David J Sherman, Lei Liu, Jennifer L Mamrosh, Jiansong Xie, John Ferbas, Brett Lomenick, Mark S Ladinsky, Rati Verma, Ingrid C Rulifson, Raymond J Deshaies
Nonalcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. A common variant in the gene PNPLA3 , encoding the protein PNPLA3-I148M, is the strongest known genetic risk factor for MASLD. Despite its discovery 20 y ago, the function of PNPLA3, and now the role of PNPLA3-I148M, remain unclear. In this study, we sought to dissect the biogenesis of PNPLA3 and PNPLA3-I148M and characterize changes induced by endogenous expression of the disease-causing variant...
April 30, 2024: Proceedings of the National Academy of Sciences of the United States of America