-09-01 韓国基礎科学研究院(IBS)

<関連情報>

• https://www.ibs.re.kr/cop/bbs/BBSMSTR_000000000738/selectBoardArticle.do
• https://www.nature.com/articles/s42255-023-00877-w

視床下部GABRA5陽性神経細胞はアストロサイトGABAを介して肥満を制御する Hypothalamic GABRA5-positive Neurons Control Obesity via Astrocytic GABA

Moonsun Sa,Eun-Seon Yoo,Wuhyun Koh,Mingu Gordon Park,Hyun-Jun Jang,Yong Ryoul Yang,Mridula Bhalla,Jae-Hun Lee,Jiwoon Lim,Woojin Won,Jea Kwon,Joon-Ho Kwon,Yejin Seong,Byungeun Kim,Heeyoung An,Seung Eun Lee,Ki Duk Park,Pann-Ghill Suh,Jong-Woo Sohn & C. Justin Lee
Nature Metabolism  Published:31 August 2023
DOI:https://doi.org/10.1038/s42255-023-00877-w

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 (GABRA5^LHA) polysynaptically project to brown and white adipose tissues in the periphery. GABRA5^LHA are a distinct subpopulation of GABAergic neurons and show decreased pacemaker firing in diet-induced obesity mouse models in males. Chemogenetic inhibition of GABRA5^LHA suppresses fat thermogenesis and increases weight gain, whereas gene silencing of GABRA5 in LHA decreases weight gain. In the diet-induced obesity mouse model, GABRA5^LHA 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 GABRA5^LHA suppresses fat accumulation and selective inhibition of astrocytic GABA is a molecular target for treating obesity.