title: Exposure to an environmentally relevant mixture of organochlorine compounds and polychlorinated biphenyls Promotes hepatic steatosis in male Ob/Ob mice.
abstract: Hepatic steatosis is recognized as an independent risk factor for the development of cardiovascular disease. While obesity and type 2 diabetes are well-established risk factors in the development of hepatic steatosis, recent studies have revealed exposure to mixtures of persistent organic pollutants (POPs), which are environmental contaminants in various fatty foods, can promote steatosis. Thus, the present study was designed to determine if exposure to a defined mixture of prevalent polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides or their metabolites promote hepatic steatosis in a genetically induced model of type 2 diabetes, the leptin-deficient ob/ob mouse. Male C57BL/6J wild type (WT) or ob/ob mice were administered an environmentally relevant mixture of PCBs and OCs for 7 weeks via oral gavage. Exposure to POPs did not significantly alter fasting serum glucose or insulin levels. However, POPs exposure significantly increased hepatic triglyceride content in ob/ob animals, while decreasing serum triglyceride levels. This POPs-mediated increase in hepatic triglyceride content did not appear to be associated with significantly increased inflammation in either the liver or adipose. Exposure to POPs significantly induced the expression of cytochrome P450 3a11 in WT animals, yet the expression of this cytochrome was significantly downregulated in ob/ob animals regardless of POPs exposure. Taken together, the present data indicate exposure to an environmentally relevant mixture of both PCBs and OC pesticides in ob/ob mice promotes hepatic steatosis while decreasing hypertriglyceridemia, which demonstrates exposure to a defined mixture of POPs alters systemic lipid metabolism in a genetically induced model of obesity and type 2 diabetes. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1399-1411, 2017.
authors.affiliation: Department of Basic Sciences, Mississippi State University, College of Veterinary Medicine, Mississippi State, Mississippi, 39762.
authors.forename: Charlee
authors.initials: C
authors.lastname: Mulligan
authors.affiliation: Department of Basic Sciences, Mississippi State University, College of Veterinary Medicine, Mississippi State, Mississippi, 39762.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kondakala
authors.affiliation: Department of Basic Sciences, Mississippi State University, College of Veterinary Medicine, Mississippi State, Mississippi, 39762.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Yang
authors.affiliation: Department of Basic Sciences, Mississippi State University, College of Veterinary Medicine, Mississippi State, Mississippi, 39762.
authors.forename: John V
authors.initials: JV
authors.lastname: Stokes
authors.affiliation: Department of Basic Sciences, Mississippi State University, College of Veterinary Medicine, Mississippi State, Mississippi, 39762.
authors.forename: James A
authors.initials: JA
authors.lastname: Stewart
authors.affiliation: Department of Basic Sciences, Mississippi State University, College of Veterinary Medicine, Mississippi State, Mississippi, 39762.
authors.forename: Barbara L F
authors.initials: BL
authors.lastname: Kaplan
authors.affiliation: Department of Basic Sciences, Mississippi State University, College of Veterinary Medicine, Mississippi State, Mississippi, 39762.
authors.forename: George E
authors.identifier: http://orcid.org/0000-0001-8761-976X
authors.initials: GE
authors.lastname: Howell
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D004785:Environmental Pollutants / Q000633:toxicity*; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010575:Pesticides / Q000633:toxicity*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D010575:Pesticides; D014280:Triglycerides; D011078:Polychlorinated Biphenyls
keywords: hepatic steatosis; inflammation; metabolic syndrome; persistent organic pollutants; triglyceride; type 2 diabetes