Eicosapentaenoic acid, but not oleic acid, stimulates β-oxidation in adipocytes

The beneficial roles of dietary fish oil in lowering serum TAG levels in animals and humans have been attributed in part to the high content of two n−3 polyunsaturated very long-chain FA, EPA, and DHA. Recent studies show that EPA induces mitochondrial β-oxidation in hepatocytes, which might contribute to the systemic lipid-lowering effect. Whether EPA affects FA storage or oxidation in adipocytes is not clear. To investigate this possibility, 3T3-L1 adipocytes incubated with EPA (100 μM) for 24 h were assayed for β-oxidation, carnitine palmitoyl transferase 1 (CPT-1) activity, protein, and mRNA expression of CPT-1. For comparison, cells treated with oleic acid, octanoic acid, and clofibrate, a synthetic ligand for peroxisome proliferator-activated receptor α were also analyzed. Mitochondria were isolated by differential centrifugation, and the mitochondrial membrane acyl chain composition was measured by GLC. EPA increased the oxidation of endogenous FA but did not inhibit lipogenesis. Oleic acid and clofibrate did not affect FA oxidation or lipogenesis, whereas octanoic acid suppressed the oxidation of endogenous FA and inhibited lipogenesis. Increased β-oxidation by EPA was associated with increased CPT-1 activity but without changes in its mRNA and protein expression. EPA treatment increased the percentage of this FA in the mitochondrial membrane lipids. We suggest that EPA increased the activity of CPT-1 and β-oxidation in adipocytes by altering the structure or dynamics of the mitochondrial membranes.