Impact of Weight Loss Strategies on Obesity-Induced DNA Damage

Tahereh Setayesh, Miroslav Mišík, Sabine A S Langie, Roger Godschalk, Monika Waldherr, Thomas Bauer, Sabine Leitner, Christoph Bichler, Gerhard Prager, Georg Krupitza, Alexander Haslberger, Siegfried Knasmüller, Tahereh Setayesh, Miroslav Mišík, Sabine A S Langie, Roger Godschalk, Monika Waldherr, Thomas Bauer, Sabine Leitner, Christoph Bichler, Gerhard Prager, Georg Krupitza, Alexander Haslberger, Siegfried Knasmüller

Abstract

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.

Keywords: DNA damage; DNA repair; Western diet; inflammation; weight loss.

Conflict of interest statement

The authors declare no conflict of interest.

© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figures

Figure 1
Figure 1
Effect of weight loss after consumption of a 40%‐R‐WD or a AL‐HCLP diet on obese animals that received a Western Diet (WD) for 14 weeks. Schematic design of the study A), impact of consumption of the different diets on body weights B and C), percentage of body fat in mice at the end of the experiment D), and energy intake (KJ) per day for each group (E). Bars show mean ± SD (with six animals per group). (a) indicates a statistically significant difference (p ≤ 0.05, Bonferroni's method).
Figure 2
Figure 2
Impact of the different diets on DNA damage, formation of oxidized purines (Fpg‐ specific sites), and NER activity in different inner organs of mice. The feeding scheme is shown in Figure 1A. The left parts of the graphs show the effects of WD feeding and weight loss on DNA damage. The middle and right sections show the effects of weight loss on net‐Fpg sensitive sites and on the NER incision activity in different organs. From each organ, three slides were made and 50 cells were analyzed per slide. Formation of oxidized purines was assessed by treatment of nuclei with formamidopyrimidine DNA glycosylase (Fpg). Bars show values obtained with the enzyme after subtraction of results obtained with the respective buffers. The final NER incision activity was calculated after subtracting the background levels. Bars show mean of the medians ± SD of six animals per group. (a) indicates a statistically significant difference (p ≤ 0.05, nonparametric Mann–Whitney U‐test).
Figure 3
Figure 3
Impact of the different diets on glucose, insulin and triglyceride levels in plasma. The animals were either fed continuously ad libitum with the WD, with the 40%‐R‐WD or with the AL‐HCLP. Bars indicate mean ± SD of six animals per group. (a) indicates a statistically significant difference (p ≤ 0.05, Bonferroni's method).
Figure 4
Figure 4
Impact of the different diets on the levels of inflammatory cytokines in plasma. The animals were either fed continuously with the AL‐WD or for 5 weeks with a 40%‐R‐WD or with the AL‐HCLP. Bars indicate mean ± SD that were obtained from six animals per group. (a) indicates statistical significance (p ≤ 0.05, Bonferroni's method).

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