| First Author | Nonogaki K | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 15784 |
| PubMed ID | 32978487 | Mgi Jnum | J:296241 |
| Mgi Id | MGI:6467054 | Doi | 10.1038/s41598-020-72975-8 |
| Citation | Nonogaki K, et al. (2020) Whey protein isolate inhibits hepatic FGF21 production, which precedes weight gain, hyperinsulinemia and hyperglycemia in mice fed a high-fat diet. Sci Rep 10(1):15784 |
| abstractText | Insufficient expression of hepatic fibroblast growth factor 21 (FGF21) and stromal cell-derived factor 2 like 1 (Sdf2l1) reportedly leads to insulin resistance and hepatosteatosis in obesity and type 2 diabetes. On the other hand, increased expression of hepatic serotonin receptor 2a (htr2a) in diet-induced obesity contributes to hepatosteatosis. Here we show that increases in circulating FGF21 levels and expression of hepatic FGF21 preceded weight gain, hyperinsulinemia, and hyperglycemia in C57BLJ6 mice fed a high-fat diet. Expression of hepatic htr2a and Sdf2l1 increased in insulin-resistant mice fed a high-fat diet. Intake of whey protein isolate decreased plasma FGF21 levels and expression of hepatic FGF21 in mice fed either a high-fat diet or a chow diet, whereas it only suppressed the overexpression of hepatic Sdf2 and htr2a in insulin-resistant mice fed a high-fat diet. Moreover, intake of whey protein isolate decreased plasma serotonin levels in mice fed either a high-fat diet or a chow diet. Genetic inhibition of tryptophan hydroxylase 1 decreased hepatic FGF21 expression and plasma FGF21 levels in mice. These findings suggest that increased hepatic FGF21 production precedes diet-induced weight gain, hyperinsulinemia, and hyperglycemia, and that intake of whey protein isolate could inhibit hepatic FGF21 production by suppressing peripheral serotonin synthesis. |
