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

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

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Obesity has been known to negatively modulate the life-span and immunosuppressive poten-tial 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 tissue-derived 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 ef-fects 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-1α axis.These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

AdiponectinAdipose-derived stromal cellsColitisGlycolytic inductionHIF1αImmunomodulationMesenchymal stromal cellsObesity

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

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Department of Pharmacology,Hanoi University of Pharmacy,Hanoi 100000,Viet Nam

College of Pharmacy,Yeungnam University,Gyeongsan 38541,Republic of Korea

Department of Precision Medicine,School of Medicine,Sungkyunkwan University,Suwon 16419,Republic of Korea

Department of Medical Biotechnology,Yeungnam University,Gyeongsan 38541,Republic of Korea

Research Institute of Cell Culture,Yeungnam University,Gyeongsan 38541,Republic of Korea

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Basic Science Research Program of the National Research Foundation of Korea(NRF)Basic Science Research Program through the National Research Foundation of Korea(NRF)

NRF-2021R1A2C10131322020R1A6A1A03044512

2024

10.1016/j.apsb.2023.10.019

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.14(1)
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