Wang Jun-Xia, Chang Shuang-Yan, Jin Zheng-Yun, Li Dongxu, Zhu Jun, Luo Zhao-Bo, Han Sheng-Zhong, Kang Jin-Dan, Quan Lin-Hu
Department of Animal Science, College of Agricultural, Yanbian University, Yanji 133002, China.
Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanbian University, Yanji 133002, China.
J Agric Food Chem. 2025 Jan 8;73(1):393-408. doi: 10.1021/acs.jafc.4c03818. Epub 2024 Dec 16.
is a well-known probiotic with beneficial effects, such as anti-insulin resistance, anti-inflammatory, and improvement of the intestinal barrier. However, the underlying mechanisms remain unclear. Here, we found that gavage of improved the intestinal barrier and glucose homeostasis in HFD-fed mice. Analysis of lipid metabolomics reveals a significant increase in eicosatrienoic acid (ETA) levels in mouse feces after gavage. We found that ETA maintain intestinal barrier integrity and improve glucose homeostasis by promoting GLP-1 secretion. Mechanistically, by using CD36 inhibitor and CD36 knockdown STC-1 cells , we elucidate that ETA activates intestinal CD36-activated PLC/IP3R/Ca signaling to promote GLP-1 secretion. administration of GLP-1R inhibitor and intestinal organoid experiments demonstrate that GLP-1 upregulates the PI3K/AKT/HIF-1α pathway by GLP-1R and increases intestinal tight junction protein expressions, which in turn enhance the intestinal barrier integrity, reduce serum LPS level, attenuate inflammation in white adipose tissue (WAT), and ultimately improve glucose homeostasis in HFD and db/db mice. Our study elucidates for the first time the mechanism by which and its enriched metabolite ETA inhibit WAT inflammation by ameliorating the intestinal barrier, ultimately improving glucose homeostasis, and provides a new treatment strategy for T2D.
是一种具有有益作用的知名益生菌，如抗胰岛素抵抗、抗炎和改善肠道屏障。然而，其潜在机制仍不清楚。在这里，我们发现给高脂饮食喂养的小鼠灌胃[具体物质]可改善肠道屏障和葡萄糖稳态。脂质代谢组学分析显示，灌胃[具体物质]后小鼠粪便中二十碳三烯酸（ETA）水平显著升高。我们发现ETA通过促进胰高血糖素样肽-1（GLP-1）分泌来维持肠道屏障完整性并改善葡萄糖稳态。从机制上讲，通过使用CD36抑制剂[具体抑制剂]和CD36基因敲低的STC-1细胞[具体细胞]，我们阐明ETA激活肠道CD36激活的PLC/IP3R/Ca信号通路以促进GLP-1分泌。给予GLP-1R抑制剂[具体抑制剂]和肠道类器官实验表明，GLP-1通过GLP-1R上调PI3K/AKT/HIF-1α通路并增加肠道紧密连接蛋白表达，进而增强肠道屏障完整性，降低血清脂多糖（LPS）水平，减轻白色脂肪组织（WAT）炎症，最终改善高脂饮食和db/db小鼠的葡萄糖稳态。我们的研究首次阐明了[具体物质]及其富集代谢物ETA通过改善肠道屏障抑制WAT炎症、最终改善葡萄糖稳态的机制，并为2型糖尿病提供了一种新的治疗策略。
