LIPID KINETICS DURING ACUTE EXERCISE IN HIV

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。研究有或无血脂异常、接受或不接受基于蛋白酶抑制剂（PI）的抗逆转录病毒治疗（ART）的hiv感染男性和女性（18-50岁）运动期间脂质代谢的动力学和特异性调节因子。具体目的：在有和没有血脂异常的hiv感染者中，接受和不接受基于pi的ART检查：1)休息时和急性次极限运动刺激期间的全身脂肪分解率，2)休息时和急性次极限运动刺激期间的全身、血浆和非血浆脂质氧化率。3)细胞内和肝内脂质含量对静止和急性运动时全身脂解率和全身、血浆和非血浆脂质氧化的作用，并探讨其在胰岛素抵抗中的作用；4)骨骼肌转录因子SREBP-1c和ppar - γ、脂肪组织转录因子SREBP-1c和ppar - α、骨骼肌酶肉碱棕榈酰基转移酶I （CPR-1）的作用。和血浆去甲肾上腺素（NE）水平与全身脂肪分解率和全身、血浆和非血浆脂质氧化率在休息和急性运动刺激期间的关系。背景：使用抗逆转录病毒治疗人类免疫缺陷病毒（HIV-1）已经显著降低了与这种慢性感染相关的发病率和死亡率。然而，ART，特别是基于pi的ART，与代谢并发症有关：糖尿病、高血脂和胆固醇水平、腹部脂肪积聚和/或手臂、腿部、面部和臀部脂肪减少。我们对HIV-ART血脂异常在休息时的脂质代谢知之甚少，在运动时则一无所知。检查运动过程中脂质代谢的动力学和调节因子可能有助于了解HIV-ART血脂异常的发病机制。研究设计：脂肪酸和甘油稳定同位素示踪剂将在次最大运动期间输注，并通过气相色谱-质谱法分析患有血脂异常的hiv感染者与无血脂异常的hiv感染者的对比。将进行骨骼肌和皮下脂肪活检，以确定上述脂质代谢调节因子的mRNA表达和蛋白质含量。身体成分将通过双能x射线分析和磁共振成像来检查，肌肉和肝脏内的脂质含量将通过磁共振光谱来测量

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. To examine the kinetics and specific regulators of lipid metabolism during exercise in HIV-infected men and women (18-50 yr old) with and without dyslipidemia, taking and not taking protease inhibitor (PI) based ant-retroviral therapy (ART). SPECIFIC AIMS: In HIV-infected people with and without dyslipidemia taking and not taking PI-based ART to examine: 1) the rate of whole body lipolysis at rest and during an acute submaximal exercise stimulua, 2) the rate of whole body, plasma, and non-plasma lipid oxidation at rest and during an acute submaximal exercise stimulus. 3) the role of intramyocellular and intra-hepatic lipid content on the rate of whold body lipolysis and whole body, plasma and non-plasma lipid oxidation at rest and during acute exercise and to examine its role n insulin resistance, and 4) the roles of the skeletal muscle transcription factors SREBP-1c and PPAR-gamma, the adipose tissue transcription factors SREBP-1c and PPAR-alpha, the skeletal muscle enzyme carnitine palmitoyltransferase I (CPR-1), and plasma norepinephrine (NE) levels in relationship to the rate of whole body lipolysis and whole body, plasma and non-plamsa lipid oxidation rates at rest and during an acute exercise stimulus. BACKGROUND: The medical treatment of the human immunodeficiency virus (HIV-1) with ART has dramatically reduced the morbidity and mortality associated with this chronic infection. However, ART, particularly PI-based ART, has been associated with metabolic comlications: diabetes, high blood lipid and cholesterol levels, fat accumulation in the abdominal region, and/or fat loss in the arms, legs, face, and buttocks regions. Little is known regarding lipid metabolism in HIV-ART dyslipidemia during rest, nothing is known during exercise. Examination of kinetics and regulators of lipid metabolism during exercise may assist in understanding the pathogenesis of HIV-ART dyslipidemia. RESEARCH DESIGN: Fatty acid and glycerol stable-isotope tracers will be infused during sub-maximal exercise and analyzed by gas chromatography-mass spectometry in HIV-infected people with dyslipidemia compared to HIV-infected people without dyslipidemia. Skeletal muscle and subcutaneous fat biopsies will be performed in order to determine mRNA expression and protein content of the above mentioned regulators of lipid metabolism. Body composition will be examined by dual energy x-ray analysis and magnetic resonance imaging and intr-muscular and intr-hepatic lipid content will be measured by magnetic resonance spectros