Lipid Kinetics During Acute Exercise in HIV

描述（由申请人提供）：目的：研究在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感染者中，有或无血脂异常的运动中脂质代谢的动力学和特异性调节因子。具体目的：在有或没有血脂异常的艾滋病毒感染者中，在休息和急性次极大运动刺激期间，我将检查：1)全身脂肪分解率，2)全身、血浆和非血浆脂质氧化率，3)心肌细胞内和肝脏脂质含量对全身脂肪分解率和全身、血浆和非血浆脂质氧化率的影响，并探讨其在胰岛素抵抗中的作用，4)骨骼肌和脂肪组织中ppar - α、ppar - γ、SREBP-1、肉碱棕榈酰基转移酶I （CPT-I）的蛋白和mRNA水平，和血浆去甲肾上腺素（NE）水平失调，以及这是否与全身脂肪分解率和全身、血浆和非血浆脂质氧化率有关。背景：基于pi的ART与血脂异常有关。运动期间的脂质代谢检查可能为HIV-ART血脂异常的发病机制提供独特的信息。设计：将使用FFA和甘油稳定同位素标记示踪方法。骨骼肌和皮下脂肪活检，以确定mRNA表达和蛋白质含量。使用DEXA和1H-MRI检查身体成分。采用1H-MRS测定心肌细胞内及肝脏脂质含量。

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.