ArticleiScience2026
Central relaxin-3/RXFP3 signaling potently drives orexigenic behaviors and attenuates cisplatin-induced anorexia and body weight loss.
Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The relaxin-3 neuropeptide system promotes energy balance by increasing feeding behavior. Here, we investigate the behavioral mechanisms mediating the orexigenic effects of relaxin-3 and the therapeutic potential of relaxin-3 to combat metabolic disorders. We show that central and peripheral administration of relaxin-3 increases high-fat diet intake by increasing meal size in obese rats. Furthermore, we deleted relaxin family peptide receptor 3 (RXFP3) neuronally using RXFP3 fl/fl hSyn-Cre+ mice and show that neuronal RXFP3 is required for the orexigenic effects of relaxin-3. In addition, central relaxin-3 administration augmented food motivation for sucrose and hyperphagia in a binge-like eating model. We then evaluated the potential of relaxin-3 to drive food intake in rats receiving acute maladaptive chemotherapy. Pretreatment of central relaxin-3 attenuated cisplatin chemotherapy-induced anorexia and body weight loss. These findings characterize the behavioral mechanisms by which the relaxin-3 system drives feeding behaviors and highlight its therapeutic potential for metabolic wasting disorders.
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