It is well known that obesity is frequently associated with low levels of serum high-density lipoprotein (HDL) cholesterol. However, the mechanism for this reduction has not been fully clarified. Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester from HDL to apolipoprotein B-containing lipoproteins and plays an important role in regulating the concentration and composition of HDL. To elucidate the mechanism for the reduction of serum HDL cholesterol in obesity, we analyzed serum lipoproteins, CETP, and postheparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities in 30 obese subjects (17 women and 13 men, age 44 +/- 14 years, mean +/- SD). We also investigated the relationship between these variables, total adiposity, and indices of body fat distribution. The average body mass index of the obese subjects was 33.1 +/- 4.8 kg/m2 (range, 26.4 to 43.8 kg/m2). The obese subjects showed significantly lower serum HDL cholesterol levels than control subjects (1.04 +/- 0.28 versus 1.50 +/- 0.34 mmol/L, P < .01). In the obese subjects, both activities and protein mass of CETP and postheparin HTGL activities were significantly increased, whereas postheparin LPL activities were significantly decreased. CETP activities, independent of postheparin HTGL and LPL activities, were correlated negatively with HDL cholesterol (r = -.39, P < .05) and the cholesteryl ester to triglyceride ratio of HDL2 and HDL3 (r = -.36, P < .05; r = -.46, P < .05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)