Identification of FGF21 ‐inducing rare sugars that reduces sugar appetite in male BL /6 mice

Dietary sugars induce the secretion of hepatic fibroblast growth factor 21 (FGF21) and subsequently activate FGF21-sensing oxytocin neurons to suppress sugar intake. We aimed to identify FGF21-inducing rare sugars as substitutes for obesogenic dietary sugars and to test their ability to suppress sugar appetite in BL/6 mice. We have identified D-allulose, D-tagatose, and D-sorbitol as potent FGF21-inducers in mouse primary hepatocytes. All three compounds were confirmed to induce FGF21 secretion and subsequently activate oxytocin neurons in mice. FGF21-inducing rare sugars administered by gastric gavage to mice reduced sugar intake, and mixing these sugars with sucrose solution significantly reduced their intake and preference in mice. The long-term lick analyses showed that an FGF21-inducing sugar made the solution palatable, but reduced the appetite for the sugar solution and prolonged the ingestion interval in mice. Therefore, using these sugars as substitutes for obesogenic dietary sugars may help to curve sugar appetite and reduce sugar intake.