Adiponectin restores the obesity-induced impaired immunomodulatory function of mesenchymal stromal cells via glycolytic reprogramming  

作　　者：Duc-Vinh Pham Thi-Kem Nguyen Bao-Loc Nguyen Jong-Oh Kim Jee-Heon Jeong Inho Choi Pil-Hoon Park 

机构地区：[1]Department of Pharmacology,Hanoi University of Pharmacy,Hanoi 100000,Viet Nam [2]College of Pharmacy,Yeungnam University,Gyeongsan 38541,Republic of Korea [3]Department of Medical Biotechnology,Yeungnam University,Gyeongsan 38541,Republic of Korea [4]Research Institute of Cell Culture,Yeungnam University,Gyeongsan 38541,Republic of Korea [5]Department of Precision Medicine,School of Medicine,Sungkyunkwan University,Suwon 16419,Republic of Korea

出　　处：《Acta Pharmaceutica Sinica B》2024年第1期273-291,共19页药学学报（英文版）

基　　金：This work was supported by the Basic Science Research Program of the National Research Foundation of Korea(NRF)(NRF-2021R1A2C1013132);Basic Science Research Program through the National Research Foundation of Korea(NRF)(2020R1A6A1A03044512).The authors thank the Core Research Support Center for Natural Products and Medical Materials(CRCNM)for the technical support regarding the confocal microscopic analysis.

摘　　要：Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells(MSC).However,it remains unclear what drives the compromised potency of obese MSC.In this study,we examined the involvement of adiponectin,an adipose tissuederived hormone,in obesity-induced impaired therapeutic function of MSC.Diet-induced obesity leads to a decrease in serum adiponectin,accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC(ADSC).Interestingly,priming with globular adiponectin(gAcrp)improved the immunomodulatory potential of obese ADSC.Similar effects were also observed in lean ADSC.In addition,gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis.Mechanistically,while obesity inhibited the glycolytic capacity of MSC,gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1a axis.These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

关 键 词：ADIPONECTIN Adipose-derived stromal cells COLITIS Glycolytic induction HIF1a IMMUNOMODULATION Mesenchymal stromal cells OBESITY 

分 类 号：R589.2[医药卫生—内分泌]