| Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on lipid synthesis and lipogenic enzymes in the rat. | |
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MedLine Citation:
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PMID: 2913289 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A single i.p. administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused within 1 wk of exposure a dose-dependent progressive inhibition of liver fatty acid synthetic rate with concomitant decreases in hepatic fatty acid synthetase and acetylcoenzyme A carboxylase activities. Similarly, hepatic cholesterol synthetic rate was markedly inhibited with increasing dosage of TCDD, although the corresponding decrease in 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was of lesser magnitude. Linear regression analyses of the reciprocals of the responses versus the dose revealed that the TCDD concentration which caused 50% inhibition of the activities of various lipogenic enzymes and of lipid synthetic rates ranged from 11 to 20 micrograms/kg (34-67 nM) with an average of 15 micrograms/kg (47 nM). Hepatic cholesterol synthesis seemed to be more sensitive to inhibition than fatty acid synthesis whether it was based on TCDD dosage or duration of exposure. The degree of inhibition of all the above parameters except fatty acid synthesis in liver and adipose tissues increased from 1 to 2 wk of exposure but was less pronounced after 4 wk exposure. Significantly, the adipose tissue was found to be more sensitive than the liver with respect to inhibition of fatty acid synthesis by increasing dosage of TCDD. Thus, the biochemical mechanism of loss of adipose mass caused by TCDD exposure may well be mediated by strong inhibition of lipid synthesis in the adipose tissue coupled with increased mobilization of depot fat. |
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Authors:
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M R Lakshman; S J Chirtel; L L Chambers; P J Coutlakis |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 248 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1989 Jan |
Date Detail:
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Created Date: 1989-03-03 Completed Date: 1989-03-03 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 62-6 Citation Subset: IM |
Affiliation:
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Lipid Research Laboratory, Veterans Administration Medical Center, Washington, DC 20422. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adipose Tissue
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drug effects,
metabolism Animals Body Weight / drug effects Dioxins / toxicity* Lipids / biosynthesis* Liver / drug effects, metabolism Male Organ Size / drug effects Rats Rats, Inbred Strains Tetrachlorodibenzodioxin / toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Dioxins; 0/Lipids; 1746-01-6/Tetrachlorodibenzodioxin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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