The absence of endogenous lipid oxidation in early stage heart failure exposes limits in lipid storage and turnover
The absence of endogenous lipid oxidation in early stage heart failure exposes limits in lipid storage and turnover
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DOI：
10.1016/j.yjmcc.2007.11.006
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发表时间：
2008-02-01
影响因子：
5
通讯作者：
Lewandowski, E. Douglas
中科院分区：
文献类型：
--
作者：
O'Donnell, J. Michael;Fields, Aaron D.;Lewandowski, E. Douglas
压力过载引起的心力衰竭的心肌内脂质处理仍然知之甚少，线粒体ATP产生的内源性和外源性脂质利用之间的平衡基本上是未知的。在这项研究中，我们确定了内源性三酰甘油（TAG）对线粒体氧化的贡献，相对于外源性棕榈酸盐、葡萄糖和内源性糖原在衰竭、压力过载的大鼠心脏中的作用。还评估TAG含量和周转率，以确定脂质可用性和流动性是否改变。用C-13标记的棕榈酸酯或葡萄糖对主动脉束带和假手术的Spraque-Dawley大鼠的完整心脏进行动态模式C-13核磁共振，以评估TAG的周转率和棕榈酸氧化率。棕榈酸酯、葡萄糖、糖原和TAG对线粒体ATP产生的部分贡献通过心脏提取物的核磁共振分析来确定。在HF中TAG氧化不明显，而在sham中TAG对氧化ATP产生的贡献是显著的。HF组TAG含量比假手术组低39%，TAG周转率比HE组低60%。在肾上腺素能刺激期间，HF组TAG源再次未被氧化。在早期心力衰竭中，内源性TAG氧化减少与碳水化合物氧化增加并行，外源性棕榈酸酯氧化没有变化。这一发现与TAG储存和动员减少一致。这些数据进一步阐明了中间质和脂质代谢在LVH进展到衰竭中的作用，并有助于将心肌底物使用中断与心肌病联系起来的新证据。(c) 2007爱思唯尔公司版权所有。
Intramyocardial lipid handling in pressure-overload-induced heart failure remains poorly understood, and the balance between endogenous and exogenous lipid utilization for mitochondrial ATP production is essentially unknown. In this study, we determined the contribution of endogenous triacylglycerols (TAG) to mitochondrial oxidation relative to that of exogenous palmitate, glucose, and endogenous glycogen in the failing, pressure-overloaded rat heart. TAG content and turnover were also assessed to determine if lipid availability and mobility were altered. Dynamic-mode C-13 NMR was performed in intact hearts from aortic banded and sham operated Spraque-Dawley rats perfused with C-13-labeled palmitate or glucose to assess TAG turnover rate and palmitate oxidation rate. The fractional contributions from palmitate, glucose, glycogen, and TAG to mitochondrial ATP production were determined from NMR analysis of heart extracts. TAG oxidation was not evident in HF, whereas the contribution of TAG to oxidative ATP production was significant in shams. TAG content was 39% lower in HF compared to sham, and TAG turnover rate was 60% lower in HE During adrenergic challenge, TAG sources were again not oxidized in the HF group. In early cardiac failure, endogenous TAG oxidation was reduced in parallel to increased carbohydrate oxidation, with no change in exogenous palmitate oxidation. This finding was consistent with reduced TAG storage and mobilization. These data further elucidate the role of intermediary and lipid metabolism in the progression of LVH to failure, and contribute to emerging evidence linking the disruption of myocardial substrate use to cardiomyopathies. (c) 2007 Elsevier Inc. All rights reserved.