FGF21 and metabolic disease: Paradoxically, despite beneficial effects in rodents, elevated FGF21 levels are reported in metabolic diseases.[2, 3, 4, 5] Consistently, FGF21 is reduced in response to corrective interventions such as lifestyle modification and bariatric surgery.[1] Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor behind these alterations in humans is unknown.