Metabolic roles of endocrine fibroblast growth factors

• Endocrine FGFs act via a membrane-bound FGF-receptor in complex with α/βKlotho.
• FGF15 regulates postprandial liver metabolism.
• FGF21 coordinates adaptive responses to nutritional and physiological stresses.
• FGF23 regulates phosphate homeostasis.
• FGF19, FGF21, and FGF1 represent potential therapies for the metabolic syndrome.

Considerable effort is currently being devoted to understanding the physiological and pharmacological action of the endocrine fibroblast growth factors (FGFs). These three proteins (FGF15/19, FGF21 and FGF23) act in a tissue-specific manner through a membrane-complex consisting of an FGF-receptor and α/βKlotho. FGF15/19 is produced in the intestine and regulates postprandial liver metabolism and gallbladder filling. FGF21 is largely liver-derived and co-ordinates adaptive changes in response to nutritional and physiological stresses. FGF23 signals from the bone to the kidney to maintain phosphate homeostasis. In pharmacological settings, FGF15/19, FGF21, and the prototypical FGF1, potentially represent novel treatments for obesity and diabetes. This review summarises the recent advances in our understanding of the biology of these important metabolic regulators.