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|Immunomanipulation of appetite and body temperature through the functional mimicry of leptin.|
|Authors: ||Fanti, B.A. (B. A.) de|
Milagro, F.I. (Fermin Ignacio)
Lamas, O. (Óscar)
Martinez-Anso, E. (Eduardo)
Martinez, J.A. (José Alfredo)
|Keywords: ||Energy balance|
|Issue Date: ||2002|
|Publisher: ||North American Association for the Study of Obesity|
|Publisher version: ||http://www.nature.com/oby/journal/v10/n8/abs/oby2002112a.html|
|Citation: ||De Fanti BA, Milagro FI, Lamas O, Martinez-Anso E, Martinez JA. Immunomanipulation of appetite and body temperature through the functional mimicry of leptin. Obes Res 2002 Aug;10(8):833-837.|
Objective: Although current obesity therapies produce some benefits, there is a need for new strategies to treat obesity. A novel proposal is the use of anti-idiotypic antibodies as surrogate ligands or hormones. These anti-idiotypic antibodies carry an internal motif that imitates or mimics an epitope in the antigen (i.e., hormone or ligand). Thus, anti-idiotypic antibodies to several ligands may mimic them in transducing signals when binding to their receptors.
Research Methods and Procedures: We developed an anti-idiotypic polyclonal antibody against the region of a leptin monoclonal antibody that competitively binds leptin, mimicking the active site structure of leptin. To test whether our anti-idiotype could also reproduce leptin functions, we examined food intake, body weight, and colonic temperature in male Wistar rats (n = 9) in response to intracerebroventricular administration of the leptin anti-idiotype.
Results: Our leptin anti-idiotype induced a significant reduction in food intake coupled with an increase in body temperature comparable to that of leptin. That is, the intracerebroventricular administration of 8.0 microg of leptin anti-idiotype or 5.0 microg leptin significantly increased colonic temperature (Delta 1.9 plusminus 0.11 °C and Delta1.7 plusminus 0.12 °C, respectively). In addition, both decreased 24-hour food intake (-26.4 plusminus 2.4% and -21.9 plusminus 2.2%) compared with the control. The gain in body weight was also decreased by acute administration of the anti-idiotype (-1.4 plusminus 0.28%) and leptin (-1.1 plusminus 0.17%) vs. the phosphate-buffered saline control (1.3 plusminus 0.15%).
Discussion: These studies revealed that the leptin anti-idiotype inhibited food intake and enhanced heat production, mimicking leptin's central actions.
|Permanent link: ||http://hdl.handle.net/10171/17706|
|Appears in Collections:||DA - CIMA - Terapia génica y Hepatología - Anticuerpos monoclonales - Artículos de Revista|
DA - Farmacia - CAFT - Artículos de revista
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