Aerobic capacity mediates susceptibility for the transition from steatosis to steatohepatitis

Key points Low intrinsic aerobic capacity is associated with increased all‐cause and liver‐related mortality in humans. Low intrinsic aerobic capacity in the low capacity runner (LCR) rat increases susceptibility to acute and chronic high‐fat/high‐sucrose diet‐induced steatosis, without observed increases in liver inflammation. Addition of excess cholesterol to a high‐fat/high‐sucrose diet produced greater steatosis in LCR and high capacity runner (HCR) rats. However, the LCR rat demonstrated greater susceptibility to increased liver inflammatory and apoptotic markers compared to the HCR rat. The progressive non‐alcoholic fatty liver disease observed in the LCR rats following western diet feeding was associated with further declines in liver fatty acid oxidation and mitochondrial respiratory capacity compared to HCR rats.