Effects of insulinogenic amino acids restriciton on the FGF21 pathway in neonatal pigs

Protein content in human infant formula is largely above what naturally occurs in human breast milk. Over-consumption of insulinogenic amino acids (IAAs) in infancy and childhood is linked to increased risk of metabolic diseases such as type 2 diabetes and obesity. Prior research has shown that there is a correlation between certain amino acid intake and obesity and insulin resistance in the body, especially pertaining to children. However, the current data focuses primarily on branched-chained amino acids (BCAAs), and not much is known about the broader spectrum of amino acids known as IAAs and how they also contribute to insulin resistance. The goal of this study was to examine the effects of restricting IAAs at 50% and 75% on the glucose metabolism in neonatal pigs. This research project utilizes an Agri-medical model of thirty-two seven-day-old male Yorkshire piglets to establish a correlation between IAAs restriction and improved insulin sensitivity and glucose homeostasis, as well as to test specific gene expression of fibroblast growth factor 21 (FGF21) and the relation to glucose homeostasis and insulin sensitivity in order to allow for new potential treatments for obesity and type 2 diabetes as well as better formula diets in humans. Here we demonstrated that IAAs restriction showed no effects on body weight, but improved glucose clearance. Additionally, FGF21, activating transcription factor 4 (ATF4), and inositol-requiring endoribonuclease 1⍺ (IRE1⍺) displayed significant expression in restricted IAAs groups, which shows a correlation between FGF21 signaling pathway and improved metabolic regulation under IAAs-restricted conditions.