Study On The GLP-1 Receptor Mediated Regulation Of Feeding In The Central Amygdala

Objective:Central amygdala is one of the important sites of glucagon-like peptide 1(GLP-1)feeding regulation.The GLP-1 receptor signaling pathway in the cental amygdala plays an important physiological role in feeding and energy metabolism.In this study,the effects of activation or blocking of GLP-1 mediated signaling pathway in amygdala on feeding in rats and its potential mechanisms were observed in fluorescence immunohistochemical staining and microinjection of the central amygdala.Methods:Adult male Wistar rats(280-320 g)were selected.Fluorescent immunohistochemical staining was used to observe the distribution of GLP-1 receptors in the central amygdala of rats.Microinjection of GLP-1R agonist Ex4 or GLP-1R antagonist Ex9 into the central amygdala were used to observe effects of activation or block of GLP-1 receptor signaling pathway on food intake,high-fat diet intake,kaolin intake,and sucrose and corn oil intake in rats.Results:(1)6-carboxyfluorescein(FAM)-labeled Ex4(GLP-1 receptor agonist)was injected into the central amygdala and caudate putamen,respectively.After 3 hours of the micro-injection,FAM with yellow fluorescence was observed in the central amygdala rather than the caudate putamen in an immune-fluorescent staining,it was confirmed that FAM was located in the central amygdala neurons.It is suggested that the expression of the GLP-1 receptor in the central amygdala is position specific.(2)Microinjection of GLP-1 receptor agonist Ex4 into the central amygdala,the cumulative food intake of rats was significantly decreased at 0-20 h(P<0.05).Microinjection of GLP-1 receptor antagonist Ex9 into the central amygdala,there was a significant increase in food intake at 0-4 h and 0-20 h(P<0.05).It suggests that endogenous GLP-1 receptor plays an important role in the feeding behavior of rats.(3)Microinjection of Ex4 into the central amygdala had no significant change in kaolin intake(P>0.05).Although the meal size decreased,the difference was not statistically significant(P>0.05).There was no significant effect on the meal number(P>0.05).It suggests that the inhibition of GLP-1 receptor uptake in amygdala is not caused by nausea.(4)Microinjection of Ex4 into the central amygdala,the intake of high-fat diet in rats decreased significantly at 9 h,lasting for 20 h(P<0.05);the meal size and meal frequency in the high-fat diet experiment were significantly lower(P<0.05);Microinjection of Ex9 into the central amygdala significantly increased the intake of high-fat diets at 0-2 h,0-4 h,0-6 h,and 0-7 h(P<0.05).It suggests that the stimulation of GLP-1 receptor signaling pathway in the central amygdala can enhance satiation(reduced meal size)or satiety(reduced meal freguency)in rats.(5)Microinjection of Ex9 into the central amygdala,the intake of sucrose and corn oil in 0-1 h,0-1.5 h and 0-2 h were significantly increased(P<0.05),and the 0-24 h sucrose total calorie intake also increased significantly(P<0.05).However,there was no significant effect on the 0-24 h corn oil total caloric intake(P>0.05).It suggests that activation of the GLP-1 receptor signaling pathway may be involved in the regulation of dietary preferences in rats.Conclusion:GLP-1 receptor exists in the central amygdala,and the GLP-1 receptor signaling pathway in the central amygdala is involved in the regulation of feeding behavior in rats,and the activation of this signaling pathway also affects dietary preferences in rats.The central amygdala is one of the important sites for regulating physiological feeding.