title: Polychlorinated biphenyl 153 is a diet-dependent obesogen that worsens nonalcoholic fatty liver disease in male C57BL6/J mice.
abstract: BACKGROUND
  Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that are detectable in the serum of all American adults. Amongst PCB congeners, PCB 153 has the highest serum level. PCBs have been dose-dependently associated with obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in epidemiological studies.
  
  
  OBJECTIVE
  The purpose of this study is to determine mechanisms by which PCB 153 worsens diet-induced obesity and NAFLD in male mice fed a high-fat diet (HFD).
  
  
  METHODS
  Male C57BL6/J mice were fed either control or 42% milk fat diet for 12 weeks with or without PCB 153 coexposure (50 mg/kg ip ×4). Glucose tolerance test was performed, and plasma and tissues were obtained at necropsy for measurements of adipocytokine levels, histology and gene expression.
  
  
  RESULTS
  In control diet-fed mice, addition of PCB 153 had minimal effects on any of the measured parameters. However, PCB 153 treatment in high-fat-fed mice was associated with increased visceral adiposity, hepatic steatosis and plasma adipokines including adiponectin, leptin, resistin and plasminogen activator inhibitor-1 levels. Likewise, coexposure reduced expression of hepatic genes implicated in β-oxidation while increasing the expression of genes associated with lipid biosynthesis. Regardless of diet, PCB 153 had no effect on insulin resistance or tumor necrosis factor alpha levels.
  
  
  CONCLUSIONS
  PCB 153 is an obesogen that exacerbates hepatic steatosis, alters adipocytokines and disrupts normal hepatic lipid metabolism when administered with HFD but not control diet. Because all US adults have been exposed to PCB 153, this particular nutrient-toxicant interaction potentially impacts human obesity/NAFLD.
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Banrida
authors.initials: B
authors.lastname: Wahlang
authors.forename: K Cameron
authors.initials: KC
authors.lastname: Falkner
authors.forename: Bonnie
authors.initials: B
authors.lastname: Gregory
authors.forename: Douglas
authors.initials: D
authors.lastname: Ansert
authors.forename: David
authors.initials: D
authors.lastname: Young
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Conklin
authors.forename: Aruni
authors.initials: A
authors.lastname: Bhatnagar
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
authors.forename: Matt
authors.initials: M
authors.lastname: Cave
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity; D005234:Fatty Liver / Q000097:blood* / Q000139:chemically induced; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D050155:Lipogenesis; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000097:blood* / Q000139:chemically induced; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D052243:Resistin / Q000097:blood
chemical_list: D052242:Adiponectin; D004785:Environmental Pollutants; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D052243:Resistin; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl
keywords: ALT; AST; AUC; AhR; CAR; CD; CPT1A; CPT2; FAS; GAPDH; GTT; H&E; HDL; HFD; HOMA-IR; IL-10; IL-6; LDL; NAFLD; NHANES; NTP; PCB; PCBs; PCR; POPs; PPARα; PXR; S.E.M.; TASH; TCDD; TNFα; alanine transaminase; area under the curve; aryl hydrocarbon receptor; aspartate transaminase; carnitine palmitoyl transferase; carnitine palmitoyl transferase 1A; constitutive androstane receptor; control diet; fatty acid synthase; glucose tolerance test; glyceraldehyde-3-phosphate dehydrogenase; hematoxylin–eosin; high-density lipoproteins; high-fat diet; homeostasis model assessment of insulin resistance; interleukin-10; interleukin-6; low-density lipoproteins; national health and nutrition examination survey; national toxicology program; nonalcoholic fatty liver disease; peroxisome proliferator-activated receptor alpha; persistent organic pollutants; polychlorinated biphenyls; polymerase chain reaction; pregnane X receptor; standard error mean; tPAI-1; tetrachlorodibenzo-p-dioxin; tissue plasminogen activator inhibitor 1.; toxicant associated steatohepatitis; tumor necrosis factor alpha