Asparagine attenuates intestinal injury, improves energy status and inhibits AMP-activated protein kinase signalling pathways in weaned piglets challenged with Escherichia coli lipopolysaccharide

Br J Nutr. 2015 Aug 28;114(4):553-65. doi: 10.1017/S0007114515001877.

Abstract

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+0 % Asn; (3) LPS+0·5 % Asn; (4) LPS+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 α-ketoglutarate dehydrogenase complex. Finally, Asn administration decreased the mRNA abundance of intestinal AMP-activated protein kinase-α1 (AMPKα1), AMPKα2, silent information regulator 1 (SIRT1) and PPARγ coactivator-1α (PGC1α), and reduced intestinal AMPKα phosphorylation. Collectively, these results indicate that Asn supplementation alleviates bacterial LPS-induced intestinal injury by modulating the AMPK signalling pathway and improving energy status.

Keywords: Asparagine; Energy status; Intestine; Lipopolysaccharide; Weaned piglets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors*
  • AMP-Activated Protein Kinases / genetics
  • Adenosine Monophosphate / metabolism
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Asparagine / pharmacology
  • Asparagine / therapeutic use*
  • Dietary Supplements
  • Disaccharidases / metabolism
  • Energy Metabolism*
  • Enterocytes / metabolism
  • Enterocytes / pathology
  • Escherichia coli
  • Intestinal Diseases / chemically induced
  • Intestinal Diseases / metabolism
  • Intestinal Diseases / pathology
  • Intestinal Diseases / prevention & control*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestine, Small / metabolism*
  • Intestine, Small / pathology
  • Lipopolysaccharides / adverse effects*
  • Male
  • Phosphorylation
  • Signal Transduction
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Swine
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Weaning

Substances

  • Lipopolysaccharides
  • Transcription Factors
  • Adenosine Monophosphate
  • Asparagine
  • Adenosine Triphosphate
  • AMP-Activated Protein Kinases
  • Disaccharidases
  • Sirtuin 1