Nicotinamide Riboside Protects Liver Cells from Palmitate-Induced Damage: Preclinical Findings

Synopsis

This study examined how excessive fat buildup in liver cells (hepatic lipotoxicity) contributes to liver damage, a key factor in metabolic liver diseases. Researchers found that exposure to palmitate, a type of fat, reduced the activity of PARP-1, an enzyme that helps protect cells. Inhibiting PARP-1 worsened the damage, but increasing PARP-1 activity with NAD+ precursors or inhibitors helped prevent it. They also discovered that PARP-1 suppression activates the mTORC1 pathway, leading to liver cell death, and identified p300 as a downstream target of this pathway. Inhibition of p300 protected liver cells from damage. Additionally, the TLR4-NF-κB pathway was found to play a role in reducing PARP-1 activity and contributing to cell death. Importantly, Nicotinamide Riboside (NR) treatment effectively increased NAD+ levels in AML12 and HepG2 cells, helping to restore PARP-1 activity and protect the cells from palmitate-induced cell death. This suggests that boosting NAD+ with NR can help prevent cell damage caused by palmitate. These findings reveal a novel molecular mechanism for hepatic lipotoxicity and suggest that boosting NAD+ levels or inhibiting its breakdown could be a promising treatment for liver damage caused by fat accumulation.

Journal

American Journal of Physiology-Cell Physiology