論文 - 詳細
| RRC ID | 64008 |
|---|---|
| 著者 | Horie T, Nakao T, Miyasaka Y, Nishino T, Matsumura S, Nakazeki F, Ide Y, Kimura M, Tsuji S, Rodriguez RR, Watanabe T, Yamasaki T, Xu S, Otani C, Miyagawa S, Matsushita K, Sowa N, Omori A, Tanaka J, Nishimura C, Nishiga M, Kuwabara Y, Baba O, Watanabe S, Nishi H, Nakashima Y, Picciotto MR, Inoue H, Watanabe D, Nakamura K, Sasaki T, Kimura T, Ono K. |
| タイトル | microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity. |
| ジャーナル | Nat Commun |
| 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. |
| 巻・号 | 12(1) |
| ページ | 843 |
| 公開日 | 2021-2-16 |
| DOI | 10.1038/s41467-021-21107-5 |
| PII | 10.1038/s41467-021-21107-5 |
| PMID | 33594062 |
| PMC | PMC7886914 |
| MeSH | Adipose Tissue, Brown / physiology Animals Body Temperature / physiology Body Weight Brain / metabolism Cell Line Cold Temperature Diet, High-Fat Endoplasmic Reticulum Stress Humans Integrases / metabolism Male Mice Mice, Obese MicroRNAs / genetics MicroRNAs / metabolism* Oxygen Consumption / physiology Phenotype Protein Subunits / genetics Protein Subunits / metabolism Receptors, GABA-A / genetics Receptors, GABA-A / metabolism Sympathetic Nervous System / physiology* Thermogenesis / genetics* |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 13 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01492 |