Grant: Discovery Grants Program - Individual

This research proposal aims to address a critical knowledge gap in the regulation of post-prandial metabolism and the intricacies of nutrient metabolism. It focuses on the pivotal roles of the gut hormones, glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), in lipid metabolism, immune responses, and gut growth. This research is important given the small intestine's remarkable ability to function as both a protective barrier and a nutrient absorption channel, requiring constant adjustment to environmental factors, diet, and growth renewal. The farming industry has utilized this knowledge previously to improve animal survival and improve feeding efficencies. The long-term research objective of this proposal is to shed light on how gut hormone secretion and bioactivity are influenced by various dietary stimuli, biological sex, and their roles in gut adaptation, immune tolerance, and metabolic changes. Therefore over the next five years our HQP (2 graduate students, supported by undergraduates) will pursue research on three main objectives: Objective 1: The first objective is to study the response of the gut, specifically L-cells, to cold stress and transitions from fasting to refeeding. This includes investigating changes in molecular signatures in the small intestine and the impact of GLP-2R signaling on gut surface area. Objective 2: The second objective focuses on evaluating the effects of intestinal GLP1R+ cell signaling on the metabolism and function of intraepithelial lymphocytes (IELs)  particularly in response to nutrient composition and stress. It examines changes in Glp1r expression in lymphoid tissues and how it affects antigen presentation and immune responses. Objective 3: The third objective continues to assess the impact of intestinal GLP1R+ cell signaling, but this time on lymphatic endothelial cells. It studies the expression of Glp1r and the potential role of GLP-1R activation in lipid uptake and metabolism within these cells. The proposal details various experiments and methodologies to achieve these objectives, including measuring microvilli length, cell proliferation, L-cell abundance, and transcription factors. It also discusses the impact of fasting, refeeding, and cold exposure on gene expression and cell function in the intestine and lymphatic system. The ultimate goal of this research program is to better understand the role of GLP-1R and GLP-2R signaling in the gut and its effects on metabolism and immune responses, with potential implications for various physiological process related to nutrient handling. Additionally, it seeks to uncover the local GLP-1 and GLP-2 gut receptor signaling, offering valuable insights that can be applied to various industrial sectors, including livestock farming, to enhance animal feeding methods to improve nutrient efficiency.