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（由申请人提供）：HIV脂肪营养不良（LD）是HIV感染及其治疗的常见并发症。它的特征是广泛的皮下脂肪流失，与胰岛素抵抗，糖尿病和高甘油三酸酯血症有关。我们发现，HIV LD也与增加的静止（REE）和每日能量总消耗有关。在LD的先天性形式中也发现了EE的这种增加，但发病机理尚不清楚。但是，我们最近表明，艾滋病毒LD的受试者分别对短期不足和过度喂养的响应分别响应REE的大幅下降和增加。 HIV LD的REE升高及其对热量摄入变化的反应性可能代表了每日能量总消耗的这一重要组成部分的自适应生热形式。这种自适应生热作用可能是对无法以正常方式存储甘油三酸酯燃料的一种反应，其继发于皮下脂肪组织的广泛损失/功能障碍。对这种适应的基础机制的见解将与一般体重调节以及超重和肥胖的流行条件具有很大的相关性。在此应用中，我们将确定与感染HIV的和健康的对照相比，在患有HIV LD和超代谢受试者的受试者中，交感神经系统是否对REE的支持更大。我们还将确定在病例对照组的骨骼肌中，线粒体解开是否增加。线粒体解偶联的增加会随着热量而消散卡路里，并导致REE增加。因此，这可能是艾滋病毒LD的超定代谢背后的潜在机制。除这些机械研究外，我们还将在HIV LD患者的高脂和高碳水化合物过度喂养期间测试对高脂和高碳水化合物过度喂养期间对底物氧化模式的能量反应。我们假设两种大量营养素的过度喂养将与LD的REE和TEE显着增加，但在对照中没有大幅增加。我们还预计，高脂过度喂养将导致LD受试者的脂肪氧化显着增加，但不会导致对照。最后，我们将确定HIV LD是否与氧化应激增加有关。 HIV LD是一种多代谢态，由于活性氧是氧气消耗的正常副产品，因此该综合征将与氧化应激增加有关是合理的。这在已经增加的糖尿病风险和动脉粥样硬化血管疾病的人群中尤其重要，因为氧化应激可能在这些疾病过程中起作用。公共卫生相关性：HIV脂肪营养不良患者的皮下脂肪组织异常低和功能障碍。它们的代谢率还高于正常代谢率。这种增加的代谢率可能是“适应性热发生”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它们，因为它们的皮下脂肪组织无法将卡路里储存为脂肪。如果可以更好地理解这一点，我们的发现将与一般的肥胖领域具有广泛的相关性，并且可以为这个常见问题打开新的治疗途径。