Hypoxia induces adipocyte differentiation of adipose-derived stem cells by triggering reactive oxygen species generation

Ji Hye Kim, Seok Ho Kim, Seung Yong Song, Won Serk Kim, Sun U. Song, Tac Ghee Yi, Myung Shin Jeon, Hyung Min Chung, Ying Xia, Jong Hyuk Sung

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42 Citations (Scopus)

Abstract

Generation of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4) induces the proliferation and migration of adiposederived stem cells (ASCs). However, the functional role of mitochondrial ROS (mtROS) generation in ASCs is unknown. Therefore, we have investigated whether hypoxia induces the differentiation of ASCs via ROS generation. We also have tried to identify the cellular mechanisms of ROS generation underlying adipocyte differentiation. Hypoxia (2%) and ROS generators, such as antimycin and rotenone, induced adipocyte differentiation, which was attenuated by an ROS scavenger. Although Nox4 generates ROS and regulates proliferation of ASCs, Nox4 inhibition or Nox4 silencing did not inhibit adipocyte differentiation; indeed fluorescence intensity of mito-SOX increased in hypoxia, and treatment with mito-CP, a mtROS scavenger, significantly reduced hypoxia-induced adipocyte differentiation. Phosphorylation of Akt and mTOR was induced by hypoxia, while inhibition of these molecules prevented adipocyte differentiation. Thus hypoxia induces adipocyte differentiation by mtROS generation, and the PI3K/Akt/mTOR pathway is involved.

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalCell Biology International
Volume38
Issue number1
DOIs
Publication statusPublished - 2014 Jan

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Kim, J. H., Kim, S. H., Song, S. Y., Kim, W. S., Song, S. U., Yi, T. G., Jeon, M. S., Chung, H. M., Xia, Y., & Sung, J. H. (2014). Hypoxia induces adipocyte differentiation of adipose-derived stem cells by triggering reactive oxygen species generation. Cell Biology International, 38(1), 32-40. https://doi.org/10.1002/cbin.10170