Impact of obesity and overweight on DNA stability: Few facts and many hypotheses

Setayesh, Tahereh; Nersesyan, Armen; Mišík, Miroslav; Ferk, Franziska; Langie, Sabine A. S.; Andrade, Vanessa Moraes de; Haslberger, Alexander G.; Knasmüller, Siegfried

doi:10.1016/j.mrrev.2018.07.001

Cited by 72 publications

(83 citation statements)

References 228 publications

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“…Many earlier studies on nutrition related cancer prevention focused on the antimutagenic properties of specific human foods . A recent evaluation of the current state of knowledge indicated that also weight loss may improve the integrity of the genetic material . However, earlier findings with humans are partly controversial and no firm conclusions can be drawn, since consumption of vitamins and minerals, which may have an impact on DNA damage, was not taken into consideration .…”

Section: Introductionmentioning

confidence: 97%

“…A recent evaluation of the current state of knowledge indicated that also weight loss may improve the integrity of the genetic material . However, earlier findings with humans are partly controversial and no firm conclusions can be drawn, since consumption of vitamins and minerals, which may have an impact on DNA damage, was not taken into consideration . The findings of animal studies were more consistent but also in these investigations the intake of micronutrients was neglected.…”

Section: Introductionmentioning

confidence: 99%

“…The migration of damaged genetic material leads to “comets” reflecting the formation of single and double strand breaks and apurininc sites (see Figure S1, Supporting Information) . Since it was postulated that glucose, insulin levels, and fatty acid metabolism may play a key role in obesity‐induced DNA damage, we measured these parameters in the different feeding groups.…”

Section: Introductionmentioning

confidence: 99%

“…It was postulated that increased body weight affects DNA repair systems via different molecular mechanisms (for review see ref. []), in particular NER, which is one of the most important repair system in eukaryotic organisms . Therefore, we monitored the impact of weight loss on the activity of this repair pathway in different inner organs in obese mice and in the weight loss groups.…”

Section: Introductionmentioning

confidence: 99%

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Impact of Weight Loss Strategies on Obesity‐Induced DNA Damage

Setayesh

Mišík

Langie

et al. 2019

Molecular Nutrition Food Res

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Scope Obesity causes DNA damage, which is causally related to several disorders including cancer, infertility, and cognitive dysfunctions. The aim of this study is to investigate whether weight loss improves the integrity of the genetic material. Methods and Results Overweight mice are fed ad libitum either with a Western diet (WD), with a 40% caloric restricted WD, or with a high carbohydrate low protein (HCLP) diet. Caloric restriction and also the HCLP diet lead to ca. 30% weight loss, which is paralleled by decreased DNA damage (“comet” formation) and oxidative damage of purines in inner organs, additionally the activity of nucleotide excision repair increased. The effects are more pronounced in animals that have received the HCLP chow. Results of biochemical analyses indicate that the reduction of DNA damage is associated with a decrease of pro‐inflammatory cytokines and lower insulin levels. Conclusion The study indicates that weight loss may prevent obesity‐associated adverse health effects due to reduction of overall DNA damage.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impact of Weight Loss Strategies on Obesity‐Induced DNA Damage

Setayesh

Mišík

Langie

et al. 2019

Molecular Nutrition Food Res

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“…Another pathway that seems to associate obesity with cancer development is genetic instability . Many studies have indicated that obesity‐related modulations in DNA damage and/or repair pathways may be involved in obesity‐induced genetic instability . However, little is known about the impact of obesity on DNA damage and DNA repair mechanisms that play critical roles in tumor initiation and progression.…”

Section: Introductionmentioning

confidence: 99%

Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability

Kompella

Vásquez

2019

Molecular Carcinogenesis

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Obesity, defined as a state of positive energy balance with a body mass index exceeding 30 kg/m2 in adults and 95th percentile in children, is an increasing global concern. Approximately one‐third of the world's population is overweight or obese, and in the United States alone, obesity affects one in six children. Meta‐analysis studies suggest that obesity increases the likelihood of developing several types of cancer, and with poorer outcomes, especially in children. The contribution of obesity to cancer risk requires a better understanding of the association between obesity‐induced metabolic changes and its impact on genomic instability, which is a major driving force of tumorigenesis. In this review, we discuss how molecular changes during adipose tissue dysregulation can result in oxidative stress and subsequent DNA damage. This represents one of the many critical steps connecting obesity and cancer since oxidative DNA lesions can result in cancer‐associated genetic instability. In addition, the by‐products of the oxidative degradation of lipids (e.g., malondialdehyde, 4‐hydroxynonenal, and acrolein), and gut microbiota‐mediated secondary bile acid metabolites (e.g., deoxycholic acid and lithocholic acid), can function as genotoxic agents and tumor promoters. We also discuss how obesity can impact DNA repair efficiency, potentially contributing to cancer initiation and progression. Finally, we outline obesity‐related epigenetic changes and identify the gaps in knowledge to be addressed for the development of better therapeutic strategies for the prevention and treatment of obesity‐related cancers.

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