Fat
-storing cells participate in the development of alcoholic liver disease. To study possible effects of ethanol on prostaglandin metabolism by fat-storing cells, we isolated them from normal rat liver. Cultured fat-storing cells produced substantial amounts (DNA, about 2 ng/pg every 24 hr) of prostaglandin E, and prostaglandin I, (measured as 6-keto prostaglandin FIJ but no significant amounts of prostadandin FZa. This production was markedly enhanced by the addition of ethanol in concentrations likely to occur in the blood during alcohol consumption. We confirmed the presence of class 1 alcohol dehydrogenase activity and isoenzymes in the cytosol of cultured fat-storing cells in their second passage. The stimulatory effect of ethanol was inhibited by 4-methylpyrazole (an alcohol dehydrogenase inhibitor), exaggerated by disulfiram (an aldehyde dehydrogenase inhibitor) and reproduced by concentrations of acetaldehyde likely to occur in the liver. Thus, our results indicate that fat-storing cells produce vasodilatory prostaglandins and that this production is enhanced by the acetaldehyde that results from the oxidation of ethanol catalized by alcohol dehydrogenase present in these cells. (HEPATOLOGY 1993;18:153-159.)
Fat-storingcells (FSC) are the principal cells of Disse's spaces. They are also called stellate cells, lipocytes or Ito cells. FSC are considered to play important roles in hepatic fibrogenesis and the storage of vitamin A. In alcoholics, they are thought to participate in the development of fibrosis, particularly after transformation to fibroblast-like transitional cells as a consequence of chronic alcohol consumption (1). Possible transformation into fibroblast or myofibroblast-like cells, which reside around terminal hepatic veins, has also been suggested in rats (2), in baboons (3) and in vitro (4). Moreover, the demonstration of contact with nerve