Effect Of Adipose-derived Exosomes To The Activation Of Renin-angiotensin-aldosterone System In The Kidney

ObjectiveBy extracting the adipose-derived exosomes,detecting the components of RAAS of in adipose,kidney and blood circulation of obese patients and high-fat feeding mice,extracting the expression of Nephrin and podocin in mice podocyte,we explore the relationship between of adipose-derived exosomes and the activation of RAAS in whole body and kidney,to identify the causes of the changes of kidney in obese patients.MethodsThe clinical data of 145 cases obese patients(OB)and 50 cases Healthy Control(HC)were collected.The patients with OB were treated with bariatric surgery,liposuction was performed in HC,and 1g subcutaneous abdominal fat was retained during operation from them.We extract exosomes from fat,also measure Ang II in adipose,Ang II and PRA in circulation,and urinary AGT in OB and HC.The urinary AGT and the adipose-derived exosomes were observed in 56 patients with ob at postoperative 12 months.8 high-fat feeding mice and 8 normal feed mice were measured for the components of RASS from the different part.Also the AGT and Ang II in renal were labeled by Immunofluorescence.were selected.We extract exosome from fat,and make it cultured with podocyte from further 8 high-fat feeding mice and 8 normal feed-feeding mice.In order to clarify the effect of adipose-derived exosomes to the activation of RAAS in the kidney,Western blotting was used to determine the expression of specific proteins in the podocyte and the expression of RAAS components in the kidney.ResultsAng II in the adipose in OB was significantly higher than HC(P<0.05).The AngII and PRA in the OB in plasma were significantly higher than the HC(P <0.05).Urinary AGT was significantly lower in the 12-month postoperative group than in the Ob group(P <0.05).The concentration of adipose-derived exosomes in the OB was higher than that in the HC(P <0.05).56 cases of OB were followed up,and the uAGT was significantly at postoperative 12 months lower than in the OB(P <0.05).AngII in obesity and renal in high fat feeding mice was higher than normal mice(P <0.05).The uAGT of high-fat mice was higher than that in normal mice(P >0.05).In the immunohistochemistry of renal tissue in high-fat mice,the expression of AGT and AngII in renal tubules and glomerular were increased.According to the H-score scores,the scores of AGT and AngII in the renal of high-fat mice were higher than those in normal mice(P <0.05).High-fat mice had a higher concentration of adipose-derived exosomes than normal mice(P <0.05).The expression of AGT,ACE and AT-1 in podocyte of high-fat mice was higher than that of normal feed-feeding mice.The expression of ACE2 in podocyte of high-fat mice was lower than that of normal feed-feeding mice.The expression of nephrin and podocin in podocyte of high-fat mice was lower than normal feed-feeding mice(P <0.05).ConclusionThere were statistical differences between RAS components in the circulatory,adipose tissue and kidney of the obese patients and the high-fat mice group.Then the RAS components decreased with weight loss after weight loss surgery.The increase of the adipose-derived exosomes in the OB and the high-fat mice,which was statistically different from the control group.There was a statistical difference between the expression of characteristic protein of podocyte cultured with the adipose-derived exosomes in high-fat mice and the control group.These suggests that adipose-derived exosomes may play a certain role in the activation of RAAS in the kidney,and make the kidney change in the end.