Malondialdehyde stimulates collagen production by hepatic lipocytes only upon activation in primary culture

Lipid aldehydes have been proposed as mediators of hepatic fibrosis in alcoholics. In this study we examined whether hepatic lipocytes, the principal matrix-producing cells in liver, exhibit enhanced collagen synthesis in response to the lipid aldehyde malondialdehyde. Lipocytes isolated from normal rat liver and plated in primary culture for 3 days were not affected by malondialdehyde in concentrations ranging from 2 to 200 microM. Cells cultured for 7 days displayed a modest increase in collagen synthesis (137% of control levels) in response to malondialdehyde, but only at a concentration of 200 microM. The malondialdehyde-induced increase in collagen synthesis was paralleled by a rise in type I procollagen mRNA. Subcultured rat fibroblasts at confluent density responded better to malondialdehyde than did 7-day lipocytes. The results indicate that lipocytes respond to the fibrogenic effects of malondialdehyde only after activation in primary culture. This delayed response suggests that lipid aldehydes may enhance, but do not initiate, alcoholic liver fibrosis in vivo.