College of Life Sciences, Sichuan Normal University, Chengdu 610101, China.
College of Life Sciences, Sichuan University, Chengdu 610065, China.
Nutrients. 2023 Aug 24;15(17):3707. doi: 10.3390/nu15173707.
Unhealthy diets rich in fats and/or sugar are considered as the major external cause of the obesity epidemic, which is often accompanied by a significant decrease in gut hormone glucagon-like peptide-1 (GLP1) levels. Numerous studies have demonstrated notable contributions of the gut microbiota in this process. Nevertheless, the underlying mechanism still needs further investigation. The role of epigenetic modifications in gene expression and metabolism has been well demonstrated, with m6A methylation on RNAs being the most prevalent modification throughout their metabolism. In the present study, we found that the expressions of small intestinal and , two key genes regulating GLP1 expression, were significantly downregulated in obese mice, associated with reduced GLP1 level. Immunohistochemistry analysis indicated that a high-fat diet slightly increased the density of enteroendocrine L cells in the small intestine, implying that decreased GLP1 levels were not caused by the changes in L cell intensity. Instead, the small intestinal m6A level as well as the expression of known "writers", and , were found to be positively correlated with the expression of and . Fecal microbiota transplantation with feces from normal and obese mice daily to antibiotic-treated mice revealed that dysbiosis in diet-induced obesity was sufficient to reduce serum GLP1, small intestinal m6A level, and intestinal expressions of , , and writer genes (, ). However, as the most direct and universal methyl donor, the production of fecal S-adenosylmethionine was neither affected by the different dietary patterns nor their shaped microbiota. These results suggested that microbial modulation of the epitranscriptome may be involved in regulating GLP1 expression, and highlighted epitranscriptomic modifications as an additional level of interaction between diet and individual health.
富含脂肪和/或糖的不健康饮食被认为是肥胖流行的主要外部原因，而肥胖常伴随着肠道激素胰高血糖素样肽-1（GLP1）水平的显著下降。大量研究表明，肠道微生物群在这一过程中起着重要作用。然而，其潜在机制仍需要进一步研究。表观遗传修饰在基因表达和代谢中的作用已经得到了很好的证明，在 RNA 的代谢过程中，m6A 甲基化是最常见的修饰。在本研究中，我们发现，调节 GLP1 表达的两个关键基因，即 和 ，在肥胖小鼠中的表达显著下调，与 GLP1 水平降低有关。免疫组织化学分析表明，高脂肪饮食略微增加了小肠中肠内分泌 L 细胞的密度，这意味着 GLP1 水平的降低不是由 L 细胞强度的变化引起的。相反，小肠 m6A 水平以及已知“书写器” 和 的表达与 和 的表达呈正相关。将来自正常和肥胖小鼠的粪便每日移植给接受抗生素处理的小鼠，发现饮食诱导肥胖导致的肠道菌群失调足以降低血清 GLP1、小肠 m6A 水平以及肠道 和 以及书写器基因（ 、 ）的表达。然而，作为最直接和普遍的甲基供体，粪便 S-腺苷甲硫氨酸的产生既不受不同饮食模式的影响，也不受其塑造的微生物群的影响。这些结果表明，微生物对表观转录组的调节可能参与了 GLP1 的表达调控，并强调了表观转录组修饰作为饮食与个体健康之间相互作用的另一个层面。
