Retinoid-mediated induction of the fat-storing phenotype in a liver connective tissue cell line (GRX)

The GRX cell line is derived from murine liver connective tissue cells. It has myofibroblastic characteristics and can be induced to display a phenotype analogous to fat-storing (Ito) cells. Retinol-mediated induction of the fat-storing phenotype was studied in vitro. Based on the incorporation of radiolabelled acetate into cell lipids, cholesterol synthesis increased and phospholipid synthesis was modified shortly after the beginning of the induction, indicating an activation of pre-existing metabolic pathways. Triacylglycerol synthesis was increased only after a delay of 4 d, indicating the de novo induction of enzymes necessary for triacylglycerol metabolism. Retinol incorporation and conversion into retinyl esters were also considerably increased by previous incubation with retinoids. Retinoid-induced changes in GRX cells provide a model for studying in vitro the interconversion of liver connective tissue cells between the myofibroblastic and fat-storing phenotypes. This interconversion is considered to be one of the major control points of normal homeostasis and of pathological modifications of liver connective tissue.