PMON295 Investigating the ileal FXR/SHP axis in regulating lipid absorption and enterohepatic recirculation of bile acids

Abstract

Abstract Lipids are biological macromolecules essential for energy storage, signaling pathways, and cell structure. Majority of these molecules come from our diet where they are digested in the small intestine through their interaction with bile acids. Lipids break down into small molecules and are brought to the intestinal brush border to be absorbed passively by diffusion or by lipid transporters. Interestingly, two essential nuclear receptors that regulate both bile acid and lipid absorption and transportation are farnesnoid X receptor (FXR) and small heterodimer partner (SHP). Many studies have shown that the linear FXR/SHP axis controls these lipid metabolic processes, however, there are evidence indicating FXR-dependent and -independent pathways of SHP. In order to ascertain the importance of FXR and SHP in intestinal lipid metabolism, we utilized the following three mice models, intestine-specific Fxr (IFxrKO), intestine-specific Shp (IShpKO), and intestine-specific Fxr and Shp (IDKO) knockout models and challenged them with high fat diet. We are assessing the intestinal absorption and transportation of triglycerides by measuring the concentration of triglyceride on circulation, liver, and intestine and the molecular level the protein expression of different transporters. Parallelly, we will examine the bile acid pool by measuring bile acid levels from the intestine, liver, gall bladder, and serum to test if changes in bile acid circulation observed in these knockout models show different contribution towards lipid/triglyceride absorption. In addition, we will inject poloxamer-407 in these mice groups to assess their chylomicron secretion rate. Finally, we will examine the histology of the small intestine by performing H&E staining to examine the morphology and perform PAS/Alcian blue staining to examine mucus production. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.