Intestinal alteration of α-gustducin and sweet taste signaling pathway in metabolic diseases is partly rescued after weight loss and diabetes remission Running Head: Intestinal α-gustducin in metabolic diseases
Résumé
Carbohydrates and sweeteners are detected by the sweet taste receptor in enteroendocrine cells (EEC). This receptor is coupled to the gustducin G-protein, which α-subunit is encoded by GNAT3 gene. In intestine, the activation of sweet taste receptor triggers a signaling pathway leading to GLP-1 secretion, an incretin hormone. In metabolic diseases GLP-1 concentration and incretin effect are reduced while partly restored after Roux-en-Y gastric bypass (RYGB). We wondered if the decreased GLP-1 secretion in metabolic diseases is caused by an intestinal defect in sweet taste transduction pathway. In our RNA-sequencing of EEC GNAT3 expression is decreased in patients with obesity and type 2 diabetes compared to normoglycemic obese patients. This prompted us to explore sweet taste signaling pathway in mice with metabolic deteriorations. During obesity onset in mice Gnat3 expression was downregulated in EEC. After metabolic improvement with entero-gastro anastomosis surgery in mice (a surrogate of the RYGB in humans), the expression of Gnat3 increased in the new alimentary tract and glucose-induced GLP-1 secretion was improved. In order to evaluate if high-fat diet-induced dysbiotic intestinal microbiota could explain the changes in the expression of sweet taste α-subunit G protein, we performed a fecal microbiota transfer in mice. However, we could not conclude if dysbiotic microbiota impacted or not intestinal Gnat3 expression. Our data highlight that metabolic disorders were associated with altered gene expression of sweet taste signaling in intestine. This could contribute to impaired GLP-1 secretion that is partly rescued after metabolic improvement.
Domaines
Alimentation et Nutrition
Fichier principal
Le Gléau et al. - 2021 - Intestinal alteration of α-gustducin and sweet tas.pdf (3.09 Mo)
Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)