Elsevier

Clinical Biochemistry

Volume 35, Issue 8, November 2002, Pages 627-631
Clinical Biochemistry

Increased oxidative stress and hypozincemia in male obesity

https://doi.org/10.1016/S0009-9120(02)00363-6Get rights and content

Abstract

Objectives

Antioxidants protect an organism from the detrimental effects of free radicals via scavenging or inhibiting their formation. Alterations in the levels of antioxidants and several essential trace elements in the plasma and various tissues of ob/ob mice have been reported previously. The aim of this study was to investigate oxidative status and trace elements in obese individuals.

Design and methods

Seventy-six obese men (body mass index (BMI) > 30 kg/m2) and 24 healthy, age-matched male control volunteers were enrolled in the study. Fasting plasma insulin, glucose, triglyceride (TG), total cholesterol, VLDL, and HDL levels, erythrocyte glutathione peroxidase (GSH-Px) and copper zinc-superoxide dismutase (CuZn-SOD) activities, and erythrocyte thiobarbituric acid reactive substances (TBARS) levels were measured in both groups. Erythrocyte copper (Cu), zinc (Zn) and iron (Fe) levels were also measured.

Results

We found that the mean Cu and Fe levels in obese individuals were not significantly different than those in the control group, whereas the mean Zn levels were significantly lower than those of the control group (p = 0.023). The mean erythrocyte CuZn-SOD and GSH-Px levels in obese individuals were significantly lower than those in controls (p = 0.001) whereas erythrocyte TBARS levels were significantly higher (p = 0.001) than those of the control group.

Conclusion

We conclude that male obesity is associated with defective antioxidant status and hypozincemia, which may have implications in the development of obesity related health problems.

Introduction

Oxidative stress, resulting from the increased production of free radicals and reactive oxygen species and/or a decrease in antioxidant defense, causes severe damage to biologic macromolecules and dysregulation of normal metabolism and physiology [1], [2].

Oxygen radicals are known to produce membrane peroxidation and malondialdehyde (MDA) formation [3], which are both detrimental to cellular function. Peroxidation can increase membrane permeability, whereas MDA can inactivate membrane transporters [3] by forming intra and intermolecular cross links [3], [4]. Such events represent an immediate risk to cell viability, although the carcinogenetic effects of MDA [5] may be more damaging in the long term. To minimize free radical damage, there is a complex antioxidant defense system, which includes the interception of free radicals with antioxidants to form less reactive compounds. Antioxidants prevent the organism from the harmful effects of free radicals by scavenging or inhibiting their formation. Cells maintain their vital functions against oxidative damage with the help of a system that involves glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase, glutathione reductase, some trace elements and vitamins A, E and C against oxidative damage [6].

Recent studies have revealed that superoxide formation is enhanced and superoxide dismutase is inhibited by nonenzymatic glycation in metabolic disorders associated with obesity. Moreover, hyperlipidemia is shown to increase endothelial superoxide production. Thus, superoxide may play a key role in the pathophysiology of cardiovascular and metabolic consequences of obesity. Of note, the circulating levels of total amounts of several essential trace elements in various tissues of genetically obese rats differ markedly from those in lean animals [7], [8], [9], [10]. The aim of this study was to evaluate oxidative status and trace elements in obese subjects.

Seventy-six male obese subjects (mean age 49.11 ± 17.44 yr) and 24 age-matched healthy male subjects (mean age 48.46 ± 16.55 yr) were enrolled into the study. Body mass index (BMI) values were greater than 30 kg/m2 in obese subjects. All obese subjects and controls were evaluated by standard physical examination, chest X-ray, baseline ECG, exercise ECG, 2D echocardiography and routine clinical laboratory tests, including liver and kidney function tests. None of the obese subjects had liver dysfunction, diabetes mellitus, heart failure, or renal failure.

Control subjects underwent routine physical and laboratory evaluations to ensure that none had diabetes mellitus, hyperlipidemia, psychiatric, metabolic, hepatic or renal disease. None of the control subjects had a family history of hyperlipidemia or diabetes. All subjects gave informed consent for participating in the study. The study was approved by the local ethics committee of Gülhane School of Medicine.

BMI was calculated as kg/m2. Waist circumference was measured at the level of the umbilicus with the subjects standing and breathing normally. Hip circumference was measured at the level of the greatest hip girth. The waist-to-hip ratio was used as an indicator of body fat distribution.

Systolic and diastolic blood pressures were measured three times in each participant with a standard mercury sphygmomanometer on the right arm. The mean of the three measurements was used in the analyses. Subjects were asked to refrain from smoking and physical activity for at least 30 min before the blood drawing. The blood tubes used were immediately protected from light and kept at 4°C until processing, which occurred within 30 min of phlebotomy. The samples were then frozen at −80°C until batch determinations were made. Batch determinations were carried out within 30 days of the blood drawing.

Fasting blood samples were collected from patients and controls between 08:00 and 08:30 am after a 12 h fasting for measurement of blood glucose, total cholesterol, triglyceride, VLDL, and HDL. Fasting blood glucose was measured by glucose oxidase -peroxidase calorimetric method using a Bayer Dax-48 system analyzer (Bayer Diagnostics Corporation, West Haven, CT, USA). Total plasma cholesterol, TG and HDL cholesterol were measured by enzymatic colorimetric method with Olympus AU 600 autoanalyzer using reagents from Olympus Diagnostics, GmbH (Hamburg, Germany). VLDL was isolated by ultracentrifugation, and VLDL cholesterol was determined enzymatically. LDL cholesterol was calculated by Friedewald’s formula. Insulin was measured by chemiluminescent enzyme immunoassay (a solid-phase, two-site sequential chemiluminescent immunometric assay) using commercial kits from Bayer Diagnostic Corporation, West Haven, CT, USA.

Blood samples were drawn after overnight fasting from antecubital vein and collected in heparinized polypropylene tubes. Plasma and erythrocytes were separated and used for measuring trace elements and antioxidant enzymes. Erythrocyte CuZn-SOD and GSH-Px activity were measured in a UV-VIS Recording Spectrophotometer (UV-2100S, Shimadzu Co., Kyoto, Japan) as previously described by Aydin et al. [11]. Erythrocyte Zinc (Zn), copper (Cu), and iron (Fe) levels were measured by flame atomic absorption spectrophotometry using Varian Atomic Absorption Spectrophotometer (30/40 model, Varian Techtron Pty Ltd., Victoria, Australia). Used wavelengths were as follows: 213.9 nm wavelength for Zn, 324.7 nm wavelength for Cu and 248.3 nm for Fe.

Erythrocyte TBARS levels were determined in erythrocyte lysates obtained after centrifugation and in accordance with the method described in our previous study [11]. After the reaction of thiobarbituric acid with MDA, the reaction product was measured spectrometrically.

All the statistical analysis were performed by using SPSS 10.0 (SPSS Inc., Chicago, IL, USA) statistical package. Multivariate regression analysis and Mann-Whitney U test was used according to the distribution of the data. p ≤ 0.05 was considered statistically significant. All results are presented as mean ± standard deviation (SD) [12].

Section snippets

Results

Table 1 shows the biochemical values, antioxidants, MDA, and trace elements in obese patients and normal control subjects. The mean weight, BMI, waist, hip, waist to hip ratio, systolic and diastolic blood pressure; plasma insulin, glucose, triglyceride, total cholesterol, LDL, and VLDL concentrations were higher in obese than in nonobese healthy subjects (p = 0.001). The mean plasma HDL levels, erythrocyte CuZn-SOD and GSH-Px activities were significantly lower (p = 0.001), whereas erythrocyte

Discussion

Our findings demonstrate that activities of erythrocyte CuZn-SOD and GSH-Px are decreased, TBARS levels are increased, and plasma levels of Zn are low in obese adult men. Lin et al. [9] demonstrated that obese mice had lower concentrations of zinc and cadmium in the serum, hair, liver and carcass than lean mice, but no difference was found in the brain. Our data confirm the existence of similar changes in obese inidviduals. Conversely, Kennedy et al. [7] demonstrated that lower concentrations

Acknowledgements

We are grateful to Dr. Gokhan Ozisik, Dept. of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School,Chicago, IL, for critical review of the manuscript.

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