title: Adipokines in the HIV/HAART-associated lipodystrophy syndrome.
abstract: The use of highly active antiretroviral therapy (HAART) in the treatment of human immunodeficiency virus has dramatically altered both the landscape of this disease and the prognosis for those affected. With more patients now receiving HAART, adverse effects such as lipodystrophy and metabolic syndrome have emerged. In HIV/HAART-associated lipodystrophy syndrome (HALS), patients demonstrate fat maldistribution with dyslipidemia, insulin resistance, and other metabolic complications. Recent studies have contributed to the elucidation of the pathophysiological abnormalities seen in this syndrome and have provided guidance for the study and use of potential treatments for these patients, but widely accepted guidelines have not yet been established. Two adipokines, leptin and adiponectin, are decreased in patients with HALS and lipoatrophy or lipodystrophy. Further, recent proof-of-concept clinical trials have proven the efficacy of leptin replacement and medications that increase circulating adiponectin levels in improving the metabolic profile of HALS patients. This review article highlights recent evidence on leptin replacement and compares leptin's efficacy to that of other treatments, including metformin and thiazolidinediones, on metabolic abnormalities such as impaired insulin-glucose homeostasis associated with lipodystrophy in patients receiving HAART. It is hoped that forthcoming large phase III clinical trials will allow the addition of leptin to our therapeutic armamentarium for use in patients suffering from this disease state.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Paruthi
authors.forename: Natasha
authors.initials: N
authors.lastname: Gill
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D052242:Adiponectin / Q000502:physiology / Q000627:therapeutic use*; D018149:Glucose Intolerance / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D020738:Leptin / Q000502:physiology / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D052242:Adiponectin; D020738:Leptin; D045162:Thiazolidinediones; D008687:Metformin
keywords: Adiponectin; HAART; HALS; HIV; HIV/HAART-associated lipodystrophy syndrome; IGF-1; IL-6; Leptin; Lipodystrophy; PPAR-gamma; TNF-α; highly active antiretroviral therapy; insulin-like growth factor 1; interleukin-6; peroxisome proliferator-activated receptor-gamma; tumor necrosis factor-alpha