title: Blunted lipolysis and fatty acid oxidation during moderate exercise in HIV-infected subjects taking HAART.
abstract: The protease inhibitor (PI) ritonavir (RTV) has been associated with elevated resting lipolytic rate, hyperlipidemia, and insulin resistance/glucose intolerance. The purpose of this study was to examine relationships between lipolysis and fatty acid (FA) oxidation during rest, moderate exercise and recovery, and measures of insulin sensitivity/glucose tolerance and fat redistribution in HIV-positive subjects taking RTV (n=12), HAART but no PI (n=10), and HIV-seronegative controls (n=10). Stable isotope tracers [1-(13)C]palmitate and [1,1,2,3,3-(2)H5]glycerol were continuously infused with blood and breath collection during 1-h rest, 70-min submaximal exercise (50% VO2 peak), and 1-h recovery. Body composition was evaluated using DEXA, MRI, and MRS, and 2-h oral glucose tolerance tests with insulin monitoring were used to evaluate glucose tolerance and insulin resistance. Lipolytic and FA oxidation rates were similar during rest and recovery in all groups; however, they were lower during moderate exercise in both HIV-infected groups [glycerol Ra: HIV+RTV 5.1+/-1.2 vs. HIV+no PI 5.9+/-2.8 vs. Control 7.4+/-2.2 micromol.kg fat-free mass (FFM)-1.min-1; palmitate oxidation: HIV+RTV 1.6+/-0.8 vs. HIV+no PI 1.6+/-0.8 vs. Control 2.5+/-1.7 micromol.kg FFM.min, P<0.01]. Fasting and orally-challenged glucose and insulin values were similar among groups. Lipolytic and FA oxidation rates were blunted during moderate exercise in HIV-positive subjects taking HAART. Lower FA oxidation during exercise was primarily due to impaired plasma FA oxidation, with a minor contribution from lower nonplasma FA oxidation. Regional differences in adipose tissue lipolysis during rest and moderate exercise may be important in HIV and warrant further study.
authors.affiliation: Department of Medicine, Washington University School of Medicine, 4444 Forest Park Blvd., St. Louis, MO 63108-2212, USA. tcade@wustl.edu
authors.forename: W Todd
authors.initials: WT
authors.lastname: Cade
authors.forename: Dominic N
authors.initials: DN
authors.lastname: Reeds
authors.forename: Bettina
authors.initials: B
authors.lastname: Mittendorfer
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Patterson
authors.forename: William G
authors.initials: WG
authors.lastname: Powderly
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Yarasheski
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001823:Body Composition; D015444:Exercise; D005215:Fasting / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005990:Glycerol / Q000493:pharmacokinetics; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption; D019308:Palmitic Acid / Q000493:pharmacokinetics
chemical_list: D005227:Fatty Acids; D019308:Palmitic Acid; D005990:Glycerol