Physiology

Fast Rising Hormone

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Science  25 Jul 2008:
Vol. 321, Issue 5888, pp. 467-468
DOI: 10.1126/science.321.5888.467c

Fibroblast growth factor 21 (FGF21) has recently taken center stage as a key metabolic hormone that helps the body to adapt to starvation. When mice are fasted, FGF21 expression levels in the liver rise dramatically. In turn, FGF21 stimulates the release of fatty acids from adipose tissue and promotes their conversion in the liver to ketone bodies, which can be used as an energy source when carbohydrates are scarce; FGF21 also promotes torpor, an energy-conserving state in mice characterized by a reduction in body temperature and physical activity.

Inagaki et al. show that the role of FGF21 in programming energy conservation during starvation may be even broader. Through the use of transgenic mice, they found that FGF21 mimics the inhibitory effects of fasting on organismal growth at both the phenotypic and molecular levels. The transgenic mice were smaller than their wild-type counterparts despite equal or greater food intake. Although the transgenic mice had higher levels of circulating growth hormone (GH) than controls, they appeared to be resistant to its actions. In the liver, FGF21 reduced the expression of a major mediator of GH action—the transcriptional regulator STAT5—and decreased the expression of key target genes implicated in organismal growth, including the gene encoding insulin-like growth factor 1 (IGF-1). Whether FGF21 has similar effects in humans remains to be determined. — PAK

Cell Metab. 8, 77 (2008).

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