Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

et al. 2018

IJMS

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.

Section: Discussionmentioning

confidence: 99%

Glycine Relieves Intestinal Injury by Maintaining mTOR Signaling and Suppressing AMPK, TLR4, and NOD Signaling in Weaned Piglets after Lipopolysaccharide Challenge

et al. 2018

IJMS

“…Protein/DNA ratio in mucosa has been employed as an indicator of intestinal growth and repair 4 . Mucosal disaccharidases, namely lactase, maltase and sucrase, reflect intestinal digestive function 32 . Claudins are major constituents of tight junctions 33 .…”

Section: Discussionmentioning

confidence: 99%

Glutamate alleviates intestinal injury, maintains mTOR and suppresses TLR4 and NOD signaling pathways in weanling pigs challenged with lipopolysaccharide

Qin

et al. 2018

Sci Rep

This experiment aimed to explore whether glutamate (Glu) had beneficial effects on intestinal injury caused by Escherichia coli LPS challenge via regulating mTOR, TLRs, as well as NODs signaling pathways. Twenty-four piglets were allotted to 4 treatments including: (1) control group; (2) LPS group; (3) LPS + 1.0% Glu group; (4) LPS + 2.0% Glu group. Supplementation with Glu increased jejunal villus height/crypt depth ratio, ileal activities of lactase, maltase and sucrase, and RNA/DNA ratio and protein abundance of claudin-1 in jejunum and ileum. In addition, the piglets fed Glu diets had higher phosphorylated mTOR (Ser2448)/total mTOR ratio in jejunum and ileum. Moreover, Glu decreased TNF-α concentration in plasma. Supplementation with Glu also decreased mRNA abundance of jejunal TLR4, MyD88, IRAK1, TRAF6, NOD2 and increased mRNA abundance of ileal Tollip. These results indicate that Glu supplementation may be closely related to maintaining mTOR and inhibiting TLR4 and NOD signaling pathways, and concomitant improvement of intestinal integrity under an inflammatory condition.

“…digestive function (37) . In the present study, villus height and disaccharidase activities in the jejunum were higher than those in the ileum, which is similar to the report of Rubio et al (38) .…”

Section: Discussionmentioning

confidence: 99%

Asparagine attenuates intestinal injury, improves energy status and inhibits AMP-activated protein kinase signalling pathways in weaned piglets challenged withEscherichia colilipopolysaccharide

Liu

et al. 2015

Br J Nutr

The intestine requires a high amount of energy to maintain its health and function; thus, energy deficits in intestinal mucosa may lead to intestinal damage. Asparagine (Asn) is a precursor for many other amino acids such as aspartate, glutamine and glutamate, which can be used to supply energy to enterocytes. In the present study, we hypothesise that dietary supplementation of Asn could alleviate bacterial lipopolysaccharide (LPS)-induced intestinal injury via improvement of intestinal energy status. A total of twenty-four weaned piglets were assigned to one of four treatments: (1) non-challenged control; (2) LPS þ 0 % Asn; (3) LPS þ 0·5 % Asn; (4) LPS þ 1·0 % Asn. On day 19, piglets were injected with LPS or saline. At 24 h post-injection, piglets were slaughtered and intestinal samples were collected. Asn supplementation improved intestinal morphology, indicated by higher villus height and villus height:crypt depth ratio, and lower crypt depth. Asn supplementation also increased the ratios of RNA:DNA and protein:DNA as well as disaccharidase activities in intestinal mucosa. In addition, Asn supplementation attenuated bacterial LPS-induced intestinal energy deficits, indicated by increased ATP and adenylate energy charge levels, and decreased AMP:ATP ratio. Moreover, Asn administration increased the activities of key enzymes involved in the tricarboxylic acid cycle, including citrate synthase, isocitrate dehydrogenase and a-ketoglutarate dehydrogenase complex. Finally, Asn administration decreased the mRNA abundance of intestinal AMP-activated protein kinase-a1 (AMPKa1), AMPKa2, silent information regulator 1 (SIRT1) and PPARg coactivator-1a (PGC1a), and reduced intestinal AMPKa phosphorylation. Collectively, these results indicate that Asn supplementation alleviates bacterial LPS-induced intestinal injury by modulating the AMPK signalling pathway and improving energy status.Key words: Asparagine: Intestine: Energy status: Weaned piglets: LipopolysaccharideThe intestine is not only important for digestion and absorption of dietary nutrients, but also plays a key role in defence against harmful bacteria-derived endogenous and exogenous agents (1) . Many factors such as infection and inflammation can cause intestinal damage and dysfunction (1 -3) . Recently, research has shown that the intestine requires a high amount of energy to maintain its health and function; thus, energy deficits in intestinal mucosa are closely related to various degrees of injury in the intestine (4) . Amino acids can serve as a central fuel source for intestinal mucosa (5) . Accumulating evidence suggests that amino acids play a critical role in intestinal integrity, function and health in animals and humans (6) .Thus, nutritional regulation (especially dietary addition of amino acids) targeting intestinal energy metabolism may hold great promise for intestinal disease prevention and improvement of animal and human health. Asparagine (Asn) is a non-essential amino acid. As has been stated in a recent review, Asn, aspartate, glu...