| Pharmacogenetic model of retinoic acid-induced dyslipidemia and insulin resistance. | |
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MedLine Citation:
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PMID: 19958091 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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AIMS: Therapeutic administration of retinoids is often accompanied with undesirable side effects, including an increase in lipid levels in up to 45% of treated patients. We tested the hypothesis of whether spontaneously hypertensive rat (SHR) and congenic SHR.PD-(D8Rat42-D8Arb23)/Cub (SHR-Lx) strains, differing only in a 14-gene region of chromosome 8 and previously shown to display differential sensitivity to the teratogenic effects of retinoic acid, could serve as a pharmacogenetic model set of the metabolic side effects of retinoid therapy. MATERIALS & METHODS: Male, 15-week old rats (n = 12/strain) of SHR and SHR-Lx strains were fed a high-sucrose diet for 2 weeks and subsequently treated either with all-trans retinoic acid (15 mg/kg) or only with a vehicle for 16 days (n = 6/strain/treatment), while still on the high-sucrose diet. We assessed the morphometric and metabolic profiles of all groups, including glucose tolerance tests, levels of insulin, adiponectin, free fatty acids, concentrations of triglycerides and cholesterol in 20 lipoprotein fractions under conditions of both high-sucrose diet and high-sucrose diet plus all-trans retinoic acid administration. RESULTS & CONCLUSION: SHR-Lx displayed substantially greater sensitivity to a number of all-trans retinoic acid-induced metabolic dysregulations compared with SHR, resulting in impairment of glucose tolerance, increased visceral adiposity, and substantially greater increase of circulating triglyceride concentrations, accompanied by a shift towards their less favorable distribution into the lipoprotein fractions. These observations closely mimic the common side effects of retinoid therapy in humans, rendering SHR-Lx an experimental pharmacogenetic model of atRA-induced dyslipidemia. |
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Authors:
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Michaela Krupková; Michaela Janků; Frantisek Liska; Lucie Sedová; Ludmila Kazdová; Drahomíra Krenová; Vladimír Kren; Ondrej Seda |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Pharmacogenomics Volume: 10 ISSN: 1744-8042 ISO Abbreviation: Pharmacogenomics Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100897350 Medline TA: Pharmacogenomics Country: England |
Other Details:
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Languages: eng Pagination: 1915-27 Citation Subset: IM |
Affiliation:
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Institute of Biology and Medical Genetics, the First Faculty of Medicine, Charles University, General Teaching Hospital, Prague, Czech Republic. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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