title: Disturbed regulation of cholesterol synthesis in monocytes of obese patients with hypercholesterolemia.
abstract: 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.
authors.affiliation: First Department of Medicine, CSL, Experimental Pathology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Paragh
authors.forename: Z
authors.initials: Z
authors.lastname: Balogh
authors.forename: E
authors.initials: E
authors.lastname: Kovács
authors.forename: M
authors.initials: M
authors.lastname: Szabolcs
authors.forename: J
authors.initials: J
authors.lastname: Szabó
authors.forename: K
authors.initials: K
authors.lastname: Csapó
authors.forename: G
authors.initials: G
authors.lastname: Fóris
mesh_terms: 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*
chemical_list: D000085:Acetates; D008078:Cholesterol, LDL; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases