Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion
Lorène J. Lebrun,
Kaatje Lenaerts,
Dorien Kiers,
Jean-Paul Pais de Barros,
Naig Le Guern,
Jiri Plesnik,
Charles Thomas,
Thibaut Bourgeois,
Cornelis H.C. Dejong,
Matthijs Kox,
Inca H.R. Hundscheid,
Naim Akhtar Khan,
Stéphane Mandard,
Valérie Deckert,
Peter Pickkers,
Daniel J. Drucker,
Laurent Lagrost,
Jacques Grober
Affiliations
Lorène J. Lebrun
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France
Kaatje Lenaerts
Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 62000 MD Maastricht, the Netherlands
Dorien Kiers
Department of Intensive Care Medicine, Radboud Institute for Health Sciences, Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 65000 HB Nijmegen, the Netherlands
Jean-Paul Pais de Barros
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France
Naig Le Guern
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France
Jiri Plesnik
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France
Charles Thomas
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France
Thibaut Bourgeois
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France
Cornelis H.C. Dejong
Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 62000 MD Maastricht, the Netherlands; Department of Surgery, Universitätsklinikum Aachen, 52074 Aachen, Germany
Matthijs Kox
Department of Intensive Care Medicine, Radboud Institute for Health Sciences, Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 65000 HB Nijmegen, the Netherlands
Inca H.R. Hundscheid
Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 62000 MD Maastricht, the Netherlands
Naim Akhtar Khan
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France
Stéphane Mandard
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France
Valérie Deckert
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France
Peter Pickkers
Department of Intensive Care Medicine, Radboud Institute for Health Sciences, Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 65000 HB Nijmegen, the Netherlands
Daniel J. Drucker
Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, ON M5G 1X5, Canada
Laurent Lagrost
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France; University Hospital of Dijon, 21000 Dijon, France
Jacques Grober
INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France; AgroSup Dijon, 21000 Dijon, France; Corresponding author
Summary: Glucagon-like peptide 1 (GLP-1) is a hormone released from enteroendocrine L cells. Although first described as a glucoregulatory incretin hormone, GLP-1 also suppresses inflammation and promotes mucosal integrity. Here, we demonstrate that plasma GLP-1 levels are rapidly increased by lipopolysaccharide (LPS) administration in mice via a Toll-like receptor 4 (TLR4)-dependent mechanism. Experimental manipulation of gut barrier integrity after dextran sodium sulfate treatment, or via ischemia/reperfusion experiments in mice, triggered a rapid rise in circulating GLP-1. This phenomenon was detected prior to measurable changes in inflammatory status and plasma cytokine and LPS levels. In human subjects, LPS administration also induced GLP-1 secretion. Furthermore, GLP-1 levels were rapidly increased following the induction of ischemia in the human intestine. These findings expand traditional concepts of enteroendocrine L cell biology to encompass the sensing of inflammatory stimuli and compromised mucosal integrity, linking glucagon-like peptide secretion to gut inflammation. : Lebrun et al. demonstrate that enteroendocrine L cells sense lipopolysaccharides (pro-inflammatory bacterial compounds) after gut injury and respond by secreting glucagon-like peptide 1. These findings expand concepts of L cell function to include roles as both a nutrient and pathogen sensor, linking glucagon-like peptide secretion to gut inflammation. Keywords: glucagon-like peptide 1, lipopolysaccharides, enteroendocrine cells, TLR4, gut injury, intestinal ischemia, inflammation