“Glucagon-like-protein-2 stimulates lacteal contractility and enhances chylomicron transport in the presence of an intact enteric nervous system
https://dacostalab.ca/wp-content/uploads/2024/07/ga1_lrg-1030x417.jpg 1030 417 DaCosta Lab DaCosta Lab https://dacostalab.ca/wp-content/uploads/2024/07/ga1_lrg-1030x417.jpgOur recent paper, ““Glucagon-like-protein-2 stimulates lacteal contractility and enhances chylomicron transport in the presence of an intact enteric nervous system,” was published in Gastro Hep Advances (June 2024). Background and Aims: Secretion and transport of intestinal chylomicrons (CM) via lymphatics to the blood circulation is stimulated primarily by fat ingestion, whereas several other factors have also been shown to play important roles in regulating CM secretion rate. Amongst these factors, active regulation of lymphatic pumping has not been appreciated to date. The gut peptide and intestinal growth factor GLP-2 has emerged as a robust enhancer of intestinal lipid mobilization and secretion. The present study aims to elucidate GLP-2’s impact on lacteal contractility and assess ENS involvement in GLP-2-induced effects on lipid mobilization. Methods: Using intravital imaging of a Prox1-EGFP rat model, we assessed GLP-2’s effect on lacteal contractility, in the presence and absence of the ENS inhibitor mecamylamine (MEC). Concurrently, to explore the physiological relevance, we examined GLP-2’s impact on lymph flow and triglyceride (TG) output in vivo in a rat lymph fistula model. Results: GLP-2 significantly increased lacteal contractility, and this effect was inhibited by MEC. In the rat lymph fistula model, GLP-2 increased lymph flow, lymph volume, cumulative lymph volume, and TG output while reducing lymph TG concentration. MEC administration blocked these effects of GLP-2. Peak enhancement of lacteal contractility and enhancement of lymph flow in vivo occurred simultaneously with maximal effect at 15 to 20 minutes post GLP-2 administration, suggesting that GLP-2 enhances lipid transport by stimulating lymphatic contractility. Conclusions: For the first time, through imaging and concurrent rat fistula studies, we demonstrated active regulation of lymphatic contractility as a key determinant of CM secretion and that intact ENS was required to observe this effect.
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