Hauton David, Caldwell Germaine M
School of Clinical and Experimental Medicine, College of Medicinal and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
Biochim Biophys Acta. 2012 Apr;1821(4):627-36. doi: 10.1016/j.bbalip.2011.12.004. Epub 2011 Dec 29.
Cardiac hypertrophy is characterised by an imbalance between lipid uptake and fatty acid β-oxidation leading to an accumulation of lipids, particularly triacylglycerol (TAG). It is unclear whether uptake mechanisms such as lipoprotein lipase (LPL) can be attenuated to diminish this uptake. Rats were cold acclimated to induce cardiac hypertrophy and increase cardiac LPL. Lipid uptake and metabolism were altered by feeding a 'Western-style' high fat diet (WSD) or feeding oxfenicine (2g/L) in the drinking water. Diastolic stiffness (increased volume change/unit pressure change) was induced in hypertrophied hearts for rats fed WSD (P<0.05) or WSD+oxfenicine (P<0.01), although absolute performance of cardiac muscle, estimated from stress-strain calculations was unchanged. Cold acclimation increased cardiac endothelial LPL (P<0.05) but this was diminished following oxfenicine. Following WSD LPL was further decreased below WSD-fed control hearts (P<0.05) with no further decrease by oxfenicine supplementation. A negative correlation was noted between plasma TAG and endothelial LPL (correlation coefficient=-0.654; P<0.001) but not cardiac TAG concentration. Transcript levels of angiopoietin-like protein-4 (ANGPTL4) were increased 6-fold by WSD (P<0.05) and increased 15-fold following WSD+oxfenicine (P<0.001). For CA-hearts fed WSD or WSD+oxfenicine ANGPTL4 mRNA levels were preserved at chow-fed levels. VLDLR protein levels were increased 10-fold (P<0.01) by CA. ANGPTL4 protein levels were increased 2-fold (P<0.05) by WSD, but restored following oxfenicine. For CA-hearts WSD increased ANGPTL4 protein levels 3-fold (P<0.01) with WSD+oxfenicine increasing ANGPTL4 protein 4-fold (P<0.01). These data suggest that endothelial LPL levels in the heart are altered to maintain FA flux and may exploit ANGPTL4.
心脏肥大的特征是脂质摄取与脂肪酸β-氧化之间失衡，导致脂质尤其是三酰甘油（TAG）蓄积。目前尚不清楚脂蛋白脂肪酶（LPL）等摄取机制是否可以减弱以减少这种摄取。将大鼠进行冷驯化以诱导心脏肥大并增加心脏LPL。通过喂食“西式”高脂肪饮食（WSD）或在饮用水中添加奥芬尼辛（2g/L）来改变脂质摄取和代谢。对于喂食WSD（P<0.05）或WSD+奥芬尼辛（P<0.01）的大鼠，肥大心脏中诱导出舒张期僵硬度（单位压力变化时体积变化增加），尽管根据应力-应变计算估计的心肌绝对性能未改变。冷驯化增加了心脏内皮LPL（P<0.05），但在奥芬尼辛处理后这种增加减弱。喂食WSD后，LPL进一步低于喂食WSD的对照心脏（P<0.05），补充奥芬尼辛后未进一步降低。血浆TAG与内皮LPL之间存在负相关（相关系数=-0.654；P<0.001），但与心脏TAG浓度无关。血管生成素样蛋白4（ANGPTL4）的转录水平在WSD处理后增加了6倍（P<0.05），在WSD+奥芬尼辛处理后增加了15倍（P<0.001）。对于喂食WSD或WSD+奥芬尼辛的冷驯化心脏，ANGPTL4 mRNA水平维持在正常饮食喂养水平。CA使极低密度脂蛋白受体（VLDLR）蛋白水平增加了10倍（P<0.01）。WSD使ANGPTL4蛋白水平增加了2倍（P<0.05），但在奥芬尼辛处理后恢复。对于冷驯化心脏，WSD使ANGPTL4蛋白水平增加了3倍（P<0.01），WSD+奥芬尼辛使ANGPTL4蛋白水平增加了4倍（P<0.01）。这些数据表明，心脏中的内皮LPL水平发生改变以维持脂肪酸通量，并可能利用ANGPTL4。
