Cardiac lipid accumulation associated with diastolic dysfunction in obese mice
Cardiac lipid accumulation associated with diastolic dysfunction in obese mice
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DOI：
10.1210/en.2003-0242
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发表时间：
2003-08-01
期刊：
影响因子：
4.8
通讯作者：
Nielsen, LB
中科院分区：
文献类型：
--
作者：
Christoffersen, C;Bollano, E;Nielsen, LB
肥胖可能由于心肌细胞中的脂质积累而导致心脏功能障碍。为了验证这个想法，我们检查了肥胖的 ob/ob 小鼠是否表现出心脏脂质积累和心脏功能障碍。与ob/+小鼠相比，ob/ob小鼠心脏介导细胞外生成、跨肌细胞细胞膜运输、细胞内运输、线粒体摄取和脂肪酸β氧化的基因表达增加。因此，ob/ob小鼠心脏比ob/+小鼠心脏含有更多的甘油三酯（6.8+/-0.4对2.3+/-0.4μg/mg；P<0.0005）。组织学检查显示，与ob/+小鼠心脏相比，ob/ob中心肌细胞内中性脂滴显着积聚，但心肌细胞之间的胶原沉积并未增加。超声心动图显示，ob/ob 小鼠的 E 与 A 间质血流速度（舒张功能的指标）之比为 1.8 +/- 0.1，ob/+ 小鼠的 E 与 A 之比为 2.5 +/- 0.1（P = 0.0001）。相比之下，与ob/+小鼠相比，ob/ob小鼠的收缩功能指数和心脑钠尿肽mRNA表达分别仅受到轻微影响和不受影响。结果表明，ob/ob 小鼠心脏心脏基因产物的表达增加，这些基因产物刺激心肌细胞脂肪酸摄取和甘油三酯储存并在心肌细胞内积累中性脂质。结果还表明，ob/ob 小鼠的心脏脂质积累与心脏舒张功能障碍是平行的。
Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and beta-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 +/- 0.4 vs. 2.3 +/- 0.4 mug/mg; P < 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 +/- 0.1 in ob/ob mice and 2.5 +/- 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.