Do Fish Oil Omega-3 Fatty Acids Enhance Antioxidant Capacity and Mitochondrial Fatty Acid Oxidation in Human Atrial Myocardium via PPARγ Activation?
Do Fish Oil Omega-3 Fatty Acids Enhance Antioxidant Capacity and Mitochondrial Fatty Acid Oxidation in Human Atrial Myocardium via PPARγ Activation?
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DOI：
10.1089/ars.2014.5888
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发表时间：
2014-09-10
影响因子：
6.6
通讯作者：
Rodriguez, Evelio
中科院分区：
文献类型：
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作者：
Anderson, Ethan J.;Thayne, Kathleen A.;Rodriguez, Evelio
实验模型研究表明，n-3多不饱和脂肪酸（PUFAs）可改善心脏的代谢和抗炎/抗氧化能力，尽管其机制尚不清楚，也缺乏转化证据。在这项研究中，患者在择期心脏手术前2-3周摄入中等剂量的n-3 PUFAs （3.4 g/天二十碳五烯酸（EPA）和二十碳六烯酸（DHA）乙基酯）。治疗前及术中取血，术中解剖右心房心肌组织。与未经治疗的标准护理对照患者相比，接受n-3 pufa治疗的患者血液EPA水平升高，心肌组织EPA和DHA水平显著升高。有趣的是，n-3 PUFA患者有更大的过氧化物酶体增殖物激活受体γ (PPAR γ)的核交易激活，脂肪酸代谢基因表达，以及棕榈酰肉碱支持的心房心肌线粒体呼吸增强，尽管线粒体含量没有差异。n-3 PUFA患者的心肌组织也显示出更高的关键抗氧化/抗炎酶的表达和活性。这些发现导致我们假设PPAR γ激活是鱼油n-3 PUFAs增强人心房心肌线粒体脂肪酸氧化和抗氧化能力的机制，并且这种术前治疗方案可能是减轻心脏手术相关氧化/炎症应激的最佳方案。
Studies in experimental models suggest that n-3 polyunsaturated fatty acids (PUFAs) improve metabolic and anti-inflammatory/antioxidant capacity of the heart, although the mechanisms are unclear and translational evidence is lacking. In this study, patients ingested a moderately high dose of n-3 PUFAs (3.4 g/day eicosapentaenoic (EPA) and doxosahexaenoic acid (DHA) ethyl-esters) for a period of 2-3 weeks before having elective cardiac surgery. Blood was obtained before treatment and at the time of surgery, and myocardial tissue from the right atrium was also dissected during surgery. Blood EPA levels increased and myocardial tissue EPA and DHA levels were significantly higher in n-3 PUFA-treated patients compared with untreated, standard-of-care control patients. Interestingly, n-3 PUFA patients had greater nuclear transactivation of peroxisome proliferator-activated receptor-gamma (PPAR gamma), fatty acid metabolic gene expression, and enhanced mitochondrial respiration supported by palmitoyl-carnitine in the atrial myocardium, despite no difference in mitochondrial content. Myocardial tissue from n-3 PUFA patients also displayed greater expression and activity of key antioxidant/anti-inflammatory enzymes. These findings lead to our hypothesis that PPAR gamma activation is a mechanism by which fish oil n-3 PUFAs enhance mitochondrial fatty acid oxidation and antioxidant capacity in human atrial myocardium, and that this preoperative therapeutic regimen may be optimal for mitigating oxidative/inflammatory stress associated with cardiac surgery.