Rennison Julie H, McElfresh Tracy A, Chen Xiaoqin, Anand Vijay R, Hoit Brian D, Hoppel Charles L, Chandler Margaret P
Department of Physiology and Biophysics, School of Medicine E558, Case Western Reserve University, Cleveland, OH 44106-4970, USA.
J Mol Cell Cardiol. 2009 Jun;46(6):883-90. doi: 10.1016/j.yjmcc.2009.02.019. Epub 2009 Mar 3.
Previous studies have reported that elevated myocardial lipids in a model of mild-to-moderate heart failure increased mitochondrial function, but did not alter left ventricular function. Whether more prolonged exposure to high dietary lipids would promote a lipotoxic phenotype in mitochondrial and myocardial contractile function has not been determined. We tested the hypothesis that prolonged exposure to high dietary lipids, following coronary artery ligation, would preserve myocardial and mitochondrial function in heart failure. Rats underwent ligation or sham surgery and were fed normal (10% kcal fat) (SHAM, HF) or high fat diet (60% kcal saturated fat) (SHAM+FAT, HF+FAT) for sixteen weeks. Although high dietary fat was accompanied by myocardial tissue triglyceride accumulation (SHAM 1.47+/-0.14; SHAM+FAT 2.32+/-0.14; HF 1.34+/-0.14; HF+FAT 2.21+/-0.20 micromol/gww), fractional shortening was increased 16% in SHAM+FAT and 28% in HF+FAT compared to SHAM and HF, respectively. Despite increased medium-chain acyl-CoA dehydrogenase (MCAD) activity in interfibrillar mitochondria (IFM) of both SHAM+FAT and HF+FAT, dietary lipids also were associated with decreased state 3 respiration using palmitoylcarnitine (SHAM 369+/-14; SHAM+FAT 307+/-23; HF 354+/-13; HF+FAT 366+/-18 nAO min(-1) mg(-1)) in SHAM+FAT compared to SHAM and HF+FAT. State 3 respiration in IFM also was decreased in SHAM+FAT relative to SHAM using succinate and DHQ. In conclusion, high dietary lipids promoted myocardial lipid accumulation, but were not accompanied by alterations in myocardial contractile function typically associated with lipotoxicity. In normal animals, high dietary fat decreased mitochondrial respiration, but also increased MCAD activity. These studies support the concept that high fat feeding can modify multiple cellular pathways that differentially affect mitochondrial function under normal and pathological conditions.
先前的研究报道，在轻至中度心力衰竭模型中，心肌脂质升高可增强线粒体功能，但不会改变左心室功能。长期暴露于高膳食脂质是否会导致线粒体和心肌收缩功能出现脂毒性表型尚未确定。我们检验了以下假设：冠状动脉结扎后长期暴露于高膳食脂质可在心力衰竭中维持心肌和线粒体功能。大鼠接受结扎或假手术，并喂食正常（10%千卡脂肪）（假手术组、心力衰竭组）或高脂肪饮食（60%千卡饱和脂肪）（假手术+脂肪组、心力衰竭+脂肪组）16周。尽管高膳食脂肪伴随着心肌组织甘油三酯积累（假手术组1.47±0.14；假手术+脂肪组2.32±0.14；心力衰竭组1.34±0.14；心力衰竭+脂肪组2.21±0.20微摩尔/克湿重），但与假手术组和心力衰竭组相比，假手术+脂肪组的缩短分数增加了16%，心力衰竭+脂肪组增加了28%。尽管假手术+脂肪组和心力衰竭+脂肪组的肌原纤维间线粒体（IFM）中的中链酰基辅酶A脱氢酶（MCAD）活性均增加，但与假手术组和心力衰竭+脂肪组相比，膳食脂质也与使用棕榈酰肉碱时状态3呼吸的降低有关（假手术组369±14；假手术+脂肪组307±23；心力衰竭组354±13；心力衰竭+脂肪组366±18纳安·分钟-1·毫克-1）。与假手术组相比，假手术+脂肪组使用琥珀酸和二氢喹啉时IFM中的状态3呼吸也降低。总之，高膳食脂质促进了心肌脂质积累，但并未伴随通常与脂毒性相关的心肌收缩功能改变。在正常动物中，高膳食脂肪降低了线粒体呼吸，但也增加了MCAD活性。这些研究支持了高脂肪喂养可改变多种细胞途径的概念，这些途径在正常和病理条件下对线粒体功能有不同影响。
