Fasting induces a subcutaneous-to-visceral fat switch mediated by microRNA-149-3p and suppression of PRDM16

Nat Commun. 2016 May 31:7:11533. doi: 10.1038/ncomms11533.

Abstract

Visceral adiposity is strongly associated with metabolic disease risk, whereas subcutaneous adiposity is comparatively benign. However, their relative physiological importance in energy homeostasis remains unclear. Here, we show that after 24-h fasting, the subcutaneous adipose tissue of mice acquires key properties of visceral fat. During this fast-induced 'visceralization', upregulation of miR-149-3p directly targets PR domain containing 16 (PRDM16), a key coregulatory protein required for the 'browning' of white fat. In cultured inguinal preadipocytes, overexpression of miR-149-3p promotes a visceral-like switch during cell differentiation. Mice deficient in miR-149-3p display an increase in whole-body energy expenditure, with enhanced thermogenesis of inguinal fat. However, a visceral-like adipose phenotype is observed in inguinal depots overexpressing miR-149-3p. These results indicate that in addition to the capacity of 'browning' to defend against hypothermia during cold exposure, the subcutaneous adipose depot is also capable of 'whitening' to preserve energy during fasting, presumably to maintain energy balance, via miR-149-3p-mediated regulation of PRDM16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / physiology
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / physiology
  • Adiposity / physiology
  • Animals
  • Antagomirs / metabolism
  • Cell Differentiation
  • DNA-Binding Proteins / physiology*
  • Energy Metabolism / physiology*
  • Fasting / psychology*
  • Female
  • Gene Knockdown Techniques
  • Groin
  • HEK293 Cells
  • Humans
  • Intra-Abdominal Fat / cytology
  • Intra-Abdominal Fat / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / physiology*
  • Subcutaneous Fat / cytology
  • Subcutaneous Fat / physiology
  • Thermogenesis / physiology
  • Tissue Culture Techniques
  • Transcription Factors / physiology*
  • Up-Regulation

Substances

  • Antagomirs
  • DNA-Binding Proteins
  • MIRN149 microRNA, mouse
  • MicroRNAs
  • Prdm16 protein, mouse
  • Transcription Factors