L-Glutamine Represses the Unfolded Protein Response in the Small Intestine of Weanling Piglets

Background: Dysfunction of the endoplasmic reticulum (ER) results in apoptosis, inflammation, and enhanced proteolysis in the small intestine of humans and animals. L-Glutamine (Gln) is required for intestinal mucosal homeostasis in piglets. However, a functional role of the ER in the enterocytes of weanling piglets and its contribution to intestinal mucosal integrity remain largely unknown. Objective: This study was conducted to test the hypothesis that preweaning administration of Gln alleviates the activation of unfolded protein response (UPR) in the small intestine of weanling piglets. Methods: Eighteen sow-reared piglets aged 7 d from 3 litters (6 piglets/litter) were assigned randomly into 1 of 3 treatment groups. Piglets were reared by sows until age 24 d, or were reared by sows and orally administered either L-alanine [1.84 g . kg body weight (BW)(-1) . d(-1)] or Gln (1.52 g . kg BW-1 . d(-1)) twice daily between 7 and 21 d of age, and then weaned to a corn- and soybean meal-based diet. The small-intestinal samples were collected at 24 d of age for analyses of abundance of proteins related to ER stress and apoptosis, concentrations of inflammatory cytokines, and mRNA abundance for genes implicated in protein degradation. Results: Compared with age-matched suckling piglets, weaning stress increased apoptosis and decreased cell proliferation in the jejunum. The abundance of proteins related to ER stress [binding immunoglobulin protein, activating transcription factor 6 alpha, phosphorylated (p)-inositol-requiring kinase 1 alpha, and p-eukaryotic initiation factor 2 alpha] was elevated by 200% to 320%, and that of apoptotic proteins (CCAAT/enhancer-binding protein homologous protein, p-Jun-N-terminal kinase, caspase-12, cleaved caspase-3, and Bcl-2-associated X) was augmented by 100% to 350% in the jejunum of weanling piglets. The protein abundance for IL-1 beta, TNF-alpha, and IL-8 was increased by 100% to 230% in the jejunum of weanling piglets. These alterations in gene and protein expression were markedly abrogated by Gln supplementation. The mRNA concentration of F-Box protein 32 in the jejunum of weanling piglets was increased by 70%, compared with the control group, and was not affected by Gln supplementation. Conclusion: Our results indicate that preweaning administration of Gln to nursing piglets alleviates the weaning-activated UPR.