Roles of Activin A and Gpnmb in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease [NAFLD]) and metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis [NASH]) are leading chronic liver diseases, driving cirrhosis, hepatocellular carcinoma, and mortality. MASLD/MASH is associated with increased senescence proteins, including Activin A, and senolytics have been proposed as a therapeutic approach. To test the role of Activin A, we induced hepatic expression of Activin A in a murine MASLD/MASH model.

Beneficial Effects of Moderate Hepatic Activin A Expression on Metabolic Pathways, Inflammation, and Atherosclerosis.

Background: Atherosclerosis is an inflammatory vascular disease marked by hyperlipidemia and hematopoietic stem cell expansion. Activin A, a member of the Activin/GDF/TGFβ/BMP (growth/differentiation factor/transforming growth factor beta/bone morphogenetic protein) family is broadly expressed and increases in human atherosclerosis, but its functional effects in vivo in this context remain unclear.

Methods: We studied LDLR mice on a Western diet for 12 weeks and used adeno-associated viral vectors with a liver-specific TBG (thyroxine-binding globulin) promoter to express Activin A or GFP (control).