Tuesday, January 18, 2022 at 2:00 PM
Assistant Professor Candidate Guest Speaker:
Dr. Ki-Suk Kim, Ph.D
Research Instructor, Department of Pediatrics (Nutrition)
University of Colorado Anschutz Medical Campus
“Bariatric Surgery Induces Intestinal Stemness via Bile Acid Signaling”
Vertical sleeve gastrectomy (VSG) is one type of bariatric surgery that substantially impacts metabolism. An increase in multiple gut peptides has been hypothesized to be a critical mechanism of surgical success because of their role in regulating various aspects of glycemia and energy homeostasis. VSG accompanies an increase in the number of enteroendocrine cells (EECs) in the intestinal epithelium and the level of specific bile acids. Notably, the beneficial effects of VSG are blocked in a mouse model lacking bile acid farnesoid X receptor (FXR). Therefore, we hypothesized that intestinal stem cells (ISCs) express FXR, and the increase in specific bile acids level after VSG drives ISC fate toward EEC differentiation. We performed VSG on a mouse model expressing eGFP in a specific ISC/progenitor marker gene, Lgr5. We then performed RNAseq on the GFP-positive cells sorted from the jejunal epithelia, where we had seen an increased number of EECs. We then treated specific bile acids that increased after VSG to a mouse intestinal organoid model to determine the level of EEC differentiation. RNAseq data revealed that FXR is expressed in ISCs and VSG explicitly altered ISC expression of several genes that regulate intestinal secretory cell development (e.g., Notch gene family and their targets), including EEC differentiation. Mouse intestinal organoids treated with specific bile acids increased EEC differentiation, whereas a potent FXR antagonist blocked this effect. Therefore, specific bile acids increased after VSG induce ISC fate into EEC differentiation through FXR signaling, which is critical to the metabolic change following VSG.
Please send an email to Dedra Jeffries (firstname.lastname@example.org) if you are interested in the seminar.