• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>other >Altered Myocardial Metabolic Adaptation to Increased Fatty Acid Availability in Cardiomyocyte-Specific CLOCK Mutant Mice
【2h】

Altered Myocardial Metabolic Adaptation to Increased Fatty Acid Availability in Cardiomyocyte-Specific CLOCK Mutant Mice

机译：改变心肌代谢适应性增加特定心肌细胞时钟突变小鼠的脂肪酸利用率

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9 weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability.
机译：脂肪酸利用率与利用率之间的不匹配会导致心脏代谢疾病（例如肥胖症，糖尿病）出现细胞/器官功能障碍。这会加剧心脏功能障碍。心脏在转录，翻译，翻译后和代谢水平上适应增加的脂肪酸利用率，从而减弱心肌病的发展。先前我们已经报道了心肌细胞昼夜节律调节心脏对脂肪酸可利用性的急剧增加（例如，短期禁食）的转录反应性。本研究的目的是研究心肌细胞昼夜节律时钟是否在心脏适应脂肪酸可利用性的慢性升高中发挥作用。在不依赖时间（链脲佐菌素（STZ）诱导的糖尿病）和依赖（高脂饮食喂养）的情况下，心肌特异性CLOCK突变体（CCM）和野生型（WT）同窝小鼠的脂肪酸利用率增加了9周）的举止。发现心肌代谢适应症（例如，底物依赖扰动）对STZ诱导的糖尿病和高脂膳食喂养的指数取决于基因型。研究了各种转录和翻译后机制，发现在STZ诱导的糖尿病期间心脏中Cte1 mRNA的诱导在CCM心脏中减弱。在功能水平上，与CCM小鼠相比，每日依赖时间的高脂膳食喂养倾向于在更大程度上影响心脏功能。总的来说，这些数据表明，CLOCK（昼夜节律时钟成分）对于心脏的代谢适应于脂肪酸可利用时间的延长很重要。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号