Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes
Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes
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DOI：
10.1016/j.bbalip.2016.03.020
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发表时间：
2016-10-01
影响因子：
4.8
通讯作者：
Lopaschuk, Gary D.
中科院分区：
文献类型：
--
作者：
Fukushima, Arata;Lopaschuk, Gary D.
肥胖和糖尿病是主要的公共健康问题，与心力衰竭的发展有关。新的数据强调了心脏能量代谢改变的重要性，它是与肥胖和糖尿病相关的心脏功能障碍的主要因素。脂肪酸氧化速率的增加和葡萄糖利用率的降低是肥胖和糖尿病患者心脏能量代谢的两个显著变化。这种代谢特征可能既是心脏胰岛素抵抗的原因，也是心脏胰岛素抵抗的结果，它伴随着心脏功能和效率的下降，以及心脏中潜在有毒脂质代谢物的积累，这可能进一步加剧胰岛素抵抗和心脏功能障碍。肥胖和糖尿病患者的高心脏脂肪酸氧化率可归因于几个因素，包括：1)增加了对心肌细胞的脂肪酸供应和摄取，2)增加了脂肪酸代谢酶的转录，3)减少了对线粒体脂肪酸摄取和脂肪酸氧化的变构控制，以及4)增加了对各种脂肪酸氧化酶的翻译后乙酰化控制。新出现的证据表明，旨在将心脏能量底物偏好的平衡从脂肪酸氧化转变为葡萄糖使用的治疗方法可以预防与肥胖和糖尿病相关的心功能障碍。调节脂肪酸氧化酶的乙酰化控制也是一个潜在的有吸引力的策略，尽管目前这仅限于烟酰胺腺嘌呤的前体或脱乙酰化的非特异性激活剂，如白藜芦醇。这篇综述将集中在肥胖和糖尿病时心脏的代谢变化，以及控制这些代谢变化的分子机制。本文是G.D.Lopaschuk编辑的题为：心脏类脂代谢特刊的一部分。(C)2016爱思唯尔B.V.保留所有权利。
Obesity and diabetes are major public health problems, and are linked to the development of heart failure. Emerging data highlight the importance of alterations in cardiac energy metabolism as a major contributor to cardiac dysfunction related to obesity and diabetes. Increased rates of fatty acid oxidation and decreased rates of glucose utilization are two prominent changes in cardiac energy metabolism that occur in obesity and diabetes. This metabolic profile is probably both a cause and consequence of a prominent cardiac insulin resistance, which is accompanied by a decrease in both cardiac function and efficiency, and by the accumulation of potentially toxic lipid metabolites in the heart that can further exaggerate insulin resistance and cardiac dysfunction. The high cardiac fatty acid oxidation rates seen in obesity and diabetes are attributable to several factors, including: 1) increased fatty acid supply and uptake into the cardiomyocyte, 2) increased transcription of fatty acid metabolic enzymes, 3) decreased allosteric control of mitochondrial fatty acid uptake and fatty acid oxidation, and 4) increased post-translational acetylation control of various fatty acid oxidative enzymes. Emerging evidence suggests that therapeutic approaches aimed at switching the balance of cardiac energy substrate preference from fatty acid oxidation to glucose use can prevent cardiac dysfunction associated with obesity and diabetes. Modulating acetylation control of fatty acid oxidative enzymes is also a potentially attractive strategy, although presently this is limited to precursors of nicotinamide adenine or nonspecific activators of deacetylation such as resveratrol. This review will focus on the metabolic alterations in the heart that occur in obesity and diabetes, as well as on the molecular mechanisms controlling these metabolic changes. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. (C) 2016 Elsevier B.V. All rights reserved.