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. 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. 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. 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. Our results indicate that preweaning administration of Gln to nursing piglets alleviates the weaning-activated UPR.

In vivo data on intestinal fat absorption in weanling piglets are scarce. This study aimed to investigate the effect of weaning stress on intestinal fat absorption. Eighteen 7-d-old sow-reared piglets (Duroc-Landrace-Yorkshire) were assigned to 3 groups (n = 6/group, 3 males and 3 females per group). Piglets were nursed by sows until 24 d of age (suckling piglets, S), or weaned at 21 d of age to a corn-soybean meal–based diet until 24 d (3 d postweaning, W3) or 28 d (7 d postweaning, W7) of age, respectively. Duodenum, jejunum, and ileum were collected to determine intestinal morphology and abundance of proteins related to fat absorption. Compared with the S group, the W3 group had lower villus height (17–34%) and villus height to crypt depth ratio (13–53%), as well as 1–1.45 times greater crypt depth; these values were 1.18–1.31, 0.69–1.15, and 1.47–1.87 times greater in the W7 group than in the W3 group, respectively. Compared with the S group, weaning stress for both W3 and W7 groups reduced intestinal alkaline phosphatase activity (26–73%), serum lipids (26–54%), and abundances of proteins related to fatty acid transport [fatty acid transport protein 4 (FATP4) and intestinal fatty acid-binding protein (I-FABP)] and chylomicron assembly [microsomal triglyceride transfer protein (MTTP), apolipoprotein A-IV (APOA4), B (APOB), and A-I (APOA1)] in the duodenum and ileum (10–55%), as well as in the jejunum (25–85%). All these indexes did not differ between W3 and W7 groups. Compared with the S group, the W3 group had lower mRNA abundances of duodenal APOA4 and APOA1 (25–50%), as well as jejunal FATP4, IFABP, MTTP, APOA4, and APOA1 (35–50%); these values were 5–15% and 10–37% lower in the W7 group than in the W3 group, respectively. Weaning stress in piglets attenuates the expression of intestinal proteins related to fatty acid transport (FATP4 and I-FABP) and chylomicron synthesis (APOA4).

Glutamine (Gln) is required for intestinal mucosal homeostasis, and it can promote triglyceride absorption. The intestinal mucosal mast cells (MMCs) are activated during fat absorption. This study investigated the potential role of Gln on fat absorption-induced activation of MMCs in rats. Lymph fistula rats (n = 24) were studied after an overnight recovery with the infusion of saline only, saline plus 85 mM L-glutamine (L-Gln) or 85 mM D-glutamine (D-Gln), respectively. On the test day, rats (n = 8/group) were given an intraduodenal bolus of 20% Intralipid contained either saline only (vehicle group), 85 mM L-Gln (L-Gln group), or 85 mM D-Gln (D-Gln group). Lymph was collected hourly for up to 6 h for analyses. The results showed that intestinal lymph from rats given L-Gln had increased levels of apolipoprotein B (ApoB) and A-I (ApoA-I), concomitant with an increased spectrum of smaller chylomicron particles. Unexpectedly, L-Gln also increased levels of rat mucosal mast cell protease II (RMCPII), as well as histamine and prostaglandin D₂ (PGD₂) in response to dietary lipid. However, these effects were not observed in rats treated with 85 mM of the stereoisomer D-Gln. Our results showed that L-glutamine could specifically activate MMCs to degranulate and release MMC mediators to the lymph during fat absorption. This observation is potentially important clinically since L-glutamine is often used to promote gut health and repair leaky gut.