Abstract

This study was conducted to envaluate whether glycine could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury by regulating intestinal epithelial energy status, protein synthesis, and inflammatory response via AMPK, mTOR, TLR4, and NOD signaling pathways. A total of 24 weanling piglets were randomly allotted to 1 of 4 treatments: (1) non-challenged control; (2) LPS-challenged control; (3) LPS + 1% glycine; (4) LPS + 2% glycine. After 28 days feeding, piglets were injected intraperitoneally with saline or LPS. The pigs were slaughtered and intestinal samples were collected at 4 h postinjection. The mRNA expression of key genes in these signaling pathways was measured by real-time PCR. The protein abundance was measured by Western blot analysis. Supplementation with glycine increased jejunal villus height/crypt depth ratio. Glycine also increased the jejunal and ileal protein content, RNA/DNA ratio, and jejunal protein/DNA ratio. The activities of citroyl synthetase in ileum, and α-ketoglutarate dehydrogenase complex in jejunum, were increased in the piglets fed diets supplemented with glycine. In addition, glycine decreased the jejunal and ileal phosphorylation of AMPKα, and increased ileal phosphorylation of mTOR. Furthermore, glycine downregulated the mRNA expression of key genes in inflammatory signaling. Meanwhile, glycine increased the mRNA expression of negative regulators of inflammatory signaling. These results indicate that glycine supplementation could improve energy status and protein synthesis by regulating AMPK and mTOR signaling pathways, and relieve inflammation by inhibiting of TLR4 and NOD signaling pathways to alleviate intestinal injury in LPS-challenged piglets.

Highlights

  • The intestinal epithelium plays a key role in digestion and absorption of nutrients, and has an important function in preventing pathogen invasion and dissemination of commensals [1]

  • Some reports showed that glycine could alleviate colitis induced by chemicals, small intestine injury induced by endotoxins, and inhibit overproduction of pro-inflammatory cytokines in rats [10,11,12]

  • There was no significant effect on intestinal morphology among the LPS-challenged piglets fed diets supplemented with glycine (p > 0.05)

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Summary

Introduction

The intestinal epithelium plays a key role in digestion and absorption of nutrients, and has an important function in preventing pathogen invasion and dissemination of commensals [1]. The intestinal epithelial health status, especially in young animals, could be injured by many factors, such as inflammation and infection [2]. Inflammation often results in intestinal mucosal damage and dysfunction, which negatively affects animal performance and health [3]. In order to alleviate the inflammation and maintain health and function, the intestine needs a high level of energy and amino acids (AAs) [4,5]. Glycine, whose structure is the simplest of all AAs, is regarded as a conditionally essential AA for young mammals, and a nutritionally essential amino acid for fetal and neonatal development of poultry [6,7]. Some reports showed that glycine could alleviate colitis induced by chemicals, small intestine injury induced by endotoxins, and inhibit overproduction of pro-inflammatory cytokines in rats [10,11,12]

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