
GLP-1R signaling modulates colonic energy metabolism, goblet cell number and survival in the absence of gut microbiota
Online ahead of print, Molecular Metabolism, March 2024
In collaboration with Daniel J Drucker at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, we made the surprising observation more than 10 years ago that GLP-1R deficient mice dies. Further work led by our team member Thomas Greiner, with the support from the Mucin Biology Groups at the University of Gothenburg, revealed involvement of goblet cells.
The microbiota increases energy availability through fermentation of dietary fibers to short-chain fatty acids in conventionally raised mice. Energy deficiency in germ-free (GF) mice increases glucagon-like peptide-1 (GLP-1) levels, which slows intestinal transit. To further analyze the role of GLP-1-mediated signaling in this model of energy deficiency, we re-derived mice lacking GLP-1 receptor (GLP-1R KO) as GF. Our findings reveal a heretofore unrecognized role for GLP-1R signaling in the maintenance of colonic physiology and survival during energy deprivation.