Radeau T, Robb M, Lau P, Borthwick J, McPherson R
Lipoprotein & Atherosclerosis Group, University of Ottawa Heart Institute, Canada.
Atherosclerosis. 1998 Aug;139(2):369-76. doi: 10.1016/s0021-9150(98)00051-3.
Adipose tissue is an important site of cholesteryl ester transfer protein (CETP) synthesis and CETP plays a local role in adipocyte cholesteryl ester accumulation from high density lipoproteins (HDL). Human adipose tissue maintained in organ culture secretes CETP, but it is not known to what extent adipose tissue CETP contributes to the plasma pool of CETP in man. Aging is associated with changes in adipose tissue composition and function, including impaired adipocyte triglyceride lipolysis. We determined pericardiac adipose tissue CETP mRNA levels and plasma concentrations of CETP and lipoproteins in middle-aged and elderly subjects (47-78 years) with stable coronary heart disease (CHD) undergoing elective coronary artery bypass grafting (CABG). Plasma concentrations of CETP were highly correlated with adipose tissue CETP mRNA abundance (r = 0.85, P < 0.002, n = 13), suggesting that adipose tissue may contribute to the plasma pool of CETP. There was an inverse correlation between age and plasma CETP concentrations in this population (r = -0.70, P <0.008, n = 13). CETP mRNA levels in pericardial adipose tissue were also negatively associated with age (r = -0.70, P < 0.035, n = 10). These relationships were independent of plasma lipids, lipoproteins and body mass index. However, adipose tissue CETP mRNA concentrations levels were related to adipocyte size. CETP mRNA abundance in pericardial adipose tissue was negatively correlated with mean adipocyte size, estimated as adipose tissue triglyceride/mg protein (r = -0.76, P < 0.02, n = 9), in accord with previous studies from this laboratory demonstrating that CETP gene expression is greatest in small lipid-poor adipocytes. A negative relationship between age and adipose tissue CETP mRNA abundance (r = -0.63, P < 0.05, n = 10) was confirmed in a separate population of healthy female subjects, aged 18-63 years, from whom subcutaneous adipose tissue was obtained at the time of reduction mammoplasty. The decrease in plasma concentrations of CETP with age may be explained in part by changes in adipose tissue CETP gene expression.
脂肪组织是胆固醇酯转运蛋白(CETP)合成的重要场所,CETP在脂肪细胞从高密度脂蛋白(HDL)中积累胆固醇酯的过程中发挥局部作用。在器官培养中维持的人体脂肪组织会分泌CETP,但尚不清楚脂肪组织中的CETP对人体血浆中CETP池的贡献程度。衰老与脂肪组织的组成和功能变化有关,包括脂肪细胞甘油三酯脂解受损。我们测定了患有稳定冠心病(CHD)并接受择期冠状动脉搭桥术(CABG)的中年和老年受试者(47 - 78岁)的心周脂肪组织中CETP mRNA水平以及血浆中CETP和脂蛋白的浓度。血浆中CETP的浓度与脂肪组织中CETP mRNA丰度高度相关(r = 0.85,P < 0.002,n = 13),这表明脂肪组织可能对血浆中CETP池有贡献。在该人群中,年龄与血浆CETP浓度呈负相关(r = -0.70,P < 0.008,n = 13)。心周脂肪组织中CETP mRNA水平也与年龄呈负相关(r = -0.70,P < 0.035,n = 10)。这些关系独立于血浆脂质、脂蛋白和体重指数。然而,脂肪组织中CETP mRNA浓度水平与脂肪细胞大小有关。心周脂肪组织中CETP mRNA丰度与平均脂肪细胞大小呈负相关,平均脂肪细胞大小通过脂肪组织甘油三酯/毫克蛋白来估计(r = -0.76,P < 0.02,n = 9),这与本实验室之前的研究结果一致,该研究表明CETP基因表达在脂质含量少的小脂肪细胞中最高。在另一组年龄为18 - 63岁的健康女性受试者中,在进行缩乳术时获取皮下脂肪组织,证实了年龄与脂肪组织中CETP mRNA丰度之间存在负相关(r = -0.63,P < 0.05,n = 10)。随着年龄增长血浆中CETP浓度的降低可能部分归因于脂肪组织中CETP基因表达的变化。