title: Anti-melanocortin-4 receptor autoantibodies in obesity.
abstract: BACKGROUND
  The melanocortin-4 receptor (MC4R) is part of an important pathway regulating energy balance. Here we report the existence of autoantibodies (autoAbs) against the MC4R in sera of obese patients.
  
  
  METHODS
  The autoAbs were detected after screening of 216 patients' sera by using direct and inhibition ELISA with an N-terminal sequence of the MC4R. Binding to the native MC4R was evaluated by flow cytometry, and pharmacological effects were evaluated by measuring adenylyl cyclase activity.
  
  
  RESULTS
  Positive results in all tests were obtained in patients with overweight or obesity (prevalence, 3.6%) but not in normal weight patients. The selective binding properties of anti-MC4R autoAbs were confirmed by surface plasmon resonance and by immunoprecipitation with the native MC4R. Finally, it was demonstrated that these autoAbs increased food intake in rats after passive transfer via intracerebroventricular injection.
  
  
  CONCLUSIONS
  These observations suggest that inhibitory anti-MC4R autoAbs might contribute to the development of obesity in a small subpopulation of patients.
authors.affiliation: Applied Pharmacology, Biozentrum, University of Basel, CH 4056 Basel, Switzerland.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Peter
authors.forename: Akkiz
authors.initials: A
authors.lastname: Bekel
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Lecourt
authors.forename: Géraldine
authors.initials: G
authors.lastname: Zipfel
authors.forename: Pierre
authors.initials: P
authors.lastname: Eftekhari
authors.forename: Maya
authors.initials: M
authors.lastname: Nesslinger
authors.forename: Matthias
authors.initials: M
authors.lastname: Breidert
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
authors.forename: Laurence
authors.initials: L
authors.lastname: Kessler
authors.forename: Karl G
authors.initials: KG
authors.lastname: Hofbauer
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001812:Blood-Brain Barrier; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000209:etiology / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4 / Q000276:immunology*; D020349:Surface Plasmon Resonance
chemical_list: D001323:Autoantibodies; D044105:Receptor, Melanocortin, Type 4