title: MyomiR-133 regulates brown fat differentiation through Prdm16.
abstract: Brown adipose tissue (BAT) uses the chemical energy of lipids and glucose to produce heat, a function that can be induced by cold exposure or diet. A key regulator of BAT is the gene encoding PR domain containing 16 (Prdm16), whose expression can drive differentiation of myogenic and white fat precursors to brown adipocytes. Here we show that after cold exposure, the muscle-enriched miRNA-133 is markedly downregulated in BAT and subcutaneous white adipose tissue (SAT) as a result of decreased expression of its transcriptional regulator Mef2. miR-133 directly targets and negatively regulates PRDM16, and inhibition of miR-133 or Mef2 promotes differentiation of precursors from BAT and SAT to mature brown adipocytes, thereby leading to increased mitochondrial activity. Forced expression of miR-133 in brown adipogenic conditions prevents the differentiation to brown adipocytes in both BAT and SAT precursors. Our results point to Mef2 and miR-133 as central upstream regulators of Prdm16 and hence of brown adipogenesis in response to cold exposure in BAT and SAT.
authors.affiliation: Institute of Molecular Health Sciences, ETH Zurich, Schafmattstrasse 22, HPL H36, 8093 Zurich, Switzerland.
authors.forename: Mirko
authors.initials: M
authors.lastname: Trajkovski
authors.forename: Kashan
authors.initials: K
authors.lastname: Ahmed
authors.forename: Christine C
authors.initials: CC
authors.lastname: Esau
authors.forename: Markus
authors.initials: M
authors.lastname: Stoffel
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008066:Lipolysis / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; C521133:Prdm16 protein, mouse; D014157:Transcription Factors