Fibroblast growth factor 21 secretion enhances glucose uptake in mono(2-ethylhexyl)phthalate-treated adipocytes.
Fibroblast growth factor 21 secretion enhances glucose uptake in mono(2-ethylhexyl)phthalate-treated adipocytes.
复制标题
DOI：
10.1016/j.tiv.2019.04.021
复制
发表时间：
2019-09
期刊：
影响因子：
--
通讯作者：
Jhih-Wei Hsu;Szu-Ching Yeh;F. Tsai;Hsin-Wei Chen;T. Tsou
中科院分区：
文献类型：
--
作者：
Jhih-Wei Hsu;Szu-Ching Yeh;F. Tsai;Hsin-Wei Chen;T. Tsou
Previous studies revealed that cellular accumulation of mono(2-ethylhexyl)phthalate (MEHP) disturbed energy metabolism in adipocytes, where glucose uptake was significantly increased. The present study aimed to determine the mechanisms underlying the increased glucose uptake. MEHP-treated 3T3-L1 adipocytes exhibited a significantly increased glucose uptake activity. Immunoblot analysis suggested that the insulin-induced signals were not responsible for the increased glucose uptake. qPCR analysis revealed that bothGlut1andGlut4genes were highly expressed during adipogenesis;Glut1mRNA levels in MEHP-treated adipocytes were significantly increased. Moreover, MEHP-treated adipocytes exhibited significantly increased levels of fibroblast growth factor 21 (FGF21) in both mRNA and secreted protein. FGF21 is a peptide hormone with pleiotropic effects on regulation of insulin sensitivity and glucose/lipid homeostasis. We found that MEHP, FGF21, and lactate in culture medium together enhancedFgf21gene expression in MEHP-treated adipocytes. FGF21 signaling requires fibroblast growth factor receptor (FGFR) and βKlotho.Fgfrfamily andβKlothogenes were actively expressed during adipogenesis; mRNA levels ofFgfr3andFgfr4genes in MEHP-treated adipocytes were significantly increased. Roles of FGF21/FGFR and phosphoinositide 3-kinase (PI3K)/AKT signal axes in regulation of glucose uptake were determined. We demonstrated that FGF21/FGFR signals played the major roles in up-regulation of the basal glucose uptake in MEHP-treated adipocytes. The in vitro evidence suggests that cellular FGF21 secretion enhances the basal glucose uptake in MEHP-treated adipocytes.
