FGF21-inducing rare sugars for addressing obesity and alcoholism.

Obesity and alcoholism are major global health burdens driven in part by maladaptive ingestive behaviors. Accordingly, functional foods that curb overeating and excessive alcohol consumption may help prevent these disorders. Ingestion of simple sugars or alcohol increases plasma fibroblast growth factor 21 (FGF21), which activates oxytocin (OXT) neurons in the paraventricular nucleus of the hypothalamus (PVH) and suppresses the specific appetite for sugar and alcohol. D-Allulose and D-tagatose are generally recognized as safe rare sugars and serve as potent inducers of FGF21. Oral administration of these sugars elevates plasma FGF21 to levels sufficient to reduce preference for simple sugars and alcohol without altering palatability. In mice, they also prevent the development of diet-induced obesity and alcohol dependence. Mechanistically, these effects involve activating transcription factor 4 (ATF4)-dependent induction of FGF21 and activation of the FGF21-PVHOXT negative feedback system. Thus, rare sugars such as D-allulose and D-tagatose may improve ingestive behaviors and help prevent obesity and alcoholism.