title: 1,2-Dichloroethane impairs glucose and lipid homeostasis in the livers of NIH Swiss mice.
abstract: Excessive exposure to 1,2-Dichloroethane (1,2-DCE), a chlorinated organic toxicant, can lead to liver dysfunction. To fully explore the mechanism of 1,2-DCE-induced hepatic abnormalities, 30 male National Institutes of Health (NIH) Swiss mice were exposed to 0, 350, or 700mg/m3of 1,2-DCE, via inhalation, 6h/day for 28days. Increased liver/body weight ratios, as well as serum AST and serum ALT activity were observed in the 350 and 700mg/m31,2-DCE exposure group mice, compared with the control group mice. In addition, decreased body weights were observed in mice exposed to 700mg/m31,2-DCE, compared with control mice. Exposure to 350 and 700mg/m31,2-DCE also led to significant accumulation of hepatic glycogen, free fatty acids (FFA) and triglycerides, elevation of blood triglyceride and FFA levels, and decreases in blood glucose levels. Results from microarray analysis indicated that the decreases in glucose-6-phosphatase catalytic subunit (G6PC) and liver glycogen phosphorylase (PYGL) expression, mediated by the activation of AKT serine/threonine kinase 1 (Akt1), might be responsible for the hepatic glycogen accumulation and steatosis. Further in vitro study demonstrated that 2-chloroacetic acid (1,2-DCE metabolite), rather than 1,2-DCE, up-regulated Akt1 phosphorylation and suppressed G6PC and PYGL expression, resulting in hepatocellular glycogen accumulation. These results suggest that hepatic glucose and lipid homeostasis are impaired by 1,2-DCE exposure via down-regulation of PYGL and G6PC expression, which may be primarily mediated by the 2-chloroacetic acid-activated Akt1 pathway.
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Department of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Rong
authors.affiliation: Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Department of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
authors.forename: Jiewei
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.affiliation: Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Department of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Zeng
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.affiliation: Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Department of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
authors.forename: Lihai
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cai
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Shangqing
authors.initials: S
authors.lastname: Tang
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Deng
authors.affiliation: Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Department of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yin
authors.affiliation: Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Department of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
authors.forename: Manqi
authors.initials: M
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Department of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Lu
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Qiansheng
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Department of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China. Electronic address: huangzhenlie@126.com.
authors.forename: Zhenlie
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Faculty of Preventive Medicine, A Key Laboratory of Guangzhou Environmental Pollution and Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: wangq27@mail.sysu.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics; D015536:Down-Regulation; D005025:Ethylene Dichlorides / Q000633:toxicity*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced / Q000235:genetics; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D025001:Glycogen Phosphorylase, Liver Form / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D005025:Ethylene Dichlorides; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D014280:Triglycerides; C024565:ethylene dichloride; D006003:Glycogen; D025001:Glycogen Phosphorylase, Liver Form; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D005952:Glucose-6-Phosphatase
keywords: 1,2-Dichloroethane; 2-Chloroacetic acid; Glycogen; Hepatotoxicity; Triglyceride