Carbohydrates and sweeteners are detected by the sweet taste receptor in enteroendocrine cells (EEC). This receptor is coupled to the gustducin G-protein, which a-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 a-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.

中文翻译：

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代谢疾病中a-gustducin和甜味信号通路的肠道改变在体重减轻和糖尿病缓解后得到部分挽救

碳水化合物和甜味剂由肠内分泌细胞 (EEC) 中的甜味受体检测。该受体与 gustducin G 蛋白偶联，其中 a 亚基由 GNAT3 基因编码。在肠道中，甜味受体的激活触发了导致 GLP-1 分泌的信号通路，这是一种肠促胰岛素激素。在代谢性疾病中，Roux-en-Y 胃绕道术 (RYGB) 后 GLP-1 浓度和肠促胰岛素作用降低，但部分恢复。我们想知道代谢疾病中 GLP-1 分泌减少是否是由甜味转导途径的肠道缺陷引起的。在我们对 EEC GNAT3 表达的 RNA 测序中，与正常血糖的肥胖患者相比，肥胖和 2 型糖尿病患者的 GNAT3 表达降低。这促使我们探索代谢恶化小鼠的甜味信号通路。在小鼠肥胖发作期间 Gnat3 表达在 EEC 中下调。在小鼠（人类 RYGB 的替代品）中通过肠-胃吻合手术改善代谢后，Gnat3 在新消化道中的表达增加，葡萄糖诱导的 GLP-1 分泌得到改善。为了评估高脂饮食诱导的肠道菌群失调是否可以解释甜味 a-亚基 G 蛋白表达的变化，我们在小鼠中进行了粪便微生物群转移。然而，我们无法断定菌群失调是否影响肠道 Gnat3 表达。我们的数据强调，代谢紊乱与肠道中甜味信号基因表达的改变有关。这可能导致 GLP-1 分泌受损，在代谢改善后部分恢复。