NAMPT Deficiency in Mouse Liver Cells Shows Minimal Impact on NAD+ and Mitochondrial Health: Preclinical Findings

Synopsis

Supplementation with NAD+ precursors such as nicotinamide riboside (NR) has been shown to improve mitochondrial function and prevent liver fat accumulation in high-fat diet (HFD)-fed rodents. However, the role of the NAD+-producing enzyme NAMPT in liver metabolism is less clear. Researchers created mice lacking NAMPT specifically in liver cells (HNKO), which reduced liver NAD+ by 50%. After 20 weeks on a high-fat diet with or without NR, NR raised NAD+ levels but did not affect fat mass, glucose tolerance, or most mitochondrial functions in HNKO mice. Mitochondrial NAD+ dropped only 20%, and HNKO mice compensated by increasing de novo NAD+ synthesis. Overall, loss of NAMPT in hepatocytes had only mild effects on mitochondrial function.

Journal

Journal of Biological Chemistry