These findings suggest that ingestion of whey protein isolate suppresses increases in plasma FGF21 levels and expression of hepatic FGF21 in mice fed a high fat-diet for 6 or 13 days, and that ingestion of whey protein isolate suppresses hyperinsulinemia, hyperglycemia, and the increased expression of hepatic htr2a and Sdf2l1 in mice fed a high-fat diet for 13 days, whereas it has no effects on plasma insulin levels, blood glucose levels, or the expression of hepatic htr2a and Sdf2l1 in mice fed a high-fat diet for 6 days. This evidence concerns the gene FGF21 and hyperinsulinism.