Association between DNA repair capacity and body mass index in women

Crespo-Orta, Ian; Ortíz, Carmen; Encarnación, Jarline; Suárez, Erick; Matta, Jaime

doi:10.1016/j.mrfmmm.2022.111813

Cited by 4 publications

(7 citation statements)

References 34 publications

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“…Women with BMI greater than 25 kg/m 2 tended to have lower DRC (adjusted for confounders) than women with BMI less than 25 kg/m 2 . Family breast cancer history, which could potentially indicate a susceptibility to low DRC as DNA damage may be both a cause and a result of cancer, did not affect this relation [7].…”

Section: Effect Of Body Mass and Weight Loss On Dna Repair Capacity A...mentioning

confidence: 87%

DNA damage, obesity and obesity-related health complications: what are new data telling us?

Włodarczyk,

Nowicka

2024

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review Obesity is associated with increased DNA damage, which may in turn contribute to the development of obesity-related complications. DNA damage can also affect adipocyte biology, resulting in increased adiposity. Carefully managed weight loss programs can reverse this process. This article surveys new data that support these contentions. Recent findings Whole exome sequencing analyses have identified rare variants linked to high BMI and adiposity. Two of the identified genes are linked to DNA damage and DNA repair, suggesting that DNA damage itself may play a role in the cause of obesity. It has also been recognized that obesity increases DNA damage in breast tissue of carriers of BRCA mutations and rates of tumour formation in BRCA1+ mice, indicating effect of obesity on cancer development in high-risk populations. In addition, obesity promotes cancer cell chemoresistance by decreasing fatty acid oxidation involved in cellular DNA damage response, leading to apoptotic cellular death. Obesity is also associated with a reduced capacity of oocytes to repair sperm DNA damage, leading to lower in-vitro fertilization rates in women with obesity. Summary DNA damage and cellular responses to DNA damage can be both the result and the cause of obesity and can strongly influence the development and treatment of obesity-associated diseases.

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Section: Effect Of Body Mass and Weight Loss On Dna Repair Capacity A...mentioning

confidence: 87%

DNA damage, obesity and obesity-related health complications: what are new data telling us?

Włodarczyk,

Nowicka

2024

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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“…[53,56] Obese individuals exhibit reduced DNA repair capacity, leading to the formation of DNA strand breaks, mutations, and genomic instability. [12][13][14] Oxidized DNA bases such as 8-OHdG are mainly repaired through base excision repair, a pathway that is catalyzed by DNA glycosylases such as Ogg1. [57] Overweight/obese persons have demonstrated higher levels of Ogg1 expression in comparison to healthy lean individuals.…”

Section: Discussionmentioning

confidence: 99%

“…[15] Polymorphisms in DNA repair genes are positively correlated with a higher risk of developing cancer in obese individuals, further supporting the role of deficient repair genes in obesity. [12] Epigenetic mechanisms may play a role in regulating genes responsible for DNA repair. Obese individuals often have unbalanced and high-fat diets, which can change the availability of methyl groups and disrupt the epigenetic control of genes responsible for DNA repair.…”

Section: Introductionmentioning

confidence: 99%

Dulaglutide reduces oxidative DNA damage and hypermethylation in the somatic cells of mice fed a high‐energy diet by restoring redox balance, inflammatory responses, and DNA repair gene expressions

Attia,

Alshamrani,

Ahmad

et al. 2024

J Biochem & Molecular Tox

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Obesity is an established risk factor for numerous malignancies, although it remains uncertain whether the disease itself or weight‐loss drugs are responsible for a greater predisposition to cancer. The objective of the current study was to determine the impact of dulaglutide on genetic and epigenetic DNA damage caused by obesity, which is a crucial factor in the development of cancer. Mice were administered a low‐fat or high‐fat diet for 12 weeks, followed by a 5‐week treatment with dulaglutide. Following that, modifications of the DNA bases were examined using the comet assay. To clarify the underlying molecular mechanisms, oxidized and methylated DNA bases, changes in the redox status, levels of inflammatory cytokines, and the expression levels of some DNA repair genes were evaluated. Animals fed a high‐fat diet exhibited increased body weights, elevated DNA damage, oxidation of DNA bases, and DNA hypermethylation. In addition, obese mice showed altered inflammatory responses, redox imbalances, and repair gene expressions. The findings demonstrated that dulaglutide does not exhibit genotoxicity in the investigated conditions. Following dulaglutide administration, animals fed a high‐fat diet demonstrated low DNA damage, less oxidation and methylation of DNA bases, restored redox balance, and improved inflammatory responses. In addition, dulaglutide treatment restored the upregulated DNMT1, Ogg1, and p53 gene expression. Overall, dulaglutide effectively maintains DNA integrity in obese animals. It reduces oxidative DNA damage and hypermethylation by restoring redox balance, modulating inflammatory responses, and recovering altered gene expressions. These findings demonstrate dulaglutide's expediency in treating obesity and its associated complications.

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“…The same trend was observed in some studies of obese subjects using an MN assay [ 42 , 43 , 44 ]. Additionally, impaired DNA repair capacity [ 45 , 46 ] and increased DNA damage [ 39 ] in obese subjects were reported in several studies. The correlation between CSAs and BMI of patients with diabetes in our study aligns with these data.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic inflammation seems to be an excellent candidate for this mechanism. On the other hand, increased frequencies of CTAs may reflect the accumulation of primary DNA damage in lymphocytes arising due to oxidative stress and impaired excision repair [ 39 , 46 ]. It cannot be excluded that this type of damage may be related to the development of different diabetes complications and comorbidities.…”

Section: Discussionmentioning

confidence: 99%

Influence of Body Mass Index and Duration of Disease on Chromosome Damage in Lymphocytes of Patients with Diabetes

Šiaulienė,

Kazlauskaitė,

Jurkėnaitė

et al. 2023

Life

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It is well-established that patients with diabetes mellitus (DM) have a higher incidence of several types of cancer. The precise mechanisms of this association are still unknown, but obesity and chronic inflammation-induced reactive oxygen species (ROS) are thought to be the main risk factors. ROS may produce different DNA damage, which could eventually lead to cancer. The main objective of this study was to evaluate the relation of chromosome aberrations (CA) with disease status, demographics, and clinical parameters in 33 subjects with type 1 DM (T1DM), 22 subjects with type 2 DM (T2DM), and 21 controls. CAs were analyzed in cultured peripheral blood lymphocytes and subdivided into chromatid (CTA)- and chromosome (CSA)-type aberrations. Compared with controls, higher levels of CTAs and CSAs were observed in T1DM (p = 0.0053 and p = 0.0203, respectively) and T2DM (p = 0.0133 and p = 0.00002, respectively). While there was no difference in CTAs between T1DM and T2DM, CSAs were higher in T2DM (p = 0.0173). A significant positive association between CTAs and disease duration (rs = 0.2938, p = 0.0099) and between CSAs and disease duration (rs = 0.4306, p = 0.0001), age (rs = 0.3932, p = 0.0004), and body mass index (BMI) (rs = 0.3502, p = 0.0019) was revealed. After multiple regression analysis, duration of disease remained significant for CTA, CSA, and CAs (p = 0.0042, p = 0.00003, and p = 0.00002, respectively). For CSA, BMI and the use of statins were the other important confounding variables (p = 0.0105 and p = 0.0763). Thus, this study demonstrated that both T1DM and T2DM patients had a higher number of all types of aberrations than controls, which increases with the prolonged disease duration. Higher BMI was associated with a higher frequency of CSA. The use of statins might be beneficial for reducing chromosome damage, but further investigations are needed to confirm this association.

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Association between DNA repair capacity and body mass index in women

Cited by 4 publications

References 34 publications

DNA damage, obesity and obesity-related health complications: what are new data telling us?

DNA damage, obesity and obesity-related health complications: what are new data telling us?

Dulaglutide reduces oxidative DNA damage and hypermethylation in the somatic cells of mice fed a high‐energy diet by restoring redox balance, inflammatory responses, and DNA repair gene expressions

Influence of Body Mass Index and Duration of Disease on Chromosome Damage in Lymphocytes of Patients with Diabetes

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