White adipose tissue (WAT) was once believed to be the only significant adipose depot in adult humans. FGF21 holds promise as a cold-induced beige adipokine with metabolic benefits of therapeutic relevance through browning of white adipose tissue. This study provides first evidence of inducible functional thermogenic beige adipogenesis in human neck fat. FGF21 is a beige adipokine capable of promoting a brown fat-like thermogenic program in WAs. Conclusion:īeige adipocytes are thermogenic in humans. Treatment of WA with FGF21-induced UCP1 expression and increased oxygen consumption, respiratory uncoupling, norepinephrine-mediated thermogenesis, fatty acid oxidation and heat production, thus recapitulating the association between cold-induced FGF21 secretion and cold-induced thermogenesis in vivo. Differentiated WA expressed β-klotho, a critical co-factor mediating FGF21 action. During BA differentiation, FGF21 gene expression and secretion were increased, and were augmented following norepinephrine exposure (a cold mimic in vitro). BA-like cells expressed beige but not classic BA markers. Under hormonal manipulation, primary human neck pre-adipocytes differentiated into adipocytes with either BA-like or WA phenotypes, on gene/protein and functional levels. Adipocyte heat production was measured by infrared thermography. Extracellular flux bioanalyzer was used to quantify adipocyte oxygen consumption and fatty acid oxidation. Real-time PCR/western blotting was used to determine cellular mRNA/protein levels. FGF21 secretion was measured by enzyme-linked immuosorbent assay. Progenitors isolated from human cervical fat were differentiated into adipocytes with either a BA-like or white adipocyte (WA) phenotype. Here, we explored (i) the adipogenic potential, thermogenic function and FGF21 secretory capacity of beige adipocytes derived from human neck fat and (ii) the role of FGF21 in modulating adipose bioenergetics.
Within the beige adipocyte transcriptome, fibroblast growth factor-21 (FGF21) is a gene whose protein product acts as an adipokine, regulating cold-induced thermogenesis in animals. However, little is known about their thermogenic function. Recent studies suggest human neck brown adipose tissue (BAT) to consist of ‘brown adipocyte (BA)-like’ or beige adipocytes.
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