Leptin replacement therapy does not improve the abnormal lipid kinetics of hypoleptinemic patients with HIV-associated lipodystrophy syndrome.

Abstract

Patients with HIV-associated dyslipidemic lipodystrophy (HADL) have characteristic lipid kinetic defects: accelerated lipolysis, blunted fat oxidation and increased hepatic fatty acid reesterification. HADL patients with lipoatrophy also have leptin deficiency. Small or non-randomized studies have suggested that leptin replacement improves glucose metabolism in HADL, with very limited data regarding its effects on the lipid kinetic abnormalities. We performed a randomized, double-blind, placebo-controlled, dose-escalating (0.02 mg/kg/d for two months; 0.04 mg/kg/d for a further two months) study of the effects of metreleptin on lipid kinetics in 17 adults with HADL, hypertriglyceridemia and hypoleptinemia. Rates of lipolysis, intra-adipocyte and intrahepatic reesterification and fatty acid oxidation were measured using infusions of (13)C(1)-palmitate and (2)H(5)-glycerol, and indirect calorimetry. Fasting lipid profiles and glucose and insulin responses to oral glucose challenge were also measured. Metreleptin treatment induced significant, dose-dependent increases in fasting plasma leptin levels. There was no significant change in total lipolysis, net lipolysis, adipocyte or hepatic re-esterification or fatty acid oxidation, or in fasting triglyceride or HDL-C concentrations, with metreleptin treatment. Metreleptin decreased fasting non-HDL-C levels (P<.01) and area-under-the-curve for glucose (P<.05). In hypoleptinemic HADL patients, treatment with metreleptin at 0.02 or 0.04 mg/kg/d does not improve abnormal fasting lipid kinetics, or triglyceride or HDL-C levels. Metreleptin does, however, improve glycemia and non-HDL-C in these patients. These results suggest a dissociation between leptin's effects on glucose metabolism compared to those on lipid kinetics in HADL.

• Authors: Rajagopal V Sekhar, Farook Jahoor, Dinakar Iyer, Anuradha Guthikonda, Jaya Paranilam, Fareed Elhaj, Ivonne Coraza, Ashok Balasubramanyam
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 61 Issue 10 Pg. 1395-403 (Oct 2012) ISSN: 1532-8600 [Electronic] United States
• PMID: 22542724 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Fatty Acids, Nonesterified
• Leptin
• Lipids

Topics

• Adult
• Blood Glucose (analysis)
• Double-Blind Method
• Fatty Acids, Nonesterified (blood)
• HIV-Associated Lipodystrophy Syndrome (drug therapy, metabolism)
• Hormone Replacement Therapy (adverse effects)
• Humans
• Leptin (deficiency, therapeutic use)
• Lipids (blood)
• Middle Aged