Nicotinamide Riboside Protects Against Fat-Induced Liver Damage: Preclinical Findings

Synopsis

This study explored how palmitate, a common saturated fat found in the bloodstream, contributes to fatty liver disease by altering cell metabolism. Researchers found that palmitate activates PPARγ, a liver receptor that regulates fat storage, while also increasing levels of nicotinamide N-methyltransferase (NNMT)—an enzyme that breaks down nicotinamide, the main precursor for NAD+ production. This NNMT upregulation caused a drop in cellular NAD+, which in turn triggered PPARγ activation. Restoring NAD+ levels using nicotinamide riboside (NR) or nicotinamide blocked this harmful process, preventing excessive fat accumulation and cell death in liver cells. These findings suggest that fat-induced NAD+ depletion via NNMT plays a central role in activating pathways that lead to fatty liver and lipotoxicity, and that boosting NAD+ levels could help protect the liver from metabolic damage caused by excess saturated fats.

Journal

American Journal of Physiology-Cell Physiology