Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome
International journal of obesity and related metabolic disorders | Int J Obes Relat Metab Disord
Zdroj
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
15007394
DOI
10.1038/sj.ijo.0802613
PII: 0802613
Knihovny.cz E-zdroje
- MeSH
- apolipoprotein C-III MeSH
- apolipoproteiny C genetika metabolismus MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- fenofibrát toxicita MeSH
- fosfoproteiny genetika metabolismus MeSH
- glukózový toleranční test MeSH
- hepatocytární jaderný faktor 4 MeSH
- hypertriglyceridemie chemicky indukované MeSH
- hypolipidemika toxicita MeSH
- inbrední kmeny potkanů MeSH
- inzulin krev MeSH
- inzulinová rezistence * genetika MeSH
- isotretinoin toxicita MeSH
- kosterní svaly metabolismus MeSH
- krysa rodu Rattus MeSH
- lipidy krev MeSH
- lipolýza účinky léků MeSH
- modely nemocí na zvířatech MeSH
- obezita chemicky indukované genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- transkripční faktory genetika metabolismus MeSH
- tuková tkáň metabolismus patologie MeSH
- velikost orgánu účinky léků 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
- apolipoprotein C-III MeSH
- apolipoproteiny C MeSH
- DNA vazebné proteiny MeSH
- fenofibrát MeSH
- fosfoproteiny MeSH
- hepatocytární jaderný faktor 4 MeSH
- hypolipidemika MeSH
- inzulin MeSH
- isotretinoin MeSH
- lipidy MeSH
- transkripční faktory MeSH
OBJECTIVE: To investigate the effect of transcription-modulating drugs, fenofibrate and isotretinoin, on metabolic profile, insulin sensitivity of adipose and muscle tissues and gene expression in a genetic model of insulin resistance syndrome, polydactylous rat strain (PD/Cub). DESIGN: Administration of fenofibrate (100 mg/kg/day), isotretinoin (30 mg/kg/day) or vehicle to adult male PD/Cub rats fed standard laboratory chow for 15 days. MEASUREMENTS: Parameters of lipid and carbohydrate metabolism-oral glucose tolerance test, serum concentrations of insulin, triglycerides (TG), free fatty acids (FFA), glycerol, total cholesterol (CH); morphometric variables, in vitro insulin sensitivity of adipose and muscle tissues, catecholamine-stimulated lipolysis and the expression of ApoC-III and Hnf-4 genes in liver. RESULTS: Both experimental groups displayed an increase in adiposity with contrasting effects on TG (lowered by fenofibrate and increased by isotretinoin) and gene expression (no change in fibrate-treated rats and increased expression of ApoC-III and Hnf-4 in isotretinoin-treated group). Fenofibrate-treated rats also showed decreased concentrations of FFA and CH with concomitant decrease of catecholamine-induced lipolysis in adipocytes, but also hyperinsulinemia and the highest insulin/glucose ratio. Isotretinoin increased glycerol concentrations and decreased the insulin sensitivity of peripheral tissues. CONCLUSION: The PD/Cub rat showed a distinct pharmacogenetic reaction to fenofibrate and isotretinoin administration. Several lines of evidence now implicate specific variant(s) of ApoC-III and/or ApoA-V alleles as responsible for the dyslipidemia observed in this genetic model. The PD/Cub strain may also serve as a pharmacogenetic model for dissection of the retinoid-induced hypertriglyceridemia.
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