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Antibodies as pharmacologic tools for studies on the regulation of energy balance

Hofbauer, K. G. and Lecourt, A. C. and Peter, J. C.. (2008) Antibodies as pharmacologic tools for studies on the regulation of energy balance. Nutrition, Vol. 24. pp. 791-797.

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Official URL: http://edoc.unibas.ch/dok/A6003558

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Abstract

OBJECTIVE: Active immunization in rats may serve several purposes: the production of a disease-like phenotype, the generation of pharmacologic tools, and the development of clinically useful therapies. We selected the melanocortin-4 receptor (MC4R) as a target because its blockade could provide a treatment for anorexia and cachexia. METHODS: We used a sequence of the N-terminal (NT) domain of the MC4R as an antigen. Rats immunized against the NT peptide produced specific MC4R antibodies (Abs) that were purified and characterized in vitro and in vivo. RESULTS: The Abs acted as inverse agonists and reduced under basal conditions the production of cyclic adenosine monophosphate in HEK-293 cells expressing the human MC4R. Rats immunized against the NT peptide developed a phenotype consistent with hypothalamic MC4R blockade, i.e., increased food intake and body weight, liver and fat-pad weights, hepatic steatosis, and increased plasma triacylglycerols. With a high-fat diet, plasma insulin levels were significantly increased. In separate experiments an increase in food intake was observed after injection of purified MC4R Abs into the third ventricle. When lipopolysaccharide was administered in NT-immunized rats the reduction of food intake was partly prevented in this model of cytokine-induced anorexia. CONCLUSION: Our results show that active immunization of rats against the MC4R resulted in the generation of specific Abs that stimulated food intake by acting as inverse agonists of the hypothalamic MC4R. Pharmacologically active monoclonal MC4R Abs could be the starting point for the development of novel treatments for patients with anorexia or cachexia.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Angewandte Pharmakologie (Hofbauer)
UniBasel Contributors:Hofbauer, Karl G.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier Science
ISSN:0899-9007
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Oct 2012 15:32
Deposited On:11 Oct 2012 15:30

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