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Bispebjerg Hospital - a part of Copenhagen University Hospital
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MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16

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  • Hang Yin
  • Alessandra Pasut
  • Vahab D Soleimani
  • C Florian Bentzinger
  • Ghadi Antoun
  • Stephanie Thorn
  • Patrick Seale
  • Pasan Fernando
  • Wilfred van Ijcken
  • Frank Grosveld
  • Robert A Dekemp
  • Robert Boushel
  • Mary-Ellen Harper
  • Michael A Rudnicki
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Brown adipose tissue (BAT) is an energy-dispensing thermogenic tissue that plays an important role in balancing energy metabolism. Lineage-tracing experiments indicate that brown adipocytes are derived from myogenic progenitors during embryonic development. However, adult skeletal muscle stem cells (satellite cells) have long been considered uniformly determined toward the myogenic lineage. Here, we report that adult satellite cells give rise to brown adipocytes and that microRNA-133 regulates the choice between myogenic and brown adipose determination by targeting the 3'UTR of Prdm16. Antagonism of microRNA-133 during muscle regeneration increases uncoupled respiration, glucose uptake, and thermogenesis in local treated muscle and augments whole-body energy expenditure, improves glucose tolerance, and impedes the development of diet-induced obesity. Finally, we demonstrate that miR-133 levels are downregulated in mice exposed to cold, resulting in de novo generation of satellite cell-derived brown adipocytes. Therefore, microRNA-133 represents an important therapeutic target for the treatment of obesity.
Original languageEnglish
JournalCell Metabolism
Volume17
Issue number2
Pages (from-to)210-24
Number of pages15
ISSN1550-4131
DOIs
Publication statusPublished - 2013

ID: 36893987