Endocrine FGFs and Klothos: emerging concepts

Endocrine fibroblast growth factors (FGFs) control a variety of physiological processes including suppression of bile acid synthesis in hepatocytes, promotion of lipolysis in adipocytes, and inhibition of phosphate reabsorption and vitamin D biosynthesis in renal tubular cells. Endocrine FGFs require the Klotho gene family of transmembrane proteins as co-receptors to bind cognate FGF receptors. Importantly, expression of endocrine FGFs is regulated by nuclear receptors whose lipophilic ligands are generated under the control of these hormones in their target organs. Thus, novel endocrine axes have emerged that regulate diverse metabolic processes through feedback loops composed of the FGF, Klotho, and nuclear receptor gene families. This review covers roles of Klotho family proteins in the regulation of activity and expression of endocrine FGFs.