Beyaz, SemirMana, Miyeko D.Roper, JatinKedrin, DmitriySaadatpour, AssiehHong, Sue-JeanBauer-Rowe, Khristian E.Xifaras, Michael E.Akkad, AdamArias, ErikaPinello, LucaKatz, YardenShinagare, ShwetaAbu-Remaileh, MontherMihaylova, Maria M.Lamming, Dudley W.Dogum, RizkullahGuo, GuojiBell, George W.Selig, MartinNielsen, G. PeturGupta, NitinFerrone, CristinaDeshpande, VikramYuan, Guo-ChengOrkin, StuartSabatini, David M.Yilmaz, Omer2016-11-182016Beyaz, 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/nature17173.0028-0836http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407826Little 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.en-USJournal Article2016-11-1810.1038/nature17173