Oxidative stress impairs HIF1α activation: a novel mechanism for increased vulnerability of steatotic hepatocytes to hypoxic stress

► We investigated the role of HIF1α in hypoxia-induced injury in steatotic hepatocytes. ► Under hypoxia, steatosis led to greater intracellular and nuclear oxidative stress. ► This led to cellular damage due to HIF1α inactivation. ► HIF1α inactivation was due to inhibition of the NF-κB pathway. ► Thus, HIF1α inactivation facilitates hypoxic injury in fat-loaded hepatocytes.