Inhibitory effect of cholephilic anions on fatty acid uptake by the perfused rat liver

The mechanisms of uptake and intracellular transport of plasma free fatty acids by the liver cell are poorly known. A cytosolic protein, termed Z protein, has been identified in the liver, intestine and other tissues; in vitro studies show a high affinity of fatty acid and organic anions for this protein and suggest that it could be involved in the cellular transport of fatty acids in vivo. The present experiments demonstrate an inhibitory effect of various organic cholephilic anions (B.S.P., D.B.S.P., flavaspidic acid, bilirubin, etc) on fatty acid uptake by the isolated perfused rat liver. This inhibition is rapidly reversible when the liver is perfused with a medium lacking cholephilic anions, which together with the absence of any functional or ultrastructural damage to the organ, excludes any hepatotoxic effect. Such an inhibition of fatty acid uptake could be due to a competition for binding either to membrane sites and/or to intracellular carriers common to both fatty acids and cholephilic anions. These data are consistent with the involvement of carrier-mediated processes in fatty acid transport in the liver. Finally, simultaneous uptake of radioactive fatty acid and cholephilic anions does not interfere with further fatty acid utilization by the cell.