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

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

doi:10.1016/j.apsb.2023.10.019

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

Acta Pharm Sin B. 2024 Jan;14(1):273-291. doi: 10.1016/j.apsb.2023.10.019. Epub 2023 Oct 28.

Authors

Duc-Vinh Pham^{1

2}, Thi-Kem Nguyen², Bao-Loc Nguyen², Jong-Oh Kim², Jee-Heon Jeong³, Inho Choi^{4

5}, Pil-Hoon Park^{2

5}

Affiliations

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 Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea.
⁴ Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea.
⁵ Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Republic of Korea.

Abstract

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 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 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-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.

Keywords: Adiponectin; Adipose-derived stromal cells; Colitis; Glycolytic induction; HIF1α; Immunomodulation; Mesenchymal stromal cells; Obesity.