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绿藻浒苔寡糖通过肠道-脑轴改善年龄匹配的糖尿病小鼠的衰老和高血糖状况。

Green Alga Enteromorpha prolifera Oligosaccharide Ameliorates Ageing and Hyperglycemia through Gut-Brain Axis in Age-Matched Diabetic Mice.

作者信息

Ouyang Yuezhen, Liu Dan, Zhang Lizhu, Li Xiaoqing, Chen Xinhua, Zhao Chao

机构信息

Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, 350002, China.

College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

出版信息

Mol Nutr Food Res. 2022 Feb;66(4):e2100564. doi: 10.1002/mnfr.202100564. Epub 2021 Dec 21.

DOI:10.1002/mnfr.202100564
PMID:34894199
Abstract

SCOPE

To investigate the anti-ageing and anti-diabetic effects of Enteromorpha prolifera oligosaccharide (EPO) in age-matched streptozocin-induced diabetic mice.

METHODS AND RESULTS

LC-MS metabolomics and 16S rRNA sequencing is used to identify the brain metabolites and gut microbiota, respectively. EPO could significantly improve glucose metabolism and activity of total superoxide dismutase in serum. It also could regulate the tricarboxylic acid cycle, arginine, and inosine-related metabolic pathways in the brain of aged diabetic mice. Inosine is found to enhance the relative expressions of daf-2, daf-16, and skn-1 in insulin-resistant Caenorhabditis elegans. Additionally, EPO could alter the composition and diversity of gut microbiota in mice. It could upregulate the Signal Transducer and Activator of Transcription 3/Forkhead Box O1 (FOXO1)/B cell lymphoma 6 (Bcl-6) pathways in the brain and the c-Jun N-terminal Kinase (JNK)/FOXO1/Bcl-6 signaling axis in the intestine to regulate glucose metabolite status and ageing in mice. EPO could also improve the levels of glucagon-like peptide type 1 (GLP1) expression in the gut, thereby inducing high expression of GLP1 receptor in the brain to control glucose metabolites through the brain-gut axis. Enterococcus is negatively correlated with AMP in the brain and could be a potential hallmark species in age-related diabetes.

CONCLUSIONS

These results suggest that EPO could be a potential novel natural drug for the treatment of diabetes in the elderly.

摘要

范围

研究浒苔寡糖(EPO)对年龄匹配的链脲佐菌素诱导的糖尿病小鼠的抗衰老和抗糖尿病作用。

方法与结果

分别采用液相色谱-质谱代谢组学和16S rRNA测序鉴定脑代谢物和肠道微生物群。EPO可显著改善血糖代谢和血清中总超氧化物歧化酶的活性。它还可以调节老年糖尿病小鼠大脑中的三羧酸循环、精氨酸和肌苷相关代谢途径。发现肌苷可增强胰岛素抵抗的秀丽隐杆线虫中daf-2、daf-16和skn-1的相对表达。此外,EPO可改变小鼠肠道微生物群的组成和多样性。它可以上调大脑中的信号转导和转录激活因子3/叉头框O1(FOXO1)/B细胞淋巴瘤6(Bcl-6)通路以及肠道中的c-Jun氨基末端激酶(JNK)/FOXO1/Bcl-6信号轴,以调节小鼠的葡萄糖代谢状态和衰老。EPO还可以提高肠道中胰高血糖素样肽1(GLP1)的表达水平,从而诱导大脑中GLP1受体的高表达,通过脑-肠轴控制葡萄糖代谢物。肠球菌与大脑中的AMP呈负相关,可能是与年龄相关糖尿病的潜在标志性物种。

结论

这些结果表明,EPO可能是一种潜在的新型天然药物,用于治疗老年人糖尿病。

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