| Acute modulation of rat hepatic lipid metabolism by sulphur-substituted fatty acid analogues. | |
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MedLine Citation:
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PMID: 7741757 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A single oral dose of two 3-thia (3-thiadicarboxylic and tetradecylthioacetic acids) and of 4-thia (tetradecylthiopropionic acid) fatty acids were administered to normolipidemic rats and their effects on lipid metabolism over a 24 hr period were studied. All three thia fatty acids could be detected in plasma 2 hr after treatment. Tetradecylthioacetic and tetradecylthiopropionic acids were detected in different hepatic lipid fractions but were incorporated mainly into hepatic phospholipids. Two hours after administration hepatic mitochondrial beta-oxidation and the total liver level of long-chain fatty acyl-CoA increased with a concomitant decrease in saturated fatty acids, total hepatic malonyl-CoA and plasma triacylglycerol levels in the 3-thia fatty acid groups. Tetradecylthiopropionic acid administration caused a decrease in mitochondrial beta-oxidation and an increase in plasma triacylglycerol at 24 hr. The activities of key lipogenic enzymes were unaffected in all treatment groups. Plasma cholesterol level was reduced only at 8 hr in 3-thiadicarboxylic acid treated rats although 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase was suppressed already at 2, 4, 8 and 12 hr. The results show that thia fatty acids are rapidly absorbed and are systemically available after oral administration but the 3-thia fatty acids reached systemic circulation more slowly and less completely than the 4-thia fatty acid. Very low levels of the thia fatty acids are detected in plasma 24 hr after a single administration. They are incorporated into all hepatic lipid classes, especially phospholipids. Rapid incorporation of a non beta-oxidizable thia fatty acid into hepatic lipids may cause a diversion of other fatty acids from glycerolipid biosynthesis to mitochondrial beta-oxidation. Stimulation of mitochondrial beta-oxidation and suppression of HMG-CoA reductase are primary events, occurring within hours, after 3-thia fatty acid administration. The hypotriglyceridemic effect of the 3-thia fatty acids observed at 2-4 hr is independent of the activities of key lipogenic and triacylglycerol synthesising enzymes. |
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Authors:
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D K Asiedu; A Demoz; J Skorve; H J Grav; R K Berge |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical pharmacology Volume: 49 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1995 Mar |
Date Detail:
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Created Date: 1995-06-02 Completed Date: 1995-06-02 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1013-22 Citation Subset: IM |
Affiliation:
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Institute of Clinical Biology, University of Bergen, Haukeland University Hospital, Norway. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Dicarboxylic Acids / blood Enzyme Induction Fatty Acids / pharmacology* Lipid Metabolism* Lipids / blood Liver / drug effects, enzymology, metabolism* Male Propionic Acids / blood Rats Rats, Wistar Sulfides / blood Sulfur Acids / pharmacology* Triglycerides / blood |
| Chemical | |
Reg. No./Substance:
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0/Dicarboxylic Acids; 0/Fatty Acids; 0/Lipids; 0/Propionic Acids; 0/Sulfides; 0/Sulfur Acids; 0/Triglycerides; 1462-53-9/1-(carboxyethylthio)tetradecane; 2921-20-2/1-(carboxymethylthio)tetradecane; 32827-49-9/1,10-bis(carboxymethylthiodecane) |
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