Document Detail


MyomiR-133 regulates brown fat differentiation through Prdm16.
MedLine Citation:
PMID:  23143398     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Mirko Trajkovski; Kashan Ahmed; Christine C Esau; Markus Stoffel
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-11
Journal Detail:
Title:  Nature cell biology     Volume:  -     ISSN:  1476-4679     ISO Abbreviation:  Nat. Cell Biol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Institute of Molecular Health Sciences, ETH Zurich, Schafmattstrasse 22, HPL H36, 8093 Zurich, Switzerland [2] Competence Center of Systems Physiology and Metabolic Disease, ETH Zurich, Schafmattstrasse 22, 8093 Zurich, Switzerland [3].
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