High fat diet enhances stemness and tumorigenicity of intestinal progenitors

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Author
Mana, Miyeko D.
Roper, Jatin
Kedrin, Dmitriy
Saadatpour, Assieh
Hong, Sue-Jean
Bauer-Rowe, Khristian E.
Xifaras, Michael E.
Akkad, Adam
Arias, Erika
Katz, Yarden
Shinagare, Shweta
Abu-Remaileh, Monther
Mihaylova, Maria M.
Lamming, Dudley W.
Dogum, Rizkullah
Guo, Guoji
Bell, George W.
Selig, Martin
Nielsen, G. Petur
Gupta, Nitin
Yuan, Guo-Cheng
Sabatini, David M.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/nature17173Metadata
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Beyaz, S., M. D. Mana, J. Roper, D. Kedrin, A. Saadatpour, S. Hong, K. E. Bauer-Rowe, et al. 2016. “High fat diet enhances stemness and tumorigenicity of intestinal progenitors.” Nature 531 (7592): 53-58. doi:10.1038/nature17173. http://dx.doi.org/10.1038/nature17173.Abstract
Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we find that high fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+ intestinal stem-cells (ISCs) of the mammalian intestine. Mechanistically, HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-d) signature in intestinal stem and (non-ISC) progenitor cells, and pharmacologic activation of PPAR-d recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-d dependent manner. Interestingly, HFD- and agonist-activated PPAR-d signaling endow organoid-initiating capacity to progenitors, and enforced PPAR-d signaling permits these progenitors to form in vivo tumors upon loss of the tumor suppressor Apc. These findings highlight how diet-modulated PPAR-d activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumors.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846772/pdf/Terms of Use
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