Fibroblast Growth Factor 21 (FGF21) creates sugar-specific taste aversion to fructose through action in the brain in mice.

Metabolic diseases such as diabetes and obesity are a growing healthcare concern, and their increasing rates are attributed to increased consumption of carbohydrate-rich diets and sugar-sweetened beverages. Fibroblast growth factor 21 (FGF21) is a complex metabolic regulator, and there is significant evidence that it may play a role in fructose metabolism, driving relative aversion to sweet taste. As such, we examined the relationship between FGF21 and the preferential intake of simple carbohydrates in mice, both as liquid solutions and as dietary additives. Genetic deletion of FGF21 or its obligate co-receptor {beta}-klotho (KLB) had no impact on preference for sugar sweetened solutions. FGF21 overexpression, however, substantially suppressed preference for fructose solutions, but had no effect on glucose or sucrose preference. Infusions of FGF21 also suppressed fructose preference specifically, an effect that was dependent on expression of KLB in the CNS. These results demonstrate that FGF21 creates sugar-specific taste aversion to fructose, which may be mediated by a KLB-dependent pathway in the brain. HighlightsO_LIFGF21 administration suppresses fructose preference in mice. C_LIO_LIPreference for glucose or sucrose is not affected by FGF21 administration. C_LIO_LIGenetic FGF21 deletion does not enhance fructose, glucose, or sucrose preference. C_LIO_LIFGF21 requires central {beta}-klotho expression to suppress fructose preference. C_LI