%20is%20the%20leading%20cause%20of%20chronic%20liver%20disease,%20with%20no%20approved%20drug%20treatments.%20This%20study%20demonstrates%20that%20a%20high-fat,%20high-sugar%20diet%20reduces%20...){kind=link}
Nicotinamide Ribosides Reverses Fatty Liver Disease: Preclinical Findings
Synopsis
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with no approved drug treatments. This study demonstrates that a high-fat, high-sugar diet reduces hepatic NAD+ levels, impairing mitochondrial function, ATP production, and fat metabolism in mice—mimicking key features of human NAFLD. Supplementation with nicotinamide riboside (NR), a natural NAD+ precursor, either prevented or reversed fatty liver disease. NR achieved this by activating SIRT1 and SIRT3, triggering a mitochondrial unfolded protein response that enhanced fat oxidation and mitochondrial activity. Even in models with impaired SIRT1 signaling, NR provided partial benefits, and it was also effective in cholesterol-related liver disease. These findings identify NAD+ repletion through NR as a promising therapeutic approach for preventing and treating NAFLD, restoring liver energy metabolism and mitochondrial health.
Journal
Hepatology