139 Calcium-Sensing Receptor and the Regulation of Nutrient Absorption and gut Health in Pigs

Abstract

The gut has a network of G protein-coupled receptors (GPCR) that can recognize nutrients, other chemicals, and microbes and then initiate a cascade of signals to regulate nutrition, gut function, and metabolism. Calcium sensing receptors (CaSR) belong to the GPCR family and are expressed in various animal tissues, and CaSR plays important role in nutrient sensing and the physiology, growth, and development of animals. Our results demonstrated that pCaSR is widely expressed in different tissues including intestinal segments in weaned piglets and the ileum has a higher expression level of pCaSR. However, pCaSR is not expressed in either isolated porcine ileal enterocytes or intestinal porcine enterocyte cell lines (IPEC-J2). We also found that the activation of pCaSR showed biased agonism through multiple signaling with a dual-luciferase reporter assay system. Besides, α-casein (90-95) and L-Tryptophan (L-Trp) are type II agonists for pCaSR. We investigated the roles of pig calcium-sensing receptor (pCaSR) ligands in gut hormone secretion and mechanism and the effects of pCaSR ligands on inflammation response, nutrient absorption and barrier function in the intestinal epithelial cells co-culture system challenged with peptidoglycan (PGN). Our results demonstrated that the pCaSR ligands (L-Trp and α-casein (90-95)) to STC-1 cells could induce the secretion of gut hormones through the regulation of CaSR in STC-cells. Plus, the GLP-1 secretion triggered by L-Trp and α-casein (90-95) in STC-cells attenuated the inflammation response, improved the nutrient absorption and barrier function in the IPEC-J2 cells. Further research is still needed to elucidate the roles of L-Trp and α-casein (90-95) on nutrient absorption and barrier function in pigs under physiological challenges. Collectively, the pCaSR is widely expressed in the porcine tissues, and the activation of pCaSR has the potential to improve gut health and growth performance in swine production.

calcium sensing receptors (CaSR), enterocytes, L-tryptophan, α-casein, pigs