Epigenetic signaling, pathological cardiac hypertrophy and Western diet

项目说明/摘要 过量食用西式饮食(WD)是临床症状发展的危险因素 比如心脏功能不全和肥胖。长期摄入这类食物会导致心肌病 收缩功能障碍和代谢紊乱，包括肥胖和糖尿病。同时， 病理性疾病，如肥胖、胰岛素抵抗和糖尿病，可能导致这种有害的疾病。 心中的环境。 因此，WD对心脏紊乱的研究大多与以下因素密切相关 糖尿病和肥胖心肌病的研究由于它们之间的天然联系和重叠。因为. 这种疾病的复杂性，最初触发心脏紊乱的分子信号 代谢综合征的研究相对较少，在该领域仍然是一个挑战。 在临床情况下，患者在心脏疾病发生前有一个相对的“健康期”(亚临床)。 过量摄入WD后的功能障碍和代谢综合征。的签名配置文件 在这个亚临床期，心脏中的有害分子信号在很大程度上仍然未知，因为明显的 人类研究中的挑战。 高碳水化合物和富含脂肪酸的饮食通常与肥胖的主要原因相似 西方世界。虽然没有富含脂肪酸的高碳水化合物饮食可以完全模仿 在人类饲料动物模型中，WD饲料已被很好地表征并广泛应用于各种动物研究。 由于长期的WD会导致肥胖、糖尿病、心力衰竭，甚至伴随冠状动脉 为了探索早期的表观遗传信号，研究人员选择了短期的WD喂养 这些全球慢性综合征的共病。 动物模型包括心脏特异的基因敲除和心脏特异的基因过度表达 转基因小鼠。这项建议的机械性发现应该会产生临床意义， 为今后的药理翻译和预防奠定基础。

PROJECT DESCRIPTION/ABSTRACT Excessive consumption of Western diet (WD) is a risk factor for the development of clinical syndromes such as cardiac dysfunction and obesity. Long-term intake of this type of food can cause cardiomyopathy with contractile dysfunction and metabolic disorders including obesity and diabetes mellitus. Meanwhile, pathological disorders such as obesity, insulin resistance, and diabetes mellitus can elicit this harmful environment in the heart. Therefore, the majority of the studies on cardiac derangement by WD have been closely associated with diabetes and obesity cardiomyopathy investigations due to their natural connection and overlap. Because of this complexity of the disease, the initial molecular signaling that triggers cardiac derangement preceding metabolic syndromes is relatively understudied and remains a challenge in the field. In clinical scenario, patients have a relative “healthy period” (subclinical) prior to the occurrence of cardiac dysfunction and metabolic syndromes after excessive consumption of WD. The signature profiles of deleterious molecular signaling in the heart in this subclinical period remains largely unknown due to obvious challenges in human studies. A high carbohydrate and fatty acid-enriched diet is generally akin to the major cause of obesity in the Western world. While there is no fatty acid-enriched, high carbohydrate diet that could exactly mimic the human diet in animal models, WD feed has been well characterized and widely used in various animal studies. Since long-term WD causes obesity, diabetes mellitus, heart failure and even concomitant coronary artery disease, the investigators chose short-term WD feeding in order to explore early epigenetic signaling without comorbidity of these global chronic syndromes. The animal models include a heart specific knockout as well as a heart specific genetic overexpression transgenic mice. The mechanistic findings from this proposal should result in clinical implications, which provide a foundation for future pharmacological translation and prevention.