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Mol Cell Endocrinol. 2019 Mar 15;484:52-58. doi: 10.1016/j.mce.2019.01.012. Epub 2019 Jan 17.

Effect of the TYK-2/STAT-3 pathway on lipid accumulation induced by mono-2-ethylhexyl phthalate.

Author information

1
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China.
2
Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China. Electronic address: jlyelin@163.com.

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.

KEYWORDS:

3T3-L1 adipocytes; Lipid metabolism; MEHP; Mitochondrial STAT-3; ROS; TYK-2/STAT-3 pathway

PMID:
30660700
DOI:
10.1016/j.mce.2019.01.012

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