The researches find that the molecules produced by the breakdown of fat, help the intestine to maintain a large pool of adult stem cells; which are crucial for keeping the intestinal lining healthy. The researchers also found that intestinal stem cells produce unusually high levels of ketone bodies even in the absence of a high-fat diet. These ketone bodies activate a well-know signaling pathway called Notch; which has previously been shows to help regulate stem cell differentiation.

Intestinal Stem Cells

“Ketone bodies are one of the first examples of how a metabolite instructs stem cell fate in the intestine;” says Omer Yilmaz, the Eisen and Chang Career Development Associate Professor of Biology and a member of MIT’s Koch Institute for Integrative Cancer Research.”These ketone bodies; which are normally thought to play a critical role in energy maintenance during times of nutritional stress; engage the Notch pathway to enhance stem cell function. Changes in ketone body levels in different nutritional states or diets enable stem cells to adapt to different physiologies.”

In a study of mice, the researchers found that a ketogenic diet gave intestinal stem cells a regenerative boost that made them better able to recover from damage to the intestinal lining, compared to the stem cells of mice on a regular diet. Yilmaz is the senior author of the study; which appears in the Aug. 22 issue of Cell. MIT postdoc Chia-Wei Cheng is the paper’s lead author. Adult stem cells; which can differentiate into many different cell types; are found in tissues throughout the body. These  are particularly important in the intestine because the intestinal lining is replaced every few days.

Analyzing gene expression

Yilmaz’ lab has previously shown that fasting enhances stem cell function in aged mice; and that a high-fat diet can stimulate rapid growth of stem cell populations in the intestine. In this study, the research team wanted to study the possible role of metabolism in the function of intestinal stem cells. By analyzing gene expression data; Cheng discovered that several enzymes involved in the production of ketone bodies are more abundant in intestinal stem cells than in other types of cells.

When a very high-fat diet is consume, cells use these enzymes to break down fat into ketone bodies; which the body can use for fuel in the absence of carbohydrates. However, because these enzymes are so active in intestinal stem cells; these cells have unusually high ketone body levels even when a normal diet is consumed.