A Novel Role for Brown Adipose Tissue Enhance Heart Function and Metabolism

棕色脂肪组织增强心脏功能和新陈代谢的新作用

• 批准号: 9367824
• 负责人: Kristin I Stanford
• 金额: $ 39.3万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9367824
• 关键词: Acute; Adipose tissue; Affect; Biology; Brown Fat; Cardiac; Cardiac Myocytes; Cardiac health; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Cells; Cessation of life; Chemicals; Communication; Comorbidity; Data; Development; Disease; Echocardiography; Endocrine; Energy Metabolism; Excision; Exercise; Fatty Acids; Gene Expression; Glucose; Goals; Health; Heart; Heart Rate; Human; Incidence; Injection of therapeutic agent; Left; Lipids; Mediating; Metabolic; Metabolism; Mitochondria; Molecular Profiling; Mus; Muscle Cells; Myocardial; Myocardial Infarction; Obesity; Oxygen Consumption; Physical Exercise; Physiologic intraventricular pressure; Physiology; Plasma; Play; Research Proposals; Risk; Rodent; Role; Signal Transduction; Testing; Therapeutic; Tissue Transplantation; Tissues; Transplantation; United States; Ventricular; Wild Type Mouse; Woman; combat; exercise training; glucose uptake; heart function; heart metabolism; human subject; improved; in vivo; innovation; men; novel; novel therapeutic intervention; novel therapeutics; oxidation; pressure; protective effect; response; tool; uptake

PROJECT SUMMARY/ABSTRACT Cardiovascular disease (CVD) is the leading cause of death in both men and women. The increasing rates of CVD have increased the importance of elucidating potential therapeutic treatments for this disease. Brown adipose tissue (BAT) is a thermogenic tissue that contains large amounts of mitochondria to dissipate chemical energy as heat. BAT has a high capacity for both glucose and lipid oxidation, making BAT a potential target to decrease plasma glucose and lipids and to protect against obesity and it's co-morbidities, including CVD. Increasing the amount of BAT by transplantation improves metabolic health, reduces adiposity, and improves heart function by increasing glucose uptake into the heart and providing a protective effect against experimentally-induced myocardial infarction. Exercise is a well-established therapeutic tool to improve overall heart health, and can also influence BAT activity. Our preliminary data demonstrate that exercise affects BAT activity by altering the BAT lipidome, specifically by increasing the signaling lipid 12,13-diHOME. Injection of this lipid into mice has a direct effect on the heart, increasing heart rate and left ventricular pressure. Taken together, our exciting preliminary data show that 1) transplantation of BAT increases glucose uptake into the heart; 2) exercise-training alters the lipid profile of BAT and increases the signaling lipid 12,13-diHOME; 3) injection of 12,13-diHOME in mice directly affects heart function; and 4) 12,13-diHOME is significantly increased after acute exercise in humans. These intriguing findings raise the possibility that BAT is involved in tissue-tissue communication affecting the heart. Here, we will test the novel paradigm that BAT exerts endocrine effects on the heart with three specific aims: 1) Determine if BAT exerts endocrine effects on the heart; 2) Determine if 12,13-diHOME is responsible for BAT-induced endocrine effect on the heart; and 3) Determine the mechanism through which 12,13-diHOME increases ventricular cardiomyocyte function and metabolism. This project will establish if BAT enhances heart function and metabolism, and specifically the role of the lipid 12,13-diHOME, which is released from BAT in response to exercise in both humans and rodents. The proposed studies have the potential to elucidate novel BAT-induced signaling lipids that affect the heart, which could be a new therapeutic approach to combat CVD. .

项目摘要/摘要 心血管疾病（CVD）是男女死亡的主要原因。率的增加 CVD提高了阐明该疾病潜在治疗治疗的重要性。棕色的 脂肪组织（BAT）是一种热组织，其中包含大量线粒体散发化学的线粒体 能量作为热量。 BAT具有葡萄糖和脂质氧化的高容量，使BAT成为潜在的目标 减少血浆葡萄糖和脂质，并预防肥胖症及其合并症，包括CVD。 通过移植增加蝙蝠的量可改善代谢健康，降低肥胖并改善 通过增加葡萄糖吸收心脏并提供保护作用，从而产生心脏功能 实验引起的心肌梗塞。运动是一种完善的治疗工具，可以改善整体 心脏健康，也会影响蝙蝠活动。我们的初步数据表明锻炼会影响蝙蝠 通过改变BAT脂肪组的活性，特别是通过增加信号脂质12,13-dihome的活性。注射 将这种脂质直接影响到心脏，增加心率和左心压。拍摄 我们令人兴奋的初步数据共同表明1）蝙蝠的移植会增加葡萄糖的吸收 心; 2）运动训练改变了蝙蝠的脂质谱并增加信号脂质12,13-dihome； 3） 在小鼠中注射12,13-dihome直接影响心脏功能； 4）12,13-Dihome显着 人类急性运动后增加。这些有趣的发现增加了蝙蝠参与的可能性 组织组织的沟通影响心脏。在这里，我们将测试蝙蝠施加的新颖范式 内分泌对心脏的影响有三个特定目的：1）确定蝙蝠是否对内分泌作用对 心; 2）确定12,13-Dihome是否负责蝙蝠引起的内分泌对心脏的影响； 3） 确定12,13-Dihome增加心室心肌细胞功能和 代谢。该项目将确定BAT是否增强了心脏功能和代谢，尤其是角色 在人类和啮齿动物的运动中，脂质12,13-dihome均从蝙蝠中释放出来。 拟议的研究有可能阐明影响心脏的新型BAT诱导的信号传导脂质， 这可能是对抗CVD的一种新的治疗方法。 。