Suraj Patel found that while global knockout of IRF3 reduces both liver insulin resistance and steatosis in obesity, hepatocyte-specific knockout of IRF3 in hepatocytes only affects insulin resistance. He was able to track a key target gene of IRF3 down: it’s Ppp2r1b, a component of the PP2A complex which affects AMPK and AKT signaling. This paper demonstrates that inflammation causes insulin resistance in liver by modulating signaling pathways that regulate gluconeogenesis. Read about it in Science Translational Medicine (Hepatic IRF3 Fuels Dysglycemia in Obesity Through Direct Regulation of Ppp2r1b. Science Translational Medicine, 2022; Mar 23;14(637):eabh3831. doi: 10.1126/scitranslmed.abh3831). Suraj’s paper was chosen for the cover image of the current issue Science Translational Medicine, seen here.