Nicotinamide Riboside Reduces Liver Inflammation and DNA Damage: Preclinical Findings

Synopsis

Obesity increases the risk of liver cancer (hepatocellular carcinoma, HCC), but the exact mechanisms were unclear. This study found that a liver protein called URI links excess nutrients to inflammation and non-alcoholic fatty liver disease (NASH), a major cause of HCC. URI causes DNA damage in liver cells, which activates immune cells called Th17 lymphocytes to release the inflammatory molecule IL-17A. This leads to fat tissue inflammation, insulin resistance, and accumulation of fat in the liver, driving NASH. Blocking Th17 cells, IL-17A, or its receptor in immune cells prevented NASH and liver cancer in experimental models. Analysis of human liver disease also showed higher IL-17A levels associated with fat buildup. These results suggest that IL-17A blockers could help prevent insulin resistance, fatty liver disease, and liver cancer in people at high risk.

Journal

Cancer Cell