Nicotinamide Riboside Protects Against NASH: Preclinical Findings

Synopsis

In a rat model of NASH driven by type 2 diabetes and an obesogenic diet, activating SIRT2 with nicotinamide riboside (NR) improved blood sugar, insulin resistance, and glucose tolerance, while reducing liver fat, abnormal blood lipids, inflammation, oxidative stress, and fibrosis. NR worked by boosting SIRT2 activity, which regulated key proteins, suppressed harmful inflammasome activation, restored energy and antioxidant pathways, and enhanced fat metabolism in the liver. Blocking SIRT2 with AGK2 reduced these benefits, showing that SIRT2 is a critical regulator of metabolism and inflammation in NASH. These findings support SIRT2 activation as a promising therapeutic strategy for metabolic liver disease and highlight the need to develop selective SIRT2-targeting drugs.

Journal

International Immunopharmacology