Guo Wen, Xie Weisheng, Lei TianGuang, Hamilton James A
Obesity Research Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Lipids. 2005 Aug;40(8):815-21. doi: 10.1007/s11745-005-1443-8.
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 beta-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 microM) for 24 h were assayed for beta-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 alpha 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 beta-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 beta-oxidation in adipocytes by altering the structure or dynamics of the mitochondrial membranes.
膳食鱼油在降低动物和人类血清甘油三酯（TAG）水平方面的有益作用，部分归因于两种n-3多不饱和超长链脂肪酸——二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）的高含量。最近的研究表明，EPA可诱导肝细胞中的线粒体β-氧化，这可能有助于产生全身降脂效果。EPA是否影响脂肪细胞中的脂肪酸储存或氧化尚不清楚。为了探究这种可能性，对用EPA（100微摩尔）孵育24小时的3T3-L1脂肪细胞进行β-氧化、肉碱棕榈酰转移酶1（CPT-1）活性、CPT-1蛋白和mRNA表达的检测。作为对照，还分析了用油酸、辛酸以及过氧化物酶体增殖物激活受体α的合成配体氯贝丁酯处理的细胞。通过差速离心分离线粒体，并用气相色谱法（GLC）测定线粒体膜酰基链组成。EPA增加了内源性脂肪酸的氧化，但未抑制脂肪生成。油酸和氯贝丁酯不影响脂肪酸氧化或脂肪生成，而辛酸抑制内源性脂肪酸的氧化并抑制脂肪生成。EPA增加的β-氧化与CPT-1活性增加相关，但其mRNA和蛋白表达没有变化。EPA处理增加了这种脂肪酸在线粒体膜脂质中的百分比。我们认为，EPA通过改变线粒体膜的结构或动力学，增加了脂肪细胞中CPT-1的活性和β-氧化。
