title: Organochloride pesticides induced hepatic ABCG5/G8 expression and lipogenesis in Chinese patients with gallstone disease.
abstract: BACKGROUND
  Organochlorine pesticides (OCPs) are one kind of persistent organic pollutants. Although they are reported to be associated with metabolic disorders, the underlying mechanism is unclear. We explored the association of OCPs with gallstone disease and its influence on hepatic lipid metabolism.
  
  
  METHODS
  OCPs levels in omentum adipose tissues from patients with and without gallstone disease between 2008 and 2011 were measured by GC-MS. Differences of gene expression involved in hepatic lipid metabolism and hepatic lipids content were compared in liver biopsies between groups with high and low level of OCPs. Using HepG2 cell lines, the influence on hepatic lipid metabolism by individual OCP was evaluated in vitro.
  
  
  RESULTS
  In all patients who were from non-occupational population, there were high levels of β-hexachlorocyclohexane (β-HCH) and p',p'-dichloroethylene (p',p'-DDE) accumulated in adipose tissues. Both β-HCH and p', p'-DDE levels were significantly higher in adipose tissues from patients with gallstone disease (294.3± 313.5 and 2222± 2279 ng/g of lipid) than gallstone-free controls (282.7± 449.0 and 2025±2664 ng/g of lipid, P< 0.01) and they were strongly related with gallstone disease (P for trend = 0.0004 and 0.0138). Furthermore, higher OCPs in adipose tissue led to increase in the expression of hepatic cholesterol transporters ABCG5 and G8 (+34% and +27%, P< 0.01) and higher cholesterol saturation index in gallbladder bile, and induced hepatic fatty acids synthesis, which was further confirmed in HepG2 cells.
  
  
  CONCLUSIONS
  OCPs might enhance hepatic secretion of cholesterol into bile via ABCG5/G8 which promoting gallstone disease as well as lipogenesis.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Center of Gallbladder Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.|Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing, China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Center of Gallbladder Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Center of Gallbladder Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Zhao-Yan
authors.initials: ZY
authors.lastname: Jiang
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5 / Q000096:biosynthesis*; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8 / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D044466:Asian People; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000032:analysis; D005260:Female; D042882:Gallstones / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000009:adverse effects / Q000032:analysis; D050155:Lipogenesis / Q000187:drug effects*; D008074:Lipoproteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D010575:Pesticides / Q000009:adverse effects* / Q000032:analysis
chemical_list: C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D008074:Lipoproteins; D010575:Pesticides
keywords: Pathology Section; adipose tissue; gallstone disease; lipogenesis; liver; organochlorine pesticides