Yu He1, Xiaoxiao Fan1, Ning Liu1, Qingqing Song1, Jiao Kou1, Yahui Shi1, Xuan Luo1, Zhaolai Dai1, Ying Yang1, Zhenlong Wu1,2, Guoyao Wu1,3. 1. State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China. 2. Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China. 3. Department of Animal Science, Texas A&M University, College Station, TX, USA.
Abstract
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 6α, phosphorylated (p)-inositol-requiring kinase 1α, and p-eukaryotic initiation factor 2α] 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-1β, TNF-α, 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.
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 6α, phosphorylated (p)-inositol-requiring kinase 1α, and p-eukaryotic initiation factor 2α] 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-1β, TNF-α, 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.
Authors: Alan W Duttlinger; Ruth E Centeno Martinez; Betty R McConn; Kouassi R Kpodo; Donald C Lay; Brian T Richert; Timothy A Johnson; Jay S Johnson Journal: J Anim Sci Date: 2021-06-01 Impact factor: 3.159
Authors: Laia Blavi; David Solà-Oriol; Pol Llonch; Sergi López-Vergé; Susana María Martín-Orúe; José Francisco Pérez Journal: Animals (Basel) Date: 2021-01-25 Impact factor: 2.752
Authors: Johannes Schregel; Johannes Schulze Holthausen; Quentin L Sciascia; Zeyang Li; Solvig Görs; Anja Eggert; Armin Tuchscherer; Jürgen Zentek; Cornelia C Metges Journal: PLoS One Date: 2022-04-27 Impact factor: 3.240