Tumor necrosis factor-alpha, interleukin-1, and interferon alpha stimulate triglyceride synthesis in HepG2 cells

Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interferon alpha (IFN-alpha) stimulate hepatic lipogenesis in vivo. We now show that TNF-alpha, IL-1, and IFN-alpha stimulate lipogenesis as measured by the incorporation of 3H-glycerol into triglyceride in cultured HepG2 cells. Incubation of HepG2 cells for approximately 24 hours with TNF or IL-1 was required to see stimulation of lipogenesis, with this effect increasing over the next four days. TNF stimulated lipogenesis by 2.4-fold after 72 hours of incubation, while a 3.5-fold stimulation was seen with IL-1. The half maximal concentration for TNF stimulation of hepatic lipogenesis was 4 ng/mL, while that for IL-1 was 0.3 ng/mL. Cells treated with TNF or IL-1 also showed increased secretion of labeled triglyceride into the media. IFN-alpha stimulated the incorporation of 3H-glycerol into triglyceride by 39% after 72 hour's incubation. In contrast, IFN-gamma had no effect on lipogenesis in HepG2 cells. These data suggest that cytokines can directly stimulate the synthesis of triglycerides in cultured Hep G2 liver cells in vitro.