Abstract
Carbohydrates and sweeteners are detected by the sweet taste receptor in enteroendocrine cells (EECs). 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 EECs, GNAT3 expression is decreased in patients with obesity and type 2 diabetes compared with 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 EECs. After metabolic improvement with enterogastro 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. 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.NEW & NOTEWORTHY Our data highlighted 1) the sweet taste transduction pathway in EECs plays pivotal role for glucose homeostasis at least at gene expression level; 2) metabolic disorders lead to altered gene expression of sweet taste signaling pathway in intestine contributing to impaired GLP-1 secretion; and 3) after surgical intestinal modifications, increased expression of GNAT3, encoding α-gustducin contributed to metabolic improvement.
Highlights
Glucagon like-peptide-1 (GLP-1) is an incretin hormone secreted from specialized L-enteroendocrine cells (EECs) which enhances glucose-dependent insulin secretion by twofold in the postprandial state
We studied the expression of Gnat3 and other genes involved in sweet taste transduction pathway during the onset of metabolic diseases in mouse models fed for 1–12 wk, either on control diet (CD), high-fat diet (HFD), or high-fat and high-fructose diet (HFD-HF) as well as in metabolic improvement induced by an enterogastro anastomosis (EGA) mouse model [28]
We showed that GNAT3 gene expression was decreased threefold in ObD patients compared with Ob patients, whereas ITPR3 was increased twofold
Summary
Glucagon like-peptide-1 (GLP-1) is an incretin hormone secreted from specialized L-enteroendocrine cells (EECs) which enhances glucose-dependent insulin secretion by twofold in the postprandial state. The mechanisms by which EECs link glucose detection to GLP-1 secretion are still debated but they involve both sugar transporters and sweet taste receptor [1]. Several lines of evidence support that T1R2–T1R3 and a-gustducin are required for glucose-stimulated GLP-1 secretion These three proteins are present in human and rodent L-cells of the small intestine [3,4,5]. Glucose-stimulated GLP-1 secretion is nearly or fully abolished in a-gustducinÀ/À, TAS1R2À/À, and TAS1R3À/À mice [3, 6, 8] This is the case, when sweet taste receptors are inhibited or silenced using RNA of a-gustducin on GLUTag and NCI-H716 cells [3, 7]. In EECs, the detection of carbohydrates and sweeteners by the sweet taste receptor
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: American Journal of Physiology-Endocrinology and Metabolism
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
