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

By F. Fisher, Sandra Kleiner, N. Douris, Elliott C. Fox, Rina J. Mepani, Francisco Verdeguer, Jun Wu, A. Kharitonenkov, J. Flier, E. Maratos-Flier and 1 more. Genes & Development, 2012

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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.

Subfields: Biochemistry, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/1127ee280b6cdd3f27ab8e0dd380241fe8780fa1

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Citations in the corpus

Ablation of PRDM16 and Beige Adipose Causes Metabolic Dysfunction and a Subcutaneous to Visceral Fat Switch (2014, background): “Cells from Adipo-PRDM16 KO mice also showed a blunted response to stimuli that induce browning, such as isoproterenol and FGF21 (Figures S2F ad S2G) (Fisher et al., 2012; Wu et al., 2013).”
FGF/FGFR signaling in health and disease (2020, background): “FGF21 improves the expression of UCP1 in WAT by upregulating PGC-1α protein level and promoting browning of WAT in adaptive thermogenesis.(559,566) FGF21 knockout mice show diminished browning of WAT and a decreased adaption to chronic cold exposure.”
Adaptive thermogenesis in adipocytes: is beige the new brown? (2013, background): “More recently, FGF21 has been shown to play a role in adaptive thermogenesis in both BATs and WATs (Hondares et al. 2010; Fisher et al. 2012).”
Beige Adipocytes are a Distinct Type of Thermogenic Fat Cell in Mouse and Human (2012, background): “Other polypeptide hormones that brown white adipose tissues in rodents, such as FGF21 (Fisher et al., 2012) and ANP (Bordicchia et al.”
Human BAT Possesses Molecular Signatures That Resemble Beige/Brite Cells (2012, background): “Alternatively, using endogenous hormones such as FGF21 [49], natriuretic peptides [50], prostaglandin [51,52], or Irisin [53] to promote browning of white fat would be a plausible approach.”
Brown Remodeling of White Adipose Tissue by SirT1-Dependent Deacetylation of Pparγ (2012, neutral): “, 2005) are insulin-sensitizers with browning properties (Fisher et al., 2012; Vernochet et al., 2009) that promote Pparg sumoylation.”
Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis (2014, methodology): “This mechanism distinguishes Metrnl from other known polypeptide inducers of thermogenesis, such as Irisin and Fgf-21, which both act directly on adipocytes to stimulate thermogenesis (Boström et al., 2012; Fisher et al., 2012; Zhang et al., 2013).”
Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. (2015, neutral): “As listed in Figure 3, such factors include BMP4 (66), BMP7 (67, 68), BMP8b (69), FGF19 (70, 71), FGF21 (72, 73), growth differentiation fac-tor-5 (GDF5) (74), natriuretic peptides (75), prostaglandins (76, 77), VEGF (78, 79), and β -aminoisobutyric acid (BAIBA) (80).”