Regulation of glucose and lipid metabolism through specific receptor-responsive FGF19 protein

我们试图制备缺乏细胞增殖活性的突变体FGF19蛋白（FGF19-7）。FGF19-7处理可轻微降低HepG2细胞中CYP7A1 mRNA水平。用FGF19-7治疗小鼠并没有刺激Ki-67阳性细胞的数量，而Ki-67是细胞增殖的标志。小鼠饲喂蛋氨酸和胆碱缺乏（MCD）饮食6周，并与FGF19或FGF19-7 （40 nmol/kg）共处理4天。MCD组小鼠血清ALT、肝脏甘油三酯和游离脂肪酸水平显著升高。在与FGF19或FGF19-7共处理的小鼠中，这些水平显著降低，程度相似。这些结果表明，用缺乏细胞增殖活性的FGF19-7治疗可预防MCD饮食诱导的脂肪性肝炎。

We tried to prepare mutant FGF19 protein (FGF19-7) that lacks the activity of cell proliferation. FGF19-7 treatment slightly decreased CYP7A1 mRNA levels in HepG2 cells. Treatment of mice with FGF19-7 did not stimulate the number of Ki-67 positive cells that is a marker of cell proliferation. Mice were fed a methionin- and choline- deficient (MCD) diet for 6 weeks and co-treated with FGF19 or FGF19-7 (40 nmol/kg) for 4 days. Serum ALT and hepatic triglyceride and free fatty acid levels were markedly increased in mice fed MCD diet. These levels were significantly decreased in the mice co-treated with FGF19 or FGF19-7 to a similar extent. These results suggest that treatment with FGF19-7 lacking the activity of cell proliferation protects against MCD diet-induced steatohepatitis.