In:
Nature Communications, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-02-16)
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-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-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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-021-21107-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2553671-0
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