Omega-oxidation of fatty acids studied in isolated liver cells

Abstract

The ω- and β-oxidation of medium- and long-chain fatty acids (C 10–C 18) were studied in hepatocytes from fasted, fed and clofibrate-fed rats. The ω-oxidation systems were most active with lauric acid (12:0) and decanoic acid (10:0) as substrates and there was decreasing activity with chain lengths from 14 to 18 carbon atoms. In fed rats no ω-oxidation of fatty acids was detected unless the mitochondrial β-oxidation was inhibited. In fasted rats the ω-oxidation was less than 2% and preincubation with (+)-decanoylcarnitine increased the ω-oxidation to 15% of the total fatty acid oxidation. Clofibrate feeding did not increase the ω-oxidation in isolated hepatocytes. Inhibition of the alcohol dehydrogenase with 4-methylpyrazole inhibited both the oxidation of ω-hydroxylated fatty acid and the initial hydroxylation of lauric acid to dicarboxylic acid, suggesting the importance of the alcohol dehydrogenase in the ω-oxidation of fatty acids. 95% of the dicarboxylic acids and 80% of the hydroxy-fatty acids were excreted from the cells in the incubations with decanoic acid (10:0). No chain-shortened dicarboxylic acids were detected with [1- 14C]decanoic- or [1- 14C]lauric acid as substrate, while small amounts C 10 and C 12 dicarboxylic acids were observed in incubations with [1- 14C]myristic acid (14:0).