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
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