Effect of the TYK-2/STAT-3 pathway on lipid accumulation induced by mono-2-ethylhexyl phthalate
Authors: Xinyue Song
Wen Qi
Yaming Zhao
Tianyang Zhao
Qi Xu
Xiaohan Zhang
Tianye Zhao
Lin Ye
Shuang Ding
Liting Zhou
Xu Han
Journal: Molecular and cellular endocrinology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: 3T3-L1 adipocytes; Lipid metabolism; MEHP; Mitochondrial STAT-3; ROS
Affiliations: Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China., Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 This 2019 paper provides an overview on notions related to additive consistency and documented related papers. However, it should be pointed out that **Definition 4 presented in this paper is conceptually wrong**. The notion of additive consistency (Definition 2) presented by Tanino in the 1984 paper (Ref[20]) has nothing to do with the condition $$w_1 + w_2 + cdots +w_n =1,quad w_i ge 0,forall i$$ As a consequence, Model (5) cannot be used to deal with additive consistency as long as the notion of additive consistency is concerned in the sense of Definition 2. Any method explicitly or implicitly based on Model (5) is technically incorrect, e.g. Model (20). See also the comment on https: pubpeer.com publications 9D08E6B4975044A654D84E4A23383E https: pubpeer.com publications 7867CDD08E699F6D01C0E11F1693E0 ![file] , 
 Dear Rhipidura Albiventris, Definition 4 and Eq. (5) are not from the review. But, I agree with you that in the review we may add a comment or a small note to clarify that the condition (Sum (w_1,...,w_n)=1) is not necessary. Moreover, ref. [34] should be ref. [14]. Thank you for your comment, and it is helpful to fix the typo. Best regards, Yucheng Dong ,