Nicotinamide adenine dinucleotide metabolism: driving or counterbalancing inflammatory bowel disease?

Abstract

Nicotinamide adenine dinucleotide (NAD) is an important electron and hydrogen carrier for oxidative metabolism and involved in energy production, antioxidant responses, and signal transduction within cells. NAD-consuming enzymes can mediate post-translational modifications, such as deacylation and ADP-ribosylation, and the production of Ca2+ -mobilizing second messengers, including OAADPR, ADPR, cADPR, and NAADP, to regulate metabolic homeostasis, DNA damage and gene expression. Inflammatory bowel disease (IBD) is a condition characterized by impaired intestinal barrier, disturbed intestinal mucosal immunity, and abnormal intestinal repair, that is caused by genetic susceptibility and environmental factors. Although various components involved in NAD biosynthesis and metabolism are upregulated in IBD, it remains disputed whether increased NAD turnover drives or counterbalances IBD progression. This review discusses the significance of increased NAD turnover in the intestinal barrier integrity and the inflammation resolution in IBD conditions. We propose that a better understanding of the reasons for the altered NAD metabolism in IBD may help identify novel treatment approaches.