Fig. 2

NAD⁺ regulates macrophage polarization. LPS challenge induces the generation of mitochondrial reactive oxygen species (mROS). This increase in ROS results in DNA damage and subsequent PARP activation, which consume NAD⁺ to repair damaged DNA and maintain genomic integrity. The NAD⁺ salvage pathway replenishes the NAD⁺ pools through increased NAMPT expression, thus initiating glycolytic reaction and programming pro-inflammatory macrophage polarization. In another context, diminished NAD⁺ levels are attributed to decreased QPRT expression in the de novo synthesis pathway. Low NAD⁺ concentration impairs mitochondrial respiration, thus inversely increasing glycolysis and facilitating inflammatory responses of macrophages. In addition, CD38 acts as another important NAD⁺-consuming enzyme during pro-inflammatory macrophage polarization.