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. This evidence concerns the gene FGF21 and Other metabolic disease.