Early weaning in pigs induces long‐term alterations in intestinal nutrient transporter function and expression

Abstract

Early life adversity (ELA) is associated with increased disease risk throughout the lifespan but the developmental mechanisms underlying the association remain elusive. Altered intestinal nutrient transporter function has been implicated as a mechanism contributing to a number of diseases associated with ELA such as Type 2 diabetes and inflammatory and functional GI disorders in humans and impaired health and growth performance in agricultural animals. Using an early weaning stress model of ELA in pigs, we investigated the link between ELA and long‐term intestinal nutrient transporter function and expression. Yorkshire breed female piglets were weaned from their sows at 15 d (Early Weaning; EW) or 28 d of age (Late Weaning; LW). Early and LW piglets were co‐housed and received the same diets. At 70 d of age, mid‐jejunum and distal ileum were harvested from EW and LW pigs and mounted on Ussing chambers to evaluate Na+‐dependent electrogenic nutrient transporter function, determined as the change in short‐circuit current (ΔIsc) in response to select luminal nutrients. Villus morphology and epithelial gene expression of nutrient transporters were assessed. Compared with age‐matched LW pigs, EW pigs exhibited reduced jejunal and ileal Na+ glucose linked transporter (SGLT1) function (by ~30%; P < 0.05) and amino transporter function for glutamate, glutamine, and alanine by (~30–35%; P < 0.05). In contrast, jejunal and ileal lysine transporter function was upregulated (by 110% and 25%, respectively; P < 0.05) in EW pigs. Gene expression for nutrient transporters (SGLT1, EAAT3, and B0AT1) were reduced (P < 0.05) while the lysine transporter CAT1 was enhanced in the EW jejunum. There were no differences observed in villus morphology between EW and LW pigs. Enteric neuronal inhibitors tetrodotoxin, atropine and propranolol, enhanced ΔIsc responses to glucose, lysine and alanine transporter function in EW but not in LW pig ileum. Together, these data show that EW in pigs induces lasting and divergent alterations in small intestinal nutrient transporter function and expression which is mediated in part by the enteric nervous system. These findings could provide new insight into the mechanisms of increased disease risk linked with ELA and thus lead to novel dietary or therapeutic strategies.Support or Funding InformationNIH R01 HD072968USDA‐NIFA #2017‐67015‐26673This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.