Lipid Kinetics During Acute Exercise in HIV

描述（由申请人提供）：目的：检测接受和不接受基于蛋白酶抑制剂（PI）的抗逆转录病毒治疗（ART）的伴或不伴血脂异常的HIV感染者在运动期间的脂质代谢动力学和特异性调节剂。具体目标：在休息期间和急性次最大运动刺激期间，有和没有血脂异常的HIV感染者接受和不接受PI为基础的ART，我将检查：1）全身脂解速率，2）全身、血浆和非血浆脂质氧化速率，3）肌细胞内和肝脂质含量对全身脂解速率和全身的作用，血浆和非血浆脂质氧化并检查其在胰岛素抵抗中的作用，和4）骨骼肌和脂肪组织蛋白质和PPAR-alpha、PPAR-gamma、SREBP-1、肉毒碱棕榈酰转移酶I（CPT-I）的mRNA水平以及血浆去甲肾上腺素（NE）水平是否失调，以及这是否与全身脂解速率和全身、血浆和非血浆脂质氧化速率有关。背景：基于PI的ART与血脂异常相关。运动过程中的脂质代谢检查可能提供有关HIV-ART血脂异常发病机制的独特信息。设计：FFA和甘油稳定同位素标记的示踪方法将被使用。将获得骨骼肌和皮下脂肪活检，以确定mRNA表达和蛋白质含量。将使用DEXA和1H-MRI检查身体成分。将使用1H-MRS测量肌细胞内和肝脏脂质含量。

DESCRIPTION (provided by applicant): Objective: To examine the kinetics and specific regulators of lipid metabolism during exercise in HIV-infected people with and without dyslipidemia on and not on protease inhibitor (PI) based anti-retroviral therapy (ART). Specific Aims: In HIV-infected people with and without dyslipidemia on and not on PI-based ART during rest and during an acute sub-maximal exercise stimulus, I will examine: 1) the rate of whole body lipolysis, 2) the rate of whole body, plasma, and non-plasma lipid oxidation, 3) the role of intra-myocellular and hepatic lipid content on the rate of whole body lipolysis and whole body, plasma and non-plasma lipid oxidation and examine its role in insulin resistance, and 4) whether skeletal muscle and adipose tissue protein and mRNA levels for PPAR-alpha, PPAR-gamma, SREBP-1, carnitine palmitoyltransferase I (CPT-I), and plasma norepinephrine (NE) levels are dysregulated, and whether this is related to the rate of whole body lipolysis and whole body, plasma and non-plasma lipid oxidation rates. Background: PI-based ART has been associated with dyslipidemia. Examination of lipid metabolism during exercise may provide unique information about the pathogenesis of HIV-ART dyslipidemia. Design: FFA and glycerol stable-isotope labeled tracer methodology will be used. Skeletal muscle and subcutaneous fat biopsies will be obtained in order to determine mRNA expression and protein content. Body composition will be examined using DEXA and 1H-MRI. Intra-myocellular and hepatic lipid content will be measured using 1H-MRS.