Adiponectin and resistin are typically secreted by the adipose tissue and are abnormally expressed in obesity. However, the underlying influential factors and mechanisms are to be elucidated. It is well known that the expression of genes is regulated by epigenetics while gut microbiota participates in epigenetic processes through its metabolites such as folate, biotin, and short-chain fatty acids (SCFAs). Therefore, we supposed that alteration of gut microbiota might affect the transcriptional expression of adiponectin and resistin through epigenetic regulation in obesity. C57BL/6J mice were fed either a high-fat diet (34.9% fat by wt., 60% kcal) or a normal-fat diet (4.3% fat by wt., 10% kcal) for 16 weeks, with ampicillin and neomycin delivered via drinking water to interfere with gut microbiota development. Fecal microbiota was analyzed by 16S rRNA high-throughput sequencing. The mRNA expression levels of genes were measured by real-time quantitative RT-PCR. SCFA contents in feces were examined using gas chromatography. Alteration of the gut microbiota induced by antibiotic use, characterized by a dramatic reduction of the phylum Firmicutes and Actinobacteria and an increase of Proteobacteria with reductions of genera including Lactobacillus, norank_f_Bacteroidales_S24-7_group, Alistipes, Desulfovibrio, Helicobacter, etc., and increases in Bacteroides, Enterobacter, Klebsiella, inhibited the body weight gain in mice fed the high-fat diet instead of the normal-fat diet. The mRNA expression of adiponectin and resistin was upregulated by antibiotic use in mice fed the high-fat diet, accompanied by increased expression of fat oxidation and thermogenesis-related genes (PPAR-α, Pgc-1α, and Atgl) in the fat and/or liver, whereas no change in the expression of adiponectin and resistin was found in mice fed the normal-fat diet. Furthermore, antibiotic use reduced DNA methylation fractions of the adiponectin and resistin promoters and downregulated the expression of DNA methyltransferase 1 and 3a (DNMT1 and DNMT3a) with the high-fat diet feeding. Alteration of gut microbiota induced by antibiotic use may affect the expression of adiponectin and resistin in mice fed the high-fat diet by modifying promoter DNA methylation, thus leading to increased fatty acid oxidation and less body weight gain.

中文翻译：

---

肠道微生物群的改变通过修饰高脂饮食诱导的肥胖小鼠中的DNA甲基化而影响脂联素和抵抗素的表达。

脂联素和抵抗素通常由脂肪组织分泌，并在肥胖症中异常表达。但是，需要阐明潜在的影响因素和机制。众所周知，基因的表达受表观遗传学的调节，而肠道菌群则通过其代谢产物（例如叶酸，生物素和短链脂肪酸（SCFA））参与表观遗传过程。因此，我们认为肠道微生物群的改变可能通过肥胖的表观遗传调控影响脂联素和抵抗素的转录表达。给C57BL / 6J小鼠喂高脂饮食（34.9％重量，60％大卡）或正常脂肪饮食（4.3％重量，10％大卡）氨苄西林和新霉素通过饮用水输送来干扰肠道菌群的发育。通过16S rRNA高通量测序分析粪便菌群。通过实时定量RT-PCR测量基因的mRNA表达水平。使用气相色谱法检查粪便中的SCFA含量。抗生素使用引起的肠道菌群的改变，其特征是菌丝菌门菌和放线菌的显着减少，变形杆菌的增加，包括乳杆菌，norank_f_Bacteroidales_S24-7_group，Alistipes，Desulfovibero，Helicobacter等的属减少，而杆菌的增加，肠杆菌，克雷伯菌抑制了高脂饮食而不是普通脂肪饮食的小鼠的体重增加。喂高脂饮食的小鼠使用抗生素会上调脂联素和抵抗素的mRNA表达，伴随着脂肪和/或肝脏中脂肪氧化和与生热相关的基因（PPAR-α，Pgc-1α和Atgl）的表达增加，而在正常小鼠中，脂联素和抵抗素的表达没有变化脂肪饮食。此外，在高脂饮食喂养下，抗生素的使用减少了脂联素和抵抗素启动子的DNA甲基化部分，并下调了DNA甲基转移酶1和3a（DNMT1和DNMT3a）的表达。抗生素使用引起的肠道菌群改变可能通过修饰启动子DNA甲基化而影响高脂饮食喂养的小鼠中脂联素和抵抗素的表达，从而导致脂肪酸氧化增加和体重减轻。正常饮食的小鼠脂联素和抵抗素的表达没有变化。此外，在高脂饮食喂养下，抗生素的使用减少了脂联素和抵抗素启动子的DNA甲基化部分，并下调了DNA甲基转移酶1和3a（DNMT1和DNMT3a）的表达。抗生素使用引起的肠道菌群改变可能通过修饰启动子DNA甲基化而影响高脂饮食喂养的小鼠中脂联素和抵抗素的表达，从而导致脂肪酸氧化增加和体重减轻。正常脂肪饮食的小鼠脂联素和抵抗素的表达未见变化。此外，在高脂饮食喂养下，抗生素的使用减少了脂联素和抵抗素启动子的DNA甲基化部分，并下调了DNA甲基转移酶1和3a（DNMT1和DNMT3a）的表达。抗生素使用引起的肠道菌群改变可能通过修饰启动子DNA甲基化而影响高脂饮食喂养的小鼠中脂联素和抵抗素的表达，从而导致脂肪酸氧化增加和体重减轻。