HIV Protease Inhibitors Stimulate Hepatic Triglyceride Synthesis

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HIV Protease Inhibitors Stimulate Hepatic Triglyceride Synthesis by James M. Lenhard, Dallas K. Croom, James E. Weiel, and Deborah A. Winegar Arterioscler Thromb Vasc Biol Volume 20(12):2625-2629 December 1, 2000 Copyright © American Heart Association, Inc. All rights reserved.

Effects of PIs on intracellular TG synthesis in HepG2 cells. Effects of PIs on intracellular TG synthesis in HepG2 cells. HepG2 cells were cultured in the presence of ABT-378, APV, IDV, NFV, RTV, or SQV at the indicated concentration for 24 hours at 37°C. Radiolabeling was initiated by the addition of [14C]acetic acid and incubation for an additional 24 hours at 37°C. Intracellular lipids were isolated through HPLC, and TG concentration was determined through coelution with known standards. Values were normalized to the value in control cells (ie, 100% is the amount of TG synthesis that occurs in the absence of PIs). Data are given as the mean±SEM (n=≥3 experiments), and significant differences between control and treated groups are indicated by *P<0.05. James M. Lenhard et al. Arterioscler Thromb Vasc Biol. 2000;20:2625-2629 Copyright © American Heart Association, Inc. All rights reserved.

Costimulation of HepG2 cells with NFV and RXR ligands. Costimulation of HepG2 cells with NFV and RXR ligands. A, HepG2 cells were cultured in the presence of 10 μmol/L NFV or with vehicle (control cells) for 24 hours, followed by radiolabeling with [14C]acetic acid for 24 hours. LG100268 or LG100754 was included in the medium as indicated at 100 nmol/L. Intracellular lipids were isolated, and TG concentration was determined. The percent of TG synthesis was normalized relative to the value in control cells (100%). B, FAS and DGAT expression in HepG2 cells treated as indicated were determined with polymerase chain reaction. The fold change in gene expression was normalized relative to the value in untreated control cells. Data are given as the mean±SEM, and significant differences between control and treated groups are indicated by *P<0.05. James M. Lenhard et al. Arterioscler Thromb Vasc Biol. 2000;20:2625-2629 Copyright © American Heart Association, Inc. All rights reserved.