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Activation of autophagy and AMPK by gamma‐tocotrienol suppresses the adipogenesis in human adipose derived stem cells
Author(s) -
Zhao Lu,
Ha JungHeun,
Okla Meshail,
Chung Soonkyu
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300157
Subject(s) - autophagy , ampk , microbiology and biotechnology , adipogenesis , adipocyte , chemistry , adipose tissue , protein kinase a , kinase , biology , apoptosis , biochemistry
Scope This study investigated the mechanistic details by which gamma‐tocotrienol (γ‐ T 3) manipulates adipocyte differentiation in human adipose derived stem cells ( h ASC s). Methods and results γ‐ T 3 specifically inhibited the early stage of adipocyte differentiation by acting on downstream of C / EBP ‐β but upstream of C / EBP ‐α in h ASC s. In searching a potential mechanism, we identified that γ‐ T 3 promoted two catabolic signaling pathways: (i) AMP kinase ( AMPK ), and (ii) enhanced autophagy, as assessed by autophagic flux and cytosolic autophagosome ( LC 3II) accumulation. In addition, chronic exposure of γ‐ T 3 induced caspase3‐mediated apoptotic cell death. The blockage of AMPK by a dominant negative mutant of AMPK was insufficient to normalize γ‐ T 3‐mediated autophagy, suggesting that enhanced autophagic activity of γ‐ T 3 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‐ T 3 activates AMPK and autophagy signaling, which synergistically contributes to the suppression of adipogenic conversion of h ASC s into adipocytes. Conclusion These results provide a novel insight into the molecular mechanism involved in anti‐adipogenic action of γ‐ T 3 in humans via AMPK and autophagy activation. Thus, γ‐ T 3 may constitute a new dietary avenue to attenuate hyperplastic obesity in humans.