Lifestyle and NR3C1 exon 1F gene methylation is associated with changes in glucose levels and insulin resistance

Souza, Marcele Lorentz Mattos de; Borçoi, Aline Ribeiro; Dutra, Bruna Aparecida Borges; Vieira, Thiago Bernardi; Mendes, Suzanny Oliveira; Nascimento, Ivana Alece Arantes; Quaioto, Bárbara Risse; Olinda, Amanda Sgrancio; Cunha, Ester Ribeiro; Freitas, Flávia Vitorino; Pinheiro, Júlia Assis; Santos, Joaquim Gasparini dos; Sorroche, Bruna Pereira; Arantes, Lídia Maria Rebolho Batista; Sartório, Carmem Luíza; Silva, Adriana Madeira Alvares da

doi:10.1016/j.lfs.2022.120940

Cited by 3 publications

(3 citation statements)

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“…Methylation of the NR3C1 gene in its promoter region is connected to diminished expression of the glucocorticoid receptor (GR) and to disruption of the hypothalamic–pituitary–adrenal (HPA) axis, and is implicated in the development of psychiatric disorders among individuals exposed to psychosocial stress, early trauma, post-traumatic stress, gestational hunger, neglect, and various other adverse conditions ( 55 , 77 , 78 ). Despite these well-established associations, particular emphasis has been placed on readily accessible peripheral tissues in studies examining life adversity, weight accumulation, associated comorbidities, and lifestyle ( 38 , 58 , 64 , 73 ). The utilization of peripheral methylation as a substitute for methylation in hippocampal cells, including the analysis of samples from individuals who died by suicide, is grounded in the notion that methylation patterns at specific loci may exhibit consistency between the brain and the periphery, indicating epigenetic reprogramming associated with psychological conditions ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

“…The models were adjusted for various socioeconomic factors (gender, age, education, location, income), psychosocial factors (stress, anxiety, BFIS, BDI-II 18), nutritional status (TyG Index, HDL-c, LDL-c, BMI, cortisol), and lifestyle factors (physical activity, smoking, drinking). These confounding variables were selected based on examples from the literature and previous research conducted by the research group ( 29 , 30 , 38 , 58 , 59 ). A generalized linear model (GzLM) was utilized to analyze the data.…”

Section: Methodsmentioning

confidence: 99%

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An industrialized diet as a determinant of methylation in the 1F region of the NR3C1 gene promoter

Vieira,

Freitas,

Silva Neto

et al. 2024

Front. Nutr.

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BackgroundDietary composition can modify gene expression, favoring the development of chronic diseases via epigenetic mechanisms.ObjectiveOur study aimed to investigate the relationship between dietary patterns and NR3C1 gene methylation in users of the Brazilian Public Unified Health System (SUS).MethodsWe recruited 250 adult volunteers and evaluated their socioeconomic status, psychosocial characteristics, lifestyle, and anthropometrics. Peripheral blood was collected and evaluated for cortisol levels, glycemia, lipid profile, and insulin resistance; methylation of CpGs 40–47 of the 1F region of the NR3C1 gene was also measured. Factors associated with degree of methylation were evaluated using generalized linear models (p < 0.05). Lifestyle variables and health variables were included as confounding factors.ResultsThe findings of our cross-sectional study indicated an association between NR3C1 DNA methylation and intake of processed foods. We also observed relevant associations of average NR3C1 DNA across the segment analyzed, methylation in component 1 (40–43), and methylation in component 2 (44–47) with a pattern of consumption of industrialized products in relation to BMI, serum cortisol levels, and lipid profile. These results may indicate a relationship between methylation and metabolic changes related to the stress response.ConclusionThese findings suggest an association of methylation and metabolic alterations with stress response. In addition, the present study highlights the significant role of diet quality as a stress-inducing factor that influences NR3C1 methylation. This relationship is further linked to changes in psychosocial factors, lifestyle choices, and cardiometabolic variables, including glucose levels, insulin resistance, and hyperlipidemia.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

An industrialized diet as a determinant of methylation in the 1F region of the NR3C1 gene promoter

Vieira,

Freitas,

Silva Neto

et al. 2024

Front. Nutr.

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“…However, there were no methylation differences between the buffy coats of individuals with and without MetS in the CpGs evaluated for the 1F region, even though the expression of these genes is similar in blood and hypothalamus. Although no association studies of MetS with NR3C1 differential methylation were found in the literature, variations in its methylation patterns have been observed for related comorbidities, such as cardiovascular diseases [ 22 ], subclinical arteriosclerosis (hypermethylation of the 1F promoter, in a study with monozygotic twins) [ 66 ], overweight (hypomethylation of the 1F region, CpGs 40 to 47) [ 51 ], unfavorable prognosis for coronary acute syndrome in individuals with depression (hypermethylation of exon 1F) [ 67 ], blood pressure (hypermethylation of 1F and 1H promoters associated with lower blood pressure) [ 68 ], and a positive association between methylation and glucose levels as well as insulin resistance [ 69 ]. Considering the multiple alternative first exons and their variability in tissue-specific expression, and that each of these exons has its own active promoter, DNA methylation and other epigenetic mechanisms should be evaluated in other regions.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population

Kolb,

Mira,

Auer

et al. 2023

Genes

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The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with the polymorphisms, methylation, and gene expression of the NR3C1 in the genetically isolated Brazilian Mennonite population, we genotyped 20 NR3C1 polymorphisms in 74 affected (MetS) and 138 unaffected individuals without affected first-degree relatives (Co), using exome sequencing, as well as five variants from non-exonic regions, in 70 MetS and 166 Co, using mass spectrometry. The methylation levels of 11 1F CpG sites were quantified using pyrosequencing (66 MetS and 141 Co), and the NR3C1 expression was evaluated via RT-qPCR (14 MetS and 25 Co). Age, physical activity, and family environment during childhood were associated with MetS. Susceptibility to MetS, independent of these factors, was associated with homozygosity for rs10482605*C (OR = 4.74, pcorr = 0.024) and the haplotype containing TTCGTTGATT (rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T, OR = 4.74, pcorr = 0.048), as well as for the CCT haplotype (rs41423247*C_ rs6877893*C_rs258763*T), OR = 6.02, pcorr = 0.030), but not to the differences in methylation or gene expression. Thus, NR3C1 polymorphisms seem to modulate the susceptibility to MetS in Mennonites, independently of lifestyle and early childhood events, and their role seems to be unrelated to DNA methylation and gene expression.

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An integrated chemical characterization based on FT-NIR, and GC–MS for the comparative metabolite profiling of 3 species of the genus Amomum

He,

Yang,

Wang

2023

Analytica Chimica Acta

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Lifestyle and NR3C1 exon 1F gene methylation is associated with changes in glucose levels and insulin resistance

Cited by 3 publications

References 77 publications

An industrialized diet as a determinant of methylation in the 1F region of the NR3C1 gene promoter

An industrialized diet as a determinant of methylation in the 1F region of the NR3C1 gene promoter

Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population

An integrated chemical characterization based on FT-NIR, and GC–MS for the comparative metabolite profiling of 3 species of the genus Amomum

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