Lipid Kinetics During Acute Exercise in HIV

描述(申请人提供)：目的：研究服用和不服用蛋白酶抑制剂(PI)抗逆转录病毒疗法(ART)的HIV感染者在运动过程中脂代谢的动力学和特异性调节。具体目的：在HIV感染者中，无论是否存在血脂异常，在休息和急性亚极量运动刺激期间，我将检测：1)全身脂解率，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和全身、血浆和非血浆脂质氧化速率的作用，并探讨其在胰岛素抵抗中的作用，以及4)骨骼肌和脂肪组织PPAR-α、PPAR-γ、SREBP-1、肉碱棕榈酰转移酶I(CPT-I)和血浆去甲肾上腺素(NE)水平失调，以及这是否与全身脂解率和全身、血浆和非血浆脂质氧化率有关。背景：以PI为基础的抗逆转录病毒治疗与血脂异常有关。运动过程中脂代谢的检测可能为HIV-ART血脂异常的发病机制提供独特的信息。设计：采用FFA和甘油稳定同位素标记示踪剂方法学。将获得骨骼肌和皮下脂肪的活检，以确定mRNA的表达和蛋白质含量。身体成分将使用DEXA和1H-MRI进行检查。将使用1H-MRS测量心肌细胞内和肝脏中的脂质含量。

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.