Myocardin-related Transcription Factor A Regulates Conversion of Progenitors to Beige Adipocytes

Cell. 2015 Jan 15;160(1-2):105-18. doi: 10.1016/j.cell.2014.12.005. Epub 2015 Jan 8.

Abstract

Adipose tissue is an essential regulator of metabolic homeostasis. In contrast with white adipose tissue, which stores excess energy in the form of triglycerides, brown adipose tissue is thermogenic, dissipating energy as heat via the unique expression of the mitochondrial uncoupling protein UCP1. A subset of UCP1+ adipocytes develops within white adipose tissue in response to physiological stimuli; however, the developmental origin of these "brite" or "beige" adipocytes is unclear. Here, we report the identification of a BMP7-ROCK signaling axis regulating beige adipocyte formation via control of the G-actin-regulated transcriptional coactivator myocardin-related transcription factor A, MRTFA. White adipose tissue from MRTFA(-/-) mice contains more multilocular adipocytes and expresses enhanced levels of brown-selective proteins, including UCP1. MRTFA(-/-) mice also show improved metabolic profiles and protection from diet-induced obesity and insulin resistance. Our study hence unravels a central pathway driving the development of physiologically functional beige adipocytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis
  • Animals
  • Bone Morphogenetic Protein 7 / metabolism
  • Diet
  • Energy Metabolism
  • Insulin Resistance
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Bone Morphogenetic Protein 7
  • MKL1 protein, mouse
  • Tgfb1 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta1
  • bmp7 protein, mouse