The Mechanism Of 2,4-dienoyl-CoA Reductase Affect The Lipolysis And Accelerate The Growth Of Cervical Cancer Cells

2,4-Dienoyl-Co A reductase(DECR1)is mainly distributed in the cytoplasm and mitochondria.DECR1 acts as a rate-limiting enzyme to participate in the β-oxidation of polyunsaturated fatty acids with base carbon atoms and even carbon atoms to generate energy for the body’s needs in the mitochondria.Many diseases are related toβ-oxidation of fatty acids,such as cardiovascular disease,cancer and diabetes.Although DECR1 is the rate-limiting enzyme in the fatty acid β-oxidation pathway,whether it is involved in the occurrence and development of diseases related to fatty acid β-oxidation,and the mechanism of its action has not yet been clearly elucidated.As one of the energy supply methods of cells,lipolysis plays an important role,and lipolysis mainly occurs in the cytoplasm.Among them,the first important enzyme involved in lipolysis was HSL.If lipid metabolism is abnormal,it can also cause metabolic diseases such as obesity and diabetes.Previous studies on DECR1 have confirmed that DECR1 is involved in the β-oxidation of fatty acids in the mitochondria,so does DECR1 have a connection with fat catabolism in the cytoplasm? Therefore,this project we will explore the mechanism of DECR1 in the cytoplasm.We found that DECR1 participates in the breakdown of fat in the cytoplasm,and preliminarily results show the mechanism of DECR1 in the lipolysis pathway.At the same time,it was also found that DECR1 has a certain connection in the occurrence and development of cervical cancer cells.The specific experimental results are as follows:1.Through immunofluorescence experiments and the determination of triglyceride content in He La cells,we found that when DECR1 is overexpressed,the number of lipid droplets in the cell decreases and the triglyceride content decreases;when DECR1 is silenced in the cell,the intracellular content of triglycerides increased.Therefore,it can be shown that DECR1 participates in the metabolism of triglycerides in the cytoplasm.2.When DECR1 was overexpressed in HL-7702 cells,ATGL,HSL,LPL,and G0S2,PPAR-α,PPAR-γ,and ch REBP were down-regulated at the mRNA expression level.At the same time,when He La cells overexpress DECR1,the protein expression of ATGL increased.When He La cells are overexpressing DECR1 and starving,the number of lipid droplets in the cells is significantly reduced or even disappeared.In summary,DECR1 is involved in the breakdown of fat.3.The results of co-immunoprecipitation and immunofluorescence experiments show that DECR1 has no interaction with ATGL;but has interaction with HSL;and it is co-localized in the cytoplasm.DECR1 acts on the N-terminal 7-314 region of HSL.When DECR1 is co-expressed with HSL,the measurement results of intracellular triglyceride and glycerol release indicate that DECR1 plays a role in promoting HSLmediated lipolysis.4.Through protein immunoblotting experiment and scratch experiment,we found that when DECR1 is expressed,the expression of P-AKT protein related to insulin sensitivity is blocked.Therefore,DECR1 can reduce insulin sensitivity;accelerate the migration rate of cervical cancer cells,and the change in migration rate is due to the up-regulation of the expression of p62 protein.This subject explores the mechanism of DECR1 in lipolysis,which can provide new ideas and targets for the development of drugs for the treatment of obesity,type 2diabetes and cancer.