Disturbed regulation of cholesterol synthesis in monocytes of obese patients with hypercholesterolemia

The aim of the present study was to clarify the influence of obesity on the functions of low-density lipoprotein receptors (LDL-R) and 3-hydroxy-3-methylglutarate-coenyzme A (HMG-CoA) reductase both in healthy control subjects and in patients with hypercholesterolemia (HC). Experiments were performed on monocytes of 15 non-obese (C I) and 11 obese (C II) healthy control subjects and on 22 non-obese (HC I) and 26 obese (HC II) patients with HC. [(125)I]LDL was used to determine LDL-R activity by measuring binding and intracellular degradation. The rate of endogenous cholesterol synthesis was measured using [(14)C]acetate incorporation into the cholesterol fraction of monocytes. The binding ability of [(125)I]LDL was identical across all groups. The [(14)C]acetate incorporation in resting monocytes was increased only in obese HC group. The 50-microg/mL LDL protein-induced inhibition of [(14)C]acetate incorporation was significantly diminished (P <.001) in the same group. A strong positive correlation was detected between the [(14)C]acetate incorporation by resting cells and LDL-induced inhibition in all groups except the obese HC group, in which their correlation was negative (P <.001). Furthermore, in the obese HC group, a significant positive correlation was detected between body mass index (BMI) and the basal level of [(14)C]acetate incorporation, whereas a negative correlation was found between BMI and LDL-induced inhibition of [(14)C]acetate incorporation. The present data suggest that in patients with HC the concomitant obesity results in dysregulation of cholesterol homeostasis, which may contribute to the accelerated atherosclerosis.