Glycine supplementation to breast-fed piglets attenuates post-weaning jejunal epithelial apoptosis: a functional role of CHOP signaling.

This study was conducted to test the hypothesis that preweaning  glycine supplementation to breast-fed piglets alleviated the post-weaning  apoptosis of jejunal epithelium through CHOP signaling. Seven-day-old sow-reared piglets were orally administrated with 0, 50, 100, or 200% of glycine intake from sow's milk twice daily for 14 days and then were weaned at 21 days of age. Tissue samples were collected at 28 days of age for determining intestinal morphology, serum diamine oxidase (DAO) activity, abundances of proteins involved in ER stress and apoptosis. Glycine (100-200%) administration increased villus height, the ratio of villus height to crypt depth in the jejunum. Glycine supplementation (200%) enhanced average daily weight gain during the first 2 weeks post-weaning. Serum DAO activity and jejunal epithelium apoptosis were decreased, but the number of goblet cells in the jejunum was increased. Western blot analysis showed that 100-200% glycine enhanced the protein levels of occludin, claudin-1, and zonula occludens (ZO)-1 without affecting those of claudin-3, ZO-2, and ZO-3. Further studies showed that protein abundances of glucose-regulated protein 78 (BiP/GRP78) and p-IRE1α, instead of ATF6α, were reduced by glycine. Among the proteins related to apoptosis, abundances of CHOP and p53 were reduced, whereas those of Bcl-2 and Bcl-xL were enhanced in the jejunum of 100-200% glycine-supplemented piglets. Collectively, our results indicated that preweaning glycine supplementation improved the intestinal development of post-weaning piglets. The beneficial effect of glycine was associated with improved intestinal mucosal barrier and reduced apoptosis of enterocytes through CHOP signaling.