Cancer: High-fat diet impacts intestinal tissue regeneration and cancer initiation

A high-fat diet increases both the number and turnover of intestinal stem cells (ISCs) in mice and intestinal organoids, and may also enhance the capacity of intestinal progenitor cells to initiate tumours, reports a paper published in Nature. The study identifies a potential biological mechanism underlying the known association between a high-fat diet and intestinal cancer.

Stem cells can replicate indefinitely, whereas progenitor cells (former stem cells that are closer to developing into more specialized cells) can usually only divide a finite number of times. Although significant epidemiological data have established a link between obesity and colorectal cancer in humans, the mechanisms through which diet affects ISC and progenitor cell biology remain poorly understood.

David Sabatini and colleagues compared mice fed a diet of 60% fat for 9-14 months to a control group fed a standard diet. They find that a high-fat diet increases the number and regenerative capacity of ISCs by activating peroxisome proliferator-activated receptor delta (PPAR-delta) signalling. The authors then show that activation of PPAR-delta gives progenitor cells the capacity to form organoids (like stem cells) and, in progenitors that lack a specific tumour suppressor gene (Apc), the ability to form intestinal tumours in mice. They conclude that dietary activation of PPAR-delta can alter the function of ISCs and progenitor cells, and also enhance their capacity to initiate tumours.