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1.
EMBO Rep ; 24(12): e57268, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37987220

RESUMO

Intermittent fasting (IF) is a promising strategy to counteract ageing shown to increase the number of adult-born neurons in the dentate gyrus of mice. However, it is 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 and, to counteract this loss, adult NSCs are found in a quiescent state which ensures their long-term maintenance. We aimed to determine if and how IF affects adult NSCs in the hippocampus. To identify the effects of every-other-day IF on NSCs and all following steps in the neurogenic lineage, we combined fasting with lineage tracing and label retention assays. We show here that IF does not affect NSC activation or maintenance and, that contrary to previous reports, IF does not increase neurogenesis. The same results are obtained 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.


Assuntos
Células-Tronco Adultas , Células-Tronco Neurais , Camundongos , Animais , Jejum Intermitente , Neurogênese , Neurônios , Hipocampo , Células-Tronco Adultas/fisiologia
2.
Nutrients ; 9(6)2017 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-28613268

RESUMO

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.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína 1 Homóloga a MutL/metabolismo , Proteínas Repressoras/metabolismo , Vitamina E/farmacologia , Animais , Quebras de DNA de Cadeia Dupla , Dano ao DNA/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Suplementos Nutricionais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 1 Homóloga a MutL/genética , Proteínas Repressoras/genética , Vitamina E/administração & dosagem
3.
Oxid Med Cell Longev ; 2017: 3079148, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28133504

RESUMO

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.


Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Metilação de DNA/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Animais , Catequina/farmacologia , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , Dano ao DNA/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 1 Homóloga a MutL/genética , Reação em Cadeia da Polimerase em Tempo Real
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