Independence of myocardial disease in the JCR:LA-corpulent rat on plasma cholesterol concentration

The JCR:LA-corpulent rat is one of the strains incorporating the corpulent (cp) gene. Animals homozygous for the cp gene are obese, insulin-resistant and hyperlipidemic. Corpulent males, but not females or lean rats, spontaneously develop atherosclerotic and ischemic myocardial lesions. Administration of clofibrate to corpulent male rats reduced the plasma cholesterol ester concentration by 50% to that of lean control rats. Unesterified cholesterol was slightly raised by the treatment. The markedly raised triglyceride concentrations were lowered modestly (from 282 to 220 mg/100 ml), but significantly in young rats and more markedly (from 305 to 136 mg/100 ml) in 9-month-old chronically treated rats. Apolipoproteins A-1 and E were reduced and Apo B increased by clofibrate treatment. Fasting plasma glucose and insulin concentrations were not altered nor was there any change in the impaired glucose tolerance in clofibrate-treated rats. Myocardial lesion frequency was also not reduced by clofibrate treatment. These results are consistent with others that showed inhibition of myocardial lesion formation only when the plasma insulin levels were reduced. Thus myocardial lesion formation in this strain of rats, while probably dependent upon the presence of hypertriglyceridemia, is most critically dependent upon hyperinsulinemia.