TY - JOUR
T1 - Fibroblast growth factor 21
T2 - From pharmacology to physiology
AU - Kliewer, Steven A.
AU - Mangelsdorf, David J.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family that functions as an endocrine hormone. Pharmacologic studies showthat FGF21 has broad metabolic actions in obese rodents and primates that include enhancing insulin sensitivity, decreasing triglyceride concentrations, and causing weight loss. In lean rodents, FGF21 expression is strongly induced in liver by prolonged fasting through a mechanism that involves the nuclear receptor peroxisome proliferator-activated receptor α. FGF21, in turn, induces the transcriptional coactivator protein peroxisome proliferator-activated receptor γ coactivator protein 1α and stimulates hepatic gluconeogenesis, fatty acid oxidation, and ketogenesis. FGF21 also blocks somatic growth and sensitizes mice to a hibernation-like state of torpor. Thus, FGF21 plays a key role in eliciting and coordinating the adaptive starvation response. Interestingly, FGF21 expression is induced in white adipose tissue by peroxisome proliferator-activated receptor γ, which suggests that it also regulates metabolism in the fed state. This article highlights recent advances in our understanding of FGF21's pharmacologic and physiologic actions.
AB - Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family that functions as an endocrine hormone. Pharmacologic studies showthat FGF21 has broad metabolic actions in obese rodents and primates that include enhancing insulin sensitivity, decreasing triglyceride concentrations, and causing weight loss. In lean rodents, FGF21 expression is strongly induced in liver by prolonged fasting through a mechanism that involves the nuclear receptor peroxisome proliferator-activated receptor α. FGF21, in turn, induces the transcriptional coactivator protein peroxisome proliferator-activated receptor γ coactivator protein 1α and stimulates hepatic gluconeogenesis, fatty acid oxidation, and ketogenesis. FGF21 also blocks somatic growth and sensitizes mice to a hibernation-like state of torpor. Thus, FGF21 plays a key role in eliciting and coordinating the adaptive starvation response. Interestingly, FGF21 expression is induced in white adipose tissue by peroxisome proliferator-activated receptor γ, which suggests that it also regulates metabolism in the fed state. This article highlights recent advances in our understanding of FGF21's pharmacologic and physiologic actions.
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U2 - 10.3945/ajcn.2009.28449B
DO - 10.3945/ajcn.2009.28449B
M3 - Article
C2 - 19906798
AN - SCOPUS:74049108945
SN - 0002-9165
VL - 91
SP - 254S-257S
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 1
ER -