Effects Of Diet/Exercise On APPL1/Akt2 Signaling Pathway And Its Relationship With TRB3 In Obese Mice Liver

Objective: To investigate the effects of diet,aerobic exercise and diet combined with aerobic exercise on the APPL1/Akt2 signaling pathway and the relationship with TRB3 in three different ways.To reveal the molecular mechanism of improving liver insulin resistance in three ways,and to provide theory evidence for the prenvention and treatment of obesity insulin resistance.Methods: 45 C57BL/6J mice which were three weeks old by stratified sampling grouping randomly.The normal group was selected 8 to feed the basal diet,the other 37 were high fat group,fed with high fat diet.After feeding for 12 weeks,obese resistance mice were eliminated,34 mice were randomly divided into four groups according to the weight by stratified random sampling: high fat diet group(HC,n = 8),the group which changed high fat diet into normal diet(HN,n = 8),the group which changed high fat diet into normal diet and exercise(HNE,n = 8),high fat exercise group(HE,n = 8).After the grouping,the HN group changed to normal diet and the exercise group exercised 60 minutes a day with treadmill running,running speed20m/min,6 days a week,and exercised for 8 weeks.After 8 weeks,before the sampling,the blood glucose was measured with ELISA,Western-Blot and RT-PCR were used to measure the liver protein and mRNA expression levels of APPL1,Akt2,P-Akt2,GLUT1 and TRB3.Results:1? Compared with the NC group,HC group weight,abdominal fat weight,lee's index were significantly increased(P <0.01).Compared with the HC group,all indexes in HN group,HE group and HNE group significantly decreased(P <0.05).Compared with the HN group and HE group,the indexes of HNE group were significantly decreased(P <0.01).2?Compared with the NC group,the levels of blood glucose and serum insulin in the HC group were significantly increased(P <0.01),the content of hepatic glycogen was decreased(P <0.05).Compared with the HC group,the levels of blood glucose and serum insulin in the HN group,HE group and HNE group were significantly decreased,the content of hepatic glycogen was increased(P <0.05).Compared with the HN group and HE group,the levels of blood glucose and serum insulin in the HNE group were decreased(P <0.05),the content of hepatic glycogen was increased(P <0.05).3?Compared with the NC group,the mRNA and protein levels of APPL1,Akt2,P-Akt2 and GLUT1 in the HC group were significantly decreased(P <0.01),while the mRNA and protein levels of TRB3 were significantly increased(P <0.01).Compared with the HC group,the mRNAand protein levels of TRB3 in HN group,HE group and HNE group were significantly decreased,the other indexes were significantly increased(P <0.05).Compared with the HN group and the HE group,the mRNA and protein levels of TRB3 in the HNE group decreased(P <0.05),and the other indexes significantly increased.Conclusion:1?Long term high fat diet induced obese mice liver TRB3 and APPL1 competitive binding with Akt2,and inhibited the phosphorylation level,and weakened the transport of glucose by GLUT1,which caused liver glucose metabolism.It is one of the mechanisms of insulin resistance.2?Aerobic exercise and diet control could increase the expression of APPL1,which was competitive binding with Akt2,and promted Akt2 phosphorylation,and increased glucose transport and the synthesis of hepatic glycogen,and improve insulin resistance effectively.Diet combined with exercise intervention is better than single diet or exercise intervention.