High-fat diet enhances stemness and tumorigenicity of intestinal progenitors
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[superscript +] intestinal stem-cells (ISCs) of the mammalian intestine. Mechanistically, HFD induces a robust...
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| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/106594 https://orcid.org/0000-0002-5516-4008 https://orcid.org/0000-0001-6093-7282 https://orcid.org/0000-0002-1446-7256 https://orcid.org/0000-0002-7577-4612 |
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| author | Saadatpour, Assieh Hong, Sue-Jean Pinello, Luca Katz, Yarden Lamming, Dudley W. Guo, Guoji Bell, George W. Selig, Martin Nielsen, G. Petur Gupta, Nitin Ferrone, Cristina R. Deshpande, Vikram Yuan, Guo-Cheng Orkin, Stuart H. Beyaz, Semir Mana, Miyeko Roper, Jatin Kedrin, Dmitriy Bauer-Rowe, Khristian E. Xifaras, Michael Akkad, Adam Arias, Erika Shinagare, Shweta Abu-Remaileh, Monther Dogum, Rizkullah Sabatini, David Yilmaz, Omer Mihaylova, Maria M. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Saadatpour, Assieh Hong, Sue-Jean Pinello, Luca Katz, Yarden Lamming, Dudley W. Guo, Guoji Bell, George W. Selig, Martin Nielsen, G. Petur Gupta, Nitin Ferrone, Cristina R. Deshpande, Vikram Yuan, Guo-Cheng Orkin, Stuart H. Beyaz, Semir Mana, Miyeko Roper, Jatin Kedrin, Dmitriy Bauer-Rowe, Khristian E. Xifaras, Michael Akkad, Adam Arias, Erika Shinagare, Shweta Abu-Remaileh, Monther Dogum, Rizkullah Sabatini, David Yilmaz, Omer Mihaylova, Maria M. |
| author_sort | Saadatpour, Assieh |
| collection | MIT |
| description | 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[superscript +] 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 (nonISC) 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 organoidinitiating 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 dietmodulated PPAR-d activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumors. |
| first_indexed | 2024-09-23T14:31:53Z |
| format | Article |
| id | mit-1721.1/106594 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:31:53Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1065942022-09-29T09:46:50Z High-fat diet enhances stemness and tumorigenicity of intestinal progenitors Saadatpour, Assieh Hong, Sue-Jean Pinello, Luca Katz, Yarden Lamming, Dudley W. Guo, Guoji Bell, George W. Selig, Martin Nielsen, G. Petur Gupta, Nitin Ferrone, Cristina R. Deshpande, Vikram Yuan, Guo-Cheng Orkin, Stuart H. Beyaz, Semir Mana, Miyeko Roper, Jatin Kedrin, Dmitriy Bauer-Rowe, Khristian E. Xifaras, Michael Akkad, Adam Arias, Erika Shinagare, Shweta Abu-Remaileh, Monther Dogum, Rizkullah Sabatini, David Yilmaz, Omer Mihaylova, Maria M. Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Koch Institute for Integrative Cancer Research at MIT Beyaz, Semir Mana, Miyeko Roper, Jatin Kedrin, Dmitriy Bauer-Rowe, Khristian E. Xifaras, Michael Akkad, Adam Arias, Erika Shinagare, Shweta Abu-Remaileh, Monther Dogum, Rizkullah Sabatini, David Yilmaz, Omer Mihaylova, Maria M. 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[superscript +] 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 (nonISC) 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 organoidinitiating 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 dietmodulated PPAR-d activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumors. Howard Hughes Medical Institute Ellison Medical Foundation (Aging Grant) United States. Department of Defense (PRCRP Career Development Award CA120198) National Institutes of Health (U.S.) (Grants R01 CA103866, AI47389, K08 CA198002, R00 AG045144, R00 AG041765, and DK043351) National Institutes of Health (U.S.) (Cancer Center Support Core Grant P30-CA14051) Kathy and Curt Marble Cancer Research Fund American Federation for Aging Research V Foundation for Cancer Research (Scholar Grant) Massachusetts Institute of Technology. Ludwig Center for Molecular Oncology (Post-doctoral Fellowship) Massachusetts General Hospital (Fellowship T32DK007191) Damon Runyon Cancer Research Foundation (Robert Black Fellowship) 2017-01-24T15:44:16Z 2017-01-24T15:44:16Z 2016-03 2015-03 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/106594 Beyaz, Semir et al. “High-Fat Diet Enhances Stemness and Tumorigenicity of Intestinal Progenitors.” Nature 531.7592 (2016): 53–58. https://orcid.org/0000-0002-5516-4008 https://orcid.org/0000-0001-6093-7282 https://orcid.org/0000-0002-1446-7256 https://orcid.org/0000-0002-7577-4612 en_US http://dx.doi.org/10.1038/nature17173 Nature Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Saadatpour, Assieh Hong, Sue-Jean Pinello, Luca Katz, Yarden Lamming, Dudley W. Guo, Guoji Bell, George W. Selig, Martin Nielsen, G. Petur Gupta, Nitin Ferrone, Cristina R. Deshpande, Vikram Yuan, Guo-Cheng Orkin, Stuart H. Beyaz, Semir Mana, Miyeko Roper, Jatin Kedrin, Dmitriy Bauer-Rowe, Khristian E. Xifaras, Michael Akkad, Adam Arias, Erika Shinagare, Shweta Abu-Remaileh, Monther Dogum, Rizkullah Sabatini, David Yilmaz, Omer Mihaylova, Maria M. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors |
| title | High-fat diet enhances stemness and tumorigenicity of intestinal progenitors |
| title_full | High-fat diet enhances stemness and tumorigenicity of intestinal progenitors |
| title_fullStr | High-fat diet enhances stemness and tumorigenicity of intestinal progenitors |
| title_full_unstemmed | High-fat diet enhances stemness and tumorigenicity of intestinal progenitors |
| title_short | High-fat diet enhances stemness and tumorigenicity of intestinal progenitors |
| title_sort | high fat diet enhances stemness and tumorigenicity of intestinal progenitors |
| url | http://hdl.handle.net/1721.1/106594 https://orcid.org/0000-0002-5516-4008 https://orcid.org/0000-0001-6093-7282 https://orcid.org/0000-0002-1446-7256 https://orcid.org/0000-0002-7577-4612 |
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