Differential effects of selective agonists of neuromedin U1 and U2 receptors in obese and diabetic mice

摘要: Background and Purpose Neuromedin U (NmU) may be a novel target for obesity treatment owing to its anorectic energy expenditure enhancing effects. Although two receptors, NMU1 NMU2, are both responsible the NmU-mediated anti-obesity effects, receptor agonist with most appropriate profiles treating diabetes in terms of efficacy safety is as yet unknown. Thus, we developed evaluated NMU1/2 receptor-selective agonists. Experimental Approach Efficacy were assessed mice diet-induced (DIO) those leptin-deficient (ob/ob) through repeated peripheral administration selective agonists (NMU-6102) NMU2 (NMU-2084), along non-selective (NMU-0002 NMU-6014). We also performed immunohistochemistry c-Fos protein expression brain probe their mechanisms action. Key Results Although NMU2-selective had high compared NMU1-selective agonist, only led relatively low adverse such diarrhoea, DIO mice. However, but not effective diabetic ob/ob Mechanistically, preferentially activate pro-opiomelanocortin neurons hypothalamic arcuate nucleus paraventricular nucleus. Conclusions Implications These results suggest that an well-balanced drug beneficial once side effects minimized.