Effect And Mechanism Of The β-catenin In High-fat Diet Induced Beta Cells Dedifferentiation And Obesity In Mice

Objective: To investigate on the effect of β-catenin on obesity in mice and its possible molecular biological mechanism affecting the dedifferentiation of islet beta cells induced by high fat.Methods: 1,The C57 mice were divided into six groups,namely,the nomal diet 4-week group,the 16-week group,the 24-week group,the high-fat diet group 4-week group,the16-week group,the 24-week group,body weight was monitored weekly.During feeding,the IGTT and ITT experiments were measured every 4 weeks.The pancreatic tissue was buried and fixed,H-E staining was observed,and immunofluorescence was detected to dedifferentiate index,including Neurogenin-3,Nanog.The protein of pancreatic islet in mice was extracted and the expression of beta-catenin protein was detected by Western blots method.2,over-express beta-catenin mice were constructed and divided these mice into four groups,and the groups were as follows: A,beta-catenin over-express mice + high-fat diet feeding group B,wild mice + high-fat feeding group C,β-catenin over-express mice + normal diet feeding group D,wild mice + normal diet feeding group,Measure the weekly weight during feeding,and IGTT and ITT experiments were done every 4 weeks.After 12 weeks of feeding,mice were put into the metabolic cages to monitor metabolic index,after the experiment collect the pancreatic tissue,liver tissue,visceral fat,subcutaneous fat and brown adipose tissue to weighing and taking photographs,embedding fixation,H-E staining observation,immunofluorescence detection of beta cells dedifferentiate index--Neurogenin-3;The group of macrophages of visceral adipose tissue was detected by flow cytometry,and the difference of islet in mice was extracted to observe morphology.Results: 1,Compared with the control group,the beta cells in mice did not dedifferentiate after 4 weeks of high-fat feeding intervention,and after 16 weeks of high-fat feeding,theislet beta cells in mice began to dedifferentiate,and after 24 weeks of continuous feeding,the phenomenon of beta cell dedifferentiation increased significantly,and the expression ofβ-catenin in pancreatic islet tissue increased significantly.2.After over-expressingβ-catenin,the body weight and insulin resistance of mice were significantly increased,and the dedifferentiation of beta cells in the pancreas of mice was obvious.Other tissues included liver,visceral fat,subcutaneous fat,and a significant increase in fat cells in brown adipose tissue.Conclusion: Overexpression of β-catenin in pancreas exacerbates high-fat diet induced obesity and insulin resistance,stimulates islet beta cells to dedifferentiate.