Document Detail

TCDD-elicited effects on liver, serum, and adipose lipid composition in C57BL/6 mice.
MedLine Citation:
PMID:  22977169     Owner:  NLM     Status:  MEDLINE    
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.
Michelle Manente Angrish; Claudia Yvette Dominici; Timothy Richard Zacharewski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-13
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  131     ISSN:  1096-0929     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-06-11     Revised Date:  2014-04-03    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  108-15     Citation Subset:  IM    
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MeSH Terms
Adipose Tissue, White / drug effects*,  metabolism,  pathology
Apolipoproteins B / blood
Blotting, Western
Body Weight / drug effects
Cholesterol / blood
Dietary Fats / administration & dosage
Fatty Acids / blood*
Fatty Liver / chemically induced,  genetics,  metabolism
Gene Expression / drug effects
Lipid Metabolism / drug effects
Liver / drug effects*,  metabolism,  pathology
Mice, Inbred C57BL
Organ Size / drug effects
Real-Time Polymerase Chain Reaction
Receptors, Aryl Hydrocarbon / metabolism*
Stearoyl-CoA Desaturase / genetics
Tetrachlorodibenzodioxin / toxicity*
Grant Support
Reg. No./Substance:
0/Apolipoproteins B; 0/Dietary Fats; 0/Fatty Acids; 0/Receptors, Aryl Hydrocarbon; 97C5T2UQ7J/Cholesterol; DO80M48B6O/Tetrachlorodibenzodioxin; EC protein, mouse; EC Desaturase

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