title: TCDD-elicited effects on liver, serum, and adipose lipid composition in C57BL/6 mice.
abstract: The aryl hydrocarbon receptor (AhR) mediates alterations in hepatic lipid composition elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to further investigate the effects of TCDD, liver, serum, and gonadal white adipose tissue (gWAT) fatty acid methyl esters (FAMEs) and lipids were examined in fasted 4-week-old female mice orally gavaged with 30 µg/kg TCDD at 24, 72, and 168 h postdose. Mean hepatic FAME levels increased (236.7 µmol/g in controls compared with 392.2 µmol/g in TCDD treated) with minimal changes in gWAT and serum. In the liver, TCDD decreased saturated fatty acids (SFAs 16:0, 18:0, 20:0, and 22:0) and increased monounsaturated fatty acids (MUFAs 16:1n7, 18:1n9, and 20:1n9). Hepatic polyunsaturated fatty acids (PUFAs) 20:2n6, 20:3n6, 18:3n3, and 22:5n3 also increased, whereas 20:4n6 and 22:6n3 levels decreased. gWAT PUFAs 20:2n6 and 20:3n6 exhibited modest increases, whereas serum 18:0 decreased and 18:1n9 increased. Serum analyses also identified a ~25% decrease in total cholesterol (CHOL), low-density lipoprotein (LDL), and high-density lipoprotein following TCDD treatment. The decrease in serum CHOL was consistent with the induction of hepatic reverse CHOL transport genes Lcat (2.0-fold), Apoa1 (1.7-fold), and Ldlr (3.6-fold), and the repression of CHOL biosynthesis genes Hmgcs1 (-2.1-fold) and Hmgcr (-2.3-fold). In addition, TCDD decreased serum Apob100 (4.4-fold) and Apob48 (2.2-fold) protein levels, suggesting serum lipid clearance and decreased hepatic efflux. Collectively, the TCDD-elicited decreases in serum lipid levels are consistent with AhR-mediated enhancement of dietary fat distribution to the liver.
authors.affiliation: Genetics Program, Center for Integrative ToxicologyMichigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Michelle Manente
authors.initials: MM
authors.lastname: Angrish
authors.forename: Claudia Yvette
authors.initials: CY
authors.lastname: Dominici
authors.forename: Timothy Richard
authors.initials: TR
authors.lastname: Zacharewski
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001055:Apolipoproteins B / Q000097:blood; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage; D005227:Fatty Acids / Q000097:blood*; D005234:Fatty Liver / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics
chemical_list: D001055:Apolipoproteins B; D004041:Dietary Fats; D005227:Fatty Acids; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D002784:Cholesterol; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase