The FGF21–adiponectin axis in controlling energy and vascular homeostasis

Whole-body energy metabolism and cardiovascular homeostasis are tightly controlled processes that involve highly coordinated crosstalk among distal organs. This is mainly achieved by a large number of hormones released from each organ. Among them, fibroblast growth factor 21 (FGF21) and adiponectin have recently gained considerable attention, since both of them possess multiple profound protective effects against a myriad of cardio-metabolic disorders. Despite their distinct structures and production sites, these two hormones share striking functional similarity. This dichotomy is recently reconciled by the demonstration of the FGF21-adiponectin axis. In adipocytes, both transcription and secretion of adiponectin are strongly induced by FGF21, which is partially dependent on PPARγ activity. Furthermore, the glucose-lowering, lipid-clearing, and anti-atherosclerotic functions of FGF21 are diminished in adiponectin-null mice, suggesting that adiponectin serves as an obligatory mediator of FGF21-elicited metabolic and vascular benefits. However, in both animals and human subjects with obesity, circulating FGF21 levels are increased whereas plasma adiponectin concentrations are reduced, perhaps due to FGF21 resistance, suggesting that dysfunctional FGF21-adiponectin axis is an important contributor to the pathogenesis of obesity-related cardio-metabolic syndrome. The FGF21-adiponectin axis protects against a cluster of cardio-metabolic disorders via mediating multi-organ communications, and is a promising target for therapeutic interventions of these chronic diseases.