title: Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet.
abstract: Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals, which is present ubiquitously in daily life. Accumulating evidence indicates that exposure to BPA contributes to metabolic syndrome. In this study, we examined whether perinatal exposure to BPA predisposed offspring to fatty liver disease: the hepatic manifestation of metabolic syndrome. Wistar rats were exposed to 50 μg/kg per day BPA or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a standard chow diet (SD) or a high-fat diet (HFD) after weaning. Effects of BPA were assessed by examination of hepatic morphology, biochemical analysis, and the hepatic expression of genes and/or proteins involved in lipogenesis, fatty acid oxidation, gluconeogenesis, insulin signaling, inflammation, and fibrosis. On a SD, the offspring of rats exposed to BPA exhibited moderate hepatic steatosis and altered expression of insulin signaling elements in the liver, but with normal liver function. On a HFD, the offspring of rats exposed to BPA showed a nonalcoholic steatohepatitis-like phenotype, characterized by extensive accumulation of lipids, large lipid droplets, profound ballooning degeneration, impaired liver function, increased inflammation, and even mild fibrosis in the liver. Perinatal exposure to BPA worsened the hepatic damage caused by the HFD in the rat offspring. The additive effects of BPA correlated with higher levels of hepatic oxidative stress. Collectively, exposure to BPA may be a new risk factor for the development of fatty liver disease and further studies should assess whether this finding is also relevant to the human population.
authors.affiliation: Key Laboratory of Environment and HealthMinistry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaKey Laboratory of Urban Environment and HealthDepartment of Environmental and Molecular Toxicology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, ChinaDepartment of Basic Medical SciencesMedical College, Xiamen University, Xiamen 361102, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
authors.affiliation: Key Laboratory of Environment and HealthMinistry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaKey Laboratory of Urban Environment and HealthDepartment of Environmental and Molecular Toxicology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, ChinaDepartment of Basic Medical SciencesMedical College, Xiamen University, Xiamen 361102, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Environment and HealthMinistry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaKey Laboratory of Urban Environment and HealthDepartment of Environmental and Molecular Toxicology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, ChinaDepartment of Basic Medical SciencesMedical College, Xiamen University, Xiamen 361102, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Environment and HealthMinistry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaKey Laboratory of Urban Environment and HealthDepartment of Environmental and Molecular Toxicology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, ChinaDepartment of Basic Medical SciencesMedical College, Xiamen University, Xiamen 361102, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Environment and HealthMinistry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaKey Laboratory of Urban Environment and HealthDepartment of Environmental and Molecular Toxicology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, ChinaDepartment of Basic Medical SciencesMedical College, Xiamen University, Xiamen 361102, China.
authors.forename: Liqiong
authors.initials: L
authors.lastname: Song
authors.affiliation: Key Laboratory of Environment and HealthMinistry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaKey Laboratory of Urban Environment and HealthDepartment of Environmental and Molecular Toxicology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, ChinaDepartment of Basic Medical SciencesMedical College, Xiamen University, Xiamen 361102, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Environment and HealthMinistry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaKey Laboratory of Urban Environment and HealthDepartment of Environmental and Molecular Toxicology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, ChinaDepartment of Basic Medical SciencesMedical College, Xiamen University, Xiamen 361102, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Key Laboratory of Environment and HealthMinistry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaKey Laboratory of Urban Environment and HealthDepartment of Environmental and Molecular Toxicology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, ChinaDepartment of Basic Medical SciencesMedical College, Xiamen University, Xiamen 361102, China xust@hust.edu.cn ylin@iue.ac.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Key Laboratory of Environment and HealthMinistry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaKey Laboratory of Urban Environment and HealthDepartment of Environmental and Molecular Toxicology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, ChinaDepartment of Basic Medical SciencesMedical College, Xiamen University, Xiamen 361102, China xust@hust.edu.cn ylin@iue.ac.cn.
authors.forename: Shunqing
authors.initials: S
authors.lastname: Xu
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: bisphenol A; fibrosis; inflammation; insulin resistance; oxidative stress; steatosis