FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis

Genes Dev. 2012 Feb 1;26(3):271-81. doi: 10.1101/gad.177857.111.

Abstract

Certain white adipose tissue (WAT) depots are readily able to convert to a "brown-like" state with prolonged cold exposure or exposure to β-adrenergic compounds. This process is characterized by the appearance of pockets of uncoupling protein 1 (UCP1)-positive, multilocular adipocytes and serves to increase the thermogenic capacity of the organism. We show here that fibroblast growth factor 21 (FGF21) plays a physiologic role in this thermogenic recruitment of WATs. In fact, mice deficient in FGF21 display an impaired ability to adapt to chronic cold exposure, with diminished browning of WAT. Adipose-derived FGF21 acts in an autocrine/paracrine manner to increase expression of UCP1 and other thermogenic genes in fat tissues. FGF21 regulates this process, at least in part, by enhancing adipose tissue PGC-1α protein levels independently of mRNA expression. We conclude that FGF21 acts to activate and expand the thermogenic machinery in vivo to provide a robust defense against hypothermia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological / genetics
  • Adaptation, Physiological / physiology*
  • Adipose Tissue, Brown / cytology*
  • Adipose Tissue, White / cytology*
  • Adipose Tissue, White / drug effects
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Cold Temperature
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / pharmacology
  • Gene Expression Regulation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA Processing, Post-Transcriptional
  • Thermogenesis / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Trans-Activators
  • Transcription Factors
  • fibroblast growth factor 21
  • Fibroblast Growth Factors