Lipid Kinetics During Acute Exercise in HIV

Washington University, Saint Louis MO

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Abstract

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.