Effects on hepatic lipid metabolism in human hepatoma cells following overexpression of TGFβ induced factor homeobox 1 or 2

Abstract

Transforming growth factor β induced factor homeobox (TGIF) 1 and 2 are two transcriptional repressors. Although TGIF1 has been found to be involved in lipid metabolism, no studies have yet investigated the role of TGIF2 in hepatic lipid metabolism. Here we aim to investigate effects on hepatic lipid metabolism following overexpression of the human and mouse TGIF1 and TGIF2 protein. We used modified mRNA molecules to transiently enhance the expression of these proteins in human hepatoma cells. We found all the mRNA molecules to be translated, except the one for human TGIF1. Transient transfection with the mouse TGIF1 mRNA molecules lowered levels of cholesterol (p < 0.001), triglycerides (p < 0.001), and apolipoprotein B (p < 0.05) in the cell media by ~40%, along with the mRNA levels of some key genes involved in lipid metabolism. In contrast, limited effects on these parameters were observed following transient transfection with the human and mouse TGIF2 mRNA molecules. To enable investigation of the effects following enhanced expression of the human TGIF1 protein, we stably overexpressed this protein in human hepatoma cells. In line with the above findings, we found cells stably overexpressing the human TGIF1 protein had lower levels of cholesterol (p < 0.05), triglycerides (p < 0.05) and apolipoprotein B (p < 0.05) in the cell media by ~30%. Hence, transient and stable overexpression of the TGIF1 protein appears to lead to an advantageous lipid profile.

Keywords: Apolipoprotein B; Cholesterol; Dyslipidemia; Triglycerides; mRNA molecules.