期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-021-21107-5
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT)
- Japan Society for the Promotion of Science (JSPS) KAKENHI [17K09860, 20K08904, 1605297, 17H04177, 17H05599, 20H03675]
- AMED [JP19fk0210112]
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Bristol Myers Squibb
- Fujiwara Memorial Foundation
- Vehicle Racing Commemorative Foundation
- Suzuken Memorial Foundation
- Grants-in-Aid for Scientific Research [20K08904, 17K09860, 17H05599, 17H04177, 20H03675] Funding Source: KAKEN
Adaptive thermogenesis is regulated by central neuronal circuits. MicroRNA-33 in the brain contributes to the maintenance of brown adipose tissue thermogenesis and whole-body energy balance via enhanced sympathetic nerve tone, and regulating the expression of GABAa receptor subunits.
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-beta -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. Adaptive thermogenesis is regulated by central neuronal circuits. Here, the authors show that microRNA-33 in the brain contributes to the maintenance of brown adipose tissue thermogenesis and whole-body energy balance via enhanced sympathetic nerve tone, and regulating the expression of GABAa receptor subunits.
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