Multi-Omics Profiling Reveals Se Deficiency-Induced Redox Imbalance, Metabolic Reprogramming, and Inflammation in Pig...

Nutritional muscle dystrophy is associated with selenium (Se) deficiency; however, the underlying mechanism remains unclear.

This study aimed to understand the crosstalk among redox status, energy metabolism, and inflammation in nutritional muscle dystrophy induced by dietary Se deficiency.

Eighteen castrated male pigs (Yorkshire, 45 d old) were fed Se-deficient (Se-D; 0.007 mg Se/kg) or Se-adequate (Se-A; in the form of selenomethionine, 0.3 mg Se/kg) diets for 16 wk. The muscle Se concentrations; antioxidant capacity; and gene expression, transcriptome, global proteome, metabolome, and lipidome profiles were analyzed. The transcriptome, metabolome, and proteome profiles were analyzed with biostatistics, bioinformatics, and pathway enrichment analysis; other data were analyzed with Student's 2-sided t tests.

The muscle Se content in the Se-D group was 96% lower than that in the Se-A group (P < 0.05). The activity of glutathione peroxidase (GPX) and thioredoxin reductase (TXNRD) in the Se-D group was 42%-69% lower than that in the Se-A group (P < 0.05). The mRNA levels of 10 selenoprotein genes were 25%-84% lower than those in the Se-A group (P < 0.05). Multi-omics analyses indicated that the levels of 1378 transcripts, 83 proteins, 22 metabolites, and 55 lipid molecules were significantly altered in response to Se deficiency. Se deficiency-induced redox imbalance led to muscle central carbon and lipid metabolism reprogramming, which enhanced the glycolysis pathway and decreased phospholipid synthesis. Inflammation and apoptosis were observed in response to Se deficiency-induced muscle oxidative stress, which may have been associated with extracellular matrix (ECM) remodeling, suppressed focal adhesion and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling, and activation of the NF-κB signaling pathway.

These results contributed to understanding the crosstalk among redox, energy metabolism, and inflammation in Se deficiency-induced muscle dystrophy in pigs, and may provide intervention targets for muscle disease treatment.