Immunomanipulation of Appetite and Body Temperature through the Functional Mimicry of Leptin

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 μg of leptin anti‐idiotype or 5.0 μg leptin significantly increased colonic temperature (Δ 1.9 ± 0.11 °C and Δ1.7 ± 0.12 °C, respectively). In addition, both decreased 24‐hour food intake (−26.4 ± 2.4% and −21.9 ± 2.2%) compared with the control. The gain in body weight was also decreased by acute administration of the anti‐idiotype (−1.4 ± 0.28%) and leptin (−1.1 ± 0.17%) vs. the phosphate‐buffered saline control (1.3 ± 0.15%). Discussion: These studies revealed that the leptin anti‐idiotype inhibited food intake and enhanced heat production, mimicking leptin's central actions.