Tag Archives: colon cancer

Fatty food drives aberrant Stem Cell growth in Mammalian Colon


Nice juicy high fat burger – just want you want – but just what you do not need.

A paper out today in Nature offers new insight into the impact of a high-fat diet  (HFD) on tumor growth and progression:

This study looked at the relationship between a high-fat diet and the how this impacted stem and progenitor cell function.  They found that a HFD in the mammalian intestine modulated a strong peroxisome proliferator-activated receptor delta (PPAR-delta) response in stem cells.  PPAR-delta not only alters the function of intestinal stem cells but importantly non-intestinal progenitor cells nearby allowing the development and growth of intestinal tumors.

Nice juicy high fat burger – just want you want – but just what you do not need.

Mice on the HFD saw a 30-50% weight gain with a  much higher incidence of intestinal tumors than control mice on a normal diet. The researchers saw a significant increase in the number of stem cell in mice on a HFD and importantly the stem cells appeared to grow in a manner which suggested that they were not receiving input immediately adjacent cells – the normal route to cell growth.  Non-stem, progenitor cells in the intestinal walls also started to act like stem cells and exhibited significantly longer lives.

There has been clear epidemiological evidence for a strong link between obesity and colorectal cancer and this study provides a clear and concise mechanism for tumor initiation and propagation. If you are on a HFD its time to change.

Original Research: Nature (2016). DOI: 10.1038/nature17173

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 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.

Original Research: Nature (2016).
DOI: 10.1038/nature17173