β-oxidation modulates metabolic competition between eicosapentaenoic acid and arachidonic acid regulating prostaglandin E2 synthesis in rat hepatocytes-Kupffer cells

The ability of n-3 PUFA to competitively inhibit the use of arachidonic acid (AA) for membrane phospholipid synthesis and prostaglandin E-2 (PGE(2)) production has been well demonstrated in single cell models In the present study, we investigated the metabolic competition between AA and eicosapentaenoic acid (EPA) for PGE(2) synthesis in a rat hepatocyte-Kupffer cell (HPC/KC) co-culture system when the cellular oxidation capacity was enhanced by exogenous L-carnitine We demonstrate that in the absence of L-carnitine, 1) beta-oxidation rates of EPA and AA were comparable in HPCs and in KCs, 2) AA and not EPA was preferentially incorporated into glycerolipids; and 3) addition of EPA significantly decreased AA-dependent PGE2 synthesis in HPCs and cyclooxygenase-2 (COX-2) expression in co-cultured HPCs/KCs However, enhancing the cellular oxidation capacity by the addition of L-carnitine 1) significantly increased beta-oxidation of EPA in HPCs, but only marginally elevated the oxidation of AA in HPCs and the oxidation of both fatty acids in KCs: 2) decreased the esterification, but did not alter the preferential incorporation of AA into glycerolipids: and 3) alleviated the significant competitive inhibition of AA-dependent PGE(2) synthesis and COX-2 expression by EPA. Taken together, the results strongly suggest that L-carnitine affects competition between AA and EPA in PG synthesis in liver cells by enhancing oxidation of EPA in HPCs This implies that the beneficial effects of n-3 PUFA, especially EPA, are affected by the cellular oxidation capacity. (C) 2010 Elsevier B.V All rights reserved