Amylin-drvien Food Intake And Thermogenesis Via MC4R-mediated In Mice

MC4R plays an important role in the body's energy metabolism balance which was supposed to associated with the Interscapular BAT(iBAT).MC4R defects lead to a severe clinical obesity in mice.Thus,MC4R is a potential target for the treatment of obesity.Amylin regulate energy metabolism balance through the central nervous system.but the relationship of MC4R and Amylin is not clearly.In this study,food intake and iBAT temperature were measured after injection Amylin(50 ?g/kg)and MC4R antagonist(SHU9119 50 ?g/kg)in C57BL/6 mice,and detected the C-Fos and MC4R co-localization used the immunofluoresce.Also,expression of pACC,pAMPK,pERK,UCP1 and MC4R in hypothalamus and iBAT were decteted by Western Blot.The results showed that pretreatment with i.p.SHU9119 followed by amylin prevented feeding suppression,indicating that SHU9119 was able to reverse the inhibition of food intake and increases in IBAT temperature observed following administration of i.p.amylin alone.The expression of C-Fos and MC4R neurons were increased after injection Amylin,but SHU9119 could weaken these effects.Amylin could significantly induced the protein expression of pACC,pAMPK,MC4R and UCP1 in hypothalamus andiBAT(P<0.01).But Amylin promotes pERK expression in the hypothalamus and inhibits pERK expression in iBAT.Similarly,these affects were faded after injection SHU9119.In conclusion,amylin could increased the expression of C-Fos and MC4R,and significantly inhibited the mice food intake but promotion the iBAT temperature.Amylin could induced the protein expression of pACC,pAMPK,pERK,UCP1 and MC4R.This research reveals the functions and relationship of Amylin and MC4R in feeding behavior and heat production.The results suggest that Amylin regulated food intake behavior and temperature may be partially mediated by the MC4R pathway.This research could provided the more understanding of MC4R regulated pathways,and promoted the application of Amylin on the treatment of obesity.