RGD Reference Report - Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome.

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Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome.
Authors:	Sedova, L Seda, O Krenova, D Kren, V Kazdova, L
Citation:	Sedova L, etal., Int J Obes Relat Metab Disord. 2004 May;28(5):719-25.
RGD ID:	1580750
Pubmed:	PMID:15007394 (View Abstract at PubMed)
DOI:	DOI:10.1038/sj.ijo.0802613 (Journal Full-text)
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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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
APOC3	Human	Insulin Resistance	treatment	ISO	Apoc3 (Rattus norvegicus)		RGD
Apoc3	Rat	Insulin Resistance	treatment	IEP			RGD
Apoc3	Mouse	Insulin Resistance	treatment	ISO	Apoc3 (Rattus norvegicus)		RGD
PD/Cub	Rat	Metabolic Syndrome	MODEL: spontaneous	IAGP			RGD

Phenotype Annotations Click to see Annotation Detail View

Mammalian Phenotype

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PD/Cub	Rat	decreased circulating cholesterol level	treatment	IAGP	fenofibrate		RGD
PD/Cub	Rat	decreased circulating free fatty acids level	treatment	IAGP	fenofibrate		RGD
PD/Cub	Rat	decreased circulating triglyceride level	treatment	IAGP	fenofibrate		RGD
PD/Cub	Rat	impaired glucose tolerance		IAGP		compared to BN/Cub	RGD
PD/Cub	Rat	increased body weight		IAGP		compared to BN/Cub	RGD
PD/Cub	Rat	increased circulating cholesterol level	treatment	IAGP	isotretinoin		RGD
PD/Cub	Rat	increased circulating free fatty acids level	treatment	IAGP	isotretinoin		RGD
PD/Cub	Rat	increased circulating free fatty acids level		IAGP		compared to BN/Cub	RGD
PD/Cub	Rat	increased circulating glucose level		IAGP		compared to BN/Cub	RGD
PD/Cub	Rat	increased circulating glycerol level	treatment	IAGP	isotretinoin		RGD
PD/Cub	Rat	increased circulating insulin level	treatment	IAGP	isotretinoin or fenofibrate		RGD
PD/Cub	Rat	increased circulating insulin level		IAGP		compared to BN/Cub	RGD
PD/Cub	Rat	increased circulating triglyceride level	treatment	IAGP	isotretinoin		RGD
PD/Cub	Rat	increased circulating triglyceride level		IAGP		compared to BN/Cub	RGD
PD/Cub	Rat	increased epididymal fat pad weight	treatment	IAGP	isotretinoin or fenofibrate		RGD
PD/Cub	Rat	increased epididymal fat pad weight		IAGP		compared to BN/Cub	RGD
PD/Cub	Rat	increased kidney weight	treatment	IAGP	isotretinoin or fenofibrate		RGD
PD/Cub	Rat	increased liver weight	treatment	IAGP	isotretinoin or fenofibrate		RGD
PD/Cub	Rat	increased systemic arterial blood pressure		IAGP		compared to BN/Cub	RGD

Objects Annotated

Genes (Rattus norvegicus)

Apoc3 (apolipoprotein C3)

Genes (Mus musculus)

Apoc3 (apolipoprotein C-III)

Genes (Homo sapiens)

APOC3 (apolipoprotein C3)

Strains

PD/Cub (polydactylous)

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Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome.

Mammalian Phenotype