Leptin enhances glycolysis via OPA1-mediated mitochondrial fusion to promote mesenchymal stem cell survival

Yang,Fan; Li,Bing; Yang,Yongyao; Huang,Minhua; Liu,Xinghui; Zhang,Yang; Liu,Hui; Zhang,Lan; Pan,Yujia; Tian,Shui; Wu,Yueting; Wang,Lijuan; Yang,Long

doi:10.3892/ijmm.2019.4189

Leptin enhances glycolysis via OPA1-mediated mitochondrial fusion to promote mesenchymal stem cell survival

Authors:
- Fan Yang
- Bing Li
- Yongyao Yang
- Minhua Huang
- Xinghui Liu
- Yang Zhang
- Hui Liu
- Lan Zhang
- Yujia Pan
- Shui Tian
- Yueting Wu
- Lijuan Wang
- Long Yang
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Affiliations: Department of Cardiology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China, Xixiu District People's Hospital, Anshun, Guizhou 561000, P.R. China
Published online on: May 9, 2019 https://doi.org/10.3892/ijmm.2019.4189
Pages: 301-312

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Abstract

Transplantation of mesenchymal stem cells (MSCs) is emerging as a potential therapy for cardiovascular diseases. However, the poor survival of transplanted MSCs is a major obstacle to improving their clinical efficacy. Accumulating evidence indicates that hypoxic preconditioning (HPC) can improve the survival of MSCs. It has been previously reported that leptin plays a critical role in HPC‑enhanced MSC survival through increasing optic atrophy 1 (OPA1)‑dependent mitochondrial fusion. Survival of MSCs mainly relies on glycolysis as an energy source. The close relationship between leptin and glucose homeostasis has attracted intense scientific interest. Furthermore, emerging evidence indicates that mitochondrial dynamics (fusion and fission) are associated with alterations in glycolysis. The aim of the present study was to investigate whether leptin increases MSC survival through metabolic regulation. Leptin‑modulated increased OPA1 expression was found to be associated with increased glycolysis. However, the glycolytic efficacy of leptin was abrogated after silencing OPA1 using a selective siRNA, suggesting that OPA1 directly regulates glycolysis. Furthermore, the activation of sodium‑glucose symporter 1 (SGLT1) was markedly induced by leptin. However, leptin‑induced glycolysis was primarily blocked by SGLT1 inhibitor treatment. Thus, leptin regulates OPA1‑dependent glycolysis to improve MSC survival primarily through SGLT1 activation. We therefore identified a pivotal leptin/OPA1/SGLT1 signaling pathway for mitochondrial dynamic‑mediated glycolysis, which may optimize the therapeutic efficiency of MSCs.

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