👤 Arianne Morissette

Chronic cold exposure in mice increases metabolic demand and food intake; the gut correspondingly expands its absorptive surface area. Gut enteroendocrine cells produce peptide hormones including glucagon-like peptide-1 (GLP-1), GLP-2, and glucose-dependent insulinotropic polypeptide (GIP) in response to a meal to facilitate nutrient absorption and post-prandial metabolism. The requirement of GLP-1, GLP-2, and GIP receptor signaling for small intestinal adaptations to chronic cold stress has not been investigated. Here, we show that male and female wild-type, double incretin receptor knockout (Glp1r Show less

Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are peptide hormones produced by enteroendocrine cells in the small intestine. Despite being produced in the gut, the leveraging of their role in potentiating glucose-stimulated insulin secretion, also known as the incretin effect, has distracted from discernment of direct intestinal signaling circuits. Both preclinical and clinical evidence have highlighted a role for the incretins in inflammation. In this review, we highlight the discoveries of GLP-1 receptor (GLP-1R)+ natural (TCRαβ and TCRγδ) and induced (TCRαβ+CD4+ cells and TCRαβ+CD8αβ+) intraepithelial lymphocytes. Both endogenous signaling and pharmacological activation of GLP-1R impact local and systemic inflammation, the gut microbiota, whole-body metabolism, as well as the control of GLP-1 bioavailability. While GIPR signaling has been documented to impact hematopoiesis, the impact of these bone marrow-derived cells in gut immunology is not well understood. We uncover gaps in the literature of the evaluation of the impact of sex in these GLP-1R and GIP receptor (GIPR) signaling circuits and provide speculations of the maintenance roles these hormones play within the gut in the fasting-refeeding cycles. GLP-1R agonists and GLP-1R/GIPR agonists are widely used as treatments for diabetes and weight loss, respectively; however, their impact on gut homeostasis has not been fully explored. Advancing our understanding of the roles of GLP-1R and GIPR signaling within the gut at homeostasis as well as metabolic and inflammatory diseases may provide targets to improve disease management. Show less

The familial chylomicronemia syndrome (FCS) is an ultra rare disease caused by lipoprotein lipase (LPL) deficiency associated with potentially lethal acute pancreatitis risk. Thrombocytopenia (platelet count < 150,000 × 10 To evaluate post-prandial fluctuations in the platelet count (PLC) and functional defects of hemostasis in FCS. PLC, functional defects in hemostasis and hematologic variables were measured up-to 5 h after a meal in 6 homozygotes for FCS causing gene variants (HoLPL), 6 heterozygotes for LPL loss-of-function variants (HeLPL) and 7 normolipidemic controls. Hourly post-prandial PLC was significantly lower in HoLPL than in controls (P < 0.009). Compared to the other groups, the PLC tended to decrease rapidly (in the first hour) post-meal in HoLPL (P = 0.03) and remained lower than baseline 5-h post-meal (P = 0.02) whereas it tended to slightly increase in normolipidemic controls (P = 0.02). Platelet function was not affected by the prandial status. In HoLPL, post-prandial fluctuations in the PLC positively correlated with the lymphocyte count (P = 0.005) and negatively with neutrophil/lymphocyte ratio (NLR). The PLC decreases post-prandially in FCS (HoLPL), is not associated with changes in functional defects of hemostasis and correlates with the NLR, a marker of acute pancreatitis severity. Show less