High fat fed hamster, a unique animal model for treatment of diabetic dyslipidemia with peroxisome proliferator activated receptor alpha selective agonists

Dyslipidemia, a major risk factor for cardiovascular disease, may be direct ly linked to diabetic hyperglycemia and insulin resistance. An appropriate dyslipidemic animal model that has diabetes would provide an important tool for research on the treatment of diabetic dyslipidemia. Ten days of high f at feeding in golden Syrian hamsters resulted in a significant increase in insulin resistance and baseline serum lipid levels accompanied by a pronoun ced dyslipidemia. Thirteen days of treatment with fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR alpha) selective agonist, prod uced a dose-dependent decrease in serum lipid levels. The pattern observed was characterized by lowered very-low-density lipoprotein (VLDL) and low-de nsity lipoprotein (LDL) and raised hi.-h-density lipoprotein (HDL) choleste rol in a fashion similar to that seen in man. Diabetic conditions were also significantly improved by fenofibrate with a normalization of impaired glu cose tolerance and an improvement of insulin sensitivity during an oral glu cose tolerance test. These data suggest that fenofibrate may correct not on ly the dyslipidemia but also the insulin resistance caused by a high fat di et, and the high fat fed hamster may be a good animal model for research on the treatment of diabetic dyslipidemia with PPAR alpha selective agonists. (C) 2001 Published by Elsevier Science B.V.