SYSTOLIC CARDIAC FUNCTION IN OBESITY AND EXERCISE

描述 （根据申请人摘要改编）候选人的近期职业目标是 研究β受体信号通路在介导心脏收缩功能中的作用， 肥胖症的功能障碍，以及运动训练在减轻肥胖症中的作用。 肥胖相关的心血管缺陷 综合部 北德克萨斯大学健康科学中心的生理学是独一无二的 帮助候选人实现这些目标。 在部门内部， 在人类、动物、体内和体外方面有各种各样的专业知识， 心血管生理学和内分泌学研究。 这将有助于 发展各种手术、实验室和化验方面的专业知识 研究心脏功能的技术。 此外，心血管研究 北德克萨斯大学健康科学中心的研究所提供 接触到分子生物学家、药理学家、 来自机构内部和附近的生理学家和医生 机构职能体系 这将通过提供机会而有利于职业发展 整合影响心血管研究的多个领域的知识。 目前的提案有三大目标：1）确定机制 与心脏收缩对β-肾上腺素能的反应性降低有关 刺激肥胖，2）以确定运动训练的作用， 减轻肥胖引起的心脏功能异常，以及3） 确定肥胖的作用，从高血压中分离出来， 久坐和训练过的动物的收缩功能障碍。 调查人员 假设有多个网站的活动减少，在β- 肥胖症的信号通路。 因此，他们将使用兔子的方法， 饮食诱导的肥胖，以比较瘦动物与肥胖动物的功能 高脂肪饮食12周后的动物。 他们会利用兰根多夫 分离的心脏制备和适当的测定和蛋白质印迹 技术来分析β-受体的作用和四个网站的后 受体活性导致肥胖症患者心脏异常。 的 研究人员还假设，在发育过程中， 肥胖症会减弱或预防肥胖相关的心血管疾病， 异常 他们将决定运动训练是否会1）减少 肥胖相关的高血压、静息心动过速和神经体液 激活，和2）减弱肥胖相关的反应性降低， β-肾上腺素能刺激他们将检查血液动力学和神经体液 体内激活，并使用离体心脏制备物来确定 运动训练在增强β-肾上腺素能反应性中的作用 刺激. 最后，他们假设肥胖有一个独立的影响， 心脏肥大和收缩功能障碍 他们会测试这个 通过在肥胖症发展时将血压维持在控制水平的假设 测试对β肾上腺素刺激的反应性 洞察力 肥胖增加充血性心力衰竭风险的机制 可能导致预防和治疗的治疗方式的进步， 肥胖患者的心力衰竭 关于行使人权的机制的资料 训练可以改善心血管风险状况和心脏性能， 肥胖可能有助于降低患心血管疾病的风险， 肥胖 因为美国人口中有这么大一部分是 超重或肥胖，从这些研究中获得的知识和见解可以 影响深远。

DESCRIPTION (Adapted from applicant's abstract) The candidate's immediate career goals are to study the role of the beta-receptor signaling pathway in mediating systolic dysfunction in obesity, and the role of exercise training in attenuating obesity-related cardiovascular defects. The Department of Integrative Physiology at the University of North Texas Health Science Center is uniquely suited to help the candidate achieve these goals. Within the department, there is a wide variety of expertise in human, animal, in vivo, and in vitro studies in cardiovascular physiology and endocrinology. This will aid in developing expertise with a variety of surgical, laboratory, and assay techniques to study cardiac function. Further, the Cardiovascular Research Institute at the University of North Texas Health Science Center provides access to research efforts of molecular biologists, pharmacologists, physiologists and physicians from within the institution and from nearby institutions. This will benefit career development by providing opportunities to integrate knowledge from many fields which impact cardiovascular research. The current proposal has three major goals: 1) to determine mechanisms associated with reduced cardiac contractile responsiveness to beta-adrenergic stimulation in obesity, 2) to determine the role of exercise training in attenuation of obesity-induced abnormalities in cardiac function, and 3) to determine the role of obesity, separate from hypertension, in contributing to systolic dysfunction in sedentary and trained animals. The investigators hypothesize that there are multiples sites of decreased activity in the beta- signaling pathway in obesity. Thus, they will use the rabbit method of dietary-induced obesity to compare function of lean animals with that of obese animals after 12 weeks of a high fat diet. They will use the Langendorff isolated heart preparation and appropriate assay and western blotting techniques to analyze the role of the beta-receptor and four sites of post- receptor activity in contributing to cardiac abnormalities in obesity. The investigators also hypothesize that exercise training during the development of obesity will attenuate or prevent obesity-related cardiovascular abnormalities. They will determine whether exercise training will 1) reduce obesity-related hypertension, resting tachycardia, and neurohumoral activation, and 2)attenuate obesity-related decreases in responsiveness to beta-adrenergic stimulation. They will examine hemodynamics and neurohumoral activation in vivo and use the isolated heart preparation to determine the role of exercise training in increasing responsiveness to beta-adrenergic stimulation. Finally, they hypothesize that obesity has an independent effect on cardiac hypertrophy and systolic dysfunction. They will test this hypothesis by maintaining blood pressure at control levels as obesity develops before testing for responsiveness to beta-adrenergic stimulation. Insight into mechanisms whereby obesity increases risk for congestive heart failure may lead to advances in therapeutic modalities for prevention and treatment of heart failure in obese patients. Information on mechanisms whereby exercise training may improve cardiovascular risk profile and cardiac performance in obesity may help reduce risk for development of cardiovascular diseases in obesity. Because such a large segment of the American population is overweight or obese, the knowledge and insight gained from these studies can have far-reaching effects.