DSSS - FGF21 and Alcohol: A Sobering Liaison

Fibroblast growth factor 21 (FGF21) is an endocrine and paracrine factor that is produced in response to nutrient and metabolic stress and is known to have diverse roles in maintaining lipid and glucose homeostasis. The most potent inducer of circulating FGF21 is alcohol consumption, a finding that is supported by human genetics. In response to alcohol, FGF21 is synthesized in the liver and immediately released into circulation. FGF21 then enters discrete regions of the brain where it mitigates many of the adverse effects of alcohol, including suppressing further intake, protecting against dehydration, and reversing intoxication. These anhedonic and amethystic properties of FGF21 are mediated through a unique receptor complex that is composed of a classic FGF receptor and an essential co-receptor, b-Klotho. Investigation into the mechanisms governing the protective effects of FGF21 has revealed the existence of a complex hepatic-CNS endocrine circuit, which in addition to regulating metabolism, also governs reward behaviors and arousal in response to alcohol.