Interestingly, in a model of early NASH, DIO1 levels and activity are increased suggesting that there is a compensatory increase to handle excess lipids.31 However, low DIO1 levels and activity have been observed in humans and rodents with advanced NASH,33 and DIO1 knockdown leads to increased intrahepatic lipid content.31 This evidence concerns the gene DIO1 and metabolic dysfunction-associated steatohepatitis.