A novel GPR120-dependent pathway of control brown fat activation mediated by FGF21

Brown adipose tissue (BAT) thermogenesis and the browning of white adipose tissue are important components of energy expenditure. An RNAseq-based analysis of the mouse BAT transcriptome led us to identify GPR120 as a gene induced by thermogenic activation. GPR120, a G protein-coupled receptor binding unsaturated long-chain fatty acids, is known to mediate some beneficial metabolic actions of polyunsaturated fatty acids. We show that pharmacological activation of GPR120 induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired browning in response to cold. n-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 (FGF-21) by brown and beige adipocytes and increases blood FGF21 levels. The effects of GPR120 activation are impaired in FGF21-null mice and cells. Thus, the lipid sensor GPR120 constitutes a novel pathway of brown fat activation and involves FGF21. Overall design: eight adult male C57BL6 mice were maintained at thermoneutral temperature (29C). After two weeks, a subset of four mice was placed at 4C environment temperature for 24h. RNAseq was performed on the BAT tissues of these 2 groups.

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Peyrou M, Cereijo R, Quesada-López T, Campderrós L, Gavaldà-Navarro A, Liñares-Pose L, Kaschina E, Unger T, López M, Giralt M, Villarroya F