Dolphin P J, Amy R M, Russell J C
Department of Biochemistry, Dalhousie University, Halifax, Edmonton, Canada.
Biochim Biophys Acta. 1990 Jan 16;1042(1):99-106. doi: 10.1016/0005-2760(90)90062-3.
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.
LA-cp大鼠是一种携带肥胖（cp）基因的品系。当cp基因纯合时，这些大鼠会出现摄食过多、高胰岛素血症、高脂血症和肥胖。肥胖雄性大鼠从小就会出现动脉粥样硬化和心肌病变，而肥胖雌性大鼠和瘦大鼠则不会出现病变。高脂血症是由于极低密度脂蛋白（VLDL）水平升高，导致胆固醇水平适度升高，三酰甘油水平显著升高。肥胖雄性和雌性大鼠在幼年时VLDL浓度相似，且两者都比瘦大鼠的水平高得多。随着动物年龄增长，肥胖雄性大鼠的VLDL高脂血症在3个月时增加，然后缓慢下降，并在12个月时再次上升。肥胖雌性大鼠在3个月龄时三酰甘油和磷脂浓度高于雄性，到9个月龄时达到超过1000mg/100ml的值，然后在12个月龄时下降。肥胖雌性大鼠的胆固醇浓度从9个月龄起高于雄性。因此，在中年以前的生命阶段，心血管疾病发病率与高脂血症程度无关。疾病进展与胰岛素抵抗和葡萄糖不耐受的严重程度相关，肥胖雄性大鼠比雌性大鼠更严重。结果表明，高脂血症必定是该品系大鼠发生动脉粥样硬化疾病的必要条件，但不是充分条件。
