- A 4-week high fat diet induces hypercholesterolemia (140% increase), strong hypertriglyceridemia (300% increase) a 50% increase in CETP activity and a 20% decrease in HDL-c/total cholesterol ratio.
- Fenofibrate lowers triglycerides and increases HDL-c/total cholesterol ratio (40% for both).
- Rosiglitazone lowers cholesterol (10%) and triglycerides (30%) plasma levels.
A nutritional hamster model combining insulin resistance/diabetes and dyslipidemia
Key Benefits
- Provides a noteworthy competitive advantage for your compound effects on both insulin resistance/diabetes, dyslipidemia and hepatic steatosis,
- To select the best drug candidate in a very reproducible model with lipoprotein metabolism similar to humans,
- To test the efficacy of novel drugs affecting both glucose and lipoprotein metabolism in a model validated with reference compounds.
Animal Model
- Background Strain: Golden Syrian Hamster
- Gender/Weight: Male/90-110 g
- Diet: High fat diet + 10% fructose in drinking water
- Time on diet: 4 weeks
- Positive reference compounds:fenofibrate, rosiglitazone, sitagliptin.
Pathophysiological features and pharmacological relevance
A
- A 4-week high fat diet increases fasting blood glucose by 60% and plasma insulin by 180%. HOMA-IR dramatically increases by 360%.
- Both fenofibrate and rosiglitazone significantly decrease fasting blood glucose (10 and 20%), plasma insulin (69 and 52%) and HOMA-IR (72 and 61%).
A
- A 4-week high fat diet induces a strong hepatic steatosis with a 203, 131 and 264% increase in total cholesterol triglycerides and fatty acids levels, respectively.
- Rosiglitazone significantly decrease liver triglycerides by 20%. Fenofibrate decreases liver total cholesterol, triglycerides and fatty acids by 34, 32 and 42%, respectively.
- Rosiglitazone significantly improves insulin sensitivity, as measured by glucose infusion rate during euglycemic hyperinsulinemic clamp.
- Sitagliptin administered acutely significantly improves glucose tolerance by 20%.
A
