Mammalian adipose tissue and muscle are major sources of lipid transfer protein mRNA.
Mammalian adipose tissue and muscle are major sources of lipid transfer protein mRNA.
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发表时间：
1991-03
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通讯作者：
Xuliang Jiang;P. Moulin;E. Quinet;Ira J. Goldberg;L. Yacoub;Luis B. Agellon;D. Compton;R. Schnitzer-Polokoff;Alan R. Tall
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作者：
Xuliang Jiang;P. Moulin;E. Quinet;Ira J. Goldberg;L. Yacoub;Luis B. Agellon;D. Compton;R. Schnitzer-Polokoff;Alan R. Tall
血浆胆固醇酯转移蛋白（CETP）催化胆固醇酯从高密度脂蛋白（HDL）转移到富含胆固醇的脂蛋白，并且在HDL的催化中起主要作用。脂蛋白脂酶（LPL）是循环甘油三酯水解的限速酶，并参与HDL的形成。我们发现，含有LPL的组织是几种哺乳动物CETP mRNA的主要来源，包括一些血浆中胆固醇酯转移活性低的动物。在仓鼠中，脂肪组织和心脏被发现是CETP和LPL mRNA最丰富的来源;原位杂交研究表明，相同的细胞类型（即脂肪细胞或肌细胞）在这些组织中含有CETP和LPL mRNA。分离的脂肪细胞合成活性CETP。饮食研究揭示了一个复杂的模式的响应CETP mRNA水平在不同的组织，这表明部分相似的LPL mRNA丰度的变化。然而，高胆固醇饮食导致脂肪组织、心脏和骨骼肌中CETP mRNA丰度增加，而LPL mRNA没有同等变化。血浆HDL胆固醇酯水平与脂肪组织中CETP mRNA丰度呈强负相关。结果表明，CETP在脂肪组织和心脏中具有保守的功能，例如与LPL协同作用以增强HDL周转。尽管CETP和LPL基因表达的组织和细胞特异性模式有相当大的重叠，但饮食研究显示，在mRNA水平上的反应只有有限的平行性。外周组织中CETP mRNA的增加响应于增加的膳食胆固醇，表明CETP合成的局部诱导可能有助于回收在膳食脂蛋白的脂解过程中沉积在这些组织中的胆固醇。
The plasma cholesteryl ester transfer protein (CETP) catalyzes the transfer of cholesteryl esters from high density lipoproteins (HDL) to triglyceride-rich lipoproteins and plays a major role in the catabolism of HDL. Lipoprotein lipase (LPL) is the rate-limiting enzyme for hydrolysis of circulating triglyceride and is involved in HDL formation. We show that tissues containing LPL are major sources of CETP mRNA in several mammalian species, including some with low cholesteryl ester transfer activity in plasma. In hamsters, adipose tissue and heart were found to be the richest sources of both CETP and LPL mRNA; in situ hybridization studies showed that the same cell types (i.e. adipocytes or myocytes) contained CETP and LPL mRNA in these tissues. Isolated adipocytes synthesized active CETP. Dietary studies revealed a complex pattern of response of CETP mRNA levels in different tissues, which showed partial similarity to the changes in LPL mRNA abundance. However, high cholesterol diets resulted in increased CETP mRNA abundance in adipose tissue, heart, and skeletal muscle, without equivalent changes in LPL mRNA. Plasma HDL cholesteryl ester levels showed strong inverse correlations with CETP mRNA abundance in adipose tissue. The results suggest a conserved function of CETP in adipose tissue and heart, such as a co-ordinate action with LPL to enhance HDL turnover. Although there is considerable overlap in the tissue- and cell-specific pattern of CETP and LPL gene expression, dietary studies revealed only limited parallelism in response at the mRNA level. The increase in CETP mRNA in peripheral tissues in response to increased dietary cholesterol suggests that local induction of CETP synthesis may help to recycle cholesterol deposited in these tissues during lipolysis of dietary lipoproteins.