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Title: microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity
Authors: Horie, Takahiro  kyouindb  KAKEN_id
Nakao, Tetsushi
Miyasaka, Yui
Nishino, Tomohiro
Matsumura, Shigenobu
Nakazeki, Fumiko
Ide, Yuya
Kimura, Masahiro
Tsuji, Shuhei
Rodriguez, Randolph Ruiz
Watanabe, Toshimitsu
Yamasaki, Tomohiro
Xu, Sijia
Otani, Chiharu
Miyagawa, Sawa
Matsushita, Kazuki
Sowa, Naoya
Omori, Aoi
Tanaka, Jin
Nishimura, Chika
Nishiga, Masataka
Kuwabara, Yasuhide
Baba, Osamu  kyouindb  KAKEN_id
Watanabe, Shin
Nishi, Hitoo
Nakashima, Yasuhiro
Picciotto, Marina R.
Inoue, Haruhisa  kyouindb  KAKEN_id  orcid (unconfirmed)
Watanabe, Dai
Nakamura, Kazuhiro
Sasaki, Tsutomu  kyouindb  KAKEN_id  orcid (unconfirmed)
Kimura, Takeshi
Ono, Koh
Author's alias: 堀江, 貴裕
中尾, 哲史
宮阪, 由依
西野, 共達
松村, 成暢
中関, 典子
井手, 裕也
木村, 昌弘
辻, 修平
渡邉, 利光
山﨑, 智弘
徐, 斯佳
大谷, 千春
宮川, 紗和
松下, 和揮
曽和, 尚也
大森, 碧
田中, 仁
西村, 知華
西賀, 雅隆
桑原, 康秀
馬場, 理
渡邉, 真
西, 仁勇
中島, 康弘
井上, 治久
渡邉, 大
中村, 和弘
佐々木, 努
木村, 剛
尾野, 亘
Keywords: Experimental models of disease
Metabolic disorders
Issue Date: 16-Feb-2021
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 12
Thesis number: 843
Abstract: Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33−/− mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress.
Description: 褐色脂肪細胞の燃焼を促す新たなメカニズムを解明 --体の熱産生にマイクロRNA-33が関与--. 京都大学プレスリリース. 2021-02-17.
Rights: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s41467-021-21107-5
PubMed ID: 33594062
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