NAD+ synthesis regulates intestinal inflammation

Nicotinamide phosphoribosyl-transferase (NAMPT) plays an important role in the cyclic biosynthetic pathway of nicotinamide adenine dinucleotide (NAD+), essential for the maintenance of cellular energy. NAMPT catalyzes NMN s, which is a direct precursor to NAD+, and is biologically indispensable and implicated in various inflammatory diseases, including rheumatoid arthritis, diabetes, and sepsis. However, the role of NAMPT in inflammatory macrophages has not been fully elucidated, particularly in the context of IBD.

To investigate the role of NAMPT in IBD, Hong and colleagues induced colitis in mice with macrophages lacking a functional NAMPT gene. This genetic alteration caused mice to suffer from prolonged, severe inflammation, although the initial inflammatory response was preserved regardless of the lack of NAMPT activity. These mice with NAMPT deficient macrophages also exhibited major reductions in body weight and lower survival rates.

While NAMPT deletion did not affect the recruitment of macrophages or the production of inflammatory cytokines, NAMPT deletion impaired a “clean-up” process (phagocytosis) of macrophages, which is important in the resolution of inflammation and restoration of tissue balance. The reduced phagocytosis impeded clearing tissue debris and dead cells derived from insufficient NAD+ levels. Collectively, these results suggest that NAMPT deletion specifically in macrophages leads to prolonged, severe colitis in a mouse model.

CH TRADITIONAL
CH TRADITIONAL