通过125I-碘苯基9-甲基十五烷酸（9MPA）评估脂肪酸代谢以及容量超负荷心脏中脂肪酸利用酶的表达。
Fatty acid metabolism assessed by 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded hearts.
作者信息
Miyamoto T, Takeishi Y, Tazawa S, Inoue M, Aoyama T, Takahashi H, Arimoto T, Shishido T, Tomoike H, Kubota I
机构信息
Yamagata University School of Medicine, Yamagata, Japan.
出版信息
Eur J Clin Invest. 2004 Mar;34(3):176-81. doi: 10.1111/j.1365-2362.2004.01312.x.
BACKGROUND
The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPARalpha and fatty acid oxidation enzymes in volume-overloaded rabbit hearts.
METHODS
Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. (125)I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by beta-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPARalpha and fatty acid oxidation enzymes were examined by Western blotting.
RESULTS
Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0.06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by beta-oxidation was faster than the sham-control hearts (P < 0.05). However, protein levels of PPARalpha and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits.
CONCLUSIONS
These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPARalpha and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli.
背景
过氧化物酶体增殖物激活受体（PPAR）α是核受体超家族的成员，可调节脂肪酸利用酶的基因表达。在压力超负荷导致的心肌肥厚和心力衰竭中，心肌能量利用恢复到胎儿模式，代谢底物从脂肪酸转变为葡萄糖。然而，容量超负荷心脏的心肌代谢尚未得到严格研究。本研究的目的是检测容量超负荷兔心脏中脂肪酸代谢以及PPARα和脂肪酸氧化酶的蛋白表达。
方法
通过颈总动脉-颈外静脉分流术诱导容量超负荷。假手术兔作为对照。慢性容量超负荷增加了左心室重量和心室腔大小，相对室壁厚度减小，表明为离心性心肌肥厚。静脉注射（125）I-碘苯基9-甲基十五烷酸（9MPA）后，在注射后5分钟处死动物。9MPA通过β氧化迅速代谢为碘苯基-3-甲基壬酸（3MNA）。采用Folch法从心肌中提取脂质，通过薄层色谱法测定代谢物的放射性分布。从左心室心肌中提取蛋白质，通过蛋白质免疫印迹法检测PPARα和脂肪酸氧化酶的水平。
结果
分流组兔心肌中9MPA的分布比假手术组更不均匀（P = 0.06）。在分流导致的容量超负荷心脏中，9MPA通过β氧化转化为3MNA的速度比假手术对照组心脏更快（P < 0.05）。然而，与假手术组兔相比，分流组兔PPARα和脂肪酸利用酶的蛋白水平没有变化。
结论
这些数据表明，容量超负荷导致的离心性心肌肥厚中，心肌脂肪酸代谢增强，而PPARα和脂肪酸利用酶的蛋白表达没有变化。我们的数据可能为响应机械刺激的心脏重塑病理过程的亚细胞机制提供新的见解。
Zotero 插件