Nr2e1 ablation impairs liver glucolipid metabolism and induces inflammation, high-fat diets amplify the damage.

Nonalcoholic fatty liver disease (NAFLD) is a common and complex metabolic disorder. Despite the widespread concern, there are still few effective treatments except lifestyle interventions. Nuclear receptor subfamily 2 group E member 1 (Nr2e1) is a transcription factor which regulates many biological processes, including development, growth, and differentiation of nerve cells. However, its specific function in hepatocyte is still unknown. In the present study, we found that the expression of Nr2e1 decreased in the livers of high-fat diet-fed mice. We generated Nr2e1 knockout (KO) mice and studied whether Nr2e1 ablation was related to NAFLD. We found that typical pathological features of NAFLD, including insulin resistance, hepatic steatosis, and inflammation, were present in Nr2e1-KO mice or high-fat diet-induced mice models. In conclusion, Nr2e1 ablation promotes liver steatosis and systemic insulin resistance. Nr2e1 may play a protective role in the formation of NAFLD and may serve as a worthy therapeutic target for NAFLD.