Acute and reversible fatty metamorphosis of cultured rat hepatocytes

Rat hepatocyte cell line M6, B347 and J525, among which only M6 is slightly deviated from diploidy, showed marked microvesicular fatty metamorphosis in response to treatment with Tweens at concentrations of 0.05-0.025% in Eagle's minimum essential medium (MEM). Within 24 h treated cells became fatty at 100% in frequency and filled with small lipid droplets, as revealed by fat staining or at the ultrastructural level. Fatty hepatocytes, however, took again non-fatty morphology 72 h after withdrawal of Tweens from the culture medium. Growth of the cell exhibited mild retardation at the early phase of the treatment but almost similar cell density to that of control cells was achieved 24 h after the treatment. Other detergents without fatty-acid moiety, including NP-40, triton X-100, sodium deoxycholic acid and sodium cholic acid, were ineffective to induce fatty change. Oleate, a fatty-acid moiety of Tween 80 or 85, and linolate caused reversible fatty metamorphosis of the cell lines at concentrations of 1.9 x 10(4) mol/L or more and 3.8 x 10(4) mol/L or more, respectively. Ethanol induced mild steatosis of the cell lines and enhanced fatty change by linolate. Hepatic fatty acid-binding protein was not detected in the cell lines before or after the induction of fatty change. These results indicate that fatty acid itself is directly incorporated in cultured rat hepatocytes and expelled 3 days later without apparent cell degeneration.