Rates of sterol synthesis in the liver and extrahepatic tissues of the SHR/N-corpulent rat, an animal with hyperlipidemia and insulin-independent diabetes.
Rates of sterol synthesis in the liver and extrahepatic tissues of the SHR/N-corpulent rat, an animal with hyperlipidemia and insulin-independent diabetes.
复制标题
SHR/N 肥胖大鼠（患有高脂血症和胰岛素非依赖性糖尿病的动物）肝脏和肝外组织中甾醇合成的速率。
作者：
S. Turley;C. Hansen
SHR/N-肥胖大鼠是一种新的遗传性肥胖品系，具有胰岛素非依赖性糖尿病和高脂血症。本研究进行了表征在这个模型中的胆固醇代谢的各种参数。在11周龄时，肥胖动物的血浆胆固醇、甘油三酯、葡萄糖和胰岛素浓度显著升高，肝脏甘油三酯浓度升高，与同窝出生的瘦动物相比。血浆中额外的胆固醇以密度小于1.006、1.020-1.055、1.055-1.095和1.095-1.21 g/ml的组分携带。肥胖大鼠肝脏中游离胆固醇含量显著降低，而胆固醇酯含量变化不大。在肥胖动物中，肝脏固醇合成明显受到抑制。然而，小肠和其他肝外组织中的甾醇合成速率通常保持不变。虽然肝脏合成受到抑制，但肥胖大鼠的整个动物甾醇合成与瘦对照组相似。这是因为，在肥胖动物中，不仅肝脏合成速率的降低部分地被肝脏质量增加超过70%所平衡，而且小肠和脂肪组织的质量也分别增加超过30%和4倍，从而使这些组织在数量上成为甾醇合成的更重要部位。当肥胖大鼠配对喂养10周时，体重和血浆胆固醇浓度仅适度降低，肝脏固醇合成速率仍然非常低。当给肥胖的老鼠喂食surfomer（一种专门阻止胆固醇吸收的药物）时，肝脏合成的抑制也持续存在。相反，喂养考来烯胺使肝脏固醇合成率恢复到瘦动物的水平。肥胖男性和女性的胆汁酸池大小是瘦对照组的2.5倍。在该模型中，肝固醇合成的抑制可能是由于胆汁酸的肠-肝循环发生了变化，这是由于胆固醇池扩大所致，或者，它可能代表了对肠和脂肪隔室中固醇及其前体过度产生的代偿性反应。
The SHR/N-corpulent rat is a new genetically obese strain that exhibits both insulin-independent diabetes and hyperlipidemia. The present studies were undertaken to characterize various parameters of cholesterol metabolism in this model. At 11 weeks of age, the obese animals had markedly elevated plasma cholesterol, triglyceride, glucose, and insulin concentrations and elevated hepatic triglyceride concentrations compared to their lean littermates. The additional cholesterol in plasma was carried in the fractions of density less than 1.006, 1.020-1.055, 1.055-1.095, and 1.095-1.21 g/ml. In the obese rats the level of free cholesterol in the liver was decreased significantly while that of cholesteryl ester showed little change. Hepatic sterol synthesis was markedly suppressed in the obese animals. However, the rate of sterol synthesis in the small intestine and other extrahepatic tissues generally remained unchanged. Although hepatic synthesis was suppressed, whole animal sterol synthesis in the obese rats was similar to that in the lean controls. This resulted because, in the obese animals, not only was the reduced rate of hepatic synthesis partly balanced by a greater than 70% increase in liver mass, but the mass of the small intestine and adipose tissue was also increased more than 30% and 4-fold, respectively, thereby making these tissues quantitatively more important sites of sterol synthesis. When obese rats were pair-fed to the intake of their lean littermates for 10 weeks, there was only a modest reduction in body weight and plasma cholesterol concentration, and the rate of hepatic sterol synthesis remained very low. The suppression of synthesis in the liver also persisted when the obese rats were fed surfomer, a drug that specifically blocks cholesterol absorption. In contrast, feeding cholestyramine restored the rate of hepatic sterol synthesis to that found in lean animals. Bile acid pool size in the obese males and females was 2.5-fold greater than in their lean controls. The suppression of hepatic sterol synthesis in this model may be due to a change in the entero-hepatic circulation of bile acids arising from an expanded pool or, alternatively, it may represent a compensatory response to overproduction of sterol and its precursors in the intestinal and adipose compartments.
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影响因子：
6.5
作者：
D. Spady;J. Dietschy
通讯作者：
D. Spady;J. Dietschy
大鼠肠系膜淋巴中胆固醇的起源。
影响因子：
6.5
作者：
Stange,EF;Dietschy,JM
通讯作者：
Dietschy,JM
影响因子：
6.5
作者：
S. Turley;J. Andersen;J. Dietschy
通讯作者：
S. Turley;J. Andersen;J. Dietschy
通过操纵预先形成的和新合成的胆固醇池来改变仓鼠和大鼠的胆汁胆固醇饱和度。
影响因子：
29.4
作者：
Turley,SD;Spady,DK;Dietschy,JM
通讯作者：
Dietschy,JM
体外和体内大鼠肠道胆固醇合成的绝对速率：切片和分离细胞中不同底物的比较。
影响因子：
6.5
作者：
Stange,EF;Dietschy,JM
通讯作者：
Dietschy,JM