SIRT3 is required for liver regeneration but not for the beneficial effect of nicotinamide riboside

• DOI: 10.1172/jci.insight.147193
• Publication Date: 2021-03-09T17:03:40Z
• Authors: Sarmistha Mukherjee; James Mo; Lauren M. Paolella; Caroline E. Perry; Jade Toth; Mindy M. Hugo; Qingwei Chu; Qian Tong; Karthikeyani Chel...; Joseph A. Baur
• Keywords: SIRT3; Liver Regeneration

Liver regeneration is critical to survival after traumatic injuries, exposure hepatotoxins, or surgical interventions, yet the underlying signaling and metabolic pathways remain unclear. In this study, we show that hepatocyte-specific loss of mitochondrial deacetylase SIRT3 drastically impairs worsens function partial hepatectomy. Sirtuins, including SIRT3, require NAD as a cosubstrate. We previously showed precursor nicotinamide riboside (NR) promotes liver regeneration, but whether involves sirtuins has not been tested. Here, despite their dependence roles in neither nor its nuclear counterpart SIRT1 required for NR enhance regeneration. improves respiration regenerating WT mutant livers rapidly increases oxygen consumption glucose output cultured hepatocytes. Our data support direct enhancement redox metabolism mechanism mediating improved supplementation exclude via SIRT3. Therefore, provide first evidence our knowledge an essential role sirtuin during insight into beneficial effects NR.