FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans

The liking and selective ingestion of palatable foods—including sweets—is biologically controlled, and dysfunction of this regulation may promote unhealthy eating, obesity, and disease. The hepatokine fibroblast growth factor 21 (FGF21) reduces sweet consumption in rodents and primates, whereas knockout of Fgf21 increases sugar consumption in mice. To investigate the relevance of these findings in humans, we genotyped variants in the FGF21 locus in participants from the Danish Inter99 cohort (n = 6,514) and examined their relationship with a detailed range of food and ingestive behaviors. This revealed statistically significant associations between FGF21 rs838133 and increased consumption of candy, as well as nominal associations with increased alcohol intake and daily smoking. Moreover, in a separate clinical study, plasma FGF21 levels increased acutely after oral sucrose ingestion and were elevated in fasted sweet-disliking individuals. These data suggest the liver may secrete hormones that influence eating behavior. [Display omitted] •Human FGF21 variants are associated with increased sweet consumption•These variants do not correlate with obesity, T2DM, or glucose intolerance•Circulating FGF21 is increased by sucrose consumption•Sweet-disliking individuals have elevated FGF21 levels What is the molecular basis for a “sweet tooth”? In a combined clinical and genetic study, Søberg, Sandholt, and colleagues link the hepatokine FGF21 to increased sweet consumption in humans, potentially by acting on the central reward system.