Leptin is a peptide hormone that appears critical in regulating Fat metabolism. Recently, circulating leptin levels were reported higher in patients with alcoholic cirrhosis. In health, hepatic stellate cells store retinoids, but following liver injury they transdifferentiate into myofibroblast-like cells with loss of the retinoid stores. Leptin expression was demonstrated by detection of leptin mRNA by RT-PCR analysis and by immunohistochemistry viewed with confocal microscopy in transdifferentiated stellate cells after 14 days, or more, of culture. Leptin expression was not found in freshly isolated quiescent stellate cells. Leptin expression was not demonstrated in freshly isolated or cultured Kupffer cells. Treatment of activated stellate cells with either 1 microM retionic acid or 10 microM retinol acetate resulted in the inhibition of leptin mRNA expression. The observation that activated stellate cells in culture can express leptin has implications for understanding adipocyte biology in liver disease and treatment of malnutrition in cirrhotics.