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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.