Epigenetic signaling, pathological cardiac hypertrophy and Western diet

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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.