Nicotinamide Riboside Restores NAD+ and Reduces Fatty Liver Damage: Preclinical Findings

Synopsis

Palmitic acid, the most common saturated fat in the blood, can cause liver inflammation, fat accumulation (steatosis), and cellular damage. This study explored how such fatty acids disrupt circadian clock genes and NAD+-dependent enzymes that protect liver health. Researchers found that palmitic acid reduced NAD+ levels and suppressed SIRT2, a protective enzyme that regulates inflammation and metabolism, along with BMAL1, a key circadian gene controlling SIRT2 expression. Liver tissue samples from patients with fatty liver disease and fibrosis showed the same pattern — lower levels of BMAL1 and SIRT2, especially in advanced disease. Importantly, restoring NAD+ with nicotinamide riboside (NR) or increasing BMAL1 activity reactivated SIRT2, reducing inflammation, oxidative stress, and lipotoxicity in healthy liver cells. The study reveals that the BMAL1–NAD+–SIRT2 pathway plays a vital role in maintaining liver health and that NR supplementation may help prevent or treat fatty liver–related inflammation and fibrosis.

Journal

Journal of Physiology and Biochemistry