High-fat diet enhances stemness and tumorigenicity of intestinal progenitors.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and ex vivo organoid mechanistic study
PubMed 26935695 · doi:10.1038/nature17173
What was done
Researchers examined the effects of high-fat diet (HFD)-induced obesity on mammalian Lgr5(+) intestinal stem cells and progenitor cells. They evaluated the mechanistic role of peroxisome proliferator-activated receptor delta (PPAR-δ) signaling using pharmacological activation, treated ex vivo intestinal organoid cultures with HFD fatty acid constituents, and tested the tumor-initiating capacity of progenitor cells following the loss of the tumor suppressor gene Apc.
What was found
The abstract reports no numerical values or statistical effect sizes. High-fat diet increased the number and function of Lgr5(+) intestinal stem cells and induced a PPAR-δ signature in both stem and progenitor cells. Pharmacological activation of PPAR-δ and ex vivo fatty acid treatment enhanced organoid self-renewal in a PPAR-δ-dependent manner. PPAR-δ signaling conferred organoid-initiating capacity to progenitor cells and permitted them to form in vivo tumors after loss of Apc.
Why it matters
This work identifies a mechanism linking pro-obesity diets to intestinal tumorigenesis, showing that dietary fatty acids and PPAR-δ activation can grant stem-like and tumor-initiating capacity to non-stem progenitor cells.
Limits
Sample sizes, effect magnitudes, animal models, and specific fatty acid formulations are omitted from the abstract. Findings are derived entirely from non-human animal and ex vivo organoid systems, so direct human relevance remains unverified.
Cited by
- supports Research by David Sabatini and colleagues at MIT demonstrated that fatty acid metabolism plays a key role in the self-renewal and activation of intestinal stem cells.