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首页> 外文期刊>Cardiovascular therapeutics >Trimetazidine Reduces Endogenous Free Fatty Acid Oxidation and Improves Myocardial Efficiency in Obese Humans
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Trimetazidine Reduces Endogenous Free Fatty Acid Oxidation and Improves Myocardial Efficiency in Obese Humans

机译：曲美他嗪减少肥胖人类的内源性游离脂肪酸氧化并提高心肌效率

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Introduction: The metabolic modulator trimetazidine (TMZ) has been suggested to induce a metabolic shift from myocardial fatty acid oxidation (FAO) to glucose utilization, but this mechanism remains unproven in humans. The oxidation of plasma derived FA is commonly measured in humans, whereas the contribution of FA from triglycerides stored in the myocardium has been poorly characterized. Aims: To verify the hypothesis that TMZ induces a metabolic shift, we combined positron emission tomography (PET) and magnetic resonance spectroscopy (1H-MRS) to measure myocardial FAO from plasma and intracellular lipids, and myocardial glucose metabolism. Nine obese subjects were studied before and after 1 month of TMZ treatment. Myocardial glucose and FA metabolism were assessed by PET with 18F-fluorodeoxyglucose and 11C-palmitate. 1H-MRS was used to measure myocardial lipids, the latter being integrated into the PET data analysis to quantify myocardial triglyceride turnover. Results: Myocardial FAO derived from intracellular lipids was at least equal to that of plasma FAs (P= NS). BMI and cardiac work were positively associated with the oxidation of plasma derived FA (P≤ 0.01). TMZ halved total and triglyceride-derived myocardial FAO (32.7 ± 8.0 to 19.6 ± 4.0 μmol/min and 23.7 ± 7.5 to 10.3 ± 2.7 μmol/min, respectively; P≤ 0.05). These changes were accompanied by increased cardiac efficiency since unchanged LV work (1.6 ± 0.2 to 1.6 ± 0.1 Watt/g × 102, NS) was associated with decreased work energy from the intramyocardial triglyceride oxidation (1.6 ± 0.5 to 0.4 ± 0.1 Watt/g × 102, P= 0.036). Conclusions: In obese subjects, we demonstrate that myocardial intracellular triglyceride oxidation significantly provides FA-derived energy for mechanical work. TMZ reduced the oxidation of triglyceride-derived myocardial FAs improving myocardial efficiency.
机译：简介：有人建议使用代谢调节剂曲美他嗪（TMZ）引起从心肌脂肪酸氧化（FAO）到葡萄糖利用的新陈代谢转变，但是这种机制在人类中仍未被证实。血浆衍生的FA的氧化通常在人体中进行测量，而心肌中储存的甘油三酸酯对FA的贡献却很差。目的：为了验证TMZ引起代谢转移的假说，我们结合了正电子发射断层扫描（PET）和磁共振波谱（1H-MRS）来从血浆和细胞内脂质以及心肌葡萄糖代谢来测量心肌FAO。在9个月的TMZ治疗前后对9名肥胖受试者进行了研究。用18 F-氟脱氧葡萄糖和11 C-棕榈酸酯通过PET评估心肌葡萄糖和FA代谢。 1H-MRS用于测量心肌脂质，后者被整合到PET数据分析中以量化心肌甘油三酸酯的转化率。结果：源自细胞内脂质的心肌FAO至少等于血浆FAs（P = NS）。 BMI和心脏工作与血浆衍生FA的氧化呈正相关（P≤0.01）。 TMZ将总的和甘油三酸酯来源的心肌FAO减半（分别为32.7±8.0至19.6±4.0μmol/ min和23.7±7.5至10.3±2.7μmol/ min;P≤0.05）。这些变化伴随着心脏效率的提高，因为不变的左室功（1.6±0.2至1.6±0.1瓦特/克×102，NS）与心肌内甘油三酸酯氧化所产生的工作能量降低有关（1.6±0.5至0.4±0.1瓦特/克） ×102，P = 0.036）。结论：在肥胖的受试者中，我们证明了心肌细胞内甘油三酸酯氧化显着提供了FA衍生的能量用于机械功。 TMZ减少了甘油三酸酯衍生的心肌FA的氧化，提高了心肌效率。

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