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National Institute of Environmental Health Sciences

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Publication Detail

Title: TCDD-elicited effects on liver, serum, and adipose lipid composition in C57BL/6 mice.

Authors: Angrish, Michelle Manente; Dominici, Claudia Yvette; Zacharewski, Timothy Richard

Published In Toxicol Sci, (2013 Jan)

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.

PubMed ID: 22977169 Exiting the NIEHS site

MeSH Terms: Adipose Tissue, White/drug effects*; Adipose Tissue, White/metabolism; Adipose Tissue, White/pathology; Animals; Apolipoproteins B/blood; Blotting, Western; Body Weight/drug effects; Cholesterol/blood; Dietary Fats/administration & dosage; Fatty Acids/blood*; Fatty Liver/chemically induced; Fatty Liver/genetics; Fatty Liver/metabolism; Female; Gene Expression/drug effects; Lipid Metabolism/drug effects; Liver/drug effects*; Liver/metabolism; Liver/pathology; Mice; Mice, Inbred C57BL; Organ Size/drug effects; Polychlorinated Dibenzodioxins/toxicity*; Real-Time Polymerase Chain Reaction; Receptors, Aryl Hydrocarbon/metabolism*; Stearoyl-CoA Desaturase/genetics

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