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MicroRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity.

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-33^f/f dopamine-?-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-33^f/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.

SUBMITTER: Horie T

PROVIDER: S-EPMC7886914 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity.

Horie Takahiro T Nakao Tetsushi T Miyasaka Yui Y Nishino Tomohiro T Matsumura Shigenobu S Nakazeki Fumiko F Ide Yuya Y Kimura Masahiro M Tsuji Shuhei S Rodriguez Randolph Ruiz RR Watanabe Toshimitsu T Yamasaki Tomohiro T Xu Sijia S Otani Chiharu C Miyagawa Sawa S Matsushita Kazuki K Sowa Naoya N Omori Aoi A Tanaka Jin J Nishimura Chika C Nishiga Masataka M Kuwabara Yasuhide Y Baba Osamu O Watanabe Shin S Nishi Hitoo H Nakashima Yasuhiro Y Picciotto Marina R MR Inoue Haruhisa H Watanabe Dai D Nakamura Kazuhiro K Sasaki Tsutomu T Kimura Takeshi T Ono Koh K

Nature communications 20210216 1

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<sup>-/-</sup> 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-33<sup>f/f</sup> dopamine-β-hyd ...[more]

PMID: 33594062

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MicroRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity.

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microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity.

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