Effect of endotoxin on cholesterol biosynthesis and distribution in serum lipoproteins in Syrian hamsters.
Effect of endotoxin on cholesterol biosynthesis and distribution in serum lipoproteins in Syrian hamsters.
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发表时间：
1993-12
影响因子：
6.5
通讯作者：
K. Feingold;Ingibjorg Hardardottir;R. Memon;Eveline J. T. Krul;Arthur H. Maser;John M. Taylor;Carl Grunfeld
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作者：
K. Feingold;Ingibjorg Hardardottir;R. Memon;Eveline J. T. Krul;Arthur H. Maser;John M. Taylor;Carl Grunfeld
感染和炎症增加啮齿动物和兔子的血清甘油三酯和胆固醇水平。内毒素（LPS）已被用作感染模型，其对甘油三酯代谢的影响已在以前的特点。在本研究中，我们证明了低剂量（100 ng/100 g体重）和高剂量（100微克/100 g体重）LPS均会增加仓鼠的血清胆固醇水平。在LPS后16小时首次观察到血清胆固醇的增加，并持续至少24小时。这种增加主要是由于低密度脂蛋白（LDL）胆固醇的增加。LPS处理后高密度脂蛋白（HDL）胆固醇水平降低。低剂量和高剂量LPS均增加肝胆固醇合成（低剂量85%，高剂量205%）和总HMG-CoA还原酶活性（低剂量2.97倍，高剂量9.96倍）。然而，LPS处理降低了活性形式的HMG-CoA还原酶的比例。此外，通过蛋白质印迹法测量的肝脏中HMG-CoA还原酶蛋白的质量在LPS后增加。此外，LPS增加肝HMG-CoA还原酶mRNA水平（低剂量3.1倍，高剂量14.2倍）。肝HMG-CoA还原酶mRNA水平的增加在LPS后4 h首次观察到，并持续至少24 h。相反，LPS对肝脏LDL受体蛋白和mRNA水平的影响很小。这些结果表明，LPS通过增加肝脏胆固醇合成来增加血清胆固醇水平。LPS给药降低了肝脏中的apoE mRNA水平，而对apoA-I mRNA水平没有影响。这些结果表明，HMG-CoA还原酶是一组肝脏蛋白的成员，这些蛋白由炎症刺激（急性时相蛋白）正调控，而apoE可以被认为是仓鼠的负急性时相蛋白。肝HMG-CoA还原酶的增加可能提供胆固醇，从而允许增加脂蛋白的产生和血清脂质水平的升高，这可能有益于身体的宿主防御。
Infection and inflammation increase serum triglyceride and cholesterol levels in rodents and rabbits. Endotoxin (LPS) has been used as a model of infection and its effects on triglyceride metabolism have been previously characterized. In the present study we demonstrate that both low (100 ng/100 g body weight) and high dose (100 micrograms/100 g body weight) LPS increase serum cholesterol levels in hamsters. The increase in serum cholesterol is first observed 16 h after LPS and persists for at least 24 h. This increase is primarily due to an increase in low density lipoprotein (LDL) cholesterol. High density lipoprotein (HDL) cholesterol levels decrease after LPS treatment. Both low and high dose LPS increase hepatic cholesterol synthesis (low dose 85%, high dose 205%) and total HMG-CoA reductase activity (low dose 2.97-fold, high dose 9.96-fold). However, the proportion of HMG-CoA reductase in the active form is reduced by LPS treatment. Additionally, the mass of HMG-CoA reductase protein in the liver, measured by Western blotting, is increased after LPS. Moreover, LPS increases hepatic HMG-CoA reductase mRNA levels (low dose 3.1-fold, high dose 14.2-fold). The increase in hepatic HMG-CoA reductase mRNA levels is first seen 4 h after LPS and persists for at least 24 h. In contrast, LPS had only minimal effects on hepatic LDL receptor protein and mRNA levels. These results suggest that LPS increases serum cholesterol levels by increasing hepatic cholesterol synthesis. LPS administration decreases apoE mRNA levels in the liver while having no effect on apoA-I mRNA levels. These results suggest that HMG-CoA reductase is a member of a group of hepatic proteins that are positively regulated by inflammatory stimuli (acute phase proteins) while apoE can be considered a negative acute phase protein in hamsters. It is possible that increases in hepatic HMG-CoA reductase provide cholesterol that allows for the increased production of lipoproteins and elevations in serum lipid levels that may be beneficial to the body's host defense.