OR15-1 Fibroblast Growth Factor 21 (FGF21) is a Brown Adipokine that induces Beige Adipogenesis and Thermogenesis in Humans

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR15-Adipokine Action
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:15 AM
Room 303 (Moscone Center)
Paul Lee*1, Charlotte D Werner1, Electron Kebebew2 and Francesco S. Celi3
1NIDDK-NIH, Bethesda, MD, 2NIH, Bethesda, MD, 3National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD
Cold exposure increases the abundance of brown adipocyte-like cells (“beige” or “brite” adipocytes) in murine white adipose tissue, transforming the tissue into a thermogenic brown fat-like phenotype. Several hormones, such as irisin, cardiac natriuretic peptides and fibroblast growth factor 21 (FGF21) promote fat browning in rodents. Whether similar phenotypic changes occur in humans and their underlying mechanisms are poorly understood. We recently demonstrated that mild cold exposure is sufficient to increase circulating FGF21 levels in humans, which correlate with the cold-induced thermogenesis (CIT) response (1).  Here, we explored the tissue origin of enhanced FGF21 secretion during cold exposure and its role in modulating adipose bioenergetics.  Under hormonal manipulation, we differentiated primary pre-adipocytes from human cervical adipose tissue biopsies (N=14, age 44±7 yr old, F=8) into mature adipocytes with either brown adipocyte-like (BA) or white adipocyte (WA) phenotypes. During BA differentiation, FGF21 gene expression was increased. Mature BA secreted FGF21 protein into culture media and the secretory response was coordinately augmented by exposure to norepinephrine (a cold mimic in vitro). Differentiated WA expressed high levels of β-Klotho, a critical co-factor mediating FGF21 action. In WA, FGF21 treatment dose-dependently up-regulated expression of beige fat transcriptome and increased oxygen consumption, respiratory uncoupling, norepinephrine-mediated thermogenesis, fatty acid oxidation and glycolysis, thus recapitulating the association between cold-induced FGF21 secretion, CIT and cold-induced metabolic changes in vivo. Collectively, these data show that FGF21 is a human brown adipokine capable of promoting a brown fat-like thermogenic program in white adipocytes. We propose that cold-activated FGF21 pathway is a promising therapeutic target in humans, exploitable for metabolic benefits through browning of white adipose tissue.

(1) Lee P et al., J Clin Endocrinol Metab. 2013;98:E98-E102.

Nothing to Disclose: PL, CDW, EK, FSC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Intramural Research Program of NIDDK: Z01-DK047057-02 and Z01-DK071044; Australian NHMRC Early Career Fellowship, the Diabetes Australia Fellowship, and the Bushell Travelling Fellowship awarded to PL.
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