Anti-melanocortin-4 receptor autoantibodies in obesity.
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.
Peter
Jean-Christophe
JC
Applied Pharmacology, Biozentrum, University of Basel, CH 4056 Basel, Switzerland.
Bekel
Akkiz
A
Lecourt
Anne-Catherine
AC
Zipfel
Géraldine
G
Eftekhari
Pierre
P
Nesslinger
Maya
M
Breidert
Matthias
M
Muller
Sylviane
S
Kessler
Laurence
L
Hofbauer
Karl G
KG
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
D001323:Autoantibodies; D044105:Receptor, Melanocortin, Type 4