Energy Expenditure in HIV Lipodystrophy

HIV 脂肪营养不良的能量消耗

• 批准号: 7581280
• 负责人: LISA A. KOSMISKI
• 金额: $ 30.12万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7581280
• 关键词: Adipose tissue; Adrenal Glands; Adult; Antioxidants; Atherosclerosis; Atrophic; Biological Markers; Body Composition; Calories; Carbohydrates; Cell physiology; Complication; Consumption; Coupled; DNA; Data; Diabetes Mellitus; Diet; Disease; Electron Microscopy; Energy Intake; Energy Metabolism; Enzymes; Epidemic; Fatty acid glycerol esters; Food; Free Radicals; Functional disorder; General Population; HIV; HIV Infections; HIV-Associated Lipodystrophy Syndrome; Heating; Hour; Hyperthyroidism; Hypertriglyceridemia; Insulin Resistance; Lead; Lipids; Lipodystrophy; Location; Macronutrients Nutrition; Metabolic; Metabolism; Mitochondria; Muscle; Obesity; Overweight; Oxidative Stress; Oxygen Consumption; Pathogenesis; Pathway interactions; Patients; Pattern; Play; Population; Process; Production; Proteins; Reactive Oxygen Species; Regulation; Relative (related person); Rest; Risk; Role; Secondary to; Skeletal Muscle; Superoxide Dismutase; Sympathetic Nervous System; Syndrome; System; Testing; Thermogenesis; Thiobarbituric Acid Reactive Substances; Triglycerides; Weight; aryldialkylphosphatase; beta-adrenergic receptor; catalase; common treatment; design; diabetes risk; insight; normal aging; oxidation; public health relevance; response; subcutaneous

DESCRIPTION (provided by applicant): HIV lipodystrophy (LD) is a common complication of HIV infection and its therapy. It is characterized by extensive subcutaneous fat loss and is associated with insulin resistance, diabetes and hypertriglyceridemia. We have found that HIV LD is also associated with increased resting (REE) and total daily energy expenditure. Such increases in EE have also been found in congenital forms of LD but the pathogenesis is unknown. However, we have recently shown that subjects with HIV LD uniquely respond to short-term under- and overfeeding with significant decreases and increases in REE, respectively. The elevated REE of HIV LD and its responsiveness to changes in caloric intake may represent true forms of adaptive thermogenesis in this important component of total daily energy expenditure. This adaptive thermogenesis may be a response to an inability to store triglyceride fuel in a normal manner secondary to extensive loss/dysfunction of subcutaneous adipose tissue. Insights into the mechanism(s) underlying this adaptation would have great relevance to weight regulation in general and to the epidemic conditions of overweight and obesity. In this application, we will determine if the sympathetic nervous system contributes more to the support of REE in subjects with HIV LD and hypermetabolism compared to HIV-infected and healthy controls. We will also determine if there is increased mitochondrial uncoupling in the skeletal muscle of cases vs controls. Increased mitochondrial uncoupling dissipates calories as heat and leads to increased REE. Therefore, this could a potential mechanism behind the hypermetabolism of HIV LD. In addition to these mechanistic studies, we will also test the energetic response to and substrate oxidation pattern during both high-fat and high-carbohydrate overfeeding in patients with HIV LD. We hypothesize that overfeeding of both macronutrients will be associated with significant increases in REE and TEE in those with LD but not in controls. We also anticipate that high-fat overfeeding will lead to significant increases in fat oxidation in LD subjects but not in controls. Finally, we will determine if HIV LD is associated with increased oxidative stress. HIV LD is a hypermetabolic state, and since reactive oxygen species are a normal byproduct of oxygen consumption, it is plausible that this syndrome will be associated with increased oxidative stress. This is especially relevant in this population already at increased risk of diabetes and atherosclerotic vascular disease as oxidative stress may play a role in these disease processes. PUBLIC HEALTH RELEVANCE: Patients with HIV lipodystrophy have both abnormally low amounts and dysfunction of their subcutaneous adipose tissue. They also have a higher then normal metabolic rate. This increased metabolic rate may be a form of "adaptive thermogenesis". In other words, these patients may convert calories to heat instead of storing them because their subcutaneous adipose tissue cannot store the calories as fat. If this could be better understood, our findings would have broad relevance to the field of obesity in general and could open up new avenues of treatment for this common problem.

描述(申请人提供)：HIV脂肪营养不良(LD)是HIV感染及其治疗的常见并发症。它的特点是广泛的皮下脂肪丢失，并与胰岛素抵抗、糖尿病和高甘油三酯血症有关。我们发现，HIV LD还与静息(REE)和每日总能量消耗增加有关。在先天性LD中也发现了这种EE的增加，但其发病机制尚不清楚。然而，我们最近表明，患有HIV LD的受试者对短期喂养不足和过度喂养的反应是独特的，分别显著减少和增加REE。HIV LD的REE升高及其对卡路里摄入量变化的反应可能代表了这一每日总能量消耗的重要组成部分中适应性生热的真实形式。这种适应性生热作用可能是对无法以正常方式储存甘油三酯燃料的反应，继而导致皮下脂肪组织的广泛丢失/功能障碍。对这种适应机制的洞察(S)将与总体上的体重调节以及超重和肥胖的流行状况有很大的相关性。在这项应用中，我们将确定交感神经系统对HIV LD和高代谢患者的REE的支持是否比HIV感染和健康对照组更多。我们还将确定与对照组相比，病例组的骨骼肌中是否存在更多的线粒体解偶联。线粒体解偶联的增加使热量以热量的形式消散，并导致稀土元素的增加。因此，这可能是HIV LD高代谢的一个潜在机制。除了这些机制研究外，我们还将测试HIV LD患者在高脂肪和高碳水化合物过量喂养时的能量反应和底物氧化模式。我们假设，在患有LD的患者中，过量摄入这两种常量营养素将与REE和TEE显著增加有关，但在对照组中则不是。我们还预计，高脂肪过量喂养将导致LD受试者脂肪氧化显着增加，但在对照组中不会。最后，我们将确定HIV LD是否与氧化应激增加有关。HIV LD是一种高代谢状态，由于活性氧是氧气消耗的正常副产品，因此这一综合征可能与氧化应激增加有关。这一点在糖尿病和动脉粥样硬化性血管疾病风险增加的人群中尤其相关，因为氧化应激可能在这些疾病过程中发挥作用。公共卫生相关性：HIV脂肪营养不良患者的皮下脂肪组织含量异常低，且功能障碍。他们的代谢率也高于正常水平。这种增加的代谢率可能是“适应性产热”的一种形式。换句话说，这些患者可能会将卡路里转化为热量，而不是储存起来，因为他们的皮下脂肪组织无法将卡路里储存为脂肪。如果能够更好地理解这一点，我们的发现将对肥胖症领域具有广泛的相关性，并可能为这一常见问题开辟新的治疗途径。