| Literature DB >> 33594062 |
Takahiro Horie1, Tetsushi Nakao2, Yui Miyasaka2, Tomohiro Nishino2, Shigenobu Matsumura3, Fumiko Nakazeki2, Yuya Ide2, Masahiro Kimura2, Shuhei Tsuji2, Randolph Ruiz Rodriguez2, Toshimitsu Watanabe2, Tomohiro Yamasaki2, Sijia Xu2, Chiharu Otani2, Sawa Miyagawa2, Kazuki Matsushita2, Naoya Sowa2, Aoi Omori2, Jin Tanaka3, Chika Nishimura4, Masataka Nishiga2, Yasuhide Kuwabara2, Osamu Baba2, Shin Watanabe2, Hitoo Nishi2, Yasuhiro Nakashima2, Marina R Picciotto5, Haruhisa Inoue6,7,8, Dai Watanabe4, Kazuhiro Nakamura9, Tsutomu Sasaki10, Takeshi Kimura2, Koh Ono11.
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.Entities:
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Year: 2021 PMID： 33594062 PMCID： PMC7886914 DOI： 10.1038/s41467-021-21107-5
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919