Fibroblast growth factor 21 secretion enhances glucose uptake in mono(2-ethylhexyl)phthalate-treated adipocytes
| Autor: | Feng-Yuan Tsai, Szu-Ching Yeh, Hsin-Wei Chen, Tsui-Chun Tsou, Jhih-Wei Hsu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty FGF21 Glucose uptake Carbohydrate metabolism Toxicology 03 medical and health sciences Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Internal medicine 3T3-L1 Cells Diethylhexyl Phthalate medicine Adipocytes Animals Insulin biology Chemistry General Medicine Fibroblast growth factor receptor 4 Fibroblast Growth Factors 030104 developmental biology Endocrinology Glucose Fibroblast growth factor receptor Adipogenesis 030220 oncology & carcinogenesis biology.protein GLUT1 Proto-Oncogene Proteins c-akt GLUT4 |
| Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA. 59 |
| ISSN: | 1879-3177 |
| Popis: | 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 both Glut1 and Glut4 genes were highly expressed during adipogenesis; Glut1 mRNA 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 enhanced Fgf21 gene expression in MEHP-treated adipocytes. FGF21 signaling requires fibroblast growth factor receptor (FGFR) and βKlotho. Fgfr family and βKlotho genes were actively expressed during adipogenesis; mRNA levels of Fgfr3 and Fgfr4 genes 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. |
| Databáze: | OpenAIRE |
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