Anti-melanocortin-4 receptor autoantibodies in obesity.
- Peter JC Applied Pharmacology, Biozentrum, University of Basel, CH 4056 Basel, Switzerland.
- Bekel A
- Lecourt AC
- Zipfel G
- Eftekhari P
- Nesslinger M
- Breidert M
- Muller S
- Kessler L
- Hofbauer KG
- 2008-12-04
Published in:
- The Journal of clinical endocrinology and metabolism. - 2009
Adult
Aged
Animals
Autoantibodies
Blood-Brain Barrier
Enzyme-Linked Immunosorbent Assay
Female
Humans
Immunoprecipitation
Male
Middle Aged
Obesity
Rats
Rats, Sprague-Dawley
Receptor, Melanocortin, Type 4
Surface Plasmon Resonance
English
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.
CONCLUSION
These observations suggest that inhibitory anti-MC4R autoAbs might contribute to the development of obesity in a small subpopulation of patients.
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.
CONCLUSION
These observations suggest that inhibitory anti-MC4R autoAbs might contribute to the development of obesity in a small subpopulation of patients.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1210/jc.2008-1749
- PMID 19050052
- Persistent URL
- https://sonar.ch/global/documents/279336
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