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
Source
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
15007394
DOI
10.1038/sj.ijo.0802613
PII: 0802613
Knihovny.cz E-resources
- MeSH
- Apolipoprotein C-III MeSH
- Apolipoproteins C genetics metabolism MeSH
- DNA-Binding Proteins genetics metabolism MeSH
- Fenofibrate toxicity MeSH
- Phosphoproteins genetics metabolism MeSH
- Glucose Tolerance Test MeSH
- Hepatocyte Nuclear Factor 4 MeSH
- Hypertriglyceridemia chemically induced MeSH
- Hypolipidemic Agents toxicity MeSH
- Rats, Inbred Strains MeSH
- Insulin blood MeSH
- Insulin Resistance * genetics MeSH
- Isotretinoin toxicity MeSH
- Muscle, Skeletal metabolism MeSH
- Rats MeSH
- Lipids blood MeSH
- Lipolysis drug effects MeSH
- Disease Models, Animal MeSH
- Obesity chemically induced genetics metabolism MeSH
- Gene Expression Regulation drug effects MeSH
- Transcription Factors genetics metabolism MeSH
- Adipose Tissue metabolism pathology MeSH
- Organ Size drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Apolipoprotein C-III MeSH
- Apolipoproteins C MeSH
- DNA-Binding Proteins MeSH
- Fenofibrate MeSH
- Phosphoproteins MeSH
- Hepatocyte Nuclear Factor 4 MeSH
- Hypolipidemic Agents MeSH
- Insulin MeSH
- Isotretinoin MeSH
- Lipids MeSH
- Transcription Factors 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.
References provided by Crossref.org
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