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

Lu Zhao, Jung Heun Ha, Meshail Okla, Soonkyu Chung

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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-T3 may constitute a new dietary avenue to attenuate hyperplastic obesity in humans.

Original languageEnglish (US)
Pages (from-to)569-579
Number of pages11
JournalMolecular Nutrition and Food Research
Volume58
Issue number3
DOIs
StatePublished - Mar 2014

Keywords

  • AMP kinase
  • Adipogenesis
  • Autophagy
  • Gamma-tocotrienol
  • Obesity

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

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