EXERCISE AND PIOGLITAZONE FOR HIV-METABOLIC SYNDROMES

运动和吡格列酮治疗艾滋病毒代谢综合征

• 批准号: 7721457
• 负责人: KEVIN E YARASHESKI
• 金额: $ 0.61万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721457
• 关键词: Abdomen; Adipose tissue; Adopted; Aerobic; Combined Modality Therapy; Computer Retrieval of Information on Scientific Projects Database; Consensus; DEXA; Deposition; Diet Modification; Disease; Dyslipidemias; Euglycemic Clamping; Exercise; Fatty acid glycerol esters; Funding; Glucose; Glucose Clamp; Grant; HIV; Hepatic; Institution; Insulin; Insulin Resistance; Intervention; Life; Lipid Mobilization; Lipids; Lipolysis; Liver; Measures; Messenger RNA; Metabolic; Metabolic Syndrome X; Metabolic syndrome; Muscle; Nonesterified Fatty Acids; Oral; PPAR alpha; PPAR gamma; Pathogenesis; Peripheral; Pioglitazone; Randomized; Rate; Research; Research Personnel; Resources; Serum; Soleus Muscle; Source; Syndrome; Testing; Thigh structure; Training; United States National Institutes of Health; Visceral; Weight Lifting; Woman; adiponectin; cardiovascular disorder risk; experience; glucose disposal; glucose output; glucose production; impaired glucose tolerance; improved; insulin sensitivity; men; protein expression; subcutaneous

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our prior research has examined the pathogenesis and potential treatments for metabolic complications in people living with HIV. We have adopted the "lipotoxicity" hypothesis for metabolic syndrome X to explain the pathogenesis of impaired glucose tolerance (IGT) and fat redistribution in HIV: increased lipolysis and mobilization of lipids and free fatty acids from subcutaneous adipose depots leads to their excessive deposition in muscle and liver which contributes to dyslipidemia, insulin resistance, increased hepatic glucose output, and possibly visceral fat accumulation. Effective treatments have not been identified. Consensus groups recommend regular exercise and dietary modifications as primary and pharmacologic interventions as secondary treatments for the syndromes. In this revised application, we propose to test the efficacy of aerobic and weight lifting exercise training and an oral insulin-sensitizing agent (pioglitazone) as treatments for HIV-associated IGT and fat redistribution. We propose a 4-month, 2-group randomized study to evaluate the efficacy of pioglitazone and exercise + pioglitazone in 40 men and 40 women living with HIV and IGT and fat redistribution. We will measure: insulin sensitivity, glucose disposal rate, hepatic glucose production rate (hyperinsulinemic, euglycemic clamp using 6,6-[2H2]-glucose); whole-body and regional fat and muscle content (1H-MRI of the abdomen and thigh & DEXA), soleus muscle and liver lipid content (1H-MRS), muscle and fat PPARgamma/alpha mRNA and protein expression, serum lipid profiles, and serum adiponectin levels before and at the end of 4 months of treatment. We hypothesize that exercise training + pioglitazone will be more effective than pioglitazone alone at improving insulin sensitivity, reducing visceral fat, liver and muscle lipid content, and increasing peripheral subcutaneous fat content in HIV-infected people. We hypothesize that combined treatment will be more effective because exercise training will activate PPARalpha expression in muscle and pioglitazone will activate PPARgamma expression in fat and muscle. We anticipate that this project will provide direct evidence that supports the combined use of exercise training and pioglitazone in people living with HIV and experiencing metabolic and anthropomorphic disorders that increase cardiovascular disease risk.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们先前的研究检查了艾滋病毒患者代谢并发症的发病机理和潜在治疗方法。 We have adopted the "lipotoxicity" hypothesis for metabolic syndrome X to explain the pathogenesis of impaired glucose tolerance (IGT) and fat redistribution in HIV: increased lipolysis and mobilization of lipids and free fatty acids from subcutaneous adipose depots leads to their excessive deposition in muscle and liver which contributes to dyslipidemia, insulin resistance, increased肝葡萄糖输出，可能是内脏脂肪的积累。尚未确定有效的治疗方法。共识小组建议定期运动和饮食修饰，作为主要和药理学干预措施，作为综合症的二级治疗。在此修订后的应用中，我们建议测试有氧运动和举重运动训练的功效，以及口服胰岛素敏化剂（Pioglitazone）作为HIV相关的IGT和脂肪再分配的治疗方法。我们提出了一项为期4个月的2组随机研究，以评估40名男性和40名患有HIV，IGT和IGT和脂肪重新分布的男性和40名男性和40名妇女的吡格列酮和运动 +吡格列酮的功效。我们将测量：胰岛素敏感性，葡萄糖处置速率，肝葡萄糖产生速率（使用6,6- [2H2] - 葡萄糖）；全身和区域脂肪和肌肉含量（腹部和大腿和Dexa的1H-MRI），比目鱼肌肉和肝脂质含量（1H-MR），肌肉和脂肪ppargamma/alpha/alpha mRNA和蛋白质表达，血清脂质谱，血清脂质谱，以及在4个月之前和治疗4个月之前的血清脂肪素水平。我们假设运动训练 +吡格列酮将比单独的吡格列酮更有效，以提高胰岛素敏感性，降低内脏脂肪，肝脏和肌肉脂质含量，并增加HIV感染的人的外周皮下脂肪含量。我们假设联合治疗将更有效，因为运动训练将激活肌肉和吡格列酮中的pparalpha表达，将激活脂肪和肌肉中的ppargamma表达。我们预计该项目将提供直接证据，以支持艾滋病毒感染者的运动训练和吡格列酮的综合使用，并经历了增加心血管疾病风险的代谢和拟人化疾病。