Fibroblast growth factors (Fgfs) are proteins of ~150-300 amino acids with diverse functions in development and metabolism. Fgf21, which is produced in several tissues, including the liver, white adipose tissue, pancreas, and muscle regulates lipid and glucose metabolism as a hormone-like signaling molecule in an endocrine manner. The pharmacological effects of Fgf21 indicate that Fgf21 has potential therapeutic effects on metabolic diseases. In this issue, Adam et al. have reported the pharmacological effects of Fgf21 in adipocyte-specific Fgfr1 knockout (Fgfr1 CKO) mice by the administration of Fgf21. Fgfr1 CKO mice showed no Fgf21-mediated lowering of blood glucose, insulin and triglycerides and no increase in energy expenditure. The evidence defines Fgfr1 in adipocytes as the key receptor/organ for the initiation of the majority of the pharmacological effects of Fgf21 in metabolism. These findings suggest that Fgf signaling in adipocytes is an attractive drug discovery target for metabolic diseases.
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