Preliminary Study On The Mechanism Of Palmitic Acid Regulating The Expression Of Irisin

Type 2 diabetes is the third chronic non-communicable disease that threatens human health after cardiovascular diseases and malignant tumors.Disorders of glucose and lipid metabolism are often accompanied by an increase in free fatty acids in the blood.In particular,free saturated fatty acids can not only cause the body to produce a variety of stress responses,but also promote insulin resistance.The main component of free fatty acids is palmitic acid,and its content is significantly increased in patients with type 2diabetes.Skeletal muscle plays an important role in the utilization of blood sugar.Most of the blood sugar conversion and glycogen storage in the human body are completed by skeletal muscle.In addition,skeletal muscle stimulated by external factors can produce various stress responses and secrete cytokines to resist external influences.Irisin is a muscle-derived factor secreted by skeletal muscle,which can regulate energy metabolism by inducing browning of white adipose tissue.Studies have found that irisin can promote gluconeogenesis and glycogen synthesis,increase glycogen accumulation and maintain glucose homeostasis.However,there are relatively few studies on the regulation mechanism of palmitic acid on irisin.In this study,a diabetic mouse model was constructed using high-fat feed to study the lipid toxicity of saturated fatty acids.After the blood glucose of the mice was significantly increased and stabilized,a glucose tolerance test was performed to determine whether the blood glucose metabolism of the mice was disturbed.The results showed that feeding with high-fat diet for about 4 weeks can cause a significant increase in blood sugar of mice and lead to the occurrence of insulin resistance in mice.Transcription factor prediction analysis found that there is a binding sequence of Zfp57 in the promoter region of the irisin gene.The diabetic model mice were humanely sacrificed,and the expression of irisin and Zfp57 in the muscle tissue was detected.It was found that a high-fat diet reduced the expression of irisin and increased the expression of Zfp57 in the muscle tissue of mice.The results of RNA-Seq high-throughput sequencing of mouse muscle tissue showed that high-fat diet caused changes in signal pathways such as AMPK and insulin.At the cellular level,palmitic acid is used to treat myoblasts to detect whether the expression of irisin is consistent with in vivo experiments.And through the blocking of the signal pathway,the interference or overexpression of related regulatory factors,and the detection of pathwayrelated molecules by techniques such as q RT-PCR and Western Blot,to further improve the exploration of the regulation mechanism of irisin expression.The results showed that palmitic acid mediates the up-regulation of Zfp57 expression by inhibiting the AMPK signaling pathway.Zfp57 binds to the promoter region of the irisin gene to negatively regulate the expression of irisin.The down-regulation of the expression of irisin mediated by Zfp57 further induces insulin resistance.To sum up,this project has carried out research on the regulation mechanism of palmitic acid on the expression of irisin,combined with high-throughput sequencing technology and bioinformatics prediction to identify the regulatory pathways and regulatory factors that affect the expression of irisin.And through cell and molecular biology experiments to verify the selected pathways.To find stronger evidence for the regulation mechanism of irisin expression under the action of palmitic acid,and to provide more experimental theoretical basis for palmitic acid to cause glucose metabolism disorders.