New research reveals that these substances can alleviate metabolic problems caused by obesity
Key words: NAD+, obesity, high blood sugar, metabolic health
Japan Researchers at Keio University School of Medicine and Washington University School of Medicine in St. Louis show that NAD+ is essential for intestinal epithelial cells to release GLP-1 (glucagon-like peptide 1), one of the most critical incretins, GLP- 1 Regulates insulin secretion and the response of blood sugar levels to sugar.
Results from human studies suggest that nutrition-induced changes in GLP-1 responses are associated with obesity and metabolic dysfunction, such as hyperglycemia. GLP-1 responses were much lower in obese and glucose intolerant subjects compared to healthy lean subjects.
The production of NAD+ and GLP-1 in enterocytes of obese mice is markedly reduced, leading to a spike in glucose levels in vivo, and these results in the absence of NAMPT (the enzyme that synthesizes NAD+ precursor NMN) in intestinal parietal cells. Repeat in non-obese mice. In the team’s study, they generated mice with the NAMPT gene deleted from intestinal epithelial cells, and these genetically altered mice all exhibited reduced GLP-1 production, decreased insulin secretion, and hyperglycemia.
Intestinal NAD+ levels, GLP-1 production and glucose metabolism were all restored in obese or intestinal NAMPT-deficient mice following water supplementation with NMN (500 mg/kg/day). The researchers speculate that oral administration of NMN enhances intestinal NAD+ synthesis via the NMN transporter in the small intestine, resulting in the production of GLP-1.
Note: (Left) Glucose levels after sugar intake in mice fed a high-fat diet (HFD) to induce obesity after 10 days of treatment with NMN (grey) or water (black). (Right) Active GLP-1 concentrations in plasma from the same mice.
Collectively, this study provides mechanistic and therapeutic insights into the gut NAD+ biology associated with obesity-related dysregulation of GLP-1 production and postprandial hyperglycemia. This paves the way for further research into the effects of NMN on insulin secretion and glucose metabolism in humans, which may have broad implications for people at risk for cardiovascular disease, type 2 diabetes and nonalcoholic fatty liver disease.
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