MicroRNA-33 Inhibits Adaptive Thermogenesis and Adipose Tissue Beiging
| Autor: | Martin Schlegel, Lianne C Shanley, Narendra Verma, Daniel Peled, Jenny Y Yoo, Coen van Solingen, Elisabetta Mueller, Yannick Cyr, Luce Perie, Kathryn J. Moore, Milessa Silva Afonso, Ann Marie Schmidt, Monika Sharma, Emma M Corr |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Adipose Tissue White Adipocytes White Adipose tissue Biology Article 03 medical and health sciences 0302 clinical medicine Adipose Tissue Brown microRNA Animals Humans Gene Regulatory Networks Adipocytes Beige Uncoupling Protein 1 Adipogenesis Autophagy Thermogenesis Adipose Tissue Beige Adaptive Thermogenesis Cell biology Mice Inbred C57BL MicroRNAs Adipocytes Brown HEK293 Cells 030104 developmental biology Gene Expression Regulation Energy Metabolism Cardiology and Cardiovascular Medicine 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Arterioscler Thromb Vasc Biol |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.120.315798 |
| Popis: | Objective:Recent studies have identified key transcriptional regulators of brown adipose tissue (BAT) differentiation and function, but posttranscriptional control of this network by microRNAs remains incompletely understood. MiR-33 critically regulates genes involved in metabolic pathways, including cholesterol efflux, reverse cholesterol transport, fatty acid oxidation, and autophagy. Given its role in metabolic homeostasis, we investigated whether miR-33 participates in the regulation of BAT activity, white adipose beiging, and adaptive thermogenesis.Approach and Results:Using primary immortalized brown adipocytes and 10T1/2 cells, we show that miR-33 levels are reduced in brown fat differentiated cells compared with preadipocytes and in response to thermogenic activators. Furthermore, in mice exposed to cold, levels of miR-33 in BAT are rapidly downregulated consistent with a role for miR-33 in repressing adaptive thermogenesis. Using in silico prediction, we identified numerous putative miR-33 target genes in the thermogenic pathway conserved in mice and humans, including regulators of brown adipocyte differentiation and function and mitochondrial activity. We focused our investigation on transcriptional regulators of UCP1 (uncoupling protein 1) and of BAT-enriched genes and demonstrate that miR-33 repressesZfp516,Dio2, andPpargc1ain vitro and in vivo. Treatment of mice with inhibitors of miR-33 increased expression of these miR-33 target genes in brown and subcutaneous white adipose tissue, upregulating expression of UCP1, and rendering mice resistant to cold challenge.Conclusions:Collectively, our findings demonstrate that miR-33 targets key genes involved in BAT activation and white adipose beiging and expand our understanding of how miR-33 coordinately regulates pathways involved in metabolic homeostasis. |
| Databáze: | OpenAIRE |
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