Inactivating upstream stimulatory factor 1 (USF1) can activate brown adipose tissue (BAT) and increase energy expenditure, which leads to improved cardiometabolic parameters. In Usf1 knockout mice, clearance of triglycerides from the plasma is enhanced and these lipids directed to BAT. Increased BAT thermogenesis and upregulation of mitochondrial respiratory chain complexes then facilitate the breakdown of these triglycerides. Moreover, plasma levels of HDL cholesterol are also increased in these mice. Importantly, the investigators identified a polymorphism in human USF1 that is associated with improvements in insulin sensitivity, lipid profiles and atherosclerosis. The team hope that USF1 might be a new therapeutic target for the treatment of cardiometabolic disease.