Dopamine gene methylation patterns are associated with obesity markers and carbohydrate intake

Ramos-López, Omar; Riezu-Boj, José Ignacio; Milagro, Fermı́n I.; Marti, Amelia; Mena,

doi:10.1002/brb3.1017

Cited by 28 publications

(22 citation statements)

References 74 publications

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“…Previously, it was reported that Slc6a3 was hypermethylated in the promoter region in response to high-fat-sucrose diet and downregulated in the nervous system of prenatally stressed female rats and murine models of diet-induced obesity [46,47]. In addition, methylation aberrations at SLC6A3 gene were related to triglyceride level and obesity in humans [30,48]. Hence, the hypermethylation event at the promoter region of SLC6A3, detected previously by our group [4], and its low expression in CRC, reported in the current study, could suggest an alteration in metabolism, such as lipogenic pathways, and probably a oxidative stress environment leading to malignancy transformation [49].…”

Section: Discussionmentioning

confidence: 99%

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Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression

Vega-Benedetti

Loi

Moi

et al. 2020

IJMS

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Colorectal cancer (CRC) is a major cause of cancer mortality. Early diagnosis is relevant for its prevention and treatment. Since DNA methylation alterations are early events in tumourigenesis and can be detected in cell-free DNA, they represent promising biomarkers for early CRC diagnosis through non-invasive methods. In our previous work, we identified 74 early altered CpG islands (CGIs) associated with genes involved in cell cross-talking and cell signalling pathways. The aim of this work was to test whether methylation-based biomarkers could be detected in non-invasive matrices. Our results confirmed methylation alterations of GRIA4 and VIPR2 in CRC tissues, using MethyLight, as well as in stool samples, using a much more sensitive technique as droplet digital PCR. Furthermore, we analysed expression levels of selected genes whose promoter CGIs were hypermethylated in CRC, detecting downregulation at mRNA and protein levels in CRC tissue for GRIA4, VIPR2, SPOCK1 and SLC6A3. Most of these genes were already lowly expressed in colon normal tissues supporting the idea that cancer DNA methylation targets genes already barely expressed in the matched normal tissues. Our study suggests GRIA4 and VIPR2 as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC.

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Section: Discussionmentioning

confidence: 99%

“…Nevertheless, it has been reported that dopamine improves the efficacy of therapy in breast and colon cancer [29]. In a different context, hypermethylation was detected in dopamine pathway genes, including SLC6A3, as a consequence of a high fat and sugar diet suggesting a link between dopaminergic signalling and metabolic control [30].…”

Section: Introductionmentioning

confidence: 99%

Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression

Vega-Benedetti

Loi

Moi

et al. 2020

IJMS

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“…; Ramos‐Lopez et al. ). According to a number of studies, the consumption of high‐fat and high‐carbohydrate diets, predisposing to obesity, causes persistent changes in the metabolism of dopamine, leading to disruption of the formation of a sense of food saturation (Lee et al.…”

Section: Introductionmentioning

confidence: 98%

Comparative analysis of the influence of a high-fat/high-carbohydrate diet on the level of anxiety and neuromotor and cognitive functions in Wistar and DAT-KO rats

et al. 2019

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We compared anxiety, neuromotor, and cognitive functions in mutant rats with different allelic variants of dopamine transporter DAT knockout receiving balanced or excess in fat and fructose diet. The experiments were performed in DAT −/− homozygotes, DAT +/− heterozygotes, and DAT +/+ wild type rats. The genotype of DAT ‐ KO rats was confirmed by restriction analysis of DAT gene compared to behavioral responses in the open field test ( OF ). Animals in the first groups of each strain were fed a balanced AIN 93M diet; and those in the second groups with a high‐fat/high‐fructose diet. Neuromotor function was studied as grip strength, and behavioral responses were assessed in the elevated plus maze and conditioned passive avoidance response tests. The mass of the internal organs and white and brown fat, as well as selected lipid and nitrogen metabolism parameters in blood plasma were determined at the end of the experiment. DAT −/− had the highest specific grip strength, and showed an increase in initial exploratory activity in comparison with DAT +/− and DAT +/+. The exploratory activity was significantly reduced in the second test compared to the first one in DAT −/− and DAT +/− of first but not second group. Anxiety decreased with age in the second groups of DAT +/− and DAT +/+ (but not in DAT −/−) and was higher in DAT +/+ than in DAT +/− and DAT −/−. Excess fat and fructose resulted in the deterioration of short‐term memory in DAT +/+. Lipidomic indices of blood plasma were less responsive to diet in DAT −/− and DAT −/+ in comparison to DAT +/+. The increased As AT /Al AT activity ratio in DAT −/− compared with those in DAT +/+ suggests the activation of catabolism activity in the mutants. The consumption of excess fat and fructose significantly modified the effects produced by DAT gene allelic variants presumably due to the influence on the processes of dopamine metabolism.

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“…In addition, a number of other relevant genes were identified as being differentially methylated as a function of SES, including genes linked to psychiatric disorders (Zinc Finger [65,66], and metabolic function (Protein Phosphatase 2 Regulatory Subunit Bdelta) [67]. These findings are in line with previous literature showing that psychiatric disorders and immunosuppression is commonly observed in individual with low SES [68][69][70][71][72], as well as in individuals exposed to early-life SES adversity with significant down-regulation of glucocorticoid-related genes in blood [73] and placenta [14], which regulates the secretion of cortisol and transduces its anti-inflammatory actions in the immune system.…”

Section: Discussionmentioning

confidence: 99%

Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status

Santos¹,

Bhattacharya

Martin

et al. 2019

Epigenetics

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This study evaluated the hypothesis that prenatal maternal socioeconomic status (SES) adversity is associated with DNA methylation in the placenta. SES adversity was defined by the presence of, as well as a summative count of, four factors: less than college education, single marital status, food and nutritional service assistance, and public health insurance. Epigenome-wide DNA methylation was assessed using the Illumina EPIC array in 426 placentas from a sample of infants born < 28 weeks of gestation from the Extremely Low Gestational Age Newborn cohort. Associations between SES adversity and DNA methylation were assessed with robust linear regressions adjusted for covariates and controlled the false discovery rate at < 10%. We also examined whether such associations were sex specific. Indicators of SES adversity were associated with differential methylation at 33 CpG sites. Of the 33 identified CpG sites, 19 (57.6%) displayed increased methylation, and 14 (42.4%) displayed decreased methylation in association with at least one of the SES adversity factors. Sex differences were observed in DNA methylation associated with summative SES score; in which placentas derived from female pregnancies showed more robust differential CpG methylation than placentas from male pregnancies. Maternal SES adversity was associated with differential methylation of genes with key role in gene transcription and placental function, potentially altering immunity and stress response. Further investigation is needed to evaluate the role of epigenetic differences in mediating the association between maternal socioeconomic status during pregnancy and later life health outcomes in children.

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Dopamine gene methylation patterns are associated with obesity markers and carbohydrate intake

Cited by 28 publications

References 74 publications

Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression

Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression

Comparative analysis of the influence of a high-fat/high-carbohydrate diet on the level of anxiety and neuromotor and cognitive functions in Wistar and DAT-KO rats

Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status

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