Selenium deficiency-induced redox imbalance leads to metabolic reprogramming and inflammation in the liver
Selenium deficiency-induced redox imbalance leads to metabolic reprogramming and inflammation in the liver
复制标题
缺硒引起的氧化还原失衡导致肝脏代谢重编程和炎症
DOI：
10.1016/j.redox.2020.101519
复制
发表时间：
2020-09-01
期刊：
影响因子：
11.4
通讯作者：
Zhang, Junmin
中科院分区：
文献类型：
--
作者：
Tang, Chaohua;Li, Shuang;Zhang, Junmin
Selenium (Se) intake disequilibrium is associated with many human diseases (e.g., Keshan disease and type 2 diabetes). To understand the mechanism of Se deficiency-induced hepatic pathogenesis, a pure line pig model was established by feeding a diet with either 0.07 mg/kg Se or 0.3 mg/kg Se for 16 weeks. The hepatic metabolome, lipidome, global proteome, and whole transcriptome were analyzed. Se deficiency causes a redox imbalance via regulation of selenoproteins at both the mRNA and protein level, and blocks the glutathione antioxidant system along with enhanced glutathione synthesis and catabolism. The Warburg effect was observed by enhanced activation of the glycolysis and phosphate pentose pathways. The tricarboxylic acid cycle was dysfunctional since the preliminary metabolites decreased and shifted from using glycolysis origin substrates to a glutamine catabolism-preferred metabolic mode. The reprogrammed central carbon metabolism induced widely restrained lipid synthesis. In addition, a Se deficiency initiated inflammation by activating the NF-kappa B pathway through multiple mechanisms. These results identified the potential metabolic vulnerability of the liver in response to a Se deficiency-induced redox imbalance and possible therapeutic or intervention targets.
