Relationship of adipose tissue cholesteryl ester transfer protein (CETP) mRNA to plasma concentrations of CETP in man

Abstract

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.