Activation of autophagy and AMPK by gamma-tocotrienol suppresses the adipogenesis in human adipose derived stem cells

Authors

• Lu Zhao, University of Florida
• Jung-Heun Ha, University of Florida
• Meshail Okla, University of Florida
• Soonkyu Chung, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2014

Citation

Published in Molecular Nutrition & Food Res. 58 (2014), pp. 569–579. doi 10.1002/mnfr.201300157

Comments

Copyright © 2013 Wiley-VCH Verlag GmbH & Co. Used by permission.

Abstract

Scope: This study investigated the mechanistic details by which gamma-tocotrienol (γ-T3) manipulates adipocyte differentiation in human adipose derived stem cells (hASCs).

Methods and results: γ-T3 specifically inhibited the early stage of adipocyte differentiation by acting on downstream of C/EBP-β but upstream of C/EBP-α in hASCs. In searching a potential mechanism, we identified that γ-T3 promoted two catabolic signaling pathways: (i) AMP kinase (AMPK), and (ii) enhanced autophagy, as assessed by autophagic flux and cytosolic autophagosome (LC3II) accumulation. In addition, chronic exposure of γ-T3 induced caspase3-mediated apoptotic cell death. The blockage of AMPK by a dominant negative mutant of AMPK was insufficient to normalize γ-T3-mediated autophagy, suggesting that enhanced autophagic activity of γ-T3 is independent of AMPK activation. Intriguingly, AMPK inhibition significantly restored PPAR-γ activation, but marginally rescued lipid-loaded adipocyte morphology due to, at least partly, a lack of lipid droplet-coating protein. These data suggest that γ-T3 activates AMPK and autophagy signaling, which synergistically contributes to the suppression of adipogenic conversion of hASCs into adipocytes.

Conclusion: These results provide a novel insight into the molecular mechanism involved in anti-adipogenic action of γ-T3 in humans via AMPK and autophagy activation. Thus, γ-T3may constitute a new dietary avenue to attenuate hyperplastic obesity in humans.