Abstract
Nonalcoholic fatty liver disease (NAFLD) occurs when excess fat is stored in the liver and it is strongly linked with metabolic syndrome and oxidative stress. Selenium (Se) is an essential micronutrient in animals, which has a variety of biological functions, including antioxidant and anti-inflammatory. However, the exact effect of dietary selenium on NAFLD and the underlying molecular mechanism are not yet clear. Herein, we fed a high-fat diet (HFD) to C57BL/6 mice to construct an in vivo NAFLD model, treated AML-12 cells with palmitic acid (PA) to construct an in vitro NAFLD model, and AML-12 cells were stimulated with H2O2 to induce hepatocyte oxidative stress and then treated with adequate selenium. We observed that adequate selenium significantly improved the hepatic injury and insulin resistance in HFD mice, and decreased the fat accumulation and the expression of lipogenic genes in PA-induced AML-12 cells. Meanwhile, selenium significantly inhibited the production of reactive oxygen species (ROS), inhibited apoptosis, and restored mitochondrial number and membrane potential in PA- induced AML-12 cells. In addition, selenium can promote selenoproteinP1 (SEPP1) synthesis to regulate the Kelch-like ECH-associated protein 1 (KEAP1)/NF-E2-related factor 2 (NRF2) pathway, so as to defend against hepatocyte oxidative stress. These findings suggest that dietary selenium supplementation can effectively resist hepatic injury and insulin resistance during NAFLD development, and regulate the KEAP1/NRF2 pathway to resist oxidative stress by promoting SEPP1 synthesis.
Highlights
In recent years, Nonalcoholic fatty liver disease (NAFLD) has been considered to be one of the most common liver diseases worldwide, with about 30% of the population in the world being affected [1].NAFLD refers to the excessive accumulation of triglycerides (TG) in liver cells without excessive alcohol stimulation or viral invasion, which is a general term for a series of diseases characterized by significant accumulation of liver lipids [2]
Our results demonstrate that Se can ameliorate hepatic injury induced by NAFLD and promote SEPP1 synthesis to regulate the Kelch-like ECHassociated protein 1 (KEAP1)/NF-E2-related factor 2 (NRF2) pathway, so as to defend against hepatocyte oxidative stress
Visual observation showed that body weight was remarkably reduced in the Se + high-fat diet (HFD) group compared with the HFD group
Summary
NAFLD has been considered to be one of the most common liver diseases worldwide, with about 30% of the population in the world being affected [1]. The second hit results in severe damage to liver function, and liver fibrosis [6,7] This suggests that hepatic injury caused by NAFLD is closely related to oxidative stress. DNA and change the expression of certain genes They can induce protein and lipid oxidation, which alters the functional activity of some enzymes, structural proteins, and cell membranes [10]. We established an NAFLD model in vivo and in vitro as well as hepatocyte oxidative stress model, and treated with appropriate Se to evaluate the role of Se defense against NAFLD, the antioxidant effect, and its latent molecular mechanism. Our results demonstrate that Se can ameliorate hepatic injury induced by NAFLD and promote SEPP1 synthesis to regulate the KEAP1/NRF2 pathway, so as to defend against hepatocyte oxidative stress
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