College of Animal Science and Technology, Sichuan Agricultural University , Chengdu, China.
Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.
Gut Microbes. 2021 Jan-Dec;13(1):1-19. doi: 10.1080/19490976.2020.1862612.
Betaine is a natural compound present in commonly consumed foods and may have a potential role in the regulation of glucose and lipids metabolism. However, the underlying molecular mechanism of its action remains largely unknown. Here, we show that supplementation with betaine contributes to improved high-fat diet (HFD)-induced gut microbiota dysbiosis and increases anti-obesity strains such as , and . In mice lacking gut microbiota, the functional role of betaine in preventing HFD-induced obesity, metabolic syndrome, and inactivation of brown adipose tissues are significantly reduced. is an important regulator of betaine in improving microbiome ecology and increasing strains that produce short-chain fatty acids (SCFAs). Increasing two main members of SCFAs including acetate and butyrate can significantly regulate the levels of DNA methylation at host miR-378a promoter, thus preventing the development of obesity and glucose intolerance. However, these beneficial effects are partially abolished by Yin yang (YY1), a common target gene of the miR-378a family. Taken together, our findings demonstrate that betaine can improve obesity and associated MS via the gut microbiota-derived miR-378a/YY1 regulatory axis, and reveal a novel mechanism by which gut microbiota improve host health.
甜菜碱是一种天然存在于常见食物中的化合物，可能在调节葡萄糖和脂质代谢方面发挥作用。然而，其作用的潜在分子机制在很大程度上仍然未知。在这里，我们表明，甜菜碱的补充有助于改善高脂肪饮食（HFD）诱导的肠道微生物失调，并增加肥胖抗性菌株，如 和 。在缺乏肠道微生物群的小鼠中，甜菜碱在预防 HFD 诱导的肥胖、代谢综合征和棕色脂肪组织失活方面的功能作用显著降低。 是甜菜碱改善微生物组生态和增加产生短链脂肪酸（SCFAs）菌株的重要调节剂。增加包括乙酸盐和丁酸盐在内的两种主要 SCFA 成员可以显著调节宿主 miR-378a 启动子的 DNA 甲基化水平，从而防止肥胖和葡萄糖不耐受的发生。然而，这些有益作用部分被 Yin yang (YY1) 所抵消，YY1 是 miR-378a 家族的常见靶基因。总之，我们的研究结果表明，甜菜碱可以通过肠道微生物群衍生的 miR-378a/YY1 调节轴改善肥胖和相关的代谢综合征，并揭示了肠道微生物群改善宿主健康的新机制。
