Physiologic growth hormone replacement improves fasting lipid kinetics in patients with HIV lipodystrophy syndrome

Background: HIV lipodystrophy syndrome (HLS) is characterized by accelerated lipolysis, inadequate fat oxidation, increased hepatic reesterification, and a high frequency of growth hormone deficiency (GHD). The effect of growth hormone (GH) replacement on these lipid kinetic abnormalities is unknown. Objective: We aimed to measure the effects of physiologic GH replacement on lipid kinetics in men with HLS and GHD. Design: Seven men with HLS and GHD were studied with the use of infusions of [ 13 C 1 ]palmitate, [ 2 H 5 ]glycerol, and [ 2 H 3 ]leucine to quantify total and net lipolysis, palmitate and free fatty acid (FFA) oxidation, and VLDL apolipoprotein B-100 synthesis before and after 6 mo of GH replacement (maximum: 5 μg · kg -1 · d -1 ). Results: GH replacement decreased the rates of total lipolysis [FFA total rate of appearance (x ± SE): from 4.80 ± 1.24 to 3.32 ± 0.76 mmol FFA kg fat -1 · h -1 ; P < 0.05] and net lipolysis (FFA net rate of appearance: from 1.87 ± 0.34 to 1.20 ± 0.25 mmol FFA · kg fat -1 · h -1 ; P < 0.05). Fat oxidation decreased (from 0.28 ± 0.02 to 0.20 ± 0.02 mmol FFA kg lean body mass -1 · h -1 ; P < 0.002), as did the rate of appearance of FFAs available for intrahepatic reesterification (from 0.50 ± 0.13 to 0.29 ± 0.09 mmol FFA kg fat -1 · h -1 ; P < 0.03). Fractional and absolute synthetic rates of VLDL apolipoprotein B-100 were unaltered. These kinetic changes were associated with a decrease in the waist-to-hip ratio but no significant change in fasting plasma lipid concentrations. Fasting plasma glucose concentrations increased after treatment (from 5.2 ± 0.2 to 5.8 ± 0.3 mmol/L; P < 0.01). Conclusions: Physiologic GH replacement has salutary effects on abnormal lipid kinetics in HLS. The effects are mediated by diminished lipolysis and hepatic reesterification rather than by increased fat oxidation.