Obesity, DNA Damage, and Development of Obesity-Related Diseases

Włodarczyk, Marta

doi:10.3390/ijms20051146

Cited by 181 publications

(137 citation statements)

References 157 publications

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“…Cigarette smoke is a genotoxic agent inducing DNA damage [24]. In addition, also obesity induces DNA damage [25] and, furthermore, free fatty acids involved in obesity induce a release of mtDNA into the cytoplasm [15]. Together with our recent observation, we speculate that conditions such as smoking or obesity, resulting in an enhanced release of DNA, may fuel the process of aging in a STINGdependent manner by augmenting senescence, endothelial inflammation, and inflamm-aging ( Fig.…”

Section: Resultssupporting

confidence: 66%

First evidence for STING SNP R293Q being protective regarding obesity-associated cardiovascular disease in age-advanced subjects – a cohort study

et al. 2020

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Obesity is a risk factor for several aging-related diseases such as type 2 diabetes, cardiovascular disease, and cancer. Especially, cardiovascular disease is triggered by obesity by inducing vascular senescence and chronic low-grade systemic inflammation, also known as inflamm-aging. Released molecules from damaged cells and their recognition by the innate immune system is one of the mechanisms driving inflamm-aging. Obesity results in mitochondrial damage, leading to endothelial inflammation triggered by cytosolic mtDNA via the cGAS/STING pathway. Recently, we have shown STING SNP R293Q to be associated with a decreased risk for aging-related diseases in current smokers. Since current smoking triggers DNA damage that, similar to obesity, may result in the release of DNA into the cytoplasm, we hypothesized that the cGAS/STING pathway can modify the phenotype of aging also in obese subjects. Therefore, the objective of our study was to investigate whether STING R293Q is associated with agingrelated diseases in obese individuals. We indeed show that STING 293Q is associated with protection from combined aging-related diseases (P = 0.014) and, in particular, cardiovascular disease in these subjects (P = 0.010). Therefore, we provide the first evidence that stratification for obesity may reveal new genetic loci determining the risk for aging-related diseases.

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Section: Resultssupporting

confidence: 66%

First evidence for STING SNP R293Q being protective regarding obesity-associated cardiovascular disease in age-advanced subjects – a cohort study

et al. 2020

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“…Obesity has been associated with low-grade sustained inflammation and oxidative stress, both classical triggers of cell cycle arrest [28]. In the present study, we demonstrated that maternal obesity increases the expression of several cell cycle regulators, i.e., 9 genes and 25 proteins, in the first trimester of pregnancy, suggesting that obesity affects placental cell cycle control already in early pregnancy.…”

Section: Discussionsupporting

confidence: 61%

Maternal Obesity Alters Placental Cell Cycle Regulators in the First Trimester of Human Pregnancy: New Insights for BRCA1

Hoch

Bachbauer

Pöchlauer

et al. 2020

IJMS

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In the first trimester of pregnancy, placental development involves a wide range of cellular processes. These include trophoblast proliferation, fusion, and differentiation, which are dependent on tight cell cycle control. The intrauterine environment affects placental development, which also includes the trophoblast cell cycle. In this work, we focus on maternal obesity to assess whether an altered intrauterine milieu modulates expression and protein levels of placental cell cycle regulators in early human pregnancy. For this purpose, we use first trimester placental tissue from lean and obese women (gestational week 5+0–11+6, n = 58). Using a PCR panel, a cell cycle protein array, and STRING database analysis, we identify a network of cell cycle regulators increased by maternal obesity in which breast cancer 1 (BRCA1) is a central player. Immunostaining localizes BRCA1 predominantly to the villous and the extravillous cytotrophoblast. Obesity-driven BRCA1 upregulation is not able to be explained by DNA methylation (EPIC array) or by short-term treatment of chorionic villous explants at 2.5% oxygen with tumor necrosis factor α (TNF-α) (50 mg/mL), leptin (100 mg/mL), interleukin 6 (IL-6) (100 mg/mL), or high glucose (25 nM). Oxygen tension rises during the first trimester, but this change in vitro has no effect on BRCA1 (2.5% and 6.5% O2). We conclude that maternal obesity affects placental cell cycle regulation and speculate this may alter placental development.

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“…The main factors associated with an increase in oxidative stress in menopausal women include obesity, aging, decreased estrogen production, and diet [4,[7][8][9]. Chronic inflammation is a hallmark of aging and obesity and has been implicated in the release of ROS from different sources, including activated macrophages and neutrophils involved in inflammation that generates oxidants, such as peroxynitrite and nitrosoperoxycarbonate, hypohalous acids, and nitrosating agent [7]. ROS can participate in lipid peroxidation and generate products such as etheno-, propano-, and malondialdehyde that interact with DNA, form DNA adducts, and damage the DNA structure [4,7].…”

Section: Introductionmentioning

confidence: 99%

“…Chronic inflammation is a hallmark of aging and obesity and has been implicated in the release of ROS from different sources, including activated macrophages and neutrophils involved in inflammation that generates oxidants, such as peroxynitrite and nitrosoperoxycarbonate, hypohalous acids, and nitrosating agent [7]. ROS can participate in lipid peroxidation and generate products such as etheno-, propano-, and malondialdehyde that interact with DNA, form DNA adducts, and damage the DNA structure [4,7]. The protective effect of estrogen on oxidative stress is mediated by translocation for specific enzymes from the cytosol that prevent mitochondrial DNA from oxidative attack by free radicals [8].…”

Section: Introductionmentioning

confidence: 99%

Parameters of Oxidative Stress in Reproductive and Postmenopausal Mexican Women

Montoya-Estrada

Velázquez-Yescas

Veruete-Bedolla

et al. 2020

IJERPH

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In the reproductive phase, women experience cyclic changes in the ovaries and uterus, and hormones regulate these changes. Menopause is the permanent loss of menstruation after 12 months of amenorrhea. Menopause is also linked to a decrease in estrogen production, causing an imbalance in oxidative stress. We aimed to compare the three stages of lipid peroxidation, protein oxidative damage, and total antioxidant capacity (TAC) between reproductive-aged women (RAW) and postmenopausal women (PMW) in Mexico. We carried out a cross-sectional study with 84 women from Mexico City, including 40 RAW and 44 PMW. To determine the oxidative stress of the participants, several markers of lipid damage were measured: dienes conjugates (DC), lipohydroperoxides (LHP), and malondialdehyde (MDA); exposure to protein carbonyl is indicative of oxidative modified proteins, and TAC is indicative of the antioxidant defense system. Biomarkers of oxidative stress were significantly lower in RAW vs. PMW. DC were 1.31 ± 0.65 vs. 1.7 ± 0.51 pmol DC/mg dry weight (p = 0.0032); LHP were 4.95 ± 2.20 vs. 11.30 ± 4.24 pmol LHP/mg dry weight (p < 0.0001); malondialdehyde was 20.37 ± 8.20 vs. 26.10 ± 8.71 pmol MDA/mg dry weight (p = 0.0030); exposure of protein carbonyl was 3954 ± 884 vs. 4552 ± 1445 pmol PC/mg protein (p = 0.042); and TAC was 7244 ± 1512 vs. 8099 ± 1931 pmol Trolox equivalent/mg protein (p = 0.027). PMW display significantly higher oxidative stress markers compared to RAW; likewise, PMW show a higher TAC.

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Obesity, DNA Damage, and Development of Obesity-Related Diseases

Cited by 181 publications

References 157 publications

First evidence for STING SNP R293Q being protective regarding obesity-associated cardiovascular disease in age-advanced subjects – a cohort study

First evidence for STING SNP R293Q being protective regarding obesity-associated cardiovascular disease in age-advanced subjects – a cohort study

Maternal Obesity Alters Placental Cell Cycle Regulators in the First Trimester of Human Pregnancy: New Insights for BRCA1

Parameters of Oxidative Stress in Reproductive and Postmenopausal Mexican Women

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