The Diverse Metabolic Actions of FGF21

Abstract

Fibroblast growth factor 21 (FGF21) is an endocrine and paracrine factor that is produced in many tissues in response to metabolic stress, including several nutrient and dietary conditions. In addition to its physiologic role in regulating the adaptive response to these conditions, pharmacologic administration of FGF21 to obese animals causes weight loss and improves insulin sensitivity. The diverse actions of FGF21 are mediated through a unique receptor complex that is composed of a classic FGF receptor and the novel co-receptor, b-Klotho. Investigation of the tissue-specificity of this FGF21 signaling pathway has revealed the existence of a complex peripheral and neural endocrine circuit, which in addition to regulating metabolism, also governs reward behaviors.