向衰竭心脏提供的膳食脂肪决定了用于核受体激活和储存甘油三酯氧化的动态脂质信号传导。
Dietary fat supply to failing hearts determines dynamic lipid signaling for nuclear receptor activation and oxidation of stored triglyceride.
作者信息
Lahey Ryan, Wang Xuerong, Carley Andrew N, Lewandowski E Douglas
机构信息
From the Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, IL.
出版信息
Circulation. 2014 Nov 11;130(20):1790-9. doi: 10.1161/CIRCULATIONAHA.114.011687. Epub 2014 Sep 29.
BACKGROUND
Intramyocardial triglyceride (TG) turnover is reduced in pressure-overloaded, failing hearts, limiting the availability of this rich source of long-chain fatty acids for mitochondrial β-oxidation and nuclear receptor activation. This study explored 2 major dietary fats, palmitate and oleate, in supporting endogenous TG dynamics and peroxisome proliferator-activated receptor-α activation in sham-operated (SHAM) and hypertrophied (transverse aortic constriction [TAC]) rat hearts.
METHODS AND RESULTS
Isolated SHAM and TAC hearts were provided media containing carbohydrate with either (13)C-palmitate or (13)C-oleate for dynamic (13)C nuclear magnetic resonance spectroscopy and end point liquid chromatography/mass spectrometry of TG dynamics. With palmitate, TAC hearts contained 48% less TG versus SHAM (P=0.0003), whereas oleate maintained elevated TG in TAC, similar to SHAM. TG turnover in TAC was greatly reduced with palmitate (TAC, 46.7±12.2 nmol/g dry weight per min; SHAM, 84.3±4.9; P=0.0212), as was β-oxidation of TG. Oleate elevated TG turnover in both TAC (140.4±11.2) and SHAM (143.9±15.6), restoring TG oxidation in TAC. Peroxisome proliferator-activated receptor-α target gene transcripts were reduced by 70% in TAC with palmitate, whereas oleate induced normal transcript levels. Additionally, mRNA levels for peroxisome proliferator-activated receptor-γ-coactivator-1α and peroxisome proliferator-activated receptor-γ-coactivator-1β in TAC hearts were maintained by oleate. With these metabolic effects, oleate also supported a 25% improvement in contractility over palmitate with TAC (P=0.0202).
CONCLUSIONS
The findings link reduced intracellular lipid storage dynamics to impaired peroxisome proliferator-activated receptor-α signaling and contractility in diseased hearts, consistent with a rate-dependent lipolytic activation of peroxisome proliferator-activated receptor-α. In decompensated hearts, oleate may serve as a beneficial energy substrate versus palmitate by upregulating TG dynamics and nuclear receptor signaling.
背景
在压力超负荷的衰竭心脏中，心肌内甘油三酯（TG）周转减少，限制了这种丰富的长链脂肪酸来源用于线粒体β氧化和核受体激活。本研究探讨了两种主要膳食脂肪，棕榈酸酯和油酸酯，在支持假手术（SHAM）和肥大（横向主动脉缩窄 [TAC]）大鼠心脏内源性TG动态变化和过氧化物酶体增殖物激活受体-α激活方面的作用。
方法与结果
为分离的SHAM和TAC心脏提供含有碳水化合物以及（13）C-棕榈酸酯或（13）C-油酸酯的培养基，用于动态（13）C核磁共振波谱分析以及TG动态变化的终点液相色谱/质谱分析。对于棕榈酸酯，TAC心脏中的TG含量比SHAM心脏低48%（P = 0.0003），而油酸酯使TAC心脏中的TG维持在升高水平，与SHAM心脏相似。使用棕榈酸酯时，TAC心脏中的TG周转大幅降低（TAC，46.7±12.2 nmol/g干重每分钟；SHAM，84.3±4.9；P = 0.0212），TG的β氧化也降低。油酸酯使TAC（140.4±11.2）和SHAM（143.9±15.6）心脏中的TG周转均升高，恢复了TAC心脏中的TG氧化。在TAC心脏中，使用棕榈酸酯时过氧化物酶体增殖物激活受体-α靶基因转录本减少70%，而油酸酯诱导正常转录水平。此外，油酸酯维持了TAC心脏中过氧化物酶体增殖物激活受体-γ-辅激活因子-1α和过氧化物酶体增殖物激活受体-γ-辅激活因子-1β的mRNA水平。有了这些代谢效应，与棕榈酸酯相比，油酸酯还使TAC心脏的收缩力提高了25%（P = 0.0202）。
结论
这些发现将细胞内脂质储存动态变化的减少与患病心脏中过氧化物酶体增殖物激活受体-α信号传导受损及收缩力受损联系起来，这与过氧化物酶体增殖物激活受体-α的速率依赖性脂解激活一致。在失代偿心脏中，与棕榈酸酯相比，油酸酯可能通过上调TG动态变化和核受体信号传导而作为有益的能量底物。
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