A new study from Japan demonstrates that NAD+ levels in the intestines are important for maintaining insulin secretion and glucose metabolism.
Researchers have long known that the level of a molecule called NAD in cells is crucial for cellular health and function. But it has been unclear whether the body’s levels of NAD, which is found in all cells of the body, are also important for the health of tissues and organs. Research in animals has suggested that the levels of NAD in the gut are significant for maintaining the health of the gut lining, the metabolism and the ability to respond to the hormone insulin. But this has not been investigated in humans.
Researchers at the University of California, San Francisco (UCSF) have now discovered that NAD levels in the body are also critical for maintaining the health of other tissues and organs. They showed that a chemical called NMN, which has been shown to increase NAD levels in cells in animal studies, can reverse the metabolic derangements caused by deleting a gene called NAMPT in mice or obesity. The scientists also found that NMN improved the insulin sensitivity of mice with diet-induced obesity. These results indicate that it may be possible to use NAD precursors such as NMN to treat or prevent metabolic disorders such as diabetes and obesity by administering NMN in the water of the mice.
Intestinal NAD+ Biosynthesis Regulates GLP-1 Production And Glucose Metabolism in Mice
NAD+ is critical for epithelial cells to release GLP-1, a hormone that helps turn food into energy. The researchers found that mice are carrying a mutation in the gene encoding NAD+ could not be made to release GLP-1. They also found that mice lacking the enzyme NAMPT, which converts NAD+ into the important molecule NMN, were no better. In other words, the NAD+ to NMN conversion was critical for releasing GLP-1 from the intestinal.
Obesity is associated with high blood sugar levels (hyperglycemia), an important predictor of developing cardiovascular diseases, type 2 diabetes, and nonalcoholic fatty liver disease. In rats fed high-fat diets, the production of the gut hormone GLP-1 called “L cells” diminishes, leading to a decrease in GLP-1 concentration and hyperglycemia in response to food. These findings suggest that reducing NAD+ levels may be an effective strategy for treating or preventing these conditions.
In addition, findings from human research imply that changes in the nutrient-induced GLP-1 response are linked to obesity and metabolic dysfunction, such as hyperglycemia. For example, in obese individuals, the levels of the nutrient-induced GLP-1 response are reduced. This suggests that manipulating the levels of NAD may be an effective strategy for treating or preventing metabolic disorders such as diabetes and obesity.