title: The effects of recombinant human leptin on visceral fat, dyslipidemia, and insulin resistance in patients with human immunodeficiency virus-associated lipoatrophy and hypoleptinemia.
abstract: BACKGROUND
  Leptin deficiency is associated with dyslipidemia and insulin resistance in animals and humans with lipoatrophy; leptin replacement ameliorates these abnormalities.
  
  
  OBJECTIVE
  The objective of the study was to evaluate the effects of leptin therapy in lipoatrophic HIV-infected patients with dyslipidemia and hypoleptinemia.
  
  
  METHODS
  This was a 6-month, open-label, proof-of-principle pilot study.
  
  
  METHODS
  Metabolic ward studies were performed before and 3 and 6 months after leptin treatment.
  
  
  METHODS
  Participants included eight HIV-infected men with lipoatrophy, fasting triglycerides greater than 300 mg/dl, and serum leptin less than 3 ng/ml.
  
  
  METHODS
  Recombinant human leptin was given by sc injection (0.01 mg/kg and 0.03 mg/kg twice daily for successive 3 month periods).
  
  
  METHODS
  Measures included fat distribution by magnetic resonance imaging and dual-energy X-ray absorptiometry; fasting lipids; insulin sensitivity by euglycemic hyperinsulinemic clamp; endogenous glucose production, gluconeogenesis, glycogenolysis, and whole-body lipolysis by stable isotope tracer studies; oral glucose tolerance testing; liver fat by proton magnetic resonance spectroscopy; and safety.
  
  
  RESULTS
  Visceral fat decreased by 32% (P = 0.001) with no changes in peripheral fat. There were significant decreases in fasting total (15%, P = 0.012), direct low-density lipoprotein (20%, P = 0.002), and non-high-density lipoprotein (19%, P = 0.005) cholesterol. High-density lipoprotein cholesterol increased. Triglycerides, whole-body lipolysis, and free fatty acids decreased during fasting and hyperinsulinemia. Fasting insulin decreased. Endogenous glucose production decreased during fasting and hyperinsulinemia, providing evidence of improved hepatic insulin sensitivity. Leptin was well tolerated but decreased lean mass.
  
  
  CONCLUSIONS
  Leptin treatment was associated with marked improvement in dyslipidemia. Hepatic insulin sensitivity improved and lipolysis decreased. Visceral fat decreased with no exacerbation of peripheral lipoatrophy. Results from this pilot study suggest that leptin warrants further study in patients with HIV-associated lipoatrophy.
authors.affiliation: Department of Medicine, University of California, San Francisco, USA. kathleen.mulligan@ucsf.edu
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
authors.forename: Hootan
authors.initials: H
authors.lastname: Khatami
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Schwarz
authors.forename: Giorgos K
authors.initials: GK
authors.lastname: Sakkas
authors.forename: Alex M
authors.initials: AM
authors.lastname: DePaoli
authors.forename: Viva W
authors.initials: VW
authors.lastname: Tai
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wen
authors.forename: Grace A
authors.initials: GA
authors.lastname: Lee
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
authors.forename: Morris
authors.initials: M
authors.lastname: Schambelan
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D001823:Body Composition / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D020738:Leptin / Q000172:deficiency / Q000627:therapeutic use*; D008060:Lipodystrophy / Q000188:drug therapy* / Q000209:etiology; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D014781:Viscera
chemical_list: D020738:Leptin; D011994:Recombinant Proteins; D014280:Triglycerides; D002784:Cholesterol