FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss

Cell Metab. 2014 Oct 7;20(4):670-7. doi: 10.1016/j.cmet.2014.07.012. Epub 2014 Aug 14.


The mechanism by which pharmacologic administration of the hormone FGF21 increases energy expenditure to cause weight loss in obese animals is unknown. Here we report that FGF21 acts centrally to exert its effects on energy expenditure and body weight in obese mice. Using tissue-specific knockout mice, we show that βKlotho, the obligate coreceptor for FGF21, is required in the nervous system for these effects. FGF21 stimulates sympathetic nerve activity to brown adipose tissue through a mechanism that depends on the neuropeptide corticotropin-releasing factor. Our findings provide an unexpected mechanistic explanation for the strong pharmacologic effects of FGF21 on energy expenditure and weight loss in obese animals.

Publication types

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

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Animals
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism
  • Energy Metabolism / drug effects*
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Fibroblast Growth Factors / pharmacology*
  • Hypothalamus / metabolism
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Obese
  • Mice, Transgenic
  • RNA, Messenger / metabolism
  • Sympathetic Nervous System / drug effects*
  • Sympathetic Nervous System / metabolism
  • Thermogenesis / genetics
  • Weight Loss / drug effects*


  • Klb protein, mouse
  • Membrane Proteins
  • RNA, Messenger
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Corticotropin-Releasing Hormone