title: Curcumin attenuates BPA-induced insulin resistance in HepG2 cells through suppression of JNK/p38 pathways.
abstract: Bisphenol A (BPA) is an artificial environmental endocrine disrupting chemicals. Accumulating evidence indicates that exposure to BPA contributes to insulin resistance through diverse mechanism including inflammation and oxidative stress. Previous studies have suggested curcumin as a safe phytochemical which can improve obesity-related insulin resistance, inflammation and oxidative stress. The present study aimed to investigate the ability of curcumin to prevent BPA-induced insulin resistance in vitro and the underlying mechanism. Following the establishmet of in vitro insulin resistance via BPA treatment in human liver HepG2 cells, the protective effects of curcumin were determiend. We showed that treatment of HepG2 cells with 100nM BPA for 5days induced significantly decreased glucose consumption, impaired insulin signaling, elevation of pro-inflammatory cytokines and oxidative stress, and activation of signaling pathways; inhibition of JNK and p38 pathways, but not ERK nor NF-κB pathways, improved glucose consumption and insulin signaling in BPA-treated HepG2 cells. Moreover, we revealed that curcumin effectively attenuated the spectrum of effects of BPA-triggered insulin resistance, whereas pretreatment with JNK and p38 agonist anisomycin could significantly compensate the effects caused by curcumin. These data illustrated the role of JNK/p38 activation in BPA-induced insulin resistance and suggested curcumin as a promising candidate for the intervention of BPA-induced insulin resistance.
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Geng
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Shijia
authors.initials: S
authors.lastname: Wang
authors.affiliation: Yangzhou Municipal Center for Disease Control and Prevention, Yangzhou 225002, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jieshu
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: cyzhong@njmu.edu.cn.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhong
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance; D015227:Lipid Peroxidation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D000098826:Bisphenol A Compounds
chemical_list: D000975:Antioxidants; D001559:Benzhydryl Compounds; D003474:Curcumin; D052244:Endocrine Disruptors; D005947:Glucose; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: BPA; Curcumin; Insulin resistance; Intervention; MAPK