Effect of age on serum lipids and lipoproteins of male and female JCR:LA-corpulent rats.

The JCR:LA-cp rat is a strain incorporating the corpulent (cp) gene. When homozygous for the cp gene, the rats are hyperphagous, hyperinsulinemic, hyperlipidemic and obese. The corpulent male rats develop atherosclerotic and myocardial lesions from an early age, while corpulent female and lean rats do not develop lesions. The hyperlipidemia is due to elevated levels of VLDL resulting in moderately raised cholesterol levels and markedly elevated triacylglycerol levels. The VLDL concentrations are similar in corpulent male and female rats at an early age with both having much higher levels than lean rats. As the animals age, the VLDL hyperlipidemia in the corpulent male increases at 3 months and then decreases slowly and rises again at 12 months of age. The corpulent female rats show higher triacylglycerol and phospholipid concentrations than the males at 3 months age and reach values over 1000 mg/100 ml by 9 months of age, then decrease at 12 months of age. The cholesterol concentrations of the corpulent females are greater than those of the males from 9 months of age. Thus, in the period of life up to middle age, the cardiovascular disease incidence does not correlate with the degree of hyperlipidemia. The disease progression does correlate with the severity of insulin resistance and glucose intolerance, which is more severe in the corpulent male than female rats. The results suggest that the hyperlipidemia must be a necessary condition for development of atherosclerotic disease in this strain of rats, but it is not a sufficient condition.