The Mechanism Of Aldolase B(ALDOB) In Promoting Lipolysis Of Liver Through ATGL

The physiological activities of living organisms are inseparable from energy metabolism,and lipolysis is one of the indispensable energy supply methods for energy metabolism.Lipolysis is a sophisticated and complex regulatory process,which is affected by many hormones,lipid-related proteins,and autophagy.The intracellular triglycerides(TG)are converted into diacylglycerols(DAG),and then the diacylglycerols are converted into monoacylglycerols and decomposed into glycerol and fatty acids.This series of decomposition processes are inseparable from the functions of ATGL,HSL,and MAGL hydrolase.In addition to providing energy for the body,the decomposition of fat is also a regulation of obesity and metabolic diseases caused by obesity.Among the factors that cause obesity,fructose occupies a high proportion.Fructose metabolism is particularly important in maintaining the body's physiological balance.Glycolysis and gluconeogenesis are essential as two energy conversion methods in the metabolic process.Fructose 1-6-bisphosphate aldolase(ALDOB)is involved in the two important pathways of glycolysis and gluconeogenesis,so it has become one of the key enzymes in fructose metabolism.After specifically knocking out the ALDOB gene in mouse liver,the accumulation of lipids in the mouse body was observed.Although there is obvious lipid accumulation,the relationship between lipid accumulation and ALDOB gene knockout has not been clearly explained.Therefore,in this study,we used ALDOB,a key enzyme in fructose metabolism,as the research object to explain the involvement of ALDOB in fat.The mechanism of decomposition.conclusion as below:1.When ALDOB was over-expressed in He La cells,the number of lipid droplets and triglyceride content in the cells were significantly less than those of the control group,and the amount of glycerol released was significantly higher than that of the control group.When ALDOB is over-expressed in Hep G2 cells,the three genes related to lipid hydrolysis,ATGL,HSL,and G0S2,are up-regulated at the m RNA expression level;SCD and FASN are two genes related to lipid synthesis.The m RNA expression level was down-regulated;the autophagy-related genes LC3 B,LAMP1,p62,and ATGL,G0S2 were up-regulated at the protein expression level.Therefore,it can be determined that ALDOB is involved in the breakdown of fat.2.The results of co-immunoprecipitation experiment,lipid droplet change observation,triglyceride content and glycerol release determination,together show that ALDOB interacts with ATGL,MAGL,G0S2,RGN;and ALDOB acts on ATGL's PT(10-178)Area,ALDOB up-regulates ATGL expression does not depend on p53 to activate ATGL expression pathway;ALDOB and RGN interact directly.ALDOB can work with ATGL,MAGL,and RGN to promote the reduction of intracellular lipid droplets,the reduction of triglyceride content,and the release of more glycerol from cells.ALDOB may inhibit the function of G0S2 in inhibiting lipolysis in cells,thereby promoting the decomposition of intracellular fat.3.The structure of the mouse ALDOB protein was analyzed.It increases the understanding of ALDOB protein,and at the same time can more directly explore the mechanism of ALDOB's participation in physiological activities,and provide a research basis for this.ALDOB participates in the decomposition of cell fat in a variety of ways.The study of this mechanism can provide new therapeutic directions for the treatment of obesity caused by excessive fructose intake and a series of metabolic diseases caused by obesity.However,the more specific mechanism of ALDOB involved in lipolysis is still to be explored.