Pharmacogenetic model of retinoic acid-induced dyslipidemia and insulin resistance
Jazyk angličtina Země Anglie, Velká Británie Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
19958091
DOI
10.2217/pgs.09.113
Knihovny.cz E-zdroje
- MeSH
- dyslipidemie krev etiologie genetika MeSH
- farmakogenetika metody MeSH
- glukózový toleranční test MeSH
- hypertenze komplikace genetika MeSH
- inzulinová rezistence genetika MeSH
- krysa rodu Rattus MeSH
- metabolismus lipidů genetika MeSH
- modely nemocí na zvířatech * MeSH
- potkani inbrední SHR MeSH
- sacharosa aplikace a dávkování MeSH
- tretinoin škodlivé účinky MeSH
- zvířata kongenní MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- sacharosa MeSH
- tretinoin MeSH
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.
Citace poskytuje Crossref.org
Pharmacogenomic analysis of retinoic-acid induced dyslipidemia in congenic rat model
