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Obesity and obesity-related complications, including various metabolic diseases and cancers, are significant health problems in developed and developing countries [...].

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Obesity is associated with inflammation, which can disturb genome stability. Tumor necrosis factor (TNF-α) polymorphism was found to affect TNF-α protein production and inflammation. Therefore, the present study illustrates the relationship between TNF-α polymorphism, the degree of inflammation assessed by serum high sensitivity C-reactive protein concentration (CRP-hs) and basal DNA damage in patients with obesity (BMI 30-34.9 kg/m 2 ) and control subjects with proper body mass (BMI < 25 kg/m 2 ). A total of 115 participants (75 obese premenopausal women; and 40 age-, and gender-matched controls) were included. Biochemical parameters (serum concentrations of total-cholesterol, HDL-cholesterol, LDL- cholesterol, triglycerides, glucose, apolipoprotein AI, CRP-hs) and endogenous DNA damage (determined by comet assay) were measured. TNF-α G-308A polymorphism (rs1800629) was analyzed by PCR-RFLP (PCR-restriction fragments length polymorphism). An effect of TNF-α genotype on serum CRP-hs concentration was noted (p = 0.031). In general, carriers of the rare A allele of the TNF-α G-308A polymorphism had significantly lower endogenous DNA damage and serum CRP-hs concentrations than GG homozygotes, however, the protective effect of the A allele was especially visible in non-obese women. Serum CRP-hs concentrations and levels of DNA damage (% DNA in tail) were significantly higher in obese than in controls (p = 0.001 and p < 0.0001, respectively). The adjusted multiple linear regression analyses revealed a significant, independent impact of obesity on DNA damage (p = 0.00000) and no effect of other covariates i.e. age, TNF-α genotype and serum CRP-hs concentration. Our study showed that obesity has a significant impact on the levels of endogenous DNA damage. Obesity abolished the protective effect of A allele of the TNF-α G-308A polymorphism on DNA damage and on inflammation development observed in non-obese A allele carriers.

Obesity has been recognized to increase the risk of such diseases as cardiovascular diseases, diabetes, and cancer. It indicates that obesity can impact genome stability. Oxidative stress and inflammation, commonly occurring in obesity, can induce DNA damage and inhibit DNA repair mechanisms. Accumulation of DNA damage can lead to an enhanced mutation rate and can alter gene expression resulting in disturbances in cell metabolism. Obesity-associated DNA damage can promote cancer growth by favoring cancer cell proliferation and migration, and resistance to apoptosis. Estimation of the DNA damage and/or disturbances in DNA repair could be potentially useful in the risk assessment and prevention of obesity-associated metabolic disorders as well as cancers. DNA damage in people with obesity appears to be reversible and both weight loss and improvement of dietary habits and diet composition can affect genome stability.

Background: Alongside obesity, insomnia and depression are common public health problems. Sleep problems are currently believed to be associated with excessive food intake and metabolic disturbances. Therefore, we aimed to explore a relationship between insomnia, depressive symptoms and eating habits as well as metabolic parameters in bariatric surgery candidates., Methods: A total of 361 unrelated obese subjects were included in this study. Severity of sleep problems was measured with Athens Insomnia Scale (AIS) and the severity of depressive symptoms was assessed with the Beck Depression Inventory (BDI-II). Obstructive sleep apnea (OSA) was assessed by the Apnea Hypopnoea Index (AHI). Information was obtained about demographics, eating habits and lifestyle. Blood samples were collected to measure concentration of lipids (cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol), and glucose., Results: The median (interquartile range) score for AIS in the study participants was 5 (3-8) with a range of 0-24 and 47% (171) participants scored ≥6 (met criteria for diagnosis of insomnia). Statistically significant correlations were found between the AIS scores and serum triglycerides and glucose concentrations, and BDI-II total scores. The highest scores on AIS and BDI-II were found in participants with high frequency of snack food consumption, in physically inactive individuals as well as in those who self-reported eating at night or who declared more than 3 intense emotions associated with a desire-to-eat. Adjusted multivariate logistic regression analysis revealed that clinical insomnia was most strongly associated with daily consumption of snack foods, with the odds ratio of 3.26 (95% CI: 1.74-6.11), while depressive symptoms were strongly associated with both eating in response to ≥3 specific emotions with OR = 2.93 (95% CI: 1.26-6.78) as well as with daily consumption of snack foods with OR = 2.87 (95% CI: 1.16-5.14)., Conclusions: The results indicate that insomnia and depression in obese individuals are associated with eating habits, and suggest that in some patients these associations appears as major factors affecting obesity development.

Enhanced DNA damage and disturbances in DNA repair mechanisms are reported to be involved in the pathogenesis of chronic diseases like obesity, atherosclerosis, metabolic syndrome, diabetes, and cancer. The aim of the present study was to evaluate whether anthropometric factors and dietary habits are related to endogenous DNA damage. One hundred and fourteen premenopausal, apparently healthy women were included in the study: 88 obese individuals and 26 controls. The comet assay was used to measure basal DNA damage. Biochemical measurements included lipids, apolipoproteinAI, fasting insulin, glucose, and C-reactive protein high sensitivity (CRP-hs). Dietary intakes were assessed by 3-day food records. The mean level of DNA damage was almost two times higher in obese than in non-obese women ( p < 0.001). Regression modeling showed that body mass index (BMI), daily intakes of energy, and vitamin C are key predictors of variance in basal DNA damage. Our data demonstrate the impact of obesity-associated inflammation on DNA damage and indicate that regardless of obesity, the level of DNA damage can be reduced by adequate intakes of vitamins C and E. It suggests that particular attention should be paid to the content of antioxidants in the diet of obese people and further studies are needed to modify dietary guidelines to prevent DNA damage in obese individuals.

Background and Aim: The aim of this study was to examine the relationship between new obesity-related indexes, anthropometric and biochemical parameters, and body composition in individuals with obesity., Methods: The study group consisted of 72 women and 34 men, aged 39.0 ± 5.9 years, with a mean body mass index (BMI) of 32.6 ± 2.4 kg/m², admitted for body weight reduction. In all participants body weight (BW), height, waist circumference (WC), hip circumference (HC), BMI, waist-to-hip-ratio (WHR), visceral adiposity index (VAI), body adiposity index (BAI), and waist-to-height ratio (WHtR) were assessed. Using bioelectrical impedance (BIA, TANITA MC 180M) the following parameters were obtained: the level of visceral adipose tissue (VAT) and body fat percentage (FM%). Serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), glucose, insulin, and insulin resistance (HOMA-IR) were determined., Results: It was observed that almost all the studied indicators: WC, WHtR, BAI, VAI, and BMI, positively correlated with VAT estimated by bioimpedance, but only VAI, WC, and WHtR were strongly associated with glucose and lipid disturbances in the obese. BAI and BMI correlated with total FM%, while WC, WHtR, and VAI correlated with total body weight., Conclusions: The results indicate that VAI, WC, and WHtR can be useful in the assessment of increased VAT accumulation associated with disturbances in glucose and lipid metabolism. BAI should be calculated separately for each sex, then it could be also useful for the prediction of disturbances in glucose metabolism. However, further studies are needed to recognise cut-off values for BAI, as a marker of body fatness, associated with adverse health effects.

Objective: To evaluate the influence of 25-hydroxyvitamin D and transforming growth factor β3 (TGF-β3) serum concentrations, weight, and family history on the risk of developing uterine fibroids., Design: Retrospective cohort study., Setting: University hospital., Patient(s): A total of 188 women, including patients admitted for uterine fibroid surgery (n = 105) as the study group and healthy women of similar age (n = 83) as controls., Intervention(s): Medical history and completion of specially designed questionnaire, transvaginal or transabdominal genital ultrasound scan, blood sampling, and measurement of vitamin D and TGF-β3 serum concentrations., Main Outcome Measure(s): Evaluation of the impact of family history, vitamin D, and TGF-β3 serum concentrations on the risk of developing uterine fibroids., Result(s): Mean 25-hydroxyvitamin D serum concentrations were 21.9 ± 8.9 ng/mL and 26.7 ± 11.9 ng/mL in patients with uterine fibroids and controls, respectively. The difference was statistically significant. The TGF-β3 serum concentrations in the fibroid-positive group ranged from 1.20 to 436.15 pg/mL (half the patients had concentrations >16.25 pg/mL). Concentrations in the control group ranged from 0.96 to 49.08 pg/mL (half the women had concentrations of >11.80 pg/mL). The differences were statistically significant. Higher body mass index (BMI) and positive family history were also found to be among the risk factors for uterine fibroids., Conclusion(s): Our study confirmed higher BMI, positive family history, and lower vitamin D and higher TGF-β3 serum concentrations as risk factors for uterine fibroids., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background & Objectives: The fat mass and obesity-associated (FTO) gene is known to be associated with obesity. However, no data are available on the relation between FTO rs9930506 polymorphism and obesity in Polish population. The aim of this study was to evaluate an association between rs9930506 variants of the FTO gene and obesity in Polish adults., Methods: The study group consisted of 442 adults, aged 33.9 ±12.7 yr, with mean BMI 27.2 ± 5.4 kg/m2. The following variables were determined for each subject: fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Real-time PCR was used to detect the A/G alleles of the rs9939506 polymorphism in the FTO gene. An association between the rs9930506 polymorphism and obesity was determined using codominant, dominant, and recessive models. The odds ratio (OR) was calculated to determine the risk of obesity associated with this polymorphism., Results: It was observed that the presence of FTO rs9939506 G allele was associated with increased risk for obesity and this association was found significant in both recessive (OR = 1.72, P = 0.014) and co-dominant (OR = 1.36, P = 0.031) models of inheritance. The FTO rs9939506 GG homozygotes had a significantly higher BMI than those with other genotypes., Interpretation & Conclusions: This study shows that FTO rs9939506 GG genotype is related to higher BMI and is associated with obesity in Polish adults.

Hypertension is a multifactorial disease caused by environmental, metabolic and genetic factors, but little is currently known on the complex interplay between these factors and blood pressure. The aim of the present study was to assess the potential impact of obesity, and angiotensin-converting enzyme (ACE) I/D polymorphism and endothelial nitric oxide synthase gene (NOS3) 4a/4b, G894T and -T786C variants on the essential hypertension. The study group consisted of 1,027 Caucasian adults of Polish nationality (45.5 ± 13.6 years old), of which 401 met the criteria for hypertension. Body weight, height and blood pressure were measured and data on self-reported smoking status were collected. Fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides were determined by standard procedures. The ACE I/D polymorphism and three polymorphisms in NOS3 gene (4a/4b, G894T, -T786C) were detected by the PCR method. Multivariable logistic regression demonstrated that age above 45 years, diabetes, dyslipidemia, smoking and male sex are important risk factors for hypertension and no significant influence of variants in ACE and NOS3 genes on this risk was recognized. Obese subjects had a 3.27-times higher risk (OR = 3.27, 95% CI: 2.37 - 4.52) of hypertension than non-obese, and in obese the NOS3 894T allele was associated with 1.37 fold higher risk of hypertension (P = 0.031). The distribution of NOS3 G894T genotypes supported the co-dominant (OR = 1.35, P = 0.034, Pfit = 0.435) or recessive (OR = 2.00, P = 0.046, Pfit = 0.286), but not dominant model of inheritance (P = 0.100). The study indicates that in obese NOS3 G894T polymorphism may enhance hypertension risk. However, in the presence of such strong risk factors as age, diabetes and smoking, the impact of this genetic variant seems to be attenuated. Further studies are needed to reveal the usefulness of G894T polymorphism in hypertension risk assessment in obese.

Background: Ongoing research shows an increase in mortality in patients with low levels of serum cholesterol, which is caused by decreasing the fraction of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein (LDL-C)., Objective: The aim of our study was to assess the relationship between the CETP gene TaqI polymorphism and concentrations of selected parameters of lipid metabolism in patients with overweight and obesity., Materials and Method: The study involved 73 people aged 24-68 years. Android obesity was found in 90.4% of women, including 66.7% in the HDL-C levels above 50 mg/dL., Results: Most of abdominal obesity was the B1B2 heterozygotes (38.1%). Abdominal obesity was present in 48.4% of men, including 25.8% in B1B2 heterozygotes and in 67.7% of HDL > 40 mg/dl. It was found statistically insignificant higher levels of TG, TC, LDL-C, the percentage of fat mass (% FM) in patients with genotype B2B2 compared to those with genotype B1B1 and B1B2. In women, higher levels of TC, LDL-C and HDL-C were found in the presence of B1B2 genotype, whereas a higher concentration of all lipid fractions studied showed the men with the B2B2 genotype, who also had the highest % FM., Conclusions: The results indicate that in obese men Tag1B polymorphism may be an independent factor influencing HDL-cholesterol.

Unlabelled: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) has not been completely explained yet. There are no clear clinical indicators of the risk of NAFLD's occurrence. By means of computed tomography (CT) quantitative assessment of the fatty liver is possible and CT is therefore a suitable method of monitoring the effectiveness of the treatment in non-alcoholic fatty liver., Aim of the Study: The assessment of the influence of the clinical factors, such as: [1] overweight, [2] the fatty tissue distribution type, [3] the lipids profile, on the risk of NAFLD occurrence. INVESTIGATED GROUP AND METHOD. The examined group and the control group comprised 113 persons (59 women and 54 men) with overweight and obesity, who, due to different clinical indications, underwent CT of the abdomen. In the CT examinations the existence of fatty liver was assessed on the basis of the range of attenuation coefficient (in Hounsfield units), that was measured in four previously chosen areas of the liver. Additionally, two measurements of spleen tissue were conducted. The density of tissues, represented in Hounsfield units, once established makes it possible to assess the increase of fat percentage in the liver with respect to the norm. Excursion criteria: [1] ethanol consumption exceeding 20 g per day; [2] existence of other diseases which may cause derivative form of non-alcoholic fatty liver and/or different clinical features of other diseases of the liver; [3] existence of focal changes of the liver that could affect the measurements of the attenuation coefficient. In the group of 59 women in 23 of them (38.9%) the features of fatty liver have been found. The group with fatty liver in comparison with the group without fatty liver was marked by significantly higher WHR index (0.9 vs 0.8; p = 0.029), higher TG concentration (209.9 mg/dl vs 160.9 mg/dl; p = 0.032) and lower HDL-C concentration (37.7 mg/dl vs 46.1 mg/dl; p = 0.004). In the group of 54 men in 22 of them (40.7%) fatty liver has been affirmed. The group with fatty liver in comparison with the group without fatty liver was characterized by higher BMI (29.2.2 vs 27.4 kg/m2; p = 0.002) and, as in women, higher TG concentration and lower HDL-C concentration in serum., Conclusions: [1] CT examination with assessment of the range of attenuation coefficient is a useful tool for fatty liver evaluation and may be used in routine diagnostic procedure in patients with NAFLD. [2] The risk factors of NAFLD development are high TG concentration and low HDL-C concentration in serum. [3] In men the risk factor of NAFLD is obesity and overweight, whereas in women fatty liver correlates not only with the BMI value, but above all with central obesity.

Background: The purpose of our study was to compare lipid profile assessed by ultracentrifugation in various types of hyperlipoproteinemia (HLP) in correlation with obesity and hepatic steatosis diagnosed in the ultrasonic examination of the abdominal cavity., Material/methods: We studied 64 patients (38 women and 26 men with a mean age of 53.5 years) with various types of HLP, divided into two groups: 1) hypercholesterolemia, 2) mixed hyperlipoproteinemia. Lipid profile by ultracentrifugation was performed simultaneously with ultrasonic examination., Results: Among 33 patients with hypercholesterolaemia, 7 had hepatic steatosis (21.2%), with a mean serum TG concentration significantly higher than in those patients without steatosis. Of the mixed HLP patients, 16 had hepatic steatosis (51.5%), with a mean serum TG level over twice the concentration found in patients without steatosis. We found significantly higher levels of total cholesterol and triglycerides in patients with steatosis than in those without. In the HDL fraction, the cholesterol concentration was lower (38.4 mg/dl) in cases of steatosis than in cases without (48.0 mg/dl)., Conclusions: Patients with steatosis showed features characteristic of insulin resistance syndrome, i.e. higher BMI values, higher mean serum TG, and low HDL cholesterol concentrations. In patients with hypercholesterolemia and hepatic steatosis, increased serum triglycerides are associated with increased TG concentration in the VLDL fraction. Mixed HLP patients with hepatic steatosis have higher TG and cholesterol in the VLDL fraction, and in these cases a significant rise in total TG is observed.