Physiogenex : IR rat + P-407

First-in-class rat model integrating all major features of the cardiometabolic syndrome(dyslipidemia/dyslipoproteinemia linked to insulin resistance)

Key benefits

To test your compound's efficacy in an innovative animal model integrating most metabolic disorders (insulin resistance and hyperlipidemia).
To highlight the competitive advantage of your compound in the cardiometabolic syndrome.
To obtain results with a model reproducing most features of the human metabolic syndrome: the dyslipoproteinemia thus obtained is close to that of the human metabolic syndrome (mixed dyslipidemia with high TG and VLDL levels)
To better anticipate the integrated pharmacological activity of your compound

Animal Model

Background Strain: Sprague Dawley (SD)
Gender/Weight/Age: Male rats, 240-260g, 7-8 weeks old
Diet: RD diet® + sub-chronic injection of a non ionic surfactant (P-407)
Time on diet: 5-8 weeks

Pathophysiological features compared to an RD diet alone

Large increase in plasma FFA and TG levels
Increase in FFA turnover
Increase in peripheral insulin resistance by exacerbation of the dyslipidemia
Large increase in triglyceride production by the liver
Large increase in total cholesterol (mainly due to elevation of non HDL-cholesterol)
Large increase in the VLDL fraction

Scientific and pharmacological relevance

Reference compounds	Pravastatin	Clofibrate
Treatment	chronic (once a day)	chronic (once a day)
Duration	15 days (starting after 6 weeks of diet)	15 days (starting after 6 weeks of diet)
Dose	8 mg/kg and 25 mg/kg	300 mg/kg

Partial improvement in fasting TG production by pravastatin 8 mg/kg
Pravastatin 25 mg/kg significantly reduces hypercholesterolemia
Confirmation of the well-known effect of clofibrate on hypertriglyceridemia (decreased TG production and increased clearance)
Results similar to those obtained in human metabolic syndrome: marked effect of fibrates on TG, mild effect of statins

Characterization of the RD diet + P-407

Validation of the RD diet + P-407

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