High Dietary Fat Selectively Increases Catalase Expression within Cardiac Mitochondria
High Dietary Fat Selectively Increases Catalase Expression within Cardiac Mitochondria
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DOI：
10.1074/jbc.m112.412890
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发表时间：
2013-01-18
影响因子：
4.8
通讯作者：
Kinter, Michael
中科院分区：
文献类型：
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作者：
Rindler, Paul M.;Plafker, Scott M.;Kinter, Michael
肥胖是糖尿病和心血管疾病的前兆。肥胖的一个后果是血脂异常，其特征是血液中甘油三酯偏高。有人提出，氧化应激，由利用脂质作为能量，有助于这些疾病。内源性抗氧化酶网络可以减轻氧化应激的影响，但对其对高脂肪利用的反应知之甚少。我们的实验使用多重定量蛋白质组学方法来测量饮食性肥胖小鼠模型心脏组织中抗氧化酶的表达。该实验显示过氧化氢酶蛋白的快速和特异性上调，随后的分析显示活性和mRNA的增加。过氧化氢酶，传统上被认为是一种过氧化物酶体蛋白，被发现存在于心脏线粒体中，在高脂肪喂养期间其含量和活性显著增加。这些数据，再加上脂肪酸氧化增强线粒体H2O2产生的事实，表明需要局部过氧化氢酶的增加来消耗脂肪代谢增加产生的过量线粒体H2O2。为了确定过氧化氢酶特异性反应是否是增加血液甘油三酯和脂肪酸氧化的生理条件的共同特征，我们测量了禁食小鼠和喂食小鼠抗氧化剂表达的变化。事实上，在禁食24小时的小鼠中观察到类似的特异性过氧化氢酶增加。我们的研究结果表明，过氧化氢酶的表达受到调节，以防止损伤，同时保持h2o2介导的饮食成分感知，在短期内适当调节胰岛素敏感性，以优先考虑脂质代谢以完全利用。
Obesity is a predictor of diabetes and cardiovascular disease. One consequence of obesity is dyslipidemia characterized by high blood triglycerides. It has been proposed that oxidative stress, driven by utilization of lipids for energy, contributes to these diseases. The effects of oxidative stress are mitigated by an endogenous antioxidant enzyme network, but little is known about its response to high fat utilization. Our experiments used a multiplexed quantitative proteomics method to measure antioxidant enzyme expression in heart tissue in a mouse model of diet-induced obesity. This experiment showed a rapid and specific up-regulation of catalase protein, with subsequent assays showing increases in activity and mRNA. Catalase, traditionally considered a peroxisomal protein, was found to be present in cardiac mitochondria and significantly increased in content and activity during high fat feeding. These data, coupled with the fact that fatty acid oxidation enhances mitochondrial H2O2 production, suggest that a localized catalase increase is needed to consume excessive mitochondrial H2O2 produced by increased fat metabolism. To determine whether the catalase-specific response is a common feature of physiological conditions that increase blood triglycerides and fatty acid oxidation, we measured changes in antioxidant expression in fasted versus fed mice. Indeed, a similar specific catalase increase was observed in mice fasted for 24 h. Our findings suggest a fundamental metabolic process in which catalase expression is regulated to prevent damage while preserving an H2O2-mediated sensing of diet composition that appropriately adjusts insulin sensitivity in the short term as needed to prioritize lipid metabolism for complete utilization.