Glycine Enhances Muscle Protein Mass Associated with Maintaining Akt-mTOR-FOXO1 Signaling and Suppressing TLR4 and NOD2 Signaling in Piglets Challenged with LPS.
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Pro-inflammatory cytokines play a critical role in the pathophysiology of muscle atrophy. We hypothesized that glycine exerted an anti-inflammatory effect and alleviated lipopolysaccharide (LPS)-induced muscle atrophy in piglets. Pigs were assigned to four treatments including: (1) non-challenged control; (2) LPS-challenged control; (3) LPS+1.0% glycine; (4) LPS+2.0% glycine. After receiving the control, 1.0% or 2.0% glycine supplemented diets, piglets were treated with either saline or LPS. At 4 h after treatment with saline or LPS, blood and muscle samples were harvested. We found that 1.0% or 2.0% glycine increased protein/DNA ratio, protein content and RNA/DNA ratio in gastrocnemius or longissimus dorsi (LD) muscles. Glycine also resulted in decreased mRNA expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) in gastrocnemius muscle. In addition, glycine restored the phosphorylation of Akt, mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1) and Forkhead Box O 1 (FOXO1) in gastrocnemius or LD muscles. Furthermore, glycine resulted in decreased plasma tumor necrosis factor-α (TNF-α) concentration and muscle TNF-α mRNA abundance. Moreover, glycine resulted in decreased mRNA expresson of toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain protein 2 (NOD2) and their respective downstream molecules in gastrocnemius or LD muscles. These results indicate glycine enhances muscle protein mass under an inflammatory condition. The beneficial roles of glycine on the muscle are closely associated with maintaining Akt-mTOR-FOXO1 signaling, and suppressing the activation of TLR4 and/or NOD2 signaling pathways.Copyright © 2016, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.