LIPID KINETICS DURING ACUTE EXERCISE IN HIV

HIV 急性运动期间的脂质动力学

• 批准号: 7377207
• 负责人: KEVIN E YARASHESKI
• 金额: $ 5.41万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377207
• 关键词: LIPID; KINETICS; DURING; ACUTE; EXERCISE

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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。研究运动过程中，服用和不服用基于蛋白酶抑制剂（PI）的抗逆转录病毒治疗（ART）的HIV感染男性和女性（18-50岁）伴或不伴血脂异常时脂质代谢的动力学和特异性调节因子。具体目标：在有和无血脂异常的HIV感染者中，使用和不使用基于PI的ART检查：1）在休息和急性次极量运动刺激期间的全身脂解率，2）在休息和急性次极量运动刺激期间的全身、血浆和非血浆脂质氧化率。3)肌细胞内和肝内脂质含量对全身脂解速率和全身、静息和急性运动期间血浆和非血浆脂质氧化的作用，并检查其在胰岛素抵抗中的作用，和4）骨骼肌转录因子SREBP-1c和PPAR-gamma，脂肪组织转录因子SREBP-1c和PPAR-alpha，骨骼肌酶肉毒碱棕榈酰转移酶I（CPR-1）和血浆去甲肾上腺素（NE）水平与全身脂解速率和全身、血浆和非血浆脂质氧化速率的关系。背景技术背景：用抗逆转录病毒疗法治疗人类免疫缺陷病毒（HIV-1），大大降低了与这种慢性感染有关的发病率和死亡率。然而，ART，特别是基于PI的ART，已经与代谢并发症相关：糖尿病、高血脂和胆固醇水平、腹部区域中的脂肪积累和/或臂、腿、面部和臀部区域中的脂肪减少。关于HIV-ART血脂异常患者在休息时的脂质代谢知之甚少，在运动时则一无所知。运动过程中脂质代谢的动力学和调节剂的检查可能有助于了解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亚极量运动期间输注，并通过气相色谱-质谱法分析伴有血脂异常的HIV感染者与不伴有血脂异常的HIV感染者。将进行骨骼肌和皮下脂肪活检，以确定上述脂质代谢调节剂的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进行检查，肌肉内和肝内脂质含量将通过磁共振光谱进行测量。