High fat diet enhances stemness and tumorigenicity of intestinal progenitors

By S. Beyaz, Miyeko D. Mana, Jatin Roper, Dmitriy Kedrin, A. Saadatpour, Sue-Jean Hong, K. Bauer-Rowe, Michael E Xifaras, Adam Akkad, Erika Arias and 18 more. Nature, 2016

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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-δ) signature in intestinal stem cells and progenitor cells (non-intestinal stem cells), and pharmacological activation of PPAR-δ 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-δ-dependent manner. Notably, HFD- and agonist-activated PPAR-δ signalling endow organoid-initiating capacity to progenitors, and enforced PPAR-δ signalling permits these progenitors to form in vivo tumours after loss of the tumour suppressor Apc. These findings highlight how diet-modulated PPAR-δ activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumours.

Subfields: Cancer Research, Genetics, Oncology

View Paper: https://www.semanticscholar.org/paper/f637f8163ee8d48f33b6ffebcd6e0cf3281570a4

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