| First Author | Beyaz S | Year | 2016 |
| Journal | Nature | Volume | 531 |
| Issue | 7592 | Pages | 53-8 |
| PubMed ID | 26935695 | Mgi Jnum | J:229664 |
| Mgi Id | MGI:5752980 | Doi | 10.1038/nature17173 |
| Citation | Beyaz S, et al. (2016) High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531(7592):53-8 |
| abstractText | Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we show that high-fat diet (HFD)-induced obesity augments the numbers and function of Lgr5(+) intestinal stem cells of the mammalian intestine. Mechanistically, a HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-delta) signature in intestinal stem cells and progenitor cells (non-intestinal stem cells), and pharmacological activation of PPAR-delta 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-delta-dependent manner. Notably, HFD- and agonist-activated PPAR-delta signalling endow organoid-initiating capacity to progenitors, and enforced PPAR-delta signalling permits these progenitors to form in vivo tumours after loss of the tumour suppressor Apc. These findings highlight how diet-modulated PPAR-delta activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumours. |
