title: 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.affiliation: Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Diabetes and Endocrinology Research Center, USA.
authors.forename: Rajagopal V
authors.initials: RV
authors.lastname: Sekhar
authors.forename: Farook
authors.initials: F
authors.lastname: Jahoor
authors.forename: Dinakar
authors.initials: D
authors.lastname: Iyer
authors.forename: Anuradha
authors.initials: A
authors.lastname: Guthikonda
authors.forename: Jaya
authors.initials: J
authors.lastname: Paranilam
authors.forename: Fareed
authors.initials: F
authors.lastname: Elhaj
authors.forename: Ivonne
authors.initials: I
authors.lastname: Coraza
authors.forename: Ashok
authors.initials: A
authors.lastname: Balasubramanyam
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy* / Q000378:metabolism; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D020738:Leptin / Q000172:deficiency* / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D020738:Leptin; D008055:Lipids