Effect of the TYK-2/STAT-3 pathway on lipid accumulation induced by mono-2-ethylhexyl phthalate. (15th March 2019)

• Record Type: Journal Article
• Authors: Qi, Wen; Zhou, Liting; Zhao, Tianye; Ding, Shuang; Xu, Qi; Han, Xu; Zhao, Yaming; Song, Xinyue; Zhao, Tianyang; Zhang, Xiaohan; Ye, Lin
• Is Part Of: Molecular and cellular endocrinology. Volume 484(2019)
• Page Start: 52
• Page End: 58
• Publication Date: 2019-03-15
• Subjects: MEHP -- TYK-2/STAT-3 pathway -- Mitochondrial STAT-3 -- 3T3-L1 adipocytes -- ROS -- Lipid metabolism; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2019.01.012
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Background: Mono-2-ethylhexyl phthalate (MEHP), an important metabolite of di (2-ethylhexyl) phthalate (DEHP), can induce lipid metabolic disorder. Previous studies have shown that MEHP promotes 3T3-L1 cell differentiation; however, the underlying mechanism is unclear. The present study was performed to investigate the effect of the TYK-2/STAT-3 pathway on lipid accumulation induced by MEHP. Methods: A 3T3-L1 precursor adipocyte differentiation model was exposed to MEHP. 3-Isobutyl-1-methylxanthine (IBMX), dexamethasone (DEX), and insulin were used to establish the 3T3-L1 precursor adipocyte differentiation model. Then the model cells were exposed to MEHP for 8 d. The lipid droplet formation in 3T3-L1 cells was determined with Oil-Red-O staining, and isopropyl alcohol was used to extract the lipid droplets for quantification. Flow cytometry was used to detect the intracellular reactive oxygen species (ROS) and mitochondrial membrane potential. Quantitative real-time polymerase chain reaction (qPCR) was used to detect mRNA expression, and western blotting was used to detect the expression of proteins encoded by TYK-2/STAT-3 pathway genes and adipogenesis-related genes. Results: MEHP treatment, compared with the control treatment, significantly promoted the differentiation of 3T3-L1 cells and increased the expression of STAT-3 mRNA and protein and P-STAT3 protein in the cells. In addition, MEHP down-regulated the phosphorylation of STAT-3 in mitochondria. MEHP was found to influence the mitochondrial membrane potential and intracellular ROS levels. Conclusion: MEHP may affect adipocyte differentiation and lead to lipid accumulation through the TYK-2/STAT-3 pathway. Highlights: We established 3T3-L1 precuisor adipocyte differentiation model. We aimed to observe the effect of exposure to MEHP during cell differentiation and evaluated the effect of MEHP accumulation on lipid metabolism by the TYK2/STAT3 pathway. We also tested the effect of mitochondrial STAT3 on lipid metabolism on 3T3-L1 cells.