NAMPT and metabolic dysfunction-associated steatohepatitis: For example, the levels of NAMPT, a rate-limiting enzyme for NAD+ biosynthesis, is reduced in the livers and plasma of patients with NAFLD.58 NAMPT functions to prevent hepatocyte apoptosis.58 The NAD+ level is reduced in the livers of patients with NASH.59 Sirtuins are the major NAD+-consuming enzymes that mediate the signaling effects of NAD+ and are thought to be the mediators of NAD+ metabolism in NAFLD.