title: Lipid regulation in lipodystrophy versus the obesity-associated metabolic syndrome: the dissociation of HDL-C and triglycerides.
abstract: BACKGROUND
  There is an inverse relationship between triglycerides and high-density lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in insulin resistance decreases triglycerides and increases HDL-C. Patients with lipodystrophy have extreme insulin resistance with high triglycerides and low HDL-C. Leptin replacement in lipodystrophy leads to a marked decrease in triglycerides (∼60%).
  
  
  OBJECTIVE
  Our objective was to study the effects of metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in triglycerides and HDL-C in interventions for the obesity-associated metabolic syndrome.
  
  
  METHODS
  This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy.
  
  
  METHODS
  Metreleptin (0.06-0.24 mg/kg/d) was administered for 24 months in lipodystrophy.
  
  
  METHODS
  Serum triglycerides and HDL-C were measured.
  
  
  RESULTS
  At baseline, lipodystrophy patients had low HDL-C (30 ± 1 mg/dL) and high triglycerides (961 ± 220 mg/dL) with an inverse relationship between the two (R = -0.37, P = .0006). There was no change in HDL-C with metreleptin despite major improvement in triglycerides, and individual changes in triglycerides only weakly predicted HDL-C change. On linear regression, in obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2 mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C.
  
  
  CONCLUSIONS
  The normal reciprocal relationship between triglyceride and HDL-C change seen in response to interventions for the obesity-associated metabolic syndrome is quantitatively different from that seen in lipodystrophy in response to metreleptin. Further work is needed to understand HDL-C regulation in this condition.
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch (J.J., E.K.C., P.G., R.J.B.), National Institute of Diabetes and Digestive and Kidney Diseases, and National Heart Lung and Blood Institute (R.D.S.), National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Jalaja
authors.initials: J
authors.lastname: Joseph
authors.forename: Robert D
authors.initials: RD
authors.lastname: Shamburek
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Cochran
authors.forename: Phillip
authors.initials: P
authors.lastname: Gorden
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D008060:Lipodystrophy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D020738:Leptin; D014280:Triglycerides; C415771:metreleptin