1. Asparagine reduces the mRNA expression of muscle atrophy markers via regulating protein kinase B (Akt), AMP-activated protein kinase α, toll-like receptor 4 and nucleotide-binding oligomerisation domain protein signalling in weaning piglets after lipopolysaccharide challenge.
- Author
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Wang X, Liu Y, Wang S, Pi D, Leng W, Zhu H, Zhang J, Shi H, Li S, Lin X, and Odle J
- Subjects
- AMP-Activated Protein Kinases antagonists & inhibitors, Animals, Enzyme Activation drug effects, F-Box Proteins analysis, F-Box Proteins genetics, Forkhead Box Protein O1 antagonists & inhibitors, Lipopolysaccharides pharmacology, Muscle Proteins metabolism, Muscle, Skeletal chemistry, Muscular Atrophy chemically induced, Nod Signaling Adaptor Proteins antagonists & inhibitors, Phosphorylation drug effects, Polycomb Repressive Complex 1 analysis, Polycomb Repressive Complex 1 genetics, RNA, Messenger analysis, Signal Transduction drug effects, Sus scrofa, Toll-Like Receptor 4 genetics, Weaning, AMP-Activated Protein Kinases metabolism, Asparagine pharmacology, Gene Expression drug effects, Muscular Atrophy genetics, Proto-Oncogene Proteins c-akt metabolism, Toll-Like Receptor 4 metabolism
- Abstract
Pro-inflammatory cytokines are critical in mechanisms of muscle atrophy. In addition, asparagine (Asn) is necessary for protein synthesis in mammalian cells. We hypothesised that Asn could attenuate lipopolysaccharide (LPS)-induced muscle atrophy in a piglet model. Piglets were allotted to four treatments (non-challenged control, LPS-challenged control, LPS+0·5 % Asn and LPS+1·0 % Asn). On day 21, the piglets were injected with LPS or saline. At 4 h post injection, piglet blood and muscle samples were collected. Asn increased protein and RNA content in muscles, and decreased mRNA expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1). However, Asn had no effect on the protein abundance of MAFbx and MuRF1. In addition, Asn decreased muscle AMP-activated protein kinase (AMPK) α phosphorylation, but increased muscle protein kinase B (Akt) and Forkhead Box O (FOXO) 1 phosphorylation. Moreover, Asn decreased the concentrations of TNF-α, cortisol and glucagon in plasma, and TNF-α mRNA expression in muscles. Finally, Asn decreased mRNA abundance of muscle toll-like receptor (TLR) 4 and nucleotide-binding oligomerisation domain protein (NOD) signalling-related genes, and regulated their negative regulators. The beneficial effects of Asn on muscle atrophy may be associated with the following: (1) inhibiting muscle protein degradation via activating Akt and inactivating AMPKα and FOXO1; and (2) decreasing the expression of muscle pro-inflammatory cytokines via inhibiting TLR4 and NOD signalling pathways by modulation of their negative regulators.
- Published
- 2016
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