Year: 2020
Type: article
Abstract: OBJECTIVE: Obesity is characterized by systemic and low-grade tissue inflammation. In the intestine, alteration of the intestinal barrier and accumulation of inflammatory cells in the epithelium are important contributors of gut inflammation. Recent studies demonstrated the role of the aryl hydrocarbon receptor (AhR) in the maintenance of immune cells at mucosal barrier sites. A wide range of ligands of external and local origin can activate this receptor. We studied the causal relationship between AhR activation and gut inflammation in obesity. METHODS: Jejunum samples from subjects with normal weight and severe obesity were phenotyped according to T lymphocyte infiltration in the epithelium from lamina propria and assayed for the mRNA level of AhR target genes. The effect of an AhR agonist was studied in mice and Caco-2/TC7 cells. AhR target gene expression, permeability to small molecules and ions, and location of cell-cell junction proteins were recorded under conditions of altered intestinal permeability. RESULTS: We showed that a low AhR tone correlated with a high inflammatory score in the intestinal epithelium in severe human obesity. Moreover, AhR activation protected junctional complexes in the intestinal epithelium in mice challenged by an oral lipid load. AhR ligands prevented chemically induced damage to barrier integrity and cytokine expression in Caco-2/TC7 cells. The PKC and p38MAPK signaling pathways were involved in this AhR action. CONCLUSIONS: The results of these series of human, mouse, and cell culture experiments demonstrate the protective effect of AhR activation in the intestine targeting particularly tight junctions and cytokine expression. We propose that AhR constitutes a valuable target to protect intestinal functions in metabolic diseases, which can be achieved in the future via food or drug ligands.
Source: Molecular Metabolism
Institutions: Centre National de la Recherche Scientifique, Inserm, Sorbonne Université, Centre de Recherche des Cordeliers, Centre de Recherche Saint-Antoine, Université Paris Dauphine-PSL, Université Paris Sciences et Lettres, Nutrition et obésité : approches systémiques, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,079
Funders: Groupe Lipides et Nutrition, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Assistance Publique - Hôpitaux de Paris, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Semnan University, Fondation Nestlé, Sorbonne Université, Seventh Framework Programme, National Institute for Physiological Sciences, CHIST-ERA
OpenAlex ID: W3023929592