ARS | Publication request: Physiologic growth hormone replacement improves fasting lipid kinetics in patients with HIV lipodystrophy syndrome

Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 2, 2006
Publication Date: July 1, 2006
Citation: D'Amico, S., Shi, J., Sekhar, R.V., Jahoor, F., Ellis, K.J., Rehman, K., Willis, J., Maldonado, M., Balasubramanyam, A. 2006. Physiologic growth hormone replacement improves fasting lipid kinetics in patients with HIV lipodystrophy syndrome. American Journal of Clinical Nutrition. 84(1):204-211.

Interpretive Summary: Patients infected with HIV are now developing a new condition called HIV lipodystrophy (HLS) syndrome. This condition is characterized by high blood cholesterol and triglyceride concentrations, which are known to cause cardiovascular disease with time. High blood cholesterol and triglyceride concentrations are usually caused by alterations in fat metabolism. In an earlier study we found that patients with the HLS syndrome were breaking down body fat faster but were using less of the released fat to make energy compared to healthy men. Hence, more fat was going to the liver to be converted to triglycerides. We also found that several of these patients had low levels of a hormone called growth hormone and wondered if this may be the reason why they had defective fat metabolism. To find out we gave small doses of growth hormone to men with HLS to normalize blood levels and looked at the effect on fat metabolism. We found that growth hormone decreased the rate at which these patients broke down body fat; hence less fat was going to the liver to be converted to triglycerides. At the same time, however, they used less fat to make energy. These findings suggest that normalizing growth hormone levels in patients with the HLS syndrome can improve fat metabolism by slowing down fat breakdown rate.

Technical Abstract: 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. We aimed to measure the effects of physiologic GH replacement on lipid kinetics in men with HLS and GHD. Seven men with HLS and GHD were studied with the use of infusions of [13C1]palmitate, [2H5]glycerol, and [2H3]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 microg x kg(-1) x d(-1)). 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 x kg fat(-1) x 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 x kg fat(-1) x h(-1); P < 0.05). Fat oxidation decreased (from 0.28 +/- 0.02 to 0.20 +/- 0.02 mmol FFA x kg lean body mass(-1) x 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 x kg fat(-1) x 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). 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.