microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity
| Autor: | Tomohiro Yamasaki, Toshimitsu Watanabe, Shigenobu Matsumura, Kazuhiro Nakamura, Chika Nishimura, Naoya Sowa, Takahiro Horie, Tomohiro Nishino, Yui Miyasaka, Sijia Xu, Masataka Nishiga, Randolph Ruiz Rodriguez, Yasuhide Kuwabara, Yasuhiro Nakashima, Chiharu Otani, Dai Watanabe, Haruhisa Inoue, Shin Watanabe, Yuya Ide, Tetsushi Nakao, Aoi Omori, Fumiko Nakazeki, Hitoo Nishi, Takeshi Kimura, Shuhei Tsuji, Osamu Baba, Jin Tanaka, Tsutomu Sasaki, Kazuki Matsushita, Sawa Miyagawa, Marina R. Picciotto, Masahiro Kimura, Koh Ono |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Sympathetic Nervous System Science Metabolic disorders GABRA4 Mice Obese General Physics and Astronomy Adipose tissue Neurotransmission Biology Diet High-Fat Article General Biochemistry Genetics and Molecular Biology Body Temperature Cell Line Mice 03 medical and health sciences Oxygen Consumption 0302 clinical medicine Adipose Tissue Brown Brown adipose tissue medicine Animals Humans Receptor Multidisciplinary Integrases Body Weight Brain Thermogenesis General Chemistry Endoplasmic Reticulum Stress Receptors GABA-A Cell biology Experimental models of disease Cold Temperature MicroRNAs Protein Subunits Phenotype 030104 developmental biology medicine.anatomical_structure Hypothalamus biology.protein GABAergic 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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