How Are Obesity and Cancer Linked? Study Examines How Fatty Diet Triggers Stem Cells

Obesity, and in particular eating a high-fat diet, has been associated with cancer in several studies in recent years. In fact, the connection between certain foods and cancer was evaluated for the first time by the advisory committee that made recommendations for the 2015-2020 Dietary Guidelines for Americans.

But why, exactly, does a fatty, high-calorie diet cause cancer? Researchers from the Whitehead Institute and MIT’s Koch Institute for Integrative Cancer Research took on this question, and found how eating poorly can affect the intestinal lining, triggering cell proliferation that can lead to tumor growth.

The findings not only uncovered new insights into how fatty diets affect stem cell behavior in the gut, but could also lead to new drug targets for tumors in cancers related to obesity.

“Not only does the high-fat diet change the biology of stem cells, it also changes the biology non-stem-cell populations, which collectively leads to an increase in tumor formation,” Omer Yilmaz, an MIT assistant professor of biology and co-leader of the research team, said in a news release.

The study, published in the journal Nature this week, found that mice who were fed a diet of 60% fat for 9-12 months gained 30% to 50% more body weight, and developed more intestinal tumors than mice on a normal diet.

The research team wanted to examine the behavior of intestinal stem cells in the mice that ate the high fat diet, because intestinal stem cells last a lifetime and are those likely to develop mutations that lead to colon cancer. Stems cells in the intestine are surrounded by other cells that regulate their growth. But if removed from that environment, the stem cells can survive in the laboratory.

When scientists removed some of the stem cells from mice on the high-fat diet, they found these cells grew more rapidly than the cells from mice fed a normal diet. Cells from the mice on the fatty diet grew “mini intestines” more quickly.

By itself, suggests behavior that would lead to tumor growth. But then researchers found that a separate group of cells, known as progenitor cells or “daughter cells” of stem cells, also began to behave like stems cells outside the body—exhibiting the “mini intestine” growth and, importantly, surviving much longer outside the body than their usual lifespan of a few days.

What’s more, the team found a nutrient-sensing pathway stimulated by the high-fat diet. A fatty acid sensor, known as the PPAR-delta, reacts to fat cells by activating the process that burns fat for energy (as opposed to carbohydrates). This discovery is key, because PPAR-delta appears to switch on a set of genes that regulate stem cell identity, and might lead scientists to a drug target for tumors that are associated with obesity.

Reference

Beyaz S, Mana MD, Roper J, et al. High-fat enhances stemness and tumorigenicity of intestinal progenitors [published March 2, 2016]. Nature. doi:10.1038/nature.2016.19484.