Abstract：
Fibroblast growth factor 21 (FGF21) has promise for treating diabetes and its associated comorbidities. It has been found to reduce blood glucose in mice and humans; however, its underlying mechanism is not known. Here, the metabolic function of FGF21 in diabetes was investigated. Diabetic db/db mice received intraperitoneal injections of FGF21 for 28 days, the serum of each mouse was collected, and their metabolites were analyzed by untargeted metabolomics using UHPLC-MS/MS. It was found that FGF21 reduced blood glucose and oral glucose tolerance without causing hypoglycemia. Moreover, administration of FGF21 reduced the levels of TG and LDL levels while increasing those of HDL and adiponectin. Importantly, the levels of 45 metabolites, including amino acids and lipids, were significantly altered, suggesting their potential as biomarkers. We speculated that FGF21 may treat T2DM through the regulation of fatty acid biosynthesis, the TCA cycle, and vitamin digestion and absorption. These findings provide insight into the mechanism of FGF21 in diabetes and suggest its potential for treating diabetes.
摘要：
成纤维细胞生长因子21（FGF21）有望治疗糖尿病及其相关合并症。已经发现它可以降低小鼠和人类的血糖；然而，其潜在机制尚不清楚。这里,研究了FGF21在糖尿病中的代谢功能。糖尿病db/db小鼠接受FGF21腹膜内注射28天，收集每只小鼠的血清，使用UHPLC-MS/MS通过非靶向代谢组学分析其代谢物。发现FGF21降低血糖和口服葡萄糖耐量而不引起低血糖。此外，FGF21的给药降低了TG和LDL的水平，同时增加了HDL和脂联素的水平。重要的是,45种代谢物的水平，包括氨基酸和脂类,发生了显著的变化，表明它们作为生物标志物的潜力。我们推测FGF21可能通过调节脂肪酸的生物合成来治疗T2DM,TCA循环,和维生素的消化吸收。这些发现提供了对FGF21在糖尿病中的机制的见解，并表明其治疗糖尿病的潜力。
