The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes

Nat Commun. 2016 Nov 17;7:13479. doi: 10.1038/ncomms13479.

Abstract

The thermogenic activity of brown adipose tissue (BAT) and browning of white adipose tissue are important components of energy expenditure. Here we show that GPR120, a receptor for polyunsaturated fatty acids, promotes brown fat activation. Using RNA-seq to analyse mouse BAT transcriptome, we find that the gene encoding GPR120 is induced by thermogenic activation. We further show that GPR120 activation induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired cold-induced browning. Omega-3 polyunsaturated fatty acids induce brown and beige adipocyte differentiation and thermogenic activation, and these effects require GPR120. GPR120 activation induces the release of fibroblast growth factor-21 (FGF21) by brown and beige adipocytes, and increases blood FGF21 levels. The effects of GPR120 activation on BAT activation and browning are impaired in FGF21-null mice and cells. Thus, the lipid sensor GPR120 activates brown fat via a mechanism that involves induction of FGF21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism*
  • Animals
  • Body Temperature Regulation / physiology
  • Cells, Cultured
  • Cold Temperature
  • Eicosapentaenoic Acid
  • Fatty Acids, Omega-3 / metabolism
  • Fibroblast Growth Factors / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Methylamines / pharmacology
  • Mice
  • Mice, Knockout
  • Propionates / pharmacology
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • FFAR4 protein, mouse
  • Fatty Acids, Omega-3
  • GW9508
  • Methylamines
  • Propionates
  • Receptors, G-Protein-Coupled
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Eicosapentaenoic Acid
  • p38 Mitogen-Activated Protein Kinases