Blunted lipolysis and fatty acid oxidation during moderate exercise in HIV-infected subjects taking HAART

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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- 13C]palmitate and [1,1,2,3,3-2H5]glycerol were continuously infused with blood and breath collection during 1-h rest, 70-min submaximal exercise (50% V̇O2 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 μmol·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 μmol·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.

Original languageEnglish
Pages (from-to)E812-E819
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume292
Issue number3
DOIs
StatePublished - Mar 1 2007

Keywords

  • Highly active antiretroviral therapy
  • Human immunodeficiency virus
  • Insulin resistance
  • Lipodystrophy
  • Mass spectrometry
  • Metabolic syndrome
  • Ritonavir

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