Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function.
Increased fatty acid oxidation enzyme activity in the hearts of mice fed a high fat diet does not correlate with improved cardiac contractile function.
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喂养高脂肪饮食的小鼠心脏中脂肪酸氧化酶的活性与改善心脏收缩功能无关。
DOI：
10.1016/j.crphys.2020.11.001
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发表时间：
2020-12
影响因子：
--
通讯作者：
Scott I
中科院分区：
文献类型：
--
作者：
Thapa D;Manning JR;Mushala BAS;Stoner MW;Zhang M;Scott I
线粒体蛋白乙酰化状态的变化与许多组织代谢功能障碍的发生有关。据报道，肥胖小鼠的心脏中赖氨酸乙酰化增加，并且与燃料代谢、氧化还原状态和线粒体氧化磷酸化的变化有关。在这项研究中，我们检查了饮食诱导的线粒体酰基辅酶A脱氢酶乙酰化变化是否影响肥胖小鼠心脏中的脂肪酸氧化酶活性和收缩功能。野生型小鼠长期摄入高脂肪饮食会导致短链和长链酰基辅酶A脱氢酶SCAD和LCAD过度乙酰化，这与其体外酶活性增加相关。在相同的饮食过量条件下，心肌细胞特异性删除线粒体乙酰转移酶相关蛋白 GCN5L1 可防止这些酶的过度乙酰化和活性增加。尽管有可能增加心脏脂肪酸氧化活性，但野生型小鼠在暴露于高脂肪饮食后并未表现出心肌收缩力的任何增加。我们的结论是，脂肪酸氧化活性升高的潜在能量益处不足以抵消高脂肪饮食对心脏功能的各种有害影响。暴露于高脂肪饮食会增加心脏脂肪酸氧化酶检测到的赖氨酸乙酰化水平。心脏中的超乙酰化脂肪酸氧化酶在体外表现出较高的活性。暴露于高脂肪饮食的心脏中乙酰化的增加取决于线粒体乙酰转移酶蛋白 GCN5L1。体外脂肪酸氧化酶活性与高脂肪饮食喂养小鼠的心脏收缩功能不相关。
Changes in the acetylation status of mitochondrial proteins have been linked to the development of metabolic dysfunction in a number of tissues. Increased lysine acetylation has been reported in the hearts of obese mice, and is associated with changes in fuel metabolism, redox status, and mitochondrial oxidative phosphorylation. In this study, we examined whether diet-induced changes in the acetylation of mitochondrial acyl-CoA dehydrogenases affected fatty acid oxidation enzyme activity and contractile function in the obese mouse heart. Exposure to a long-term high fat diet in wildtype mice led to the hyperacetylation of short- and long-chain acyl-CoA dehydrogenases SCAD and LCAD, which correlated with their increased enzymatic activity in vitro. Cardiomyocyte-specific deletion of the mitochondrial acetyltransferase-related protein GCN5L1 prevented both the hyperacetylation and increased activity of these enzymes under the same conditions of dietary excess. Despite the potential for increased cardiac fatty acid oxidation activity, wildtype mice did not display any increase in cardiac contractility following exposure to a high fat diet. We conclude that the potential energetic benefits of elevated fatty acid oxidation activity are not sufficient to counter the various deleterious effects of a high fat diet on cardiac function. Exposure to a high fat diet increases the levels of lysine acetylation detected on cardiac fatty acid oxidation enzymes. Hyperacetylated fatty acid oxidation enzymes in the heart display increased rates of activity in vitro. Increased acetylation in high fat diet-exposed hearts is dependent on the mitochondrial acetyltransferase protein GCN5L1. In vitro fatty acid oxidation enzyme activity does not correlate with cardiac contractile function in high fat diet fed mice.
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影响因子：
16
作者：
Hirschey MD;Shimazu T;Jing E;Grueter CA;Collins AM;Aouizerat B;Stančáková A;Goetzman E;Lam MM;Schwer B;Stevens RD;Muehlbauer MJ;Kakar S;Bass NM;Kuusisto J;Laakso M;Alt FW;Newgard CB;Farese RV Jr;Kahn CR;Verdin E
通讯作者：
Verdin E
影响因子：
16.6
作者：
Wang L;Scott I;Zhu L;Wu K;Han K;Chen Y;Gucek M;Sack MN
通讯作者：
Sack MN
DOI：
10.1042/bj20120118
发表时间：
2012-05-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Scott I;Webster BR;Li JH;Sack MN
通讯作者：
Sack MN
DOI：
10.1074/jbc.ac118.005462
发表时间：
2018-11-16
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Thapa D;Wu K;Stoner MW;Xie B;Zhang M;Manning JR;Lu Z;Li JH;Chen Y;Gucek M;Playford MP;Mehta NN;Harmon D;O'Doherty RM;Jurczak MJ;Sack MN;Scott I
通讯作者：
Scott I
影响因子：
20.1
作者：
Davidson, Michael T.;Grimsrud, Paul A.;Lai, Ling;Draper, James A.;Fisher-Wellman, Kelsey H.;Narowski, Tara M.;Abraham, Dennis M.;Koves, Timothy R.;Kelly, Daniel P.;Muoio, Deborah M.
通讯作者：
Muoio, Deborah M.