Involvement of endogenous neuromedin U and neuromedin S in thermoregulation

We investigated the possible involvement of neuromedin U (NMU) and neuromedin S (NMS) in thermoregulation in rats. Intracerebroventricular (icv) injection of NMU or NMS increased the back surface temperature (BS-T) in a dose-dependent manner during both the light and dark periods. Pre-treatment with the β3 blocker SR59230A, and the cyclooxygenase blocker indomethacin, inhibited the increase in BS-T induced by NMS. Icv injection of NMS and NMU increased the expression of mRNAs for prostaglandin E synthase and cyclooxygenase 2 (COX2) in the hypothalamus, and that of mRNA for uncoupling protein 1 (UCP1) in the brown adipose tissue. Comparison of thermogenesis in terms of body temperature under normal and cold conditions revealed that NMS-KO and double-KO mice had a significantly low BS-T during the active phase, whereas NMU-KO mice did not. Exposure to low temperature decreased the BS temperature in all KO mice, but BS-T was lower in NMS-KO and double-KO mouse than in NMU-KO mice. Calorie and oxygen consumption was also significantly lower in all KO mice than in wild-type mice during the dark period. These results suggest that NMU and NMS are involved in thermoregulation via the prostaglandin E2 and β3 adrenergic receptors, but that endogenous NMS might play a more predominant role than NMU. •Intracerebroventricular injection of neuromedin U (NMU) and S (NMS) increase body temperature.•NMU and NMS increase mRNA expression for PGE synthase and cyclooxygenase 2 in hypothalamus.•NMU and NMS increase mRNA expression for uncoupling protein 1 (UCP1) in the brown adipose tissue.•Calorie and oxygen consumption was lower in NMU-KO, NMS-KO and double-KO mice.•NMS-KO and double-KO mice had a significantly low body temperature under normal condition.