Obesity as a multifactorial disorder involves low-grade inflammation, increased reactive oxygen species incidence, gut microbiota aberrations, and epigenetic consequences. Thus, prevention and therapies with epigenetic active antioxidants, (−)-Epigallocatechin-3-gallate (EGCG), are of increasing interest. DNA damage, DNA methylation and gene expression of DNA methyltransferase 1, interleukin 6, and MutL homologue 1 were analyzed in C57BL/6J male mice fed a high-fat diet (HFD) or a control diet (CD) with and without EGCG supplementation. Gut microbiota was analyzed with quantitative real-time polymerase chain reaction. An induction of DNA damage was observed, as a consequence of HFD-feeding, whereas EGCG supplementation decreased DNA damage. HFD-feeding induced a higher inflammatory status. Supplementation reversed these effects, resulting in tissue specific gene expression and methylation patterns of DNA methyltransferase 1 and MutL homologue 1. HFD feeding caused a significant lower bacterial abundance. The Firmicutes/Bacteroidetes ratio is significantly lower in HFD + EGCG but higher in CD + EGCG compared to control groups. The results demonstrate the impact of EGCG on the one hand on gut microbiota which together with dietary components affects host health. On the other hand effects may derive from antioxidative activities as well as epigenetic modifications observed on CpG methylation but also likely to include other epigenetic elements.
Obesity is associated with low-grade inflammation, increased ROS production and DNA damage. Supplementation with antioxidants might ameliorate DNA damage and support epigenetic regulation of DNA repair. C57BL/6J male mice were fed a high-fat (HFD) or a control diet (CD) with and without vitamin E supplementation (4.5 mg/kg body weight (b.w.)) for four months. DNA damage, DNA promoter methylation and gene expression of Dnmt1 and a DNA repair gene (MLH1) were assayed in liver and colon. The HFD resulted in organ specific changes in DNA damage, the epigenetically important Dnmt1 gene, and the DNA repair gene MLH1. Vitamin E reduced DNA damage and showed organ-specific effects on MLH1 and Dnmt1 gene expression and methylation. These results suggest that interventions with antioxidants and epigenetic active food ingredients should be developed as an effective prevention for obesity—and oxidative stress—induced health risks.
Intermittent fasting (IF) is a promising non-pharmacological strategy to counteract ageing which has been shown to increase the number of adult-born neurons in the dentate gyrus of mice. However, it is still unclear which steps of the adult neurogenesis process are regulated by IF. The number of adult neural stem cells (NSCs) decreases with age in an activation-dependent manner. To counteract the loss of the stem cell pool, adult NSCs are mostly found in an inactive, quiescent state which ensures their long-term maintenance. We aimed to determine if and how IF impacts the activity and maintenance of adult NSCs in the hippocampus. We chose an every-other-day fasting protocol with food re-administration at night, which we found effectively induces fasting features and preserves the circadian activity pattern of mice. To determine the effects of IF on NSCs and all following steps in the neurogenic lineage, we combined fasting with lineage tracing and label retention assays. We found that IF does not affect NSC activation or maintenance. Contrary to previous reports, we also found that IF does not increase hippocampal neurogenesis. We obtained the same results regardless of strain, sex, diet length, tamoxifen administration or new-born neuron identification method. Our data suggest that NSCs maintain homeostasis upon IF and that this intervention is not a reliable strategy to increase adult neurogenesis.
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