Although activated macrophages also accumulate in adipose tissue and further fuel insulin resistance and hepatic lipid accumulation during NAFLD31,32, we found that Irg1 and itaconate expression was essentially confined to the macrophages of the liver, consistent with their unique roles in integrating signals from the gut/diet and as drivers of the progression of NAFLD to fibrosis and advanced steatohepatitis31. Here, ACOD1 is linked to Insulin resistance.