CHOLESTERYL ESTER TRANSFER PROTEIN (CETP) MESSENGER-RNA ABUNDANCE IN HUMAN ADIPOSE-TISSUE - RELATIONSHIP TO CELL-SIZE AND MEMBRANE CHOLESTEROL CONTENT

Cholesteryl ester transfer protein (CETP) has a well-defined role in p lasma neutral lipid transport. CETP synthesized by human adipose tissu e may contribute to the plasma CETP pool. CETP mRNA abundance increase s in subcutaneous adipose tissue in response to cholesterol feeding an d we have hypothesized that CETP gene expression is regulated by a spe cific pool of cellular sterol. In the present study, we have quantifie d CETP mRNA levels in subcutaneous adipose tissue of 10 female subject s using a solution hybridization RNase protection assay. Particulate ( membrane cholesterol) and lipid droplet cholesterol (core cholesterol) were determined by gas chromatography. CETP mRNA abundance in these a dipose tissue specimens correlated significantly with membrane cholest erol expressed as a fraction of membrane protein (r - 0.67, P = 0.031) . There was also a linear relationship between CETP mRNA abundance and membrane cholesterol to core triglyceride ratio (r = 0.57, P = 0.009) and a strong correlation between the percentage of cellular cholester ol in the membrane fraction (ratio of membrane to core cholesterol) an d CETP mRNA abundance (r = 0.91, P = 0.0002). In contrast, there was a negative relationship between each of lipid droplet cholesterol and t riglyceride and CETP mRNA levels. Human adipose tissue maintained in o rgan culture for several days was shown. to secrete CETP into the cult ure medium. Incubation with cholesterol-rich chylomicron remnants elic ited a dose-dependent increase in both membrane and core cholesterol a nd a concomitant increase in the level of CETP mRNA. These studies dem onstrate that adipose tissue CETP mRNA abundance is a function of memb rane cholesterol concentration rather than lipid droplet cholesterol a nd that CETP mRNA increases with adipocyte cholesterol enrichment via chylomicron remnants. CETP gene expression is highest in small lipid-p oor adipocytes, suggesting that CETP synthesized and secreted by adipo cytes may have a role in promoting cellular cholesterol accumulation.