Selenium deficiency-induced redox imbalance leads to metabolic reprogramming and inflammation in the liver

Redox Biology

Xiaoqing Guo¹  Jing Li¹  Shuang Li¹  Tengfei Zhan¹  Junmin Zhang²  Kai Zhang²  Qingyu Zhao²  Chaohua Tang²  Yunsheng Han² 

[1] Scientific Observing and Experiment Station of Animal Genetic Resources and Nutrition in North China of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193, China;State Key Laboratory of Animal Nutrition, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193, China;

关键词: Selenium deficiency;    Redox imbalance;    Metabolic reprogramming;    Inflammation;    Pig liver;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 anti-oxidant 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-κB 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.

【 授权许可】

Unknown