TY - JOUR TI - microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity AU - Horie, Takahiro AU - Nakao, Tetsushi AU - Miyasaka, Yui AU - Nishino, Tomohiro AU - Matsumura, Shigenobu AU - Nakazeki, Fumiko AU - Ide, Yuya AU - Kimura, Masahiro AU - Tsuji, Shuhei AU - Rodriguez, Randolph Ruiz AU - Watanabe, Toshimitsu AU - Yamasaki, Tomohiro AU - Xu, Sijia AU - Otani, Chiharu AU - Miyagawa, Sawa AU - Matsushita, Kazuki AU - Sowa, Naoya AU - Omori, Aoi AU - Tanaka, Jin AU - Nishimura, Chika AU - Nishiga, Masataka AU - Kuwabara, Yasuhide AU - Baba, Osamu AU - Watanabe, Shin AU - Nishi, Hitoo AU - Nakashima, Yasuhiro AU - Picciotto, Marina R. AU - Inoue, Haruhisa AU - Watanabe, Dai AU - Nakamura, Kazuhiro AU - Sasaki, Tsutomu AU - Kimura, Takeshi AU - Ono, Koh T2 - Nature Communications AB - 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. DA - 2021/02/16/ PY - 2021 DO - 10.1038/s41467-021-21107-5 DP - www.nature.com VL - 12 IS - 1 SP - 843 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-021-21107-5 Y2 - 2021/02/16/21:01:41 ER -