A comparison of the hydrolysis and metabolism in rats of fatty acid ethyl esters within human low density lipoproteins and rat low density lipoproteins

Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, have been implicated as toxic mediators of ethanol ingestion. To study the effects of FAEE in vivo, it is necessary to make them soluble on a lipid carrier, such as low density lipoprotein (LDL). Testing for FAEE- induced cytotoxicity in vivo requires the use of an animal model, and one option is the rat. Rat LDL is a non-abundant lipoprotein, while human LDL is readily obtained in large quantities. To determine whether FAEE metabolism in rat blood in vivo and in vitro is the same when bound to human LDL and to rat LDL, we compared the in vivo hydrolysis and metabolism of FAEE reconstituted into either human or rat LDL which were injected into rats. We also compared the hydrolysis and metabolism of FAEE reconstituted into human LDL and incubated with either human or rat whole blood in vitro. In vivo FAEE hydrolysis and the metabolism of the fatty acid derived from FAEE in rat liver were very similar when the FAEE were reconstituted into either human or rat LDL. In vitro, the FAEE hydrolysis was more rapid when incubated with rat blood than with human blood, but the metabolism of the liberated fatty acid was essentially the same for both. Taken together, for studies performed under conditions in our experiments, human LDL and rat LDL carriers can be used interchangeably to investigate FAEE hydrolysis and metabolism in rat blood in vivo and in vitro.