Role of hepatic vitamin A and lipocyte distribution in experimental hepatic fibrosis

ABSTRACT— Lipocytes are the major site of hepatic vitamin A storage, and they have been demonstrated to lose their vitamin A content in the process of hepatic fibrosis. To investigate the relationship between hepatic vitamin A content and the degree of hepatic fibrosis, we measured levels of retinyl palmitate and retinol in the CCl₄-induced fibrotic liver using high-performance liquid chromatography. We estimated hepatic collagen content using a spectrophotometric analysis with sirius red, and also by measuring hydroxyproline levels. Lipocytes were detected by an immunoperoxidase method with anti-desmin antibody, and were counted morphometrically through a Texture Analyzing System. A significant negative correlation was observed between the level of retinyl palmitate and collagen content (r = –0.64) as well as the hydroxyproline level (r = –0.69) in the CCl₄-induced fibrotic liver. In the process of fibrosis, hepatic retinol levels were elevated in association with a decrease in retinyl palmitate. In particular in the early stage of fibrosis, lipocytes increased remarkably in number in fibrotic areas in spite of a decrease in total hepatic vitamin A. The present study suggests that an increase in hepatic retinol as well as a decrease in retinyl palmitate may facilitate the process of hepatic fibrosis produced by lipocytes.