AMPK promotes survival and adipogenesis of ischemia-challenged ADSCs in an autophagy-dependent manner

Some studies have shown that transplanted fat tissues usually cannot survive for long if adipose-derived stem cells (ADSCs) are removed from the tissues in advance. It is more meaningful to explore the mechanism mediating survival and differentiation of ADSCs in the transplanted microenvironment. AM...

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Published in:Biochimica et biophysica acta. Molecular and cell biology of lipids 2018-12, Vol.1863 (12), p.1498-1510
Main Authors: Li, Chichi, Chen, Kewei, Jia, Minghui, Ding, Xi, Jiang, Zipei, Li, Liqun, Zhang, Dan
Format: Article
Language:English
Subjects:
Adipogenesis
Adipose Tissue - cytology
Adipose Tissue - metabolism
Adipose-derived stem cells
AMP-activated protein kinase
AMP-Activated Protein Kinases - metabolism
Autophagy
Autophagy - drug effects
Autophagy-Related Protein 7 - antagonists & inhibitors
Autophagy-Related Protein-1 Homolog - metabolism
Cell Differentiation
Cell Hypoxia
Cell Survival
Cells, Cultured
Humans
Intracellular Signaling Peptides and Proteins - metabolism
Ischemia
RNA, Small Interfering - pharmacology
Sirolimus - pharmacology
Stem Cells - cytology
Stem Cells - metabolism
TOR Serine-Threonine Kinases - metabolism
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Summary:Some studies have shown that transplanted fat tissues usually cannot survive for long if adipose-derived stem cells (ADSCs) are removed from the tissues in advance. It is more meaningful to explore the mechanism mediating survival and differentiation of ADSCs in the transplanted microenvironment. AMP-activated protein kinase (AMPK) has been shown to be one of the energy receptors that regulate many aspects of cellular metabolism. AMPK activation has been implicated in models of adult ischemic injury, but the mechanism and the regulating effects of AMPK on survival and adipogenesis of transplanted ADSCs are still little known. In this study, we simulated the transplanted microenvironment using oxygen-glucose deprivation (OGD) to test the survival and adipogenesis of ADSCs. We found that OGD treatment triggered significant apoptosis and promoted autophagy. Simultaneously, OGD hindered the differentiation of ADSCs into mature adipocytes. After inhibiting AMPK, the OGD-induced apoptosis rate increased but autophagy was inhibited. The adipogenesis level also decreased. To show that the effects of AMPK on apoptosis and adipogenesis were autophagy-dependent, we pre-inhibited or pre-promoted autophagy with siATG7 or rapamycin while blocking AMPK. We found that inhibiting or improving autophagy exacerbated or alleviated the role of AMPK prohibition in apoptosis and adipogenesis. Furthermore, we showed that AMPK inhibition significantly lowered ULK1 activity but promoted mTOR activity, so that to inhibit autophagy. Our study shows that AMPK plays a protective role in maintaining survival and adipogenesis of OGD-challenged ADSCs partly by positively regulating autophagy. AMPK positively regulates autophagy by inhibiting mTOR but promoting ULK1 activity in OGD condition. •AMPK plays a pivotal role in protecting ADSCs against OGD-induced apoptosis.•AMPK plays a protective role in survival and adipogenesis of OGD-challenged ADSCs.•Effects of AMPK are partly dependent on its positively regulating role on autophagy.
ISSN:1388-1981
1879-2618
DOI:10.1016/j.bbalip.2018.10.002