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 directly 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 fat feeding in golden Syrian hamsters resulted in a significant increase in insulin resistance and baseline serum lipid levels accompanied by a pronounced dyslipidemia. Thirteen days of treatment with fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARalpha) selective agonist, produced a dose-dependent decrease in serum lipid levels. The pattern observed was characterized by lowered very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) and raised high-density lipoprotein (HDL) cholesterol in a fashion similar to that seen in man. Diabetic conditions were also significantly improved by fenofibrate with a normalization of impaired glucose tolerance and an improvement of insulin sensitivity during an oral glucose tolerance test. These data suggest that fenofibrate may correct not only the dyslipidemia but also the insulin resistance caused by a high fat diet, and the high fat fed hamster may be a good animal model for research on the treatment of diabetic dyslipidemia with PPARalpha selective agonists.
Wang
P R
PR
Department of Atherosclerosis and Endocrinology, R80W250 Merck Research Laboratory, Merck & Co., Rahway, NJ 07065, USA. pei_ran.wang@pharma.novartis.com
Guo
Q
Q
Ippolito
M
M
Wu
M
M
Milot
D
D
Ventre
J
J
Doebber
T
T
Wright
S D
SD
Chao
Y S
YS
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D015243:Cholesterol, VLDL / Q000097:blood / Q000187:drug effects; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D010084:Oxidation-Reduction / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D014157:Transcription Factors / Q000819:agonists
D001786:Blood Glucose; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D004041:Dietary Fats; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D007328:Insulin; D008055:Lipids; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D006903:Hydroxymethylglutaryl CoA Reductases; D011345:Fenofibrate