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J Clin Endocrinol Metab. 2009 Mar;94(3):793-800. Epub 2008 Dec 2.
Comment in:
* J Clin Endocrinol Metab. 2009 Mar;94(3):757-9.
Anti-melanocortin-4 receptor autoantibodies in obesity.
Peter JC, Bekel A, Lecourt AC, Zipfel G, Eftekhari P, Nesslinger M,
Breidert M, Muller S, Kessler L, Hofbauer KG.
Applied Pharmacology, Biozentrum, University of Basel, CH 4056 Basel,
Switzerland.
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.
PMID: 19050052 |
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