8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV San Francisco, California - September 24 - 26, 2006

ROSIGLITAZONE THERAPY MARKEDLY IMPROVES ADIPOCYTE RE-ESTERIFICATION IN HIV LIPODYSTROPHY SYNDROME

Antiviral Therapy 2006; 11:L27 (abstract no. 40)

RV Sekhar¹, S D’Amico¹, K Rehman¹, F Jahoor², A Balasubramanyam¹, J Shi¹, S Patel¹ and F Visnegarwala^3
1Translational Metabolism Unit, Division of Diabetes, Endocrinology and Metabolism, ³Division of Infectious Diseases, Department of Medicine; ²USDA Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA

BACKGROUND: The insulin resistant HIV lipodystrophy syndrome (HLS) of fat wasting and severe hypertriglyceridemia, is characterized by marked abnormalities of lipid kinetics, and associated with increased risk of cardiovascular disease. We hypothesized that Rosiglitazone therapy will improve lipid kinetics, and peripheral lipoatrophy in HLS.

DESIGN: Lipid kinetics, glycaemic indices and body composition were studied in nine men with HLS before and after 3 months of treatment with Rosiglitazone (8 mg/d). Total and net lipolysis, adipocyte and hepatic reesterification, and plasma free fatty acid (FFA) oxidation were measured with infusions of [¹³C₁]palmitate and [²H₅]glycerol.

RESULTS: (mean ±SE): Rosiglitazone therapy significantly increased total lipolysis (Ra FFA_total from 3.37 ±0.40 versus 4.57 ±0.68 mmol FFA.kg-fat^-1.h^-1, P<0.05), and intraadipocyte reesterification (1.25 ±0.35 versus 2.43 ±0.65 mmol FFA.kg-fat^-1.h^-1, P<0.05). There were no differences in net lipolysis (Ra FFA_net 2.47 ±0.43 versus 2.42 ±0.37 mmol FFA.kg-fat^-1.h^-1), plasma FFA oxidation (0.35 ±0.06 versus 0.36 ±0.05 mmol FFA.kg-LBM^-1.h^-1), or the Ra FFA available for intrahepatic reesterification (0.82 ±0.29 versus 0.56 ±0.10 mmol FFA.kg-fat^-1.h^-1). There was a significant decrease in fasting plasma insulin (14.5 ±1.6 versus 9.9 ±1.5 U/L, P<0.05) and HOMA-IR (3.59 ±0.41 versus 2.35 ±0.42, P<0.05), but not in fasting plasma glucose or triglyceride levels. The waist-to-hip ratio (0.98 ±0.02 versus 0.95 ±0.02, P<0.05) significantly decreased and the hip circumference (92.78 ±2.12 versus 94.67 ±2.04 cm, P<0.05) significantly increased, but were not accompanied by changes in other indices of body composition.

CONCLUSIONS: These data suggest that Rosiglitazone treatment of subjects with HIV lipodystrophy primarily increases adipocyte reesterification rate. However, this is offset by an increase in the rate of total lipolysis, and results in increasing FFA futile cycling. Despite the unchanged net lipolytic rate, the reduction in waist-to-hip ratio, and hip circumference strongly suggest that there is an overall effect toward fat retention in peripheral adipocytes with Rosiglitazone therapy. Rosiglitazone therapy could benefit patients with HIV lipodystrophy syndrome by increasing adipocyte reesterification, and result in improvement of peripheral lipoatrophy.

Download PDF of this abstract.

2006-09-24
40

Copyright © 2006 - International Medical Press Ltd. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Medical Editor, International Medical Press, 36 St Mary-at-Hill, London EC3R 8DU, United Kingdom.