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.
Paragh
G
G
First Department of Medicine, CSL, Experimental Pathology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
Balogh
Z
Z
Kovács
E
E
Szabolcs
M
M
Szabó
J
J
Csapó
K
K
Fóris
G
G
D000085:Acetates / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002469:Cell Separation; D002784:Cholesterol / Q000096:biosynthesis*; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006937:Hypercholesterolemia / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*
D000085:Acetates; D008078:Cholesterol, LDL; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases