FGF15/FGF19 alleviates insulin resistance and upregulates placental IRS1/GLUT expression in pregnant mice fed a high-fat diet. (1st September 2021)

• Record Type: Journal Article
• Authors: Zhao, Shanshan; Wang, Dongyu; Li, Zhuyu; Xu, Shuqia; Chen, Haitian; Ding, Wenjing; Yang, Juan; Zhao, Weihua; Sun, Bo; Wang, Zilian
• Is Part Of: Placenta. Volume 112(2021)
• Page Start: 81
• Page End: 88
• Publication Date: 2021-09-01
• Subjects: Fibroblast growth factor 15/19 -- Insulin resistance -- Gestational diabetes mellitus -- Insulin receptor substrate 1 -- Glucose transporters; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2021.07.286
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: This study aimed to evaluate whether FGF19 can alleviate insulin resistance and change the expression of placental IRS1/GLUTs. Methods: Mice transgenic for Fgf15 (the murine homologue of human FGF19) were constructed, and human recombinant FGF19 was administered to pregnant high-fat diet mice. Then, glycolipid metabolism parameters and the weight of foetus and placenta were observed. The expression levels of key molecules of the insulin signalling pathway and glucose transporters in placentae were detected by qRT-PCR and western blotting. Primary trophoblasts and JAR cells were cultured in high-glucose medium, and FGF19 was added to observe its regulatory effects on IRS1/GLUTs. Results: Overexpressing FGF15 or exogenously administering FGF19 reduced the levels of fasting blood glucose, HOMA-IR, triglycerides, and free fatty acids in pregnant high-fat diet mice compared to control mice ( P < 0.05). FGF15/FGF19 did not significantly affect placental weight, foetal weight or litter size ( P > 0.05). In addition, FGF15/FGF19 upregulated the expression of p-IRS1 and GLUT4 in the placentae of high-fat diet mice and upregulated GLUT1 levels in the placentae of normal diet-fed mice ( P < 0.05), while it did not significantly alter total IRS1 and GLUT3 levels ( P > 0.05). Consistent with the results of the animal experiments, FGF19 increased the expression of p-IRS1 and GLUT4 in trophoblast cells cultured in high-glucose medium ( P < 0.05). Discussion: Overexpressing FGF15 or administering FGF19 to pregnant high-fat diet mice can improve glycolipid metabolism and alleviate systemic and local insulin resistance. The possible underlying mechanism may involve upregulation of placental expression of p-IRS1 and GLUT4. Highlights: Administering FGF19 to pregnant high-fat diet mice alleviated insulin resistance. FGF15/FGF19 did not affect placental weight, foetal weight or litter size. FGF15/FGF19 upregulated p-IRS1, GLUT4 expression in placentae of high-fat diet mice. FGF19 increased p-IRS1, GLUT4 expression in trophoblast cells in high-glucose medium.