Mutagenesis Unit, Institute for Medical Research and Occupational Health (IMROH), 10001 Zagreb, Croatia.
Special Hospital for Extended Treatment of Duga Resa, 47250 Duga Resa, Croatia.
Nutrients. 2023 Feb 10;15(4):899. doi: 10.3390/nu15040899.
Although obesity with its comorbidities is linked with higher cancer risk, the data on genome stability in the obese/severely obese are scarce. This is the first study with three DNA damage assessment assays (Fpg-modified and alkaline comet assays and micronucleus assay) performed on a severely obese population (n = 53) where the results were compared with daily intake of food groups, nutrient intake, dietary inflammatory index (DII), and anthropometric and biochemical parameters usually measured in obese individuals. Results demonstrated the association between DNA damage levels and a decrease in cell proliferation with anthropometric measurements and the severity of obese status, together with elevated levels of urates, inorganic phosphates, chlorides, and hs troponin I levels. DII was connected with oxidative DNA damage, while BMI and basal metabolic rate (BMR) were associated with a decrease in cell proliferation and DNA damage creation. Measured daily BMR and calculated daily energy intake from the food frequency questionnaire (FFQ) demonstrated no significant difference (1792.80 vs. 1869.86 kcal day mean values). Groups with higher DNA damage than expected (tail intensity in comet assay >9% and >12.4%, micronucleus frequency >13), consumed daily, weekly, and monthly more often some type of food groups, but differences did not show a clear influence on the elevated DNA damage levels. Combination of all three DNA damage assays demonstrated that some type of damage can start earlier in the obese individual lifespan, such as nuclear buds and nucleoplasmic bridges, then comes decrease in cell proliferation and then elevated micronucleus frequencies, and that primary DNA damage is not maybe crucial in the overweight, but in severely obese. Biochemically changed parameters pointed out that obesity can have an impact on changes in blood cell counts and division and also on genomic instability. Assays were able to demonstrate groups of sensitive individuals that should be further monitored for genomic instability and cancer prevention, especially when obesity is already connected with comorbidities, 13 different cancers, and a higher mortality risk with 7-10 disease-free years loss. In the future, both DNA damage and biochemical parameters should be combined with anthropometric ones for further obese monitoring, better insight into biological changes in the severely obese, and a more individual approach in therapy and treatment. Patients should also get a proper education about the foodstuff with pro- and anti-inflammatory effect.
尽管肥胖及其合并症与更高的癌症风险有关,但关于肥胖/重度肥胖人群基因组稳定性的数据却很少。这是第一项使用三种 DNA 损伤评估检测(Fpg 修饰和碱性彗星检测以及微核检测)对重度肥胖人群(n=53)进行的研究,结果与食物组的日常摄入量、营养素摄入量、饮食炎症指数(DII)以及肥胖人群中通常测量的人体测量学和生化参数进行了比较。结果表明,DNA 损伤水平与细胞增殖的降低与人体测量学测量和肥胖程度的严重程度有关,同时尿酸盐、无机磷酸盐、氯化物和高敏肌钙蛋白 I 水平升高。DII 与氧化 DNA 损伤有关,而 BMI 和基础代谢率(BMR)与细胞增殖减少和 DNA 损伤形成有关。从食物频率问卷(FFQ)中测量的每日 BMR 和计算的每日能量摄入没有显示出显著差异(1792.80 与 1869.86 kcal·天平均值)。与预期相比 DNA 损伤较高的组(彗星检测中尾部强度>9%和>12.4%,微核频率>13),每天、每周和每月更频繁地消耗某些类型的食物组,但差异并未显示出对升高的 DNA 损伤水平的明显影响。所有三种 DNA 损伤检测的组合表明,某些类型的损伤可能在肥胖个体的生命早期就开始发生,例如核芽和核质桥,然后是细胞增殖减少,然后是微核频率升高,并且超重时原发性 DNA 损伤可能并不重要,但在重度肥胖时则不然。生化改变的参数表明,肥胖会影响血细胞计数和分裂的变化,也会影响基因组不稳定。这些检测能够证明一些敏感个体的存在,这些个体应该进一步监测基因组不稳定和癌症预防,尤其是当肥胖已经与合并症、13 种不同的癌症以及 7-10 年无疾病生存时间的损失相关时。未来,DNA 损伤和生化参数都应与人体测量学参数结合起来,以进一步监测肥胖,更好地了解重度肥胖人群中的生物学变化,并在治疗和治疗中采取更个体化的方法。患者还应接受关于具有促炎和抗炎作用的食物的适当教育。