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r-metHuLeptin improves highly active antiretroviral therapy-induced lipoatrophy and the metabolic syndrome, but not through altering circulating IGF and IGF-binding protein levels: observational and interventional studies in humans

Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, E/St 816, 330 Brookline Avenue, Boston, Massachusetts 02215, USA¹ Division of Infectious Diseases, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA

(Correspondence should be addressed to C S Mantzoros; Email: cmantzor{at}bidmc.harvard.edu)

^* (A M Brennan and J H Lee contributed equally to the study)

Objective: Leptin is an adipocyte secreted hormone and an important regulator of neuroendocrine, metabolic, and immune function. Both r-metHuLeptin and IGF1 administration result in reduced central adipose tissue in subjects with highly active antiretroviral therapy-induced metabolic syndrome (HAART-MS) but whether the effects of leptin are mediated through increasing IGF levels remains unknown.

Methods: To assess whether r-metHuLeptin improves the HAART-MS by regulating circulating IGF and IGFBPs, we first conducted a cross-sectional study of 118 men and women with HIV infection and >6 months of exposure to antiretroviral medications to examine any association between circulating IGF1 and leptin levels. We also performed a randomized, double-blinded, placebo-controlled, crossover trial of recombinant human leptin (r-metHuLeptin) administration to seven HIV positive men with lipoatrophy and leptin deficiency (leptin <3 ng/ml) related to antiretroviral medication use.

Results: In the observational study, leptin levels were inversely associated with circulating IGF1 levels after adjusting for age and gender (r=0.27 P=0.002), but this inverse association became non-significant after adjustment for % body fat and exercise. In the interventional leptin study, leptin levels increased significantly during r-metHuLeptin treatment (from 1.34±0.20 ng/ml at baseline to 17±5.05 ng/ml after 8 weeks P=0.046) and metabolic parameters improved including reduced fasting insulin levels and reduced homeostasis model assessment-insulin resistance (HOMA-IR). Despite the increase in circulating leptin levels, there was no change in IGF1, IGF2, free IGF1, or IGF-binding proteins during the 2-month treatment period.

Conclusion: The effects of r-metHuLeptin in patients with HAART-MS are not mediated through increasing IGF or IGFBP levels.

This article has been cited by other articles:

				T. Kelesidis, I. Kelesidis, S. Chou, and C. S. Mantzoros Narrative Review: The Role of Leptin in Human Physiology: Emerging Clinical Applications Ann Intern Med, January 19, 2010; 152(2): 93 - 100. [Abstract] [Full Text] [PDF]

				C. S. Mantzoros Whither Recombinant Human Leptin Treatment for HIV-Associated Lipoatrophy and the Metabolic Syndrome? J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1089 - 1091. [Full Text] [PDF]