Analysis of liver metabolism in a rat model of heart failure
Analysis of liver metabolism in a rat model of heart failure
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DOI：
10.1016/j.ijcard.2011.07.056
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发表时间：
2012-11-29
影响因子：
3.5
通讯作者：
Shioi, Tetsuo
中科院分区：
文献类型：
--
作者：
Kato, Takao;Niizuma, Shinichiro;Shioi, Tetsuo
背景：恶病质，即身体消瘦，是充血性心力衰竭（CHF）病例的常见并发症。尽管神经体液和免疫异常与该病有关，但分解代谢和合成代谢的不平衡究竟如何导致消耗过程尚不清楚。方法：我们分析了 Dahl 盐敏感大鼠的恶病质标志物，这些大鼠在 11 周龄时显示出明显的高血压，但收缩功能保留，在 17-19 周龄时显示出 CHF。我们还分析了与 CHF 相关的肝脏代谢变化，因为肝脏在分解代谢和合成代谢的系统调节中起着核心作用。 结果：在 CHF 大鼠中，观察到生长障碍，血液肝蛋白水平降低，与血液促炎细胞因子水平增加相关，表明 Dahl 大鼠可作为心脏恶病质的模型。食物摄入量减少，血糖和胰岛素水平降低。尽管处于明显的禁食状态，但血液脂肪酸水平降低，甘油三酯水平升高。 CHF大鼠肝脏摄入葡萄糖较多，糖异生相关基因表达减少，脂肪生成相关基因表达增加，肝脏甘油三酯含量增加。禁食大鼠中甘油三酯合成的反常产生与肝脏促炎症反应有关。结论：Dahl盐敏感大鼠可用作心脏恶病质的模型。恶病质与肝脏代谢异常有关，这可能是 CHF 进展过程中的一种适应不良反应。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
Background: Cachexia, namely body wasting, is a common complication in cases of congestive heart failure (CHF). Although, neurohumoral and immune abnormalities are associated with the condition, precisely how the imbalance of catabolism and anabolism is responsible for the wasting process is not known.Methods: We analyzed markers of cachexia in Dahl salt-sensitive rats which show marked hypertension with preserved systolic function at 11 weeks and CHF at 17-19 weeks of age. We also analyzed the change in hepatic metabolism associated with CHF since liver plays a central role in the systemic regulation of catabolism and anabolism.Results: In CHF rats, a failure to grow was observed and blood hepatic protein levels were decreased associated with increased blood proinflammatory cytokine levels, indicating that Dahl rats serve as a model of cardiac cachexia. Food intake was reduced, and blood sugar and insulin levels were decreased. Despite the apparent fasting condition, blood fatty acid levels were decreased and triglycerides levels were increased. In CHF rats, liver incorporated more glucose, the gene expression related to gluconeogenesis was decreased, the gene expression related to lipogenesis was increased, and the triglyceride content of the liver was increased. The paradoxical production of triglycerides synthesis in fasting rats was associated with a proinflammatory response in liver.Conclusions: The Dahl salt-sensitive rat can be used as a model of cardiac cachexia. The cachexia was associated with abnormal hepatic metabolism that might work as a maladaptive response during the progression of CHF. (C) 2011 Elsevier Ireland Ltd. All rights reserved.