MicroRNA-125a Expression Dysregulation In Obesity-related Insulin Resistance And Glucose And Lipid Metabolism Disorders In The Role And Mechanism Research

In recent years,with the improvement of living standards,people's dietary structure has undergone significant changes.The number of obesity in the world,including China,has increased year by year,which has seriously affected people's physical and mental health and quality of life.Obesity is a kind of metabolic disease with excessive fat accumulation or abnormal distribution in the body.Obesity has been linked to a variety of metabolic diseases,such as insulin resistance,high blood pressure,type 2 diabetes and even cancer.MicroRNA(miRNA)is a kind of endogenous small molecule non-coding RNA,which consists of about 19-25 nucleotides.It regulates the expression of eukaryotic genes from the post transcriptional level through complementary binding with the 3 'untranslated regions(3' UTR)of the target gene m RNA,and then regulates cell proliferation,differentiation,apoptosis and other biological functions.Studies have shown that miRNA is an important regulator of glucose and lipid metabolism homeostasis and insulin secretion,and plays an important role in maintaining metabolic homeostasis.Metabolic disorders are often accompanied by abnormal expression of a large number of miRNAs.Our experiments found that in the genetic model of obesity and high-fat diet,the expression level of miR-125 a in liver tissue decreased.Overexpression of miR-125 a in Hep G2 and Hepa1-6 cells can enhance insulin signaling,reduce lipid accumulation in cells and alter the expression of genes related to lipid metabolism.Injecting ago-miR-125 a through the tail vein of mice can significantly reduce the content of triglycerides and total cholesterol in the liver and serum of mice,and increase the sensitivity of mice to insulin.Injecting antago-miR-125 a and inhibiting miR-125 a expression can up-regulate triglyceride and total cholesterol levels in the liver and serum of mice and reduce the sensitivity of mice to insulin.In addition,injecting agomiR-125 a in a high-fat diet obese mouse model,overexpression of miR-125 a in the liver can significantly improve glucose and lipid metabolism and liver fat accumulation in obese mice.Through bioinformatics analysis and fluorescence report system detection,it was found that miR-125 a can directly target fatty acid elongase 6(elongase of long chain fatty acids family 6,ELOVL6).Mi R-125 a and ELOVL6 were overexpressed in Hep G2 and Hepa1-6 cells at the same time.It was found that miR-125a-mediated insulin sensitivity and lipid metabolism regulation were achieved through targeted regulation of ELOVL6.It is concluded that miR-125 a is involved in the regulation of obesity-related insulin resistance and lipid metabolism disorders through targeting ELOVL6.This study provides a new target and theoretical basis for the treatment and diagnosis of metabolic diseases such as obesity-related insulin resistance and liver steatosis.