Laboratory of Diabetes and Nutrition, Tohoku University New Industry Creation Hatcher Center, 6-6-11 Aramakiaza-Aoba, Aoba-ku, Sendai, Miyagi, 980-8579, Japan.
Sci Rep. 2020 Sep 25;10(1):15784. doi: 10.1038/s41598-020-72975-8.
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.
据报道，肝成纤维细胞生长因子 21（FGF21）和基质细胞衍生因子 2 样 1（Sdf2l1）的表达不足会导致肥胖和 2 型糖尿病患者的胰岛素抵抗和肝脂肪变性。另一方面，饮食诱导肥胖中肝 5-羟色胺受体 2a（htr2a）的表达增加会导致肝脂肪变性。在这里，我们表明，在高脂肪饮食喂养的 C57BLJ6 小鼠中，循环 FGF21 水平和肝 FGF21 表达的增加先于体重增加、高胰岛素血症和高血糖。在高脂肪饮食喂养的胰岛素抵抗小鼠中，肝 htr2a 和 Sdf2l1 的表达增加。乳清蛋白分离物的摄入降低了高脂肪饮食或标准饮食喂养的小鼠的血浆 FGF21 水平和肝 FGF21 的表达，而仅抑制了高脂肪饮食喂养的胰岛素抵抗小鼠中肝 Sdf2 和 htr2a 的过表达。此外，乳清蛋白分离物的摄入降低了高脂肪饮食或标准饮食喂养的小鼠的血浆 5-羟色胺水平。色氨酸羟化酶 1 的基因抑制降低了小鼠的肝 FGF21 表达和血浆 FGF21 水平。这些发现表明，肝 FGF21 产生的增加先于饮食诱导的体重增加、高胰岛素血症和高血糖，并且乳清蛋白分离物的摄入可能通过抑制外周 5-羟色胺合成来抑制肝 FGF21 的产生。
