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

Abstract

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 metabolismForal 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 retinoidinduced hypertriglyceridemia.

Structural Changes of Gut Microbiota during Berberine-Mediated Prevention of Obesity and Insulin Resistance in High-Fat Diet-Fed Rats

“…The food intake of HFD-fed rats was reduced by berberine, particularly in the last 8 weeks, whereas smaller decrease in food intake was observed in NCD-fed rats (Figure 1C). The adiposity index was calculated as body fat weight (represented as the sum of epididymal and perirenal fat pads) per 100 g total body weight [32]. Berberine significantly decreased the adiposity index in HFD-fed rats but not in NCD-fed rats (Figure 1B).…”

The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats

“…All agents were dissolved in methylcellulose. The doses of the different agents were chosen according to results obtained in other studies [37-39]. Administration of test substances was initiated one week after surgery, and lasted for four months.…”

Contribution of Hepatic Retinaldehyde Dehydrogenase Induction to Impairment of Glucose Metabolism by High‐Fat‐Diet Feeding in C57BL/6J Mice

“…RALDH induction indicated more retinoic acid formation which, in turn, affected lipid metabolism. Several reports have shown that retinoic acid-based medicine such as isotretinoin (13-cis retinoic acid) caused elevation of plasma triglyceride levels in human patients [38][39][40][41][42][43] and rats [40,[44][45][46][47][48]. Furthermore, retinoic acid increased biosynthesis of fatty acids via inducing expression of SREBP-1c and fatty acid synthase [49,50].…”