Nampt-flox Mouse

Nicotinamide phosphoribosyltransferase (NAMPT), also known as visfatin, is a key regulator of the intracellular nicotinamide adenine dinucleotide (NAD) pool. It catalyzes the rate-limiting step in NAD biosynthesis from nicotinamide, influencing the activity of NAD-dependent enzymes and thus regulating cellular metabolism. NAD is an essential coenzyme in cellular redox reactions and a substrate for NAD-dependent enzymes involved in various biological processes, including DNA repair, gene expression, and cellular metabolism [1,3,4,6].

In cancer, NAMPT is often overexpressed in tumour tissues. Inhibition of NAMPT, for example, using the inhibitor FK866, suppresses cancer stem-like cells associated with therapy-induced senescence in ovarian cancer, which may contribute to chemoresistance. This suggests that targeting NAMPT could be a promising anti-cancer strategy to deplete NAD and impair cellular metabolism [2,6]. In experimental necrotizing enterocolitis, NAMPT inhibition by FK866 alleviates intestinal inflammation by regulating macrophage activation, reducing M1 macrophage polarization [5]. Also, in senile osteoporosis, reduction of NAMPT in bone marrow mesenchymal stem cells (BMSCs) promotes lipogenic differentiation and age-related bone loss, while overexpression of Nampt ameliorates senescence-associated phenotypes and promotes osteogenic potential. The NAMPT activator P7C3 is a novel strategy for reducing senile osteoporosis bone loss [7].

In conclusion, NAMPT plays a crucial role in multiple biological processes and diseases. Studies using loss-of-function models, such as NAMPT inhibition in in vivo studies, have revealed its significance in cancer, intestinal inflammation, and senile osteoporosis. These findings suggest that NAMPT could be a potential therapeutic target for these diseases.