Effects Of Lipotoxicity On Dedifferentiation Of β Cells And Protective Mechanism Of Bezafibrate

Objective:To observe the effect of high-fat diet on the dedifferentiation of mouse islet β cells,and whether the lipid-lowering drug bezafibrate can inhibit its dedifferentiation and play a role in β-cell protection.Methods:The C57BL/6J mouse obesity model was established by feeding with high fat diet.The obese mice were randomly divided into high fat diet group(HF+NS)and high fat diet + bezafibrate intervention group(HF+BZ).Also set up Normal Diet Group(NC+NS).The HF+BZ group was given a daily dose of bezafibrate 50 mg/kg,and the HF+NS and NC+NS groups were given a corresponding volume of normal saline.The rats were continuously gavage for 8 weeks.After the end of the stomach,the serum levels of TG,TC and FBG were measured in the three groups.Mouse pancreatic tissue was taken and the expression of insulin,FoxO1 and Nanog in mouse islet β cells was detected by immunofluorescence staining.Results:1.The expression of insulin and FoxO1 is decreased in pancreatic islet β cells in high-fat diet group,and FoxO1 is transferred to the nucleus.2.Increased expression of progenitor cell marker Nanog in islet β cells in the high-fat diet group.3.Intervention with bezafibrate significantly decreased serum TG in the HF+BZ group.4.In the HF+BZ group,the expression of insulin and FoxO1 increased,and the expression of progenitor cell marker Nanog decreased.Conclusion:1.High-fat diet induces dedifferentiation of islet β cells,mainly manifested in:1)decreased FoxO1 expression and caused nuclear transfer;2)promote mature β cells to lose their differentiated phenotype and cell characteristics,and have certain ancestral features2.Bezafibrate can not only regulate the lipid metabolism disorder in obese mice,but also improve the dedifferentiation of β cells induced by high fat.