Details

Autor(en) / Beteiligte

• Beyaz, Semir
• Mana, Miyeko D
• Roper, Jatin
• Kedrin, Dmitriy
• Saadatpour, Assieh
• Hong, Sue-Jean
• Bauer-Rowe, Khristian E
• Xifaras, Michael E
• Akkad, Adam
• Arias, Erika
• Pinello, Luca
• 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
• Ferrone, Cristina R
• Deshpande, Vikram
• Yuan, Guo-Cheng
• Orkin, Stuart H
• Sabatini, David M
• Yilmaz, Ömer H

Titel

High-fat diet enhances stemness and tumorigenicity of intestinal progenitors

Ist Teil von

• Nature (London), 2016-03, Vol.531 (7592), p.53-58

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.