Ghosh Sanjoy, Kewalramani Girish, Yuen Gloria, Pulinilkunnil Thomas, An Ding, Innis Sheila M, Allard Michael F, Wambolt Richard B, Qi Dake, Abrahani Ashraf, Rodrigues Brian
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
Free Radic Biol Med. 2006 Nov 1;41(9):1413-24. doi: 10.1016/j.freeradbiomed.2006.07.021. Epub 2006 Aug 4.
Increased awareness of obesity has led to a dietary shift toward "heart-friendly" vegetable oils containing omega-6 polyunsaturated fatty acid (omega-6 PUFA). In addition to its beneficial effects, omega-6 PUFA also exhibits proinflammatory and prooxidative properties. We hypothesized that chronic dietary omega-6 PUFA can induce free radical generation, predisposing the cardiac mitochondria to oxidative damage. Male Wistar rats were fed a diet supplemented with 20% w/w sunflower oil, rich in omega-6 PUFA (HP) or normal laboratory chow (LP) for 4 weeks. HP feeding augmented phospholipase A(2) activity and breakdown of cardiolipin, a mitochondrial phospholipid. HP hearts also demonstrated elevated inducible nitric oxide synthase expression, loss of Mn superoxide dismutase, and increased mitochondrial nitrotyrosine levels. In these hearts, oxidative damage to mitochondrial DNA (mDNA) was demonstrated by 8-hydroxyguanosine immunopositivity, overexpression of DNA repair enzymes, and a decrease in the mRNA expression of specific respiratory subunits encoded by the mDNA. Functionally, at higher workloads, HP hearts also demonstrated a greater decline in cardiac work than LP, suggesting a compromised mitochondrial reserve. Our study, for the first time, demonstrates that consumption of a high fat diet rich in omega-6 PUFA for only 4 weeks instigates mitochondrial nitrosative damage and causes cardiac dysfunction at high afterloads.
对肥胖问题认识的提高促使人们在饮食上转向富含ω-6多不饱和脂肪酸（ω-6 PUFA）的“有益心脏健康”的植物油。除了有益作用外，ω-6 PUFA还具有促炎和促氧化特性。我们推测，长期饮食摄入ω-6 PUFA会诱导自由基生成，使心脏线粒体易受氧化损伤。将雄性Wistar大鼠分为两组，一组喂食富含ω-6 PUFA的20%（w/w）向日葵油补充饲料（HP组），另一组喂食正常实验室饲料（LP组），持续4周。喂食HP饲料会增加磷脂酶A2活性以及心磷脂（一种线粒体磷脂）的分解。HP组大鼠的心脏还表现出诱导型一氧化氮合酶表达升高、锰超氧化物歧化酶缺失以及线粒体硝基酪氨酸水平增加。在这些心脏中，线粒体DNA（mDNA）的氧化损伤通过8-羟基鸟苷免疫阳性、DNA修复酶的过表达以及mDNA编码的特定呼吸亚基mRNA表达的降低得以证实。在功能方面，在更高的工作负荷下，HP组心脏的心脏功能下降幅度也比LP组更大，这表明线粒体储备功能受损。我们的研究首次表明，仅4周的富含ω-6 PUFA的高脂肪饮食摄入就会引发线粒体亚硝化损伤，并在高后负荷情况下导致心脏功能障碍。
