Effects Of Orexins Feeding And Energy Metabolism In Mice

Objective:To investigate the effects of orexins on feeding and energy metabolism in mice.Methods:The distribution of orexin positive neurons in the brain was analyzed by immunohistochemistry.The effects of different doses of orexin-A(1.5nmol,3.5nmol or 15 nmol)or orexin-B(1.5,3.5 or 15 nmol)on the food intake during 0-2h and 0-4h were observed via Third ventricle catheterization.ELISA method was used to observe the effects of different doses of orexin-A(1.5nmol,3.5nmol or 15 nmol)or orexin-B(1.5,3.5 or 15 nmol)on the activity of citrate synthase in the liver mitochondria of mice.In addition to the third ventricle injection of orexin-A through catheter,application of metabolic measurement device were observed in light and dark and under fasting conditions respiratory quotient(RQ= VCO2 production of carbon dioxide and oxygen consumption VO2 ratio)and the changes of metabolic rate.Results: Immunohistochemical analysis showed that Orexin-A immunoreactive neurons were mainly expressed in the lateral hypothalamic area(LHA)in the central nervous system.The feeding results show that compared with the NS group and orexin-A 3.5nmol group,after injection of low dose(1.5nmol)or high dose(15nmol)orexin-A into the third ventricle 0-2 hours and 0-4 hours,food intake increased significantly(P<0.05),and compared with the NS group,the third ventr icle injection of 3.5nmol orexin-A,the food intake no significant change(P>0.05).The third ventricle injection of any dose of orexin-B had no significant influence on the food intake of mice(P>0.05).In order to further investigate the effect of orexin on mitochondrial function of the major metabolic organ,the effects of third ventricle injection of orexin-A and orexin-B on the activity of citrate synthase in liver mitochondria were examined.Compared withthe third ventricle were injected with low dose(1.5nmol),the third ventricle were injected withmiddle dose(3.5nmol)or high dose(15nmol)orexin-A could significantly increase the mitochondrial citrate synthase activity and(P<0.05)a significant dose dependent relationship(P<0.05~0.01).Compared with the NS group,the third ventricle injection of orexin-B did not cause the activity of the citrate synthase altered in the liver mitochondria(P>0.05).The effect of energy metabolism was observed after injection of 3.5nmol orexin-A into the third ventricle.The results showed that orexin-A could increase(P< 0.05)the metabolic rate by decreasing the respiratory quotient(P<0.05).In the dark cycle,orexin-A had no effect on RQ,but Orexin-A induced a more persistent increase in metabolic rate(P<0.05).In fasted mice,3.5nmol(orexin-A)was injected into the third ventricle,and its respiratory entropy(RQ)was transiently elevated and metabolic rate increased significantly(P > 0.05).Conclusion: Orexin-A can promote the feeding in mice,which is related to the receptor specific OXR2(OXR1),and orexin-A can promote energy metabolism,which is related to circadian rhythm...