Alterations of DNA methylation and expression of genes related to thyroid hormone metabolism in colon epithelium of obese patients

Shimi, Ghazaleh; Pourvali, Katayoun; Ghorbani, Abdolbaset; Nooshin, Sajad; Karizi, Shohreh Zare; Iranirad, Reza; Zand, Hamid

doi:10.1186/s12920-022-01387-6

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…Thyroid hormone receptors are coded by two genes: alfa and beta. The epigenetic regulation of THRB has previously been shown to be involved in many human phenotypes such as cancer, obesity, and aging (Joseph et al 2007; Ling et al 2010; Kim et al 2013; Pawlik-Pachucka et al 2018; Shimi et al 2022), and affected by exposures to e.g. thyroid hormones and environmental toxins in mice (Cho et al 2021; Laufer et al 2022), and thus we were interested in investigating if that is the case also in the context of avian maternal hormones, and chose THRB for the methylation analyses.…”

Section: Methodsmentioning

confidence: 99%

From maternal glucocorticoid and thyroid hormones to epigenetic regulation of gene expression: an experimental study in a wild bird species

Hukkanen

Hsu

Cossin-Sevrin

et al. 2023

Preprint

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Offspring phenotype at birth is determined by its genotype and the prenatal environment including exposure to maternal hormones. Variation in both maternal glucocorticoids and thyroid hormones can affect offspring phenotype. However, the underlying molecular mechanisms shaping the offspring phenotype, especially those contributing to long-lasting effects, remain unclear. Epigenetic changes (such as DNA methylation) have been postulated as mediators of long-lasting effects of early-life environment. In this study, we determined the effects of elevated prenatal glucocorticoid and thyroid hormones on handling stress response (breath rate), DNA methylation and gene expression of glucocorticoid receptor (GCR) and thyroid hormone receptor (THR) in great tit (Parus major). Eggs were injected before incubation onset with corticosterone (main avian glucocorticoid) and/or thyroid hormones (thyroxine and triiodothyronine) to simulate variation in maternal hormone deposition. Breath rate during handling and gene expression of GCR and THR were evaluated 14 days after hatching. Methylation status of GCR and THR genes were analyzed from the longitudinal blood samples taken 7 and 14 days after hatching, as well as in the following autumn. Elevated prenatal corticosterone level significantly increased the breath rate during handling, indicating enhanced stress response and/or metabolism. Prenatal corticosterone manipulation had CpG-site-specific effects on DNA methylation at the GCR putative promoter region, while it did not significantly affect GCR gene expression. GCR expression was negatively associated with earlier hatching date and chick size. THR methylation or expression did not exhibit any significant relationship with the hormonal treatments or the examined covariates, suggesting that TH signaling may be more robust due to its crucial role in development. This study supports the view that maternal corticosterone may influence offspring metabolism and stress response via epigenetic alterations, yet their possible adaptive role in optimizing offspring phenotype to the prevailing conditions, context-dependency, and the underlying molecular interplay needs further research.

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Section: Methodsmentioning

confidence: 99%

From maternal glucocorticoid and thyroid hormones to epigenetic regulation of gene expression: an experimental study in a wild bird species

Hukkanen

Hsu

Cossin-Sevrin

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Thyroid hormone receptors are coded by two genes: alfa and beta. The epigenetic regulation of THRB has previously been shown to be involved in many human phenotypes such as cancer, obesity, and aging (Joseph et al, 2007; Kim et al, 2013; Ling et al, 2010; Pawlik‐Pachucka et al, 2018; Shimi et al, 2022), and affected by exposures to, for example, thyroid hormones and environmental toxins in mice (Cho et al, 2021; Laufer et al, 2022), and thus we were interested in investigating if that is the case also in the context of avian maternal hormones, and chose THRB for the methylation analyses.…”

Section: Methodsmentioning

confidence: 99%

From maternal glucocorticoid and thyroid hormones to epigenetic regulation of offspring gene expression: An experimental study in a wild bird species

Hukkanen,

Hsu,

Cossin‐Sevrin

et al. 2023

Evolutionary Applications

View full text Add to dashboard Cite

Offspring phenotype at birth is determined by its genotype and the prenatal environment including exposure to maternal hormones. Variation in both maternal glucocorticoids and thyroid hormones can affect offspring phenotype, but the underlying molecular mechanisms, especially those contributing to long‐lasting effects, remain unclear. Epigenetic changes (such as DNA methylation) have been postulated as mediators of long‐lasting effects of early‐life environment. In this study, we determined the effects of elevated prenatal glucocorticoid and thyroid hormones on handling stress response (breath rate) as well as DNA methylation and gene expression of glucocorticoid receptor (GR) and thyroid hormone receptor (THR) in great tits (Parus major). Eggs were injected before incubation onset with corticosterone (the main avian glucocorticoid) and/or thyroid hormones (thyroxine and triiodothyronine) to simulate variation in maternal hormone deposition. Breath rate during handling and gene expression of GR and THR were evaluated 14 days after hatching. Methylation status of GR and THR genes was analyzed from the longitudinal blood cells sampled 7 and 14 days after hatching, as well as the following autumn. Elevated prenatal corticosterone level significantly increased the breath rate during handling, indicating an enhanced metabolic stress response. Prenatal corticosterone manipulation had CpG‐site‐specific effects on DNA methylation at the GR putative promoter region, while it did not significantly affect GR gene expression. GR expression was negatively associated with earlier hatching date and chick size. THR methylation or expression did not exhibit any significant relationship with the hormonal treatments or the examined covariates, suggesting that TH signaling may be more robust due to its crucial role in development. This study provides some support to the hypothesis suggesting that maternal corticosterone may influence offspring metabolic stress response via epigenetic alterations, yet their possible adaptive role in optimizing offspring phenotype to the prevailing conditions, context‐dependency, and the underlying molecular interplay needs further research.

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“…However, the underlying mechanism of gut microbiome and metabolites on obesity remains unclear. Changes in colonic transcriptome was observed in HFD-induced obesity [9] and human [10], suggesting that gut microbiota and metabolites may affect colonic gene expression. Qin et al [11] suggested that the gut microbiome stimulates a reprogramming of the enhancer landscape in the colon, with downstream effects on transcription factors under specific dietary exposures.…”

mentioning

confidence: 99%

“…However, the underlying mechanism of gut microbiome and metabolites on obesity remains unclear. Changes in colonic transcriptome was observed in HFD‐induced obesity [ 9 ] and human [ 10 ], suggesting that gut microbiota and metabolites may affect colonic gene expression. Qin et al .…”

mentioning

confidence: 99%

In‐depth multiomic characterization of the effects of obesity in high‐fat diet‐fed mice

Li,

Chen,

et al. 2024

FEBS Open Bio

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High‐fat diet (HFD)‐fed mice have been widely used in the clinical investigation of obesity. However, the long‐term effect of HFD on gut microbiota and metabolites, plasma and liver metabolomics, colonic and liver transcriptomics remain largely unknown. In this study, 6‐week‐old C57BL/6J male mice fed with HFD for 14 weeks showed increased obesity‐related indexes including alanine aminotransferase, aspartate aminotransferase, total cholesterol, total triglyceride, free fatty acids, lipopolysaccharides, IL‐6, and TNFα. Furthermore, microbial diversity and richness were also significantly decreased. In the colon, genes involved in tryptophan metabolism, PPAR signaling pathway, cholesterol metabolism, and lipid localization and transport, were upregulated. While in the liver, MAPK signaling and unsaturated fatty acid biosynthesis were upregulated. Metabolomic analyses revealed decreased levels of glycerophospholipids and fatty acyl, but increased amino acids, coenzymes and vitamins, and organic acids in the colon, suggesting high absorption of oxidized lipids, while acyl‐carnitine, lysophosphatidylcholine, lysophosphatidylethanolamine, and oxidized lipids were reduced in the liver, suggesting a more active lipid metabolism. Finally, correlation analyses revealed a positive correlation between gut microbiota and metabolites and the expression of genes associated with lipid localization, absorption, and transport in the colon, and nutrients and energy metabolism in the liver. Taken together, our results provide a comprehensive characterization of long‐term HFD‐induced obesity in mice.

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Alterations of DNA methylation and expression of genes related to thyroid hormone metabolism in colon epithelium of obese patients

Cited by 7 publications

References 38 publications

From maternal glucocorticoid and thyroid hormones to epigenetic regulation of gene expression: an experimental study in a wild bird species

From maternal glucocorticoid and thyroid hormones to epigenetic regulation of gene expression: an experimental study in a wild bird species

From maternal glucocorticoid and thyroid hormones to epigenetic regulation of offspring gene expression: An experimental study in a wild bird species

In‐depth multiomic characterization of the effects of obesity in high‐fat diet‐fed mice

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