Article

Paraoxonase (PON)-1 Activity in Overweight and Obese Children and Adolescents: Association with Obesity-Related Inflammation and Oxidative Stress.

Authors:
  • Oogziekenhuis Zonnestraal, Amsterdam, The Netherlands
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Abstract

Background: Paraoxonase-1 (PON1) is a HDL-attached extracellular esterase which is believed to contribute to the anti-atherogenic and anti-inflammatory properties of HDL. A decrease in PON1 is a risk factor for cardiovascular disease and has recently been found to be associated with juvenile obesity. The issue of a possible association between enzyme activity and/or its phenotype distribution and obesity-related metabolic abnormalities, inflammation, and oxidative stress has not been addressed yet. Objectives: To evaluate PON1 activity and phenotype distribution with respect to obesity and obesity-related metabolic disorders, inflammation and oxidative stress in children and adolescents. Material and methods: PON1 arylesterase activity was measured spectrophotometrically in 156 children and adolescents (47 lean, 27 overweight and 82 obese). Enzyme phenotype was determined using dual substrate (phenyl acetate/paraoxon) method. PON1 activity and phenotype distribution were related to the presence of obesity, metabolic syndrome, insulin resistance, hyperinsulinemia, hypertriglyceridemia, high blood pressure, low HDL level, impaired fasting glucose and/or glucose tolerance as well as inflammatory and oxidative stress indices. Results: PON1 arylesterase activity decreased in general and central obesity, high blood pressure, and hyperinsulinemia conditions and correlated with BMI, CRP, adipocyte fatty acid-binding protein, superoxide dismutase, catalase, glutathione peroxidase, free thiols, and HOMA in a gender-dependent manner. PON1 decreases were independently associated with central obesity in girls, explaining 17% in PON1 variability, and with elevated CRP in boys, explaining 12% in its variability. PON1 phenotype was not associated with frequency of metabolic abnormalities. Conclusions: PON1 decreases in central obesity, exacerbating obesity-related inflammation and oxidative stress. The enzyme associations are gender-dependent: obesity and oxidative stress affects PON1 in girls whereas inflammation in boys.

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... Paraoxonase-1 (PON-1) is a HDL-attached extracellular esterase that contributes to the antiatherogenic, antioxidant, and anti-inflammatory properties of HDL. 132 A decrease in PON-1 is a risk factor for CVD and has recently been found to be associated with obesity. 133 Activation of the NOX system and reninangiotensin system and stimulation of proinflammatory cytokine release also induce ROS production and the progression of vascular disease. ...
... 138 Higher Ox-LDL in obese subjects may be due to lower serum activity of antioxidant enzymes 139 or reduced PON-1 levels. 132 Obesity, oxidative stress, and carcinogenesis. In vivo studies. ...
Article
Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk factors, and potential strategies to regulate body weight loss/gain for better health benefits.
... 11---13,16,23---25 No entanto, poucas referiram aumento da enzima associada ao IMC conforme observado no atual estudo. 13,24,25 As divergências quanto ao efeito do IMC sobre a enzima podem decorrer da idade dos indivíduos selecionados, uma vez que muitas amostras misturam crianças e adolescentes. A obesidade nessas duas fases da vida cursa com diferenças que vão desde o tempo de exposição ao aumento do tecido adiposo, do nível das citocinas pró--inflamatórias até o status hormonal. ...
... 11,23---25 Um maior tempo de exposição ao excesso de peso e um aumento do estado inflamatório, ainda que esse seja de baixo grau, podem refletir num efeito inibitório sobre a enzima. 25,26 Porém, na infância o aumento de peso e de formação de espécies reativas de oxigênio poderiam ser compensados pela elevação da enzima. 13 Convém registrar que a natureza complexa da obesidade limita as especulações, pois além dos aspectos citados ainda há influências do estilo de vida e da atividade física. ...
Article
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Objective The cardioprotective enzyme paraoxonase‐1 (PON1) suffers an important influence from genetic polymorphisms and nutritional factors. The aim of this study was to investigate the influence of diet, nutritional status, and the C(‐107)T polymorphism on PON1 arylesterase activity in children. Methods This was a cross‐sectional study with 97 children, aged between 5 and 8 years, of both genders, from a pediatric outpatient clinic in southern Brazil. A sociodemographic, behavioral, and food consumption questionnaire was applied, and anthropometric measurements and laboratory blood samples were taken. PON1 arylesterase activity was measured by phenol extinction (U/mL), and DNA extraction and analysis of the PON1 C(‐107)T polymorphism were performed. The Hardy–Weinberg equilibrium was tested with the chi‐squared test and linear regression was used to estimate PON1 activity according to four adjustment models, with an acceptable error of 5%. Results In the sample, the male gender accounted for 50.5%, 39.2% were 6 years of age, 54.5% had normal weight, and 51.5% had PON1 activity below the median (90.0, 15–30 U/mL). Genotype frequency was 54.6% (53/97), 31.0% (30/97), and 14.4% (14/97), respectively, for CT, CC, and TT, consistent with the Hardy–Weinberg equilibrium (p = 0.22). In the regression analysis, the model that included sociodemographic variables as well as frequency of consumption of fruits, vegetables, legumes, dairy products, and beans estimated a variability of 14.8% in PON1 activity combined with the PON1 C(‐107)T polymorphism. Conclusions During childhood, a good‐quality diet with greater inclusion of healthy foods was important to predict the activity of the cardioprotective enzyme PON1 combined with the C(‐107)T polymorphism of the PON1 gene.
... In obese adults, both low (18)(19)(20)(21) or unchanged levels of Po.ase and Ar.ase (22) have been reported. Similarly, in obese children and adolescents, either low (11,23,24), unaffected levels of Po.ase and Ar.ase (25)(26)(27) or incresed levels of Ar.ase (28) have also been observed. Recently, unchanged (25) or reduced (14) levels of Lct.ase activity (assayed with dihydrocoumarin and 5-thiobutyl butyrolactone, respectively) have been reported in obese children. ...
... HDL lipidic and proteic components interact in order to promote PON1 secretion as well as maintaining its stability in the blood stream (30). As in our study, reduced HDL levels have been previously reported in obese children (11,13,14,23,25). These alterations have been attributed to both an enhancement in the uptake of HDL by the adipocytes and an increase in the apoA-I catabolism in HDL particles. ...
Article
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Serum paraoxonase-1 (PON1) binds mainly to high density lipoproteins (HDLs) and protects low density lipoproteins (LDLs) against oxidation. While paraoxonase and arylesterase activities are traditionally assayed, lactonase activity, accounting for protection against LDL oxidation, was less investigated in obese children and adolescents. Therefore, we aimed to measure lactonase, paraoxonase and arylesterase activities, oxidized LDL (ox-LDL) and malondialdehyde (MDA) levels in obese children and adolescents. Study population included 68 children (35 obese and 33 normal-weight). Arylesterase and paraoxonase activities were assayed spectrophotometrically. Lactonase activity, ox-LDL and MDA levels were measured using a pH-sensitive colorimetric assay, an ELISA technique and a fluorimetric method, respectively. The lipid profile was assessed by common methods. Lactonase and arylesterase activities were decreased in the presence of obesity. MDA, but not ox-LDL levels, showed significant differences between groups. Multiple regression analysis identified a reciprocal relationship and a possible association between lactonase and arylesterase activities and obesity.
... Paraoxonase-1 (PON-1) is a multipurpose antitoxic and antioxidant enzyme and is believed to contribute to the antioxidant and anti-inflammatory properties of HDL [94,95]. In particular, it can reduce lipid peroxidation and protect LDL and tissue from oxidative stress [96]. ...
... In a study of lean, overweight and obese adolescents, decreased levels of PON-1 were associated with central obesity and metabolic syndrome. Additionally, lower levels of PON-1 were associated with hypertension, hypertriglyceridemia, insulin resistance, impaired glucose tolerance, and increased oxidative stress [94]. Another study of women with and without metabolic syndrome showed a negative correlation between PON-1 levels and the presence of CAD in metabolic syndrome patients [96]. ...
Article
Introduction: Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic syndrome and this panel can aid in early detection and management of metabolic syndrome in high risk populations, such as in West Virginia. Methods: A literature review was conducted using PubMed, Science Direct, and Google Scholar to search for markers related to metabolic syndrome. Biomarkers searched included adipokines (leptin, adiponectin), neuropeptides (ghrelin), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-10), markers of antioxidant status (OxLDL, PON-1, uric acid), and prothrombic factors (PAI-1). Results: According to the literature, the concentrations of pro-inflammatory cytokines (IL-6, TNF-α), markers of pro-oxidant status (OxLDL, uric acid), and prothrombic factors (PAI-1) were elevated in metabolic syndrome. Additionally, leptin concentrations were found to be elevated in metabolic syndrome as well, likely due to leptin resistance. In contrast, concentrations of anti-inflammatory cytokines (IL-10), ghrelin, adiponectin, and antioxidant factors (PON-1) were decreased in metabolic syndrome, and these decreases also correlated with specific disorders within the cluster. Conclusion: Based on the evidence presented within the literature, the aforementioned biomarkers correlate significantly with metabolic syndrome and could provide a minimally-invasive means for early detection and specific treatment of these disorders. Further research is encouraged to determine the efficacy of applying these biomarkers to diagnosis and treatment in a clinical setting.
... La PON-1 es una enzima lipolactonasa asociada con el C-HDL capaz de prevenir la elevación de LDL y la oxidación de la membrana celular; por lo tanto, se considera que es una enzima ateroprotectora 63 . Se cree que las reducciones en la actividad del C-HDL y de la PON-1 se encuentran en varias enfermedades con componentes inflamatorios; esta condición conduce a niveles disfuncionales de C-HDL, lo que conlleva inflamación y aterosclerosis 64 . ...
... En un estudio con adolescentes con sobrepeso y obesidad se encontró que los niveles disminuidos de PON-1 se asociaban a obesidad central y SM. Además, los niveles más bajos de PON-1 se asociaron con hipertensión arterial, hipertrigliceridemia, RI, tolerancia a la glucosa alterada y aumento del estrés oxidativo 63 . La literatura sugiere que la PON-1 podría desempeñar un papel importante en la atenuación de los componentes del SM que surgen como resultado del estrés oxidativo. ...
... Peroxidation of lipids can be limited by the activity of paraoxonase-1 (PON-1) [15][16][17]. PON-1 is a HDL-bound and calcium-dependent extracellular hydrolase [18][19][20][21], produced in the liver and secreted into the bloodstream [11]. This enzyme has the ability to delay or inhibit the initiation of lipoproteins oxidation induced by metal ions and to hydrolyse preformed lipid hydroperoxides [20,21]. ...
... The activity of this enzyme was shown to be modulated under oxidative stress conditions, such as exposure to tobacco smoke xenobiotics [18]. It was also recognized as an agent modulating antioxidative and anti-inflammatory role of HDL [19][20][21]. Due to its potential ability to hydrolyse proinflammatory mediator-plateletactivating factor (PAF), PON-1 may exert anti-inflammatory effects [15,24]. ...
Article
Aim: The study investigated the extent to which tobacco smoke exposure causes changes in lipids biochemistry through measurement blood concentrations of: paraoxonase-1 (PON-1) activities as lipid-bound enzyme into cell membrane, concentration of malonyldialdehyde (MDA), protein adducts of 4-hydroxynonenal (HNE-adducts), oxidized low density lipoproteins (oxLDL), total cholesterol (CH) and high-density lipoprotein cholesterol (HDL). Additionally, the activity of P isoform of glutathione S-transferase (GST-π) was measured. Methods: Investigations were performed in the blood of patients with acute pancreatitis (AP) on the 1 st , 3 rd and 7 th day of hospitalization and in healthy volunteers. The activities of PON-1 forms, GST-π were determined spectrophotometrically. Concentrations of PON-1, MDA, HNE-adducts, oxLDL, HDL, CH were measured using commercial tests. Results: Near 2-fold higher concentrations of MDA, HNE-adducts, oxLDL, correlating with inflammatory markers in AP patients compared to healthy subjects were demonstrated, which were accompanied by gradually increasing CH/HDL ratio during hospitalization. During hospital treatment, decreased activities of all PON-1 subtypes were observed in AP patients compared to healthy subjects, more pronounced in tobacco smokers. A decreased PON-1 phosphotriesterase activity in non-AP control group smokers compared to non-smokers was noted. In non-smoking AP patients GST-π activity normalized during hospitalization in contrast to smokers. Conclusions: GST-π and PON-1 phosphotriesterase activities seem to be a sensitive marker of pro/antioxidative imbalance in smokers. Lipids peroxidation products generated during AP can intensify preexisting inflammation. Increasing stay in the hospital was associated with worsening of lipids peroxidation markers and the parameters of lipid profile, in both non-smoking and smoking AP patients, what can indicate that the oxidative-inflammatory process are not extinguished.
... 11---13,16,23---25 However, few have reported an increase in the enzyme associated with BMI, as observed in the current study. 13,24,25 Divergences regarding the BMI effect on the enzyme may be due to the age of the selected individuals, since many samples include both children and adolescents. Obesity in these two phases of life courses with differences that range from the time of exposure to adipose tissue increase, to the level of proinflammatory cytokines, to hormonal status. ...
... 11,23---25 A longer time of exposure to excess weight and an increase in the inflammatory status, even if it is of a low degree, may result in an inhibitory effect on the enzyme. 25,26 However, in childhood, the weight increase and the formation of reactive oxygen species could be compensated by the increase in the enzyme. 13 It should be noted that the complex nature of obesity limits speculation, since in addition to the aforementioned aspects, there are also the influence of lifestyle and physical activity. ...
Article
Full-text available
Objective The cardioprotective enzyme paraoxonase-1 (PON1) suffers an important influence from genetic polymorphisms and nutritional factors. The aim of this study was to investigate the influence of diet, nutritional status, and the C(-107)T polymorphism on PON1 arylesterase activity in children. Methods This was a cross-sectional study with 97 children, aged between 5 and 8 years, of both genders, from a pediatric outpatient clinic in southern Brazil. A sociodemographic, behavioral, and food consumption questionnaire was applied, and anthropometric measurements and laboratory blood samples were taken. PON1 arylesterase activity was measured by phenol extinction (U/mL), and DNA extraction and analysis of the PON1 C(-107)T polymorphism were performed. The Hardy–Weinberg equilibrium was tested with the chi-squared test and linear regression was used to estimate PON1 activity according to four adjustment models, with an acceptable error of 5%. Results In the sample, the male gender accounted for 50.5%, 39.2% were 6 years of age, 54.5% had normal weight, and 51.5% had PON1 activity below the median (90.0, 15–30 U/mL). Genotype frequency was 54.6% (53/97), 31.0% (30/97), and 14.4% (14/97), respectively, for CT, CC, and TT, consistent with the Hardy–Weinberg equilibrium (p = 0.22). In the regression analysis, the model that included sociodemographic variables as well as frequency of consumption of fruits, vegetables, legumes, dairy products, and beans estimated a variability of 14.8% in PON1 activity combined with the PON1 C(-107)T polymorphism. Conclusions During childhood, a good-quality diet with greater inclusion of healthy foods was important to predict the activity of the cardioprotective enzyme PON1 combined with the C(-107)T polymorphism of the PON1 gene.
... Serum PON1 binds to high density lipoprotein (HDL) and contributes to the elimination of organophosphorus compounds and free radicals. PON1 is one of the endogenous free-radical scavenging systems in the human organism (1,2). Serum PON1 and ARE have been demonstrated to function as a single enzyme (3). ...
... HDL-associated PON1 and ARE are among the enzymes involved in such systems. These enzymes contribute to the detoxification of organophosphorus compounds and carcinogenic lipid-soluble radicals from lipid peroxidation (1)(2)(3). Studies have revealed that PON1 expression is alleviated in human lung cancer (23), pancreatic (24), and gastric cancer (25). Accordingly, in our study, we found PON1 and ARE activities to be significantly lower in the MM, CRC and BC patients compared to the healthy subjects. ...
Article
Full-text available
Background: Human serum paraoxonase-1 (PON1) shows wide variation among different ethnic groups around the world. The aim of the present study was to determine the phenotype distribution and enzymatic activity of PON1 and ARE (arylesterase) in colorectal cancer (CRC), bladder cancer (BC) and multiple myeloma (MM) patients compared to healthy subjects. Methods: A total of 160 subjects (40 CRC patients, 40 BC patients, 40 MM patients and 40 healthy controls) were admitted to the study. The phenotype distribution of PON1 was determined by using the dual substrate (paraoxon and phenylacetate) method. Results: PON 1 and ARE activities were significantly lower in the cancer patients compared to the control group. The following phenotype distributions were assessed in the cancer and control groups: MM: 52.5% (QQ), 40% (QR), 7.5% (RR); CRC: 52.5% (QQ), 40% (QR), 7.5% (RR); BC: 55% (QQ), 35% (QR), 10% (RR); and controls: 40% (QQ), 57.5% (QR), 2.5% (RR). Conclusions: We found that MM, CRC and BC patients were associated with lower PON1, ARE and stPON1 enzyme activities compared to the healthy subjects. However, PON1 phenotypes were similar between the cancer groups and control group.
... By modulating the oxidation of LDL, PON1 abolishes the oxidized LDL stimulated induction of monocyte-chemotactic protein-1 (MCP-1) production by endothelial cells, thereby preventing monocyte/endothelial cell interaction in one of the earliest processes of atherosclerosis [12,13]. Previous studies by us and by other authors have demonstrated that PON1 is significantly lower in obese patients [4,[14][15][16]. We also investigated the levels of leptin in cord blood and maternal blood. ...
... This is the first study addressed to PON1 activity in obese pregnant women and in cord blood of their newborns. Previous studies by us and by other authors have shown a lower PON1 activity in obese subjects [4,[14][15][16]. We confirmed a lower PON1 activity in obese women at eight month of pregnancy. ...
Article
Full-text available
Abstract Objective Obesity and / or psychopathological disorders of parents represent risk factors for childhood obesity. The aim of the study was to investigate the link between obesity in pregnancy and oxidative stress. Methods. Venous blood was collected from 37 women at the eighth month of gestation (19 obese e 28 normal weight). Cord blood was obtained at birth from newborns of obese mothers and controls. Cord blood and maternal blood was used to separate plasma to be used for the evaluation of leptin, oxidized LDL and paraoxonase (PON1) activity. Results Higher levels of leptin were observed both in maternal blood and cord blood of children of obese women compared to normal weight women. The data showed also lower levels of PON1 activity in plasma of obese women and in the cord blood of their children. Furthermore, a positive correlation was established between levels of PON1 activity in maternal blood and cord blood, suggesting a relationship between PON1 in maternal plasma and fetal cord blood. Conclusions Essential obesity in pregnancy is associated with hyperleptinemia. PON1 exerts an antioxidant role therefore our results demonstrated that obesity exposes to an increased susceptibility to oxidative damage in both mothers and newborns.
... Increasing oxidative status involves changes in PON1 and ARE activities [21,22]. The antioxidant effect of PON1 and ARE has been defined as preventing the oxidation of LDL and preventing oxygen radical damage to the cell membrane [23,24]. The decrease in activity of the enzymes PON1 and ARE in this study shows obesity-related compromise of the antioxidant system. ...
Article
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Obesity is known to lead to complications involving several systems. The basic mechanism in obesity-related complications is chronic inflammation and increased oxidative stress. Trace element levels in obese children may vary due to poor nutritional habits. The purpose of this study was to investigate the relation between serum paraoxonase (PON1) and arylesterase (ARE) levels, markers of the oxidant-antioxidant balance in the body, and serum zinc (Zn), copper (Cu), manganese (Mn), and selenium (Se) concentrations in obese children. Fifty-seven overweight patients aged 6-17 and 48 age- and sex-matched healthy children were included in the study. Serum PON1 and ARE activity levels were measured, together with Cu, Zn, Mn, Se, total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, glucose, aspartate amino transferase, and alanine amino transferase levels. PON1 and ARE activity levels were significantly lower in obese patients compared to those in healthy individuals (P < 0.05). Various changes were determined in Cu, Zn, Mn, and Se levels between the study and control groups (P < 0.05). In terms of the relation between trace elements and PON1 and ARE levels, a significant positive correlation was determined between serum Se and PON1 levels in the study group (P < 0.05, r = 0.31). No significant correlation was determined between other trace element levels and PON1 and ARE levels (P > 0.05). In conclusion, the detection in our study of a positive correlation between Se and PON1 levels in obese children may be significant in terms of showing a relation between Se and antioxidant systems in obese children.
... Пацієнти з гіпертонічною хворобою (ГХ) мають більш високу продукцію гідропероксиду ліпідів. Крім того, існує кореляція між активацією реніну і підвищеним окислювальним стресом, що може свідчити про те, що ангіотензин II є стимулятом оксидантного стресу при АГ [17][18][19][20]. ...
... PON1 is an enzyme that influences HDL antioxidant capacity, and its activity was found to be diminished in obese children compared with normal weight children. 38,39 The implications of these glycoprofile changes associated with SQ-LNS in the context of growth and development in lowerincome settings are currently unknown, and further work on their mechanism is needed. ...
Article
Full-text available
Prenatal plus postnatal small-quantity lipid-based nutrient supplements (SQ-LNS) improved child growth at 18 months in the International Lipid-Based Nutrient Supplements DYAD trial in Ghana. In this secondary outcome analysis, we determined whether SQ-LNS versus prenatal iron and folic acid (IFA) supplementation improves the cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) particles and alters their lipidomic, proteomic, or glycoproteomic composition in a subset of 80 children at 18 months of age. HDL CEC was higher among children in the SQ-LNS versus IFA group (20.9 ± 4.1 vs 19.4 ± 3.3%; one-tailed p = 0.038). There were no differences in HDL lipidomic or proteomic composition between groups. Twelve glycopeptides out of the 163 analyzed were significantly altered by SQ-LNS, but none of the group differences remained significant after correction for multiple testing. Exploratory analysis showed that 6 out of the 33 HDL-associated proteins monitored differed in glycopeptide enrichment between intervention groups, and 6 out of the 163 glycopeptides were correlated with CEC. We conclude that prenatal plus postnatal SQ-LNS may modify HDL protein glycoprofiles and improve the CEC of HDL particles in children, which may have implications for subsequent child health outcomes. This trial was registered at clinicaltrials.gov as NCT00970866.
... Many authors have found that there is a reduction in serum PON1 activity in obese children and adolescents compared to those of normal weight [5,12,18,25,26]. Our results are consistent with others [27,28] that assessed children of a very similar age group, and found that PON1 activity was higher in obese children than in those of normal weight. ...
Article
Full-text available
Background Paraoxonase 1 (PON1) is an enzyme that possesses anti-atherogenic and anti-inflammatory properties with serum levels determined by genetic and exogenous factors. Lower serum PON1 arylesterase activity is associated to metabolic alterations related to childhood overweight and onset and/or development of diabetes and CVD later in life. However, data on the relationship between genetic PON1 polymorphisms and nutritional status as well as lipid profile in children are limited.To investigate the distribution of the C(−107)T PON1 gene polymorphism and its relation with serum PON1 enzyme activity, nutritional status and lipid profile in children. MethodsA cross-sectional study was performed including 73 children aged 5 to 7 years who attended public pediatric clinics. PON1 C(−107)T, arylesterase activity, body mass index for the age, and serum lipid profile were evaluated. ResultsPON1 activity was higher in overweight children compared to the normal weight ones (p = 0.02). The genotypic frequency did not differ between the two groups (p > 0.05). Carriers of CC genotype had higher enzyme activity than T allele carriers, and this difference was greater among normal weight children. HDL levels were higher among normal weight children carrying CC genotype, compared to those carrying the T allele (p < 0.01). Conclusion The PON1 C(−107)T polymorphism is associated with higher serum enzyme activity in children, as observed previously in adults. In addition, this polymorphism also shows association to higher high density lipoprotein (HDL) levels and serum PON1 arylesterase activity in the normal weight children studied.
... For example, Ox-LDL decreases the release of adiponectin, which inhibits ROS synthesis [101]. Increased Ox-LDL in obese patients with dyslipidemia may be due to loss of antioxidant capacity caused by low serum activity of the antioxidant enzyme (SOD) [12] or low HDL-associated paraoxonase-1 (PON-1), HDL attached extracellular esterase which contributes to the anti-atherogenic, anti-oxidant and anti-inflammatory properties of HDL [102]. Moreover, an increase in Ox-LDL could also be due to increased oxidant capacity, for example, by elevated expression of NOX2, which, in turn, induces further decreased production of adiponectin, increased pro-inflammatory cytokines levels, and generation of ROS in vascular and immune cells circulating in blood vessels. ...
Article
Full-text available
Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS). Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases.
... [13][14][15] Besides, PON1 could be employed as a biomarker for inflammation and kidney diseases. [16,17] Lipids metabolic disturbance is an important pathogenesis of ONFH. Apolipoprotein A and B are 2 key proteins for lipid metabolism which are involved in the onset of ONFH. ...
Article
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The purpose of this study was to investigate the relationship between Paraoxonase-1 (PON1) gene rs662, rs854555 polymorphisms and osteonecrosis of the femoral head (ONFH) in Han population, northern China. Polymerase chain reaction-restriction fragment length polymorphism was used to determine genotypes of PON1 polymorphisms in 84 patients with ONFH and 96 healthy persons. χ² test was used to compare distribution differences of genotype, allele, and haplotype between the case and control groups. The odds ratio (OR) and 95% confidence interval (CI) were calculated to reveal the effects of PON1 polymorphisms on risk of ONFH, and the results were adjusted using logistic regression analysis. The linkage disequilibrium and haplotype analysis were performed with haploview software. That people carrying AA genotype of rs662 were easier to be attacked by ONFH than GG genotype carriers (OR = 2.53, 95% CI = 1.05–6.07, P = .038). Meanwhile, the frequency of A allele in the case group was significantly higher than the controls and it was a risk factor for ONFH (OR = 1.56, 95% CI = 1.03–2.38, P = .038). The A-A haplotype frequency of rs854555-rs662 in PON1 was significantly correlated to the increased susceptibility to ONFH (OR = 2.74, 95% CI = 1.28–5.84). The rs662 polymorphism in PON1 may be associated with ONFH susceptibility, but not rs854555 in Han population, northern China. Additionally, haplotype is also a nonignorable risk factor.
... This syndrome becomes a basic risk for the development of obesity among children. Currently 40-45% of youngsters are caught by this developing issue [87]. Oxidative stress is also a main disorder that leads towards obesity and can cause numerous diseases including hypertension and dyslipidemia. ...
Chapter
Abstract: Obesity is characterized by an excessive accumulation of white adipose tissue (WAT) causing increases in body weight and Body Mass Index (BMI >30 kg/m2). WAT stores energy and releases free fatty acids, but it is also a dynamic endocrine organ that triggers the production of a wide array of bioactive products such as adipokines, leptin, tumor necrosis factor (TNF-a), cytokines and interleukins (IL-1, IL-6, IL-11). Adipokines regulate appetite, insulin sensitivity, angiogenesis, blood pressure and immune response. Leptin reduces body weight. TNF-a, cytokines and interleukins are pro-inflammatory and activate atherosclerosis and oxidative stress, leading to the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS adversely affects structure and function of cellular membrane and damages DNA. Obesity can be seen as the mother of numerous non-communicable chronic diseases, namely: diabetes mellitus, metabolic syndrome, dyslipidemia, several cardiovascular dis eases, nephropathy, neurodegenerative disorders (dementia, Alzheimer’s disease), osteoarthritis, sleep apnea, depression, and enhanced risk of breast and colon cancer, resulting in high morbidity and mortality among obese patients. The burden of healthcare for obesity-related diseases is escalating worldwide. This review highlights the incidences of obesity-related diseases and their preventive strategies through synthetic drugs and alternative therapies such as Ayurvedic remedies, herbal medicines, dietary interventions, nutraceuticals, lifestyle modifications, and psychotherapy. Currently nutraceuticals, probiotics, herbal remedies, and Mediterranean-type diets that are rich in fibers, fresh fruits and vegetables, olive oil, fish, poultry and dairy products are being promoted for the prevention and management of obesity-related chronic diseases and metabolic pathologies. Anti-obesity drugs assist with weight reduction by reducing appetite or decreasing the absorption of carbohydrates and saturated fats in the gut. Naturally occurring dietary polyphenols, nutraceuticals, and bioactive ingredients present in plants and spices (resveratrol, green tea catechins, quercetin, berberine, turmeric, cinnamon, red chili, black pepper, fenugreek, thymol, rosemary) are recommended for their anti-obesity actions produced through metabolism stimulation. Phytotherapies or botanical extracts attenuate adipose tissue expansion and cause adipocyte remodeling by altering inflammation-related mechanisms. Several plant-derived remedies such as Ginko biloba, Momordica charantia, Aegle marmelos, Azadirachta indica have anti-oxidant and anti-inflammatory potential, and are indicated for the prevention and treatment of obesity associated metabolic syndrome and chronic diseases such as type 2 diabetes, cancers, kidney pathology, as well as numerous cardiovascular and neurodegenerative disorders. The alternative therapies, healthy foods and exercise interventions are safe and effective therapeutic options to improve metabolism in body and obesity reduction. This review summarizes the mounting evidence that dietary therapies, healthy food habits, and increases in physical activity are helpful in reducing obesity and treating obesity-related complications. The purported underlying mechanisms of complementary and alternative therapies are also discussed. Keywords: Obesity, White adipose tissue, Oxidative stress, Non-communicable chronic diseases, Preventive strategies, Allopathic drugs.
... Besides, there is evidence that showed the association between lower PON-1 levels and abdominal obesity and MetS in pediatrics. The reduced level Hot Topic of this enzyme is also related to some MetS components including blood pressure, high triglyceride, impaired glucose tolerance, and insulin resistance while the decreasing level of PON-1 is related to increased oxidative stress [76]. Another study reported that PON-1 levels are associated with coronary artery disease in women with MetS, inversely [77]. ...
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Metabolic syndrome (MetS) was first defined by Reaven, but its diagnostic criteria are controversial, particularly in children and adolescents. MetS is a common health problem globally, and many studies revealed its association with diabetes and cardiovascular diseases, and hence an agreed definition would be useful. To date, many attempts have been performed to achieve consensus and a more accurate definition by investigating new criteria, and introducing new markers and cutoff values. The prevalence of MetS varies greatly, in part due to the application of these different criteria. This variation in definition makes it difficult for public health professionals to accurately identify and manage MetS in pediatrics. New components in defining MetS, such as hyperuricemia, have been added to the standard criteria. An attempt has also been made to identify reliable biomarkers for the identification of MetS, but these have been inconsistent. Even for standard components including obesity, new cutoff criteria that have been adopted for different ethnicities, and gender, the search for a better understanding of MetS is continuing especially in pediatrics.
... Human serum paraoxonase (PON1) is an HDLassociated esterase capable of hydrolyzing lipid peroxides; thus, it is an anti-inflammatory enzyme that may protect against atherosclerosis (18,19). Decreased PON1 activity has been found in obese children (20) and in children undergoing hemodialysis (21). ...
Article
We undertook this study to evaluate the relationship between PON1, SOD and metabolic syndrome (MetS) in pediatric patients undergoing peritoneal dialysis, hemodialysis and patients in early stages of CKD. We carried out an analytical cross-sectional study of 134 children 6-17 years old. We registered anthropometric variables, vital signs, basic biochemical parameters, intact PTH (iPTH), high sensitivity CRP (hs-CRP), paraoxonase-1; SOD; PON1/HDL-cholesterol and homocysteine. For statistical analyses we used t test, Mann Whitney U test, χ(2), Fisher exact test, linear or logistic regression models, using SPSS v.16.0. p values <0.05 were considered as significant. There were 66 (49.3%) females; 39 (29.1%) had CKD stages 2-4 (predialysis), 42 (31.3%) on hemodialysis (HD) and 53 (39.6%) on automated peritoneal dialysis (PD). Time from diagnosis was 26 months. Significant differences were observed in mean, systolic and diastolic blood pressure, C-peptide, triglycerides, and HDL-cholesterol as well as PON1/HDL-cholesterol ratio and SOD. This study demonstrates that PON1 and SOD may be predictors for the presence of MetS in pediatric patients under treatment with peritoneal dialysis. The positive correlation observed in PON1/HDL-cholesterol ratio may reflect the protector effect of HDL-cholesterol in patients with CKD according with the modality of treatment.
... 12 Previous studies demonstrated that PON1, PAF-AH, and LCAT protect LDL-C from oxidative modification and consequently prevent lipid-peroxide accumulation on LDL-C. Studies have shown that plasma PON1 activity is decreased in several diseases, including coronary artery diseases (CAD), 13 diabetes mellitus, 14 obesity, 15 and renal failure. 16 PON-1 activity is more closely related to the HDL-C concentration. ...
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Background: Coronary heart diseases are inversely related to plasma high-density lipoprotein (HDL) level. Paraoxonase-1 (PON1) is mainly associated with HDL and plays a vital role in protection of low-density lipoprotein (LDL) and HDL. The aim of this study was to investigate the association between paraoxonase activity (PON1) with lipid profile, apoA-І, apoB and apoB/apoA-І ratio in subjects with different level of HDL cholesterol (HDL-C). Methods: 135 subjects, 20–60 years old, contributed to this study. The subjects were divided into three groups (45 in each group) with different levels of HDL-C (High, Normal and Low). For each group, the activity of PON1 was measured using paraoxon as a substrate. Moreover, the serum level of lipid profile, ApoA and apoB were measured. The statistical analysis was performed using SPSS software. Results: PON-1 activity and apoA-І level were decreased in subjects with lower level of HDL-C (P < 0.001). ApoB and apoB/apoA-І ratio were higher in subjects with lower level of HDL-C (P < 0.001). Serum PON-1 activity was positively correlated with TC, TG, apo A-B, and LDL-C levels (P < 0.01). Conclusions: In conclusion, determination of serum PON1 activity and lipoproteins may play important role in earlier prediction of CAD and help to design a therapeutic for treatment of CAD toward PON1 activity regulation.
... The clinical significance of PON1 has been evaluated mainly in cardiovascular diseases (reviewed in [11]). However, diminished enzyme activity has also been observed in infectious diseases (reviewed in [12]) as well as both acute and low-grade inflammatory conditions [13][14][15]. Despite potential relevance of PON1 for sepsis development and progression, data on the enzyme status in sepsis remains scanty. ...
Article
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Oxidative stress and uncontrolled inflammation are hallmarks of sepsis, leading to organ failure and death. As demonstrated in animal studies, oxidative stress can be alleviated by antioxidant therapies. Paraoxonase-1 (PON1) is a serum-based antioxidant, anti-inflammatory agent, detoxifier, and quorum-sensing factor found to be a prognostic marker in sepsis. However, its associations with multiple organ dysfunction syndrome (MODS), a complication of sepsis and the leading cause of death in the surgical intensive care units (ICU), as well as with specific organ dysfunction, infection site, and invading pathogen remain unknown. Therefore, we measured arylesterase activity of PON1 in 87 individuals (35 with MODS) and related it to the clinical type, organ failure, infection site, pathogens, and hematological and biochemical indices of inflammation at admission to ICU and during a five-day follow-up. Suitability of PON1 and its indices derived from a follow-up as biomarkers in MODS was evaluated as well. MODS was associated with decreased PON1, more so in patients with septic shock, displaying an excellent accuracy as a marker of MODS (91%) and a fair one as a marker in differentiating septic shock from severe sepsis (76%). Decreased admission PON1 accompanied cardiovascular insufficiency (CVI), and, as its marker, PON1 displayed a good accuracy (82%). It was also associated with the abdomen as a site of infection but not with an invading pathogen. In multivariate analysis, 50% of variability in PON1 activity in patients with MODS was explained by the patients’ age, CVI, and abdomen as a site of infection. Patients with septic shock, CVI, and abdominal MODS had distinctly different dynamics of PON1 during a follow-up. Mean PON1 activity during the follow-up reflected the associations observed for admission PON1 but was also significantly associated with metabolic dysfunction. Our results show PON1 potential as a biomarker in MODS, particularly as an indicator of CVI.
... In the case of PON1 activity in the context of obesity, some studies have found decreased paraoxonase and arylesterase activities in the obese [11,23,24], whereas others have not [25][26][27]. Similar findings have been observed in children, with some authors observing altered PON1 activities [34][35][36], and others finding no PON1 activity changes in obesity in children [37]. PON1 activity is known to be influenced by environmental factors, such as age, diet or medications, but the main cause of variation is genetics [101]. ...
Article
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Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications.
... In the multivariate analyses, age and BMI are predictors of circulating PON lactonase activity in CKD subjects. This finding is corroborated by previous studies showing that decrease in PON activity is associated with decrease in age [61][62][63][64] and an increase in BMI [65][66][67][68]. Notably, hemodialysis patients show a significant correlation between PON-1 activity and BMI, where obese patients had significantly lower PON-1 paraoxonase activity compared to controls [69]. ...
Article
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The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying the pathogenesis of CKD. We aimed to assess the prognostic value of circulating PON-1 protein and PON lactonase activity on adverse clinical outcomes across various stages and etiologies of CKD. Circulating PON-1 protein levels and PON lactonase activity were measured simultaneously in patients with CKD as well as a cohort of apparently healthy non-CKD subjects. Both circulating PON-1 protein levels and PON lactonase activity were significantly lower in CKD patients compared to the non-CKD subjects. Similarly, across all stages of CKD, circulating PON-1 protein and PON lactonase activity were significantly lower in patients with CKD compared to the non-CKD controls. Circulating PON lactonase activity, but not protein levels, predicted future adverse clinical outcomes, even after adjustment for traditional risk factors. The combination of lower circulating protein levels and higher activity within the CKD subjects were associated with the best survival outcomes. These findings demonstrate that diminished circulating PON lactonase activity, but not protein levels, predicts higher risk of future adverse clinical outcomes in patients with CKD.
... Recently published data have shown conflicting reports, while Krzystek-Korpacka et al. [18] reported that PON1 arylesterase activity decreased in general and central obesity, high blood pressure, and hyperinsulinemia conditions, and was correlated with superoxide dismutase, catalase, and glutathione peroxidase. Desai et al. [19] demonstrated that livers of non-alcoholic steatohepatitis (NASH) patients exhibited elevated mRNA expression of catalase and ...
Article
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Background: Paraoxonase-1 (PON1) enzyme is reported in various types of tissues and linked to numerous pathophysiological disorders. It is a potential biomarker in many pathological conditions such as cardiovascular diseases. Material and methods: We conducted several small-scale studies to evaluate PON1 performance as affected by sample types, storage, and interferences. We also carried out short-term studies to compare the performance of the widely used PON1 assay to the similar commercially available PON1 kit assay method; sample size for the method comparison was N=40, and the number varied for other validation experiments. Results: Our studies using various types of anticoagulants show that samples collected in tubes with NaF, citrate, EDTA, clot activator, and sodium heparin have increased PON1 levels that are 49%, 24.5%, 19.8%, 11.4%, and 8%, respectively, higher compared to serum samples collected in plain tubes. However, samples collected in lithium heparin tubes demonstrated 10.4% lower PON1 levels compared to serum collected in plain tubes. Biological interference such as hemolysis has little effect on PON1 levels; however, samples spiked with lipids have shown 13% lower PON 1 levels. Our studies comparing the PON1 method commonly available for PON1 assay and a similar non-ELISA commercially available PON1 kit method showed a weak Spearman correlation coefficient of R2=0.40 for the range of 104.9-245.6 U/L. Conclusions: The current study provides new validation data on enzyme PON1 performance. While no appreciable change was seen with storage, samples type affects the enzyme performance. Our results should encourage additional clinical studies to investigate other aspects of factors known to affect PON1 enzyme function and performance.
... Reduction of antioxidant defense activity is also a key factor triggering oxidative stress (Li et al., 2016). Previous studies have reported the decrease of antioxidant activity in obese or overweight patients of NAFLD (Krzystek-Korpacka et al., 2013). Supplement with antioxidant may attenuate ROSinduced mitochondrial dysfunction of ob/ob mice (Shin et al., 2019). ...
Article
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Corilagin (Cori) possesses multiple biological activities. To determine whether Cori can exert protective effects against nonalcoholic fatty liver disease (NAFLD) and its potential mechanisms. C57BL/6 mice were fed with high-fat diet (HFD) alone or in combination with Cori (20 mg/kg, i.p.) and AML12 cells were exposed to 200 μM PA/OA with or without Cori (10 μM or 20 μM). Phenotypes and key indicators relevant to NAFLD were examined both in vivo and in vitro. In this study, Cori significantly ameliorated hepatic steatosis, confirmed by improved serum lipid profiles, and hepatic TC, TG contents, and the gene expression related to lipid metabolism in livers of HFD mice. Moreover, Cori attenuated HFD-mediated autophagy (including mitophagy) blockage by restoring autophagic flux, evidenced by increased number of autophagic double vesicles containing mitochondria, elevated LC3II protein levels, decreased p62 protein levels, as well as enhanced colocalization of autophagy-related protein (LC3, Parkin) and mitochondria. In accordance with this, Cori also reduced the accumulation of ROS and MDA levels, and enhanced the activities of antioxidative enzymes including SOD, GSH-Px, and CAT. In addition, Cori treatment improved mitochondrial dysfunction, evidenced by increased mitochondrial membrane potential (ΔΨm). In parallel with this, Cori decreased mitochondrial DNA oxidative damage, while increased mitochondrial biogenesis related transcription factors expression, mitochondrial DNA content and oxygen consumption rate (OCR). In conclusion, these results demonstrate that Cori is a potential candidate for the treatment of NAFLD via diminishing oxidative stress, restoring autophagic flux, as well as improving mitochondrial functions.
... In conditions in which oxidative stress rises, the equilibrium between the oxidant and antioxidant systems in the body is compromised, and PON1 levels decrease. Due to the anti-inflammatory and antioxidant effects of PON1, there may be a decline in enzyme activity directly proportional to the severity of inflammation and oxidative stress in obese children (41)(42)(43). ...
Article
Obesity is known to be associated with many diseases in the long and short terms. Elevated oxidative stress contributes to the development of such obesity-related diseases as dyslipidemia, diabetes mellitus and hypertension. Levels of the endogenous antioxidants paraoxonase and arylesterase have been shown to decrease in such diseases. The purpose of this study was to investigate whether or not changes in lifestyle and metformin therapy would affect serum paraoxonase and arylesterase levels. The study was performed with 25 overweight, 26 obese and 25 morbidly obese patients aged 6–15 years as well as 27 healthy children. Serum paraoxonase (PON1) and arylesterase (ARE) activity levels and total cholesterol, triglyceride, low-density protein, high-density protein, very low-density protein, glucose, aspartate amino transferase and alanine amino transferase levels were measured. Enrolled patients were assessed at initial presentation and again at 6 months. No procedure was performed in the control group, while the overweight, obese and morbidly obese groups were recommended diet and exercise and given metformin therapy (insulin-resistant subjects only). Serum PON1 activity levels in patients with metabolic syndrome were significantly lower than those in individuals without metabolic syndrome (p
... Ferre et al (2013) reported that PON1 may play a role in the onset and development of metabolic alterations in childhood obesity [56]. In a juvenile population, decreased PON-1 activity is potentially relevant for the development of atherosclerosis and this may occur independently from effects on HDL-C [57]. However, some studies found contradictory results, hypothesizing that a regulatory increase of the antioxidant system could be present to compensate for the higher oxidative stress levels [48,58]. ...
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Purpose: To investigate the alterations in nitro-oxidative stress (OS) and antioxidant status in adolescents with metabolic syndrome (MetS) and whether these alterations occur independently from effects of overweight or obesity. Methods: Blood was collected in 47 adolescents with MetS and 94 adolescents without MetS as assessed with the International Diabetes Federation criteria. The International Obesity Task Force (IOTF) criteria were used to classify the subjects into those with overweight or obesity. We measured nitro-oxidative biomarkers including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), and malondialdehyde (MDA), and antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter (TRAP), paraoxonase (PON)-1 activity, thiol (SH-) groups, as well as tumor necrosis factor-α, glucose, insulin, triglycerides, uric acid and high-density lipoprotein cholesterol (HDL-C). Results: Logistic regression analysis showed that increased MDA and NOx and a lowered TRAP/uric acid ratio were associated with MetS. Machine learning including soft independent modeling of class analogy (SIMCA) showed that the top-3 most important features of MetS were increased glucose and MDA and lowered HDL-C. Support vector machine using MDA, glucose, insulin, HDL-C, triglycerides and body mass index as input variables yielded a 10-fold cross-validated accuracy of 89.8% when discriminating MetS from controls. The association between MetS and increased MDA was independent from the effects of overweight-obesity. glucose, insulin, triglycerides and HDL-C. Conclusion: In adolescents, increased MDA formation is a key component of MetS, indicating that increased production of reactive oxygen species with consequent lipid peroxidation and aldehyde formation participate in the development of MetS.
... Ferre et al (2013) reported that PON1 may play a role in the onset and development of metabolic alterations in childhood obesity [56]. In a juvenile population, decreased PON-1 activity is potentially relevant for the development of atherosclerosis and this may occur independently from effects on HDL-C [57]. However, some studies found contradictory results, hypothesizing that a regulatory increase of the antioxidant system could be present to compensate for the higher oxidative stress levels [48,58]. ...
Preprint
Full-text available
Purpose: To investigate the alterations in nitro-oxidative stress (OS) and antioxidant status in adolescents with metabolic syndrome (MetS) and whether these alterations occur independently from effects of overweight or obesity.Methods: Blood was collected in 47 adolescents with MetS and 94 adolescents without MetS as assessed with the International Diabetes Federation criteria. The International Obesity Task Force (IOTF) criteria were used to classify the subjects into those with overweight or obesity. We measured nitro-oxidative biomarkers including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), and malondialdehyde (MDA), and antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter (TRAP), paraoxonase (PON)-1 activity, thiol (SH-) groups, as well as tumor necrosis factor-α, glucose, insulin, triglycerides, uric acid and high-density lipoprotein cholesterol (HDL-C).Results: Logistic regression analysis showed that increased MDA and NOx and a lowered TRAP/uric acid ratio were associated with MetS. Machine learning including soft independent modeling of class analogy (SIMCA) showed that the top-3 most important features of MetS were increased glucose and MDA and lowered HDL-C. Support vector machine using MDA, glucose, insulin, HDL-C, triglycerides and body mass index as input variables yielded a 10-fold cross-validated accuracy of 89.8% when discriminating MetS from controls. The association between MetS and increased MDA was independent from the effects of overweight-obesity. glucose, insulin, triglycerides and HDL-C.Conclusion: In adolescents, increased MDA formation is a key component of MetS, indicating that increased production of reactive oxygen species with consequent lipid peroxidation and aldehyde formation participate in the development of MetS.
... The present study showed an association between decreased serum PON1 activity and MetS in childhood obesity. Our results confirm previous reports in children [29], and in adults with MetS [30,31]. MetS is characterized by several metabolic abnormalities that lead to an increased risk of cardiovascular disease. ...
Article
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To investigate the relationships between serum paraoxonase-1 (PON1), insulin resistance, and metabolic syndrome (MetS) in childhood obesity. We studied 110 obese children and 36 non-obese children with a similar gender and age distribution. We measured serum PON1 activity against 5-thiobutyl butyrolactone (TBBLase) and against paraoxon (paraoxonase). PON1 concentration was measured separately as were the levels of several standard metabolic variables. The homeostasis model assessment (HOMA) index was calculated as an estimate of insulin resistance. TBBLase was significantly decreased in obese children (P=0.008), while paraoxonase activity and PON1 concentrations showed non-significant trends towards decrease and increase, respectively (P=0.054 and P=0.060). TBBLase and paraoxonase specific activities were significantly decreased (P=0.004 and P=0.018, respectively). TBBLase specific activity was inversely associated with BMI, percentage body fat, insulin, HOMA, triglycerides, and C-reactive protein, and directly associated with HDL-cholesterol. Paraoxonase specific activity showed similar associations with BMI, percentage fat, HDL-cholesterol, and C-reactive protein. Obese children with MetS had lower TBBLase activities than obese children without MetS (P=0.018). Linear regression analyses showed that TBBLase was independently associated with HDL-cholesterol, BMI, percentage body fat and PON155 polymorphism, but paraoxonase activity was associated only with PON1192 polymorphism. Our results suggest that PON1 may play a role in the onset and development of metabolic alterations in childhood obesity leading to diabetes and cardiovascular disease later in life. However, being derived from statistical association study, this finding cannot be seen as showing cause-effect.
Article
The SNP rs662 in the paraoxonase 1 gene (PON1 Q192R) has been associated with obesity, dyslipidemia and cardiovascular risk. In this study, DNA samples of 117 children aged 6 to 12 years from San Luis Potosí, México were genotyped for Q192R polymorphism of the PON1 gene. Genotypic frequencies were determined by allelic discrimination assay by real-time PCR using TaqMan fluorogenic probes. Anthropometry, lipid profile, glucose and insulin were analyzed by genotype. The distribution of allele frequency in the population was Q = 65 and R = 35 following the Hardy Weinberg equilibrium (χ(2) = 3.15, p = 0.076). The Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index showed statistically significant differences among QQ/QR/RR genotypes (p = 0.032). The odds ratio for the carriers of the RR genotype was associated with HOMA-IR corresponding to the 95(th) percentile or higher for Mexican children based on sex and age (OR = 4.68; 95% confidence intervals, 1.23-17.8; p = 0.016). When the absolute mean of HOMAR-IR was set as the cutoff, an increased odds was observed (OR = 6.52; 95% confidence intervals, 1.68-25.3; p = 0.008). According to our results, PON1 Q192R polymorphism is a risk marker for insulin resistance, a pathological factor involved in the development of metabolic syndrome. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.
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Reactive oxygen species induce oxidative modification of critical macromolecules. Oxygen derived free radicals may act as potential cytotoxic intermediates inducing inflammatory and degenerative processes, or as signal messengers for the regulation of gene expression. This dual effect mainly depends on the availability of free radicals in terms of concentration, as well as on the environmental characteristics in which they are produced. The formation of free radicals has been proposed to be the linking factor between certain metabolic disturbances and cancer. Circulating mononuclear cells of patients with high cholesterol levels, insulin resistance, metabolic syndrome or obesity present lower levels of antioxidant enzymes and increased concentrations of oxidative stress by-products such as isoprostanes or the DNA oxidized and highly mutagenic base 8-oxo-7,8-dihydro-2'-deoxyguanosine. Overweight or obese subjects also exhibit hormonal changes as a consequence of the increase of mass fat, and these hormonal alterations have been implicated in the alteration of different signal transduction mechanisms and in cell growth and differentiation. A significant correlation has been found between body mass index and cancer. The biological factors and molecular mechanisms implicated in obesity associated cancer susceptibility will be reviewed.
Article
Children are more susceptible to exposures in utero and during early childhood that may result in developmental problems and chronic diseases. Novel discoveries in the field of molecular epidemiology that can help explain susceptibility to exposures and disease will be demonstrated using the multifunctional enzyme paraoxonase 1 (PON1) as an example. The broad PON1 variability in humans, partly due to differences in genetics and age, can confer differential susceptibility because this enzyme can detoxify organophosphate pesticides and has antioxidant properties. Epigenetics plays a significant role in the mediation of the effects of environmental exposure on human health and is hypothesized to be a major contributing factor to the early-life origins of adult disease. Studies highlighted in this review demonstrate the relationship of PON1 polymorphisms with microRNA binding in addition to a link between DNA methylation in the transcriptional regulatory region with changes in PON1 enzyme levels. Other important methodologies such as ancestry informative markers and lactonase activity can enhance studies involving PON1. This PON1 model demonstrates that integrating genetic and epigenetic factors, as well as other novel methodologies, can improve our understanding of important susceptibility factors linked to pediatric disease.
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Oxidative stress (OS) is important in the pathogenesis of atherosclerosis. Paraoxonase-1 (PON1) is an enzyme found in the circulation associated with high-density lipoprotein (HDL). HDL-associated enzyme PON1 has an important role in the attenuation of atherogenic low-density lipoprotein (LDL) oxidation. The aim of this study was to determine PON1 and arylesterase (AREST) enzyme levels in relation to insulin resistance (IR) or obesity among children and adolescents. The study included healthy school children and adolescents. Blood was drawn for the determination of blood glucose, lipid, PON1 and AREST enzyme levels. Overall, we observed a positive correlation between PON1 enzyme activity and high-density lipoprotein cholesterol (HDL-C) levels (r = 0.189, P = 0.014). The correlation appeared to be more significant in boys (r = 0.271, P = 0.009). For subjects with IR and obesity, PON1 enzyme activity did not correlate with HDL-C levels (r = 0.038, P = 0.790), instead PON1 levels correlated negatively with BMI (r = -0.309 and P = 0.026). Multiple linear regression analysis was performed to find the predictors of log PON1 activity. HDL-C level was the strongest predictor of PON1 activity in the lean control group, while BMI appeared to be the strongest predictor in the subjects with obesity or IR. In conclusion, determinants of PON1 enzyme activity are variable in children and adolescents based on IR and obesity. Future studies will shed light on the underlying mechanisms and biomarkers of OS in children and may reveal possible targets for therapeutic intervention.
Article
Objective: Oxidative stress has been reported to be involved in the pathogenesis of metabolic disorders related with obesity. The aim of the study was to investigate the association of oxidative stress and paraoxonase activities with non-alcoholic fatty liver disease (NAFLD) as well as metabolic syndrome. Materials and methods: A total of 109 obese children and adolescents and 44 healthy and lean control subjects were enrolled in the study. According to their ultrasonographic steatosis scores, they were classified into four groups as follows: healthy children; obese, non-NAFLD; obese, grade I-NAFLD; and obese, grade II-III NAFLD. The biochemical parameters and insulin resistance (HOMA-IR) were evaluated from fasting samples. The plasma total antioxidant status (TAS), total oxidant status (TOS), and serum paraoxonase activities were measured and then oxidative stress index (OSI) was calculated as the indicator of degree of oxidative stress. Results: As the steatosis increased, the alanine aminotransferase, C-reactive protein, HOMA-IR, total cholesterol, and LDL cholesterol increased, whereas HDL cholesterol decreased. The TAS measurements were higher in the obese NAFLD group compared with that of the healthy control group. The TOS and OSI measurements did not differ between the groups. Paraoxonase activities increased significantly as steatosis increased. Conclusions: Among the children in this study, no relationship could be demonstrated between obesity with/without steatosis and oxidant/antioxidant status.
Article
Parkinson's disease (PD) is an oxidative stress-mediated neurodegenerative disorder caused by selective dopaminergic neuronal death in the midbrain substantia nigra. Paraoxonase 1 (PON1) is a potent inhibitor of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) against oxidation by destroying biologically active phospholipids with potential protective effects against oxidative stress-induced inflammatory disorders. In a previous study, we constructed protein transduction domain (PTD) fusion PEP-1-PON1 protein to transduce PON1 into cells and tissue. In this study, we examined the role of transduced PEP-1-PON1 protein in repressing oxidative stress-mediated inflammatory response in microglial BV2 cells after exposure to lipopolysaccharide (LPS). Moreover, we identified the functions of transduced PEP-1-PON1 proteins which include, mitigating mitochondrial damage, decreasing reactive oxidative species (ROS) production, matrix metalloproteinase-9 (MMP-9) expression and protecting against 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity in SH-SY5Y cells. Furthermore, transduced PEP-1-PON1 protein reduced MMP-9 expression and protected against dopaminergic neuronal cell death in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model. Taken together, these results suggest a promising therapeutic application of PEP-1-PON1 proteins against PD and other inflammation and oxidative stress-related neuronal diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.
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The growth promoting effect of supplementing animal feed with antibiotics like tetracycline has traditionally been attributed to their antibiotic character. However, more evidence has been accumulated on their direct anti-inflammatory effect during the last two decades. Here we used a pig model to explore the systemic molecular effect of feed supplementation with sub therapeutic levels of oxytetracycline (OTC) by analysis of serum proteome changes. Results showed that OTC promoted growth, coinciding with a significant down regulation of different serum proteins related to inflammation, oxidation and lipid metabolism, confirming the anti-inflammatory mechanism of OTC. Interestingly, apart from the classic acute phase reactants also down regulation was seen of a hibernation associated plasma protein (HP-27), which is to our knowledge the first description in pigs. Although the exact function in non-hibernators is unclear, down regulation of HP-27 could be consistent with increased appetite, which is possibly linked to the anti-inflammatory action of OTC. Given that pigs are good models for human medicine due to their genetic and physiologic resemblance, the present results might also be used for rational intervention in human diseases in which inflammation plays an important role such as obesity, type 2 diabetes and cardiovascular diseases. This article is protected by copyright. All rights reserved.
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In the last few years, several studies have shown a strong association among obesity, altered redox state and inflammation; these studies have also shown that such alterations may be the link between obesity and obesity-related diseases (including Type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease and cancer). Obese subjects usually show high levels of reactive oxygen or nitrogen species, impaired antioxidant defences and increased levels of inflammatory adipokines. Oxidative stress is certainly a result of excessive fat accumulation, but it has also been shown that oxidative stress, per se, leads to weight gain; therefore, it is not easy to establish the correct cause-effect relationship between obesity and oxidative stress. This chapter analyses the main aspects linking oxidative stress to obesity, describing human studies in support of the association between alterations of redox homeostasis and obesity, the molecular mechanisms underlying these modifications and potential non-pharmacological strategies (including weight loss, physical activity, diet, dietary supplementation and microbiota modulation) aimed at reducing oxidative stress in obese individuals.
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The paraoxonases (PONs) are antioxidant enzymes associated with beneficial effects against several diseases and some exposures. Little is known, however, about the role of PONs in human reproduction. This work was conducted to investigate whether any association existed between the activities of the PON enzymes (1, 2, and 3) with the follicular size and fertility parameters in assisted reproduction. The study included 100 subfertile women (patients) and 55 proven fertile women (oocyte donors), all undergoing an ovarian stimulation cycle. Follicular fluid from small (diameter <12 mm) and large (diameter ≥18 mm) follicles was collected from each woman. The PONs were quantified in follicular fluid by immunoblotting. PON1 arylesterase and paraoxonase, PON2 methyl paraoxonase and PON3 simvastatinase activities from both donors and patients were significantly higher (P < 0.001) in follicular fluid from large follicles compared with small ones. In large follicles, PON3 activity was significantly higher (P < 0.01) in donors compared with patients. Follicular fluid PON1 arylesterase and paraoxonase activity was positively correlated with the number of retrieved oocytes in donors. This study shows an increase in the activities of PONs with follicle size, thus providing indirect evidence for the role of PONs in follicle maturation.
Chapter
Osteoarthritis (OA) is a highly prevalent debilitating and painful pathology derived from progressive degeneration of articular joints. Obesity has long been recognized as a significant and potentially preventable risk factor for OA incidence, progression, and disability. Biomechanical loading, together with metabolic and inflammatory imbalances of the joint, strongly contributes to obesity-induced OA pathophysiology. Adipose-tissue derived cytokines—adipokines—have demonstrated roles in modulating pro/anti-inflammatory and anabolic/catabolic joint balance, with implications in cartilage and bone homeostasis. Mechanical stress may lead to considerable increases in proinflammatory mediators within the joint. Therefore, adipokines emerged as potential candidates to link mechanical, metabolic and inflammatory components of obesity-induced osteoarthritis. Herein we summarize the biology of adipokines in joint tissues, highlighting their implications in the dysregulation of joint homeostasis and, thus OA pathogenesis. Many of the aspects of the adipokine network remain largely unknown and further insights into the intimate mechanisms of adipokines activity will be of great relevance to develop disease-modifying osteoarthritis drugs, especially for obese patients.
Chapter
Obesity is characterized by an excessive accumulation of white adipose tissue (WAT) causing increases in body weight and Body Mass Index (BMI >30 kg/m²). WAT stores energy and releases free fatty acids, but it is also a dynamic endocrine organ that triggers the production of a wide array of bioactive products such as adipokines, leptin, tumor necrosis factor (TNF-α), cytokines and interleukins(IL-1, IL-6, IL-11). Adipokines regulate appetite, insulin sensitivity, angiogenesis, blood pressure and immune response. Leptin reduces body weight. TNF-α, cytokines and interleukins are pro-inflammatory and activate atherosclerosis and oxidative stress, leading to the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS adversely affects structure and function of cellular membrane and damages DNA. Obesity can be seen as the mother of numerous non-communicable chronic diseases, namely: diabetes mellitus, metabolic syndrome, dyslipidemia, several cardiovascular diseases, nephropathy, neurodegenerative disorders (dementia, Alzheimer’s disease), osteoarthritis, sleep apnea, depression, and enhanced risk of breast and colon cancer, resulting in high morbidity and mortality among obese patients. The burden of healthcare for obesity-related diseases is escalating worldwide. This review highlights the incidences of obesity-related diseases and their preventive strategies through synthetic drugs and alternative therapies such as Ayurvedic remedies, herbal medicines, dietary interventions, nutraceuticals, lifestyle modifications, and psychotherapy. Currently nutraceuticals, probiotics, herbal remedies, and Mediterranean-type diets that are rich in fibers, fresh fruits and vegetables, olive oil, fish, poultry and dairy products are being promoted for the prevention and management of obesity-related chronic diseases and metabolic pathologies. Anti-obesity drugs assist with weight reduction by reducing appetite or decreasing the absorption of carbohydrates and saturated fats in the gut. Naturally occurring dietary polyphenols, nutraceuticals, and bioactive ingredients present in plants and spices (resveratrol, green tea catechins, quercetin, berberine, turmeric, cinnamon, red chili, black pepper, fenugreek, thymol, rosemary) are recommended for their anti-obesity actions produced through metabolism stimulation. Phytotherapies or botanical extracts attenuate adipose tissue expansion and cause adipocyte remodeling by altering inflammation-related mechanisms. Several plant-derived remedies such as Ginko biloba, Momordica charantia, Aegle marmelos, Azadirachta indica have anti-oxidant and anti-inflammatory potential, and are indicated for the prevention and treatment of obesity associated metabolic syndrome and chronic diseases such as type 2 diabetes, cancers, kidney pathology, as well as numerous cardiovascular and neurodegenerative disorders. The alternative therapies, healthy foods and exercise interventions are safe and effective therapeutic options to improve metabolism in body and obesity reduction. This review summarizes the mounting evidence that dietary therapies, healthy food habits, and increases in physical activity are helpful in reducing obesity and treating obesity-related complications. The purported underlying mechanisms of complementary and alternative therapies are also discussed.
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Metabolic syndrome (MS) has become one of the top major health burdens for over three decades not only due to its effects on cardiovascular health but also its implications in orthopedics. Extensive research has shown that MS is tightly linked to osteoarthritis and inflammation, a process which appears to primarily occur in the subchondral bone via the incidence of bone-marrow lesions (BMLs). Numerous studies identify obesity, dyslipidemia, insulin resistance and hypertension as the top metabolic risk factors, the so-called “deadly quartet”. These factors are responsible for the disruptive physiological processes that culminate in detrimental alterations within the subchondral bone, cartilage damage and, overall, the predominant pro-inflammatory joint microenvironment. Although it has long been thought that osteoarthritis was limited to the cartilage component of the joint, other studies indicate that the disease may originate from the harmful alterations that occur primarily in the subchondral bone, especially via means of vascular pathology. Since metabolic risk factors are manageable to a certain extent, it is therefore possible to decelerate the progression of OA and mitigate its devastating effects on the subchondral bone and subsequent articular cartilage damage. Methods Literature was reviewed using PubMed and Google Scholar in order to find a correlation between metabolic syndrome and osteoarthritic progression. The investigation included a combination of nomenclature such as: “metabolic syndrome”, “obesity”, “insulin resistance”, “hypertension”, “dyslipidemia”, “low-grade systemic inflammation”, “osteoarthritis”, “subchondral bone”, “cartilage” and “inflammatory biomarkers”. Conclusion Based on several studies, there seems to be a significant association between The Deadly Quartet (metabolic syndrome), dysregulation of both pro- and anti-inflammatory biomarkers, and osteoarthritic progression arising from unbridled systemic inflammation.
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Lowered high-density lipoprotein (HDL) cholesterol has been reported in major depressive disorder, bipolar disorder, first episode of psychosis, and schizophrenia. HDL, its major apolipoprotein component, ApoA1, and the antioxidant enzyme paraoxonase (PON)1 (which is normally bound to ApoA1) all have anti-atherogenic, antioxidant, anti-inflammatory, and immunomodulatory roles, which are discussed in this paper. The paper details the pathways mediating the anti-inflammatory effects of HDL, ApoA1 and PON1 and describes the mechanisms leading to compromised HDL and PON1 levels and function in an environment of chronic inflammation. The molecular mechanisms by which changes in HDL, ApoA1 and PON1 might contribute to the pathophysiology of the neuroprogressive disorders are explained. Moreover, the anti-inflammatory actions of ApoM-mediated sphingosine 1-phosphate (S1P) signalling are reviewed as well as the deleterious effects of chronic inflammation and oxidative stress on ApoM/S1P signalling. Finally, therapeutic interventions specifically aimed at improving the levels and function of HDL and PON1 while reducing levels of inflammation and oxidative stress are considered. These include the so-called Mediterranean diet, extra virgin olive oil, polyphenols, flavonoids, isoflavones, pomegranate juice, melatonin and the Mediterranean diet combined with the ketogenic diet.
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Objective To explore the association between Triglyceride/High-density lipoprotein cholesterol (TG/HDL-C) index and these enzymes and proteins in a pediatric population.Methods Children and adolescents (7–14 y old) were recruited (n = 150) and anthropometric data were registered. Glucose, TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C plus cholesteryl ester transfer protein (CETP), lipoprotein-associated phospholipase A2 (Lp-PLA2) and paraoxonase 1 (PON1) activities were determined.ResultsTwenty-five individuals presented TG/HDL-C ratio ≥ 3.0. These individuals exhibited higher TG [164 (126–186) vs. 65 (48–72) mg/dL; p < 0.01] CETP [250 (232–263) vs. 223 (193–237)% mL/min; p < 0.01] and Lp-PLA2 (4.5 ± 1.9 vs. 3.5 ± 1.3; p < 0.05) plus lower HDL-C [41 (37–49) vs. 52 (48–62) mg/dL; p < 0.01] compared to an age-matched group with TG/HDL-C < 3.0. TG/HDL-C ratio was associated to CETP (p < 0.01) and Lp-PLA2 (p < 0.05). Multiple lineal regression analyses showed TG/HDL-C index as an independent predictor of CETP (r2 = 0.29; beta = 0.49; p < 0.01) and Lp-PLA2 (r2 = 0.21; beta = 0.32; p < 0.05) activities.Conclusion Children and adolescents with TG/HDL-C ≥ 3.0 presented a more atherogenic lipid profile and higher CETP and Lp-PLA2 activities, which would indicate alterations in lipoprotein metabolism and quality.
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This study evaluated the effects of ice creams produced from blends of orange (Citrus sinensis) and shaddock (Citrus maxima) peels on the blood lipid profile, glycemic index, and antioxidant indices in the liver and heart of rats. Formulated ice cream was produced at a different proportion of citrus (orange and shaddock) blends and fed to rats for 28 days. The result showed that the formulated ice cream enriched with citrus peels blends caused a significant increase in high-density lipoprotein-cholesterol level in the plasma and antioxidant status in the liver and heart homogenates, decreased the glycemic index, concentration of total cholesterol, triglycerides, and low-density lipoprotein in the plasma as against rats fed on plain and commercial ice creams. To conclude, the use of ice creams from blends of orange and shaddock peels could serve as a functional food for weight reduction, glycemic index, management of lipid-related diseases, and prevention of oxidative stress-related complications in the liver and heart. Practical applications The consumption of ice creams has increased in many parts of the world. However, there have been limited efforts aimed at improving the medicinal properties of frozen dairy products. Hence, these ice creams could be produced on a large scale under regulated condition since they have improved medicinal properties which would be a good option for preventing/combating degenerative conditions and their related complications.
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Background and Aims Childhood obesity is associated to complications such as insulin resistance and dyslipidemia. High density lipoproteins (HDL) constitute the only lipoprotein fraction with ateroprotective properties. The aim of the present study was to analyze inflammatory markers, carbohydrate metabolism, lipid profile and HDL functionality in obese children and adolescents compared to healthy controls. Methods and Results Twenty obese children and adolescents (Body mass index z score >3.0) (9-15 years old) and 20 age and sex similar controls were included in the study. Triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C, apolipoproteins (apo) A-I and B, glucose and insulin levels were quantified. Lipid indexes and HOMA-IR were calculated. Cholesterol efflux (CEC), lipoprotein associated phospholipase A2 (Lp-PLA2), lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein, plus paraoxonase and arylesterase (ARE) activities were evaluated. Obese children and adolescents showed significantly higher TG [69 (45-95) vs 96 (76-121); p<0.05], non-HDL-C [99 ±34 vs 128 ±26; p<0.01], TC/HDL-C [2.8 ±0.6 vs 4.7 ±1.5; p<0.01], TG/HDL-C [1.1 (1.0-1.8) vs 2,2 (1.4-3.2); p<0.01], and HOMA-IR [1.5 (1.1-1.9) vs. 2.6 (2.0-4.5); p<0.01] values, plus Lp-PLA2 activity [8.3 ± 1.9 vs 7.1 ± 1.7 umol/ml.h; p<0,05] in addition to lower HDL-C [57 ±10 vs 39 ±9; p<0.01], apo A-I [143 ±25 vs 125 ±19; p<0.05], and CEC [6.4 (5.1-6.8) vs. 7.8 (5.7-9.5); p<0.01] plus LCAT [12.6 ±3.3 vs 18.7 ±2.6; p<0.05] and ARE [96 ± 19 vs. 110 ± 19; p<0.05] activities. Lp-PLA2 activity correlated with LDL-C (r=0.72,p<0.01), non-HDL-C (r=0.76,p<0.01), and apo B (r=0.60,p<0.01). LCAT activity correlated with triglycerides (r=-0.78,p<0.01), HDL-C (r=0.64,p<0.01), and apo A-I (r=0.62, p<0.05). ARE activity correlated with HDL-C (r=0.32,p<0.05) and apoA-I (r=0.43,p<0.01). CEC was negatively associated with BMI z-score (r=-0.36,p<0.05), and triglycerides (r=-0.28,p<0.05), and positively with LCAT activity (r=0.65,p<0.05). In multivariate analysis, BMI z-score was the only parameter significantly associated to CEC (r2=0.43, beta=-0.38, p<0.05). Conclusion The obese group showed alterations in carbohydrate and lipid metabolism, which were associated to the presence of vascular specific inflammation and impairment of HDL atheroprotective capacity. These children and adolescents would present qualitative alterations in their lipoproteins which would determine higher risk of suffering premature cardiovascular disease.
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Background and Aim: The aim of this study was to make a comparison between the effects of eight weeks aerobic and resistance training on paraoxonase-1, arylesterase activity and lipid profile in obese girls. Material and method: 30 obese women with mean values for age 30±5years, height 1.60±2m and weight 85.23±6.7kg, and body mass index of 31-33kg/m2 were divided randomly into three aerobic exercise (n=10), resistance training (n=10) and control (n=10) groups. Experimental groups performed aerobic exercise on treadmill between 60 to 75% of heart rate reserve and resistance training between 55 to 75% 1RM for 8 weeks. Blood samples were taken from the subjects 48 hours before and 48 hours after training and also after 12 hours of fasting. Data were analyzed by use of ANOVA and Tukey post hoc test. P≤0.05was considered significant. Results: The results showed that aerobic exercise had a significant effect on serum concentrations of paraoxonase-1 (P=0.001) and arylesterase (P=0.006) in obese girls. However, there was no significant difference between the effects of eight weeks of aerobic and resistance training on the plasma levels of cholesterol, triglycerides and LDL in obese girls (P≤0.05). Also, the results showed that plasma HDL levels significantly increased after eight weeks of aerobic training in obese girls (P=0.007). The effects of eight weeks of aerobic and resistance training on plasma VLDL level, were significantly different from those of the control group (P=0.001). Conclusion: According to the results of this study, it seems that aerobic exercise can increase paraoxonase-1 and arylesterase plasma levels and also modify lipid profile which can result in reduced risk of cardiovascular diseases in obese people. © 2016, Kurdistan University of Medical Sciences. All rights reserved.
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Paraoxonase-1 (PON1) is an antioxidant enzyme, that resides on high-density lipoprotein (HDL). PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL. In order to evaluate the atheroprotective potential of PON1, we assessed the relationships among PON1-genotype, PON1-activity and risk of future coronary artery disease (CAD), in a large prospective case-control study. Cases (n = 1138) were apparently healthy men and women aged 45-79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n = 2237) were matched by age, sex and enrollment time. PON1-activity was similar in cases and controls (60.7+/-45.3 versus 62.6+/-45.8 U/L, p = 0.3) and correlated with HDL-cholesterol levels (r = 0.16, p<0.0001). The PON1-Q192R polymorphism had a profound impact on PON1-activity, but did not predict CAD risk (Odds Ratio [OR] per R allele 0.98[0.84-1.15], p = 0.8). Using conditional logistic regression, quartiles of PON1-activity showed a modest inverse relation with CAD risk (OR for the highest versus the lowest quartile 0.77[0.63-0.95], p = 0.01; p-trend = 0.06). PON1-activity adjusted for Q192R polymorphism correlated better with HDL-cholesterol (r = 0.26, p<0.0001) and more linearly predicted CAD risk (0.79[0.64-0.98], p = 0.03; p-trend = 0.008). However, these relationships were abolished after adjustment for HDL (particles-cholesterol-size) and apolipoproteinA-I (0.94[0.74-1.18], p-trend = 0.3). This study, shows that PON1-activity inversely relates to CAD risk, but not independent of HDL, due to its close association with the HDL-particle. These data strongly suggest that a low PON1-activity is not a causal factor in atherogenesis.
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Research into the paraoxonase (PON) gene family has flourished over the past few years. In the 1970s and 1980s, only PON1 was known, and the investigations were conducted, essentially, by toxicologists focusing on protection against organophosphate poisoning. Since then, two new members of the family, PON2 and PON3, have been identified, both being shown to play antioxidant and anti-inflammatory roles. Evidence exists indicating that the PON family is central to a wide variety of human illnesses such as cardiovascular disease, diabetes mellitus, metabolic syndrome, obesity, non-alcoholic steatohepatitis, and several mental disorders. However, research is hampered considerably by the methods currently available to measure the activity of these enzymes. In this review, we summarize the state of knowledge on PON biochemistry and function, the influence of genetic variations, and the involvement of PON in several diseases. The problems associated with PON measurement, such as sample acquisition, lack of reference methods, and variety of substrates, will be presented. Also, we cover some of the present lines of research and propose some others for future progress in this field.
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To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points. International survey of six large nationally representative cross sectional growth studies. Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States. 97 876 males and 94 851 females from birth to 25 years of age. Body mass index (weight/height(2)). For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m(2) for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2-18 years. The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.
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In a recent study on Gulf War veterans who developed delayed neurotoxicity symptoms, we found their levels of serum paraoxonase (PON1) isozyme type Q to be significantly lower than in the control, unaffected veteran group. These results were obtained in 25 ill veterans and 20 well control subjects, of which 10 were deployed and 10 were nondeployed battalion members who remained in the United States during the Gulf War. The blood samples were also assayed for serum butyrylcholinesterase in our laboratory, and more recently in Dr. C. Broomfield's laboratory for somanase and sarinase activities. The cholinesterase activities showed no significant correlation with the PON1 isozyme levels or the severity of the clinical symptoms, but the somanase and sarinase levels ran parallel to the PON1 type Q isozyme concentrations. Although there is no direct evidence that these Gulf War veterans were directly exposed to or encountered either of these nerve gases, they may have been exposed to some environmental or chemical toxin with a similar preference for hydrolysis by the PON1 type Q isozyme. The number of subjects is relatively small, but the results should encourage other investigators to examine both the individual phenotypes and the levels of PON1 isozymes in other groups exhibiting neurological symptoms.
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The oxidation of low-density lipoprotein (LDL) is centrally involved in the initiation and progression of atherosclerosis. High-density lipoprotein (HDL) paraoxonase 1 (PON1) retards the oxidation of LDL and is a major antiatherosclerotic component of HDL. The PON1 gene contains a number of functional polymorphisms in both the coding and the promoter regions, which affect either the level or the substrate specificity of PON1. Genetic case-control and prospective studies conducted to date have produced confusing results. Meta-analysis of these studies indicates no simple relationship between the PON1 polymorphisms and the presence of coronary heart disease (CHD). However, at the present moment in time, it seems that PON1 status, i.e., activity and/or concentration, is more closely related to CHD, and indeed, PON1 has shown to be an independent risk factor for CHD in a prospective study, compared to the genetic polymorphisms. PON1 levels can also be modulated by environmental\lifestyle and possibly pharmaceutical factors. Larger, better designed, preferably prospective studies are needed to determine further the association of PON1 genetic polymorphisms and status with CHD.
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In humans, a chronically increased circulating level of C-reactive protein (CRP), a positive acute-phase reactant, is an independent risk factor for cardiovascular disease. This observation has led to considerable interest in the role of inflammatory proteins in atherosclerosis. In this review, after discussing CRP, we focus on the potential role in the pathogenesis of human vascular disease of inflammation-induced proteins that are carried by lipoproteins. Serum amyloid A (SAA) is transported predominantly on HDL, and levels of this protein increase markedly during acute and chronic inflammation in both animals and humans. Increased SAA levels predict the risk of cardiovascular disease in humans. Recent animal studies support the proposal that SAA plays a role in atherogenesis. Evidence is accruing that secretory phospholipase A(2), an HDL-associated protein, and platelet-activating factor acetylhydrolase, a protein associated predominantly with LDL in humans and HDL in mice, might also play roles both as markers and mediators of human atherosclerosis. In contrast to positive acute-phase proteins, which increase in abundance during inflammation, negative acute-phase proteins have received less attention. Apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, decreases during inflammation. Recent studies also indicate that HDL is oxidized by myeloperoxidase in patients with established atherosclerosis. These alterations may limit the ability of apoA-I to participate in reverse cholesterol transport. Paraoxonase-1 (PON1), another HDL-associated protein, also decreases during inflammation. PON1 is atheroprotective in animal models of hypercholesterolemia. Controversy over its utility as a marker of human atherosclerosis may reflect the fact that enzyme activity rather than blood level (or genotype) is the major determinant of cardiovascular risk. Thus, multiple lipoprotein-associated proteins that change in concentration during acute and chronic inflammation may serve as markers of cardiovascular disease. In future studies, it will be important to determine whether these proteins play a causal role in atherogenesis.
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Serum paraoxonase (PON1) is an enzyme associated with HDL, and its ability to protect LDL from oxidation is one mechanism by which HDL protects against atherosclerosis. Low concentrations of PON1 are found in patients with type 2 diabetes or coronary heart disease. Serum PON1 activity may also be important in avoidance of organophosphate toxicity in industry. The generally accepted method for determining PON1 activity requires use of a recording spectrophotometer and is not suited to large numbers of samples; in addition, automation presents particular problems because of the extreme toxicity of substrates such as paraoxon. We established a relatively safe microtiter plate method that facilitates the determination of PON1 activity at a rate of 120 samples per hour. PON1 activity was determined by the generally accepted method (x) and the new method (y); results correlated with a slope close to unity (y = 0.93x + 8; r = 0.97; P < 0.0001; n = 101). Examination of differences by Bland-Altman plots showed a weak concentration-dependent difference (r = 0.33; P < 0.0001; n = 101). The intra- and interassay sample CVs, obtained with samples with PON1 activities ranging from 41 to 348 nmol x min(-1) x mL(-1), were 3.5% and 2.7%, respectively (n = 16). The proposed method for determination of PON1 activity is simple, relatively safe, and inexpensive and is suitable for analysis of large numbers of samples.
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Paraoxonase 1 (PON1) seems to have a relevant role in detoxifying processes and in atherosclerosis. The aim of this study was to determine PON1 activity, the total antioxidant capacity, as well as entire lipid profile in children for screening of possible risk of atherosclerosis development. Serum PON1 arylesterase/paraoxonase activities were determined spectrophotometrically. The total antioxidant capacity of the serum was measured by TEAC method. Parameters of lipid profile were analyzed by routine laboratory methods. It has been shown that PON1 arylesterase/ paraoxonase activities were very similar to values found in adults. In children, no significant correlation between PON1 arylesterase activity and HDL was observed. PON1 paraoxonase activity correlated only with atherogenic index. PON1 arylesterase activity was significantly higher in girls than in boys. The antioxidant capacity was inversely related to the body mass index. In this study, PON1 activity was determined in healthy children aged 11 to 12 years and we found a similarity in PON1 activities of children and adults. Moreover, the results of our study support the hypothesis that higher body weight of children may contribute to a greater risk for development of atherosclerosis in which oxidative stress plays a role.
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Introduction Central distribution of adipose tissue poses the risk of metabolic syndrome in children and youth. Early diagnosis based on current appropriate standards and recommendations of leading paediatric and scientific societies appears to be of great importance. Aim The aim of the study was to determine the percentile distributions of waist circumference (WC) in children and youth of Łódź. An attempt was made to answer the question whether WC exceeding half of the body height (Ht/2) may be considered a simple criterion for discrimination of abdominal obesity in the developmental age. Material and methods A total of 26 542 children and adolescents (13 358 girls and 13 184 boys) aged 7–19 years were examined and subjected to measurements of basic anthropometric parameters (body-weight and height, waist and hip circumferences). The LMS method based on Box-Cox transformation was used for construction of percentile curves. Results Mean WC values in boys in all age groups were higher than in girls. WC values corresponding to the c95 level in both 18-year-old boys and girls of Łódź are distinctly lower as compared with critical values established for adults that define abdominal obesity (88 cm for women; 102 cm for men). Conclusions The presented percentile distributions of waist circumference for school children and adolescents in Łódź should be used together with the general assessment of a child's obesity, e.g. while applying local percentile distributions of the BMI index. The knowledge of both indices (BMI and WC) enhances the evaluation of potential risk for excessive adiposity in which the centrally located adipose tissue plays a significant role. The LMS method used for construction of percentile distributions provides optimal adjustment and smoothing of curves also enabling easy transformation of individual WC values in cm into their percentile representation. A critical WC value for an examined child equal to or exceeding half of its body height can be considered a simplified criterion similar for both sexes distinguishing abdominal obesity.
Background In adults the metabolic syndrome imposes a substantial risk for type 2 diabetes mellitus and premature coronary heart disease. Even so, no national estimate is currently available of the prevalence of this syndrome in adolescents.Objective To estimate the prevalence and distribution of a metabolic syndrome among adolescents in the United States.Design and Setting Analyses of cross-sectional data obtained from the Third National Health and Nutrition Examination Survey (1988-1994), which was administered to a representative sample of the noninstitutionalized civilian population of the United States.Participants Male and female respondents aged 12 to 19 years (n = 2430).Main Outcome Measures The prevalence and distribution of a metabolic syndrome among US adolescents, using the National Cholesterol Education Program (Adult Treatment Panel III) definition modified for age.Results The overall prevalence of the metabolic syndrome among adolescents aged 12 to 19 years was 4.2%; 6.1% of males and 2.1% of females were affected (P= .01). The syndrome was present in 28.7% of overweight adolescents (body mass index [BMI], ≥95th percentile) compared with 6.8% of at-risk adolescents (BMI, 85th to <95th percentile) and 0.1% of those with a BMI below the 85th percentile (P<.001). Based on population-weighted estimates, approximately 910 000 US adolescents have the metabolic syndrome.Conclusions Perhaps 4% of adolescents and nearly 30% of overweight adolescents in the United States meet these criteria for a metabolic syndrome, a constellation of metabolic derangements associated with obesity. These findings may have significant implications for both public health and clinical interventions directed at this high-risk group of mostly overweight young people.
Article
Objective To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points. Design International survey of six large nationally representative cross sectional growth studies. Setting Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States. Subjects 97 876 males and 94 851 females from birth to 25 years of age. Main outcome measure Body mass index (weight/height 2 ). Results For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m 2 for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2›18 years. Conclusions The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.
Article
Adipocyte fatty acid-binding protein (A-FABP) links obesity and metabolic syndrome (MetS) and might be targeted in future therapies. Its utility as a MetS biomarker has been suggested in adults but has not been examined in children/adolescents. Our objectives were to identify metabolic parameters associated with A-FABP elevation in children and adolescents and to evaluate the effect of obesity intervention and A-FABP diagnostic utility. A-FABP and anthropometric, metabolic, and inflammatory indices were measured in 31 lean and 114 overweight/obese children and adolescents and reassessed after obesity intervention (1 year; diet and enhanced physical activity, with or without metformin). A-FABP was significantly higher in overweight/ obese than lean individuals, where it correlated with insulin, waist circumference (WC), and 2-h glucose independent of body mass index (BMI), age, gender, and developmental stage. The pattern of A-FABP associations differed between sexes. As a MetS indicator, A-FABP had 68% accuracy. The weight reduction program was effective in reducing A-FABP, BMI%, WC, triglycerides, and cholesterol. In conclusion, elevation in A-FABP is associated with MetS components independent of BMI status and can be reduced by diet and enhanced physical activity. A-FABP as a single MetS biomarker has a moderate accuracy.
Article
In type 2 diabetes mellitus, circulating C-reactive protein (CRP) is increased, whereas the high density lipoprotein (HDL)-associated, anti-oxidative and anti-inflammatory enzyme, paraoxonase-I, is decreased. Both high CRP and low paraoxonase-I activity may predict cardiovascular disease. It is unknown whether lower paraoxonase-I activity contributes to higher CRP levels in diabetes. In type 2 diabetic and control subjects, we determined the relationship of CRP with paraoxonase-I when taking account of plasma levels of pro- and anti-inflammatory adipokines. In 81 type 2 diabetic patients and 89 control subjects, plasma high-sensitive CRP, serum paraoxonase-I activity (arylesterase activity, assayed as the rate of hydrolysis of phenyl acetate into phenol), plasma leptin, adiponectin, resistin and lipids were determined. Body mass index (BMI), waist, insulin resistance, triglycerides, CRP, leptin and resistin levels were higher (P < 0.05 to P < 0.001), whereas HDL cholesterol, paraoxonase-I activity and adiponectin levels were lower (P = 0.02 to P < 0.001) in diabetic compared to control subjects. Multiple linear regression analysis demonstrated that, after controlling for age and gender, CRP was inversely related to paraoxonase-I activity (beta = -0.15, P = 0.028) and adiponectin (beta = -0.18, P = 0.009), and positively to leptin (beta = 0.33, P < 0.001) and BMI (beta = 0.22, P = 0.007), independently of the diabetic state (or of fasting glucose or HbA1c), insulin resistance and lipids (P > 0.20 for all). Low paraoxonase-I activity is related to higher CRP, independently of adipokines, as well as of obesity and lipids. Low paraoxonase-I activity in type 2 diabetes mellitus may contribute to increased cardiovascular risk via an effect on enhanced systemic low-grade inflammation.
Article
Few previous studies have examined the validity of the fasting glucose-to-insulin ratio (FGIR), homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI) in pediatric populations. To compare simple indices of insulin resistance calculated from fasting glucose and insulin levels with insulin sensitivity indices (area under the response curve [AUCinsulin], insulin sensitivity index [ISI-compositeL) determined by oral glucose tolerance testing (OGTT) in obese children. One hundred and forty-eight obese children and adolescents (86 girls and 62 boys, mean age: 10.86 +/- 3.08 years, mean body mass index (BMI): 27.7 +/- 4.2) participated in the study. OGTT was performed in all participants. After glucose and insulin measurements from OGTT, the children were divided into two groups according to the presence or absence of insulin resistance. Insulin sensitivity indices obtained from the OGTT were compared between the groups. The total plasma glucose response and insulin secretion were evaluated from the AUC estimated by the trapezoid rule. Cut-off points, and sensitivity and specificity calculations were based on insulin resistance with receiver operating characteristic curve (ROC) analysis. The prevalence of insulin resistance, glucose intolerance and dyslipidemia was 37.1%, 24.3% and 54% in obese children, respectively. The groups consisted of 93 children without insulin resistance (54 girls and 39 boys; mean age: 10.5 +/- 3.3 years; mean BMI: 27.0 +/- 4.2) and 55 children with insulin resistance (32 girls and 23 boys; mean age: 11.4 +/- 2.5 years; mean BMI: 27.9 +/- 3.9). There were significant differences in mean FGIR (10.0 +/- 7.2 vs 5.6 +/- 2.8, p < 0.001), HOMA-IR (3.2 +/- 2.3 vs 4.9 +/- 2.3, p < 0.001) and QUICKI (0.33 +/- 0.03 vs 0.30 +/- 0.02, p < 0.001) between the groups. The cut-off points for diagnosis of insulin resistance were < 5.6 for FGIR (sensitivity 61.8, specificity 76.3), > 2.7 for HOMA-IR (sensitivity 80, specificity 59.1), and < 0.328 for QUICKI (sensitivity 80, specificity 60.2). Indices derived from fasting samples for diagnosis of insulin sensitivity are reliable criteria in obese children and adolescents. HOMA-IR and QUICKI appeared to have similar sensitivity and specificity and to have higher sensitivity than FGIR.
Article
The association of visfatin, an adipocytokine relevant to the development of inflammation and metabolic disorders, with juvenile obesity needs to be re-established as previously used tests occurred to be nonspecific. To evaluate visfatin association with a metabolic profile of 88 overweight/obese and 26 lean children/adolescents as well as changes in its levels following weight reduction programme (diet + enhanced physical activity ± metformin). A case-control and cohort study. Visfatin was higher in obese than lean and overweight individuals (2·07 vs. 1·53 and 1·47 ng mL(-1) , P = 0·034). Of metabolic syndrome components, central obesity combined with either insulin resistance (IR) or hyperinsulinemia (HI) was associated with increases in circulating visfatin. In girls, visfatin correlated with leptin (r = 0·40, P = 0·009) and thiols (r = -0·36, P = 0·009), which explained 24% in visfatin variability. In boys, visfatin correlated with waist circumference (r = 0·36, P = 0·036), BMI% (r = 0·38, P = 0·025), whole body insulin sensitivity index (r = -0·36, P = 0·036), IL-6 (r = 0·38, P = 0·024) and thiobarbituric acid reactive substances (TBARS) (r = 0·52, P = 0·001), of which IL-6 and TBARS were independent predictors of visfatin elevation, explaining 42% in data variability. Visfatin was significantly lower following weight reduction programme than at baseline (1·43 vs. 1·83 ng mL(-1) , P = 0·033). Visfatin reduction correlated neither with changes in metabolic parameters nor was it affected by metformin. ΔVisfatin correlated exclusively with baseline visfatin (r = 0·612, P < 0·0001), which explained 38% in data variability. Central obesity combined with HI/IR contributes to visfatin elevation. Visfatin association with metabolic/biochemical variables is gender dependent. Diet + enhanced physical activity are effective in visfatin reduction, the degree of which depends on baseline visfatin.
Article
Hyperuricemia may underlie obesity and related disorders, but the impact of weight reduction and metformin on serum uric acid (sUA) in Caucasian children/adolescents is unknown. One hundred and thirteen children/adolescents were enrolled (83 completed) into 1-year weight reduction program (diet+exercise) without or with metformin. Anthropometric and biochemical measurements were conducted at baseline and at the end of follow-up (13 ± 3 months). sUA decreased in 86% females and 67% males. Significantly more patients substantially (≥ 10%) reduced their sUA than body mass index (BMI)%. In females, sUA decreased regardless of type of intervention, but more markedly in the metformin group, and ΔsUA correlated positively with ΔBMI%, ΔWHtR (waist-to-height ratio), Δinsulin, ΔHOMA (homeostasis model of assessment), and Δtriglycerides/high density lipoprotein (HDL), but correlated negatively with baseline sUA, HOMA, insulin, and triglycerides/HDL. Of these, metformin treatment, baseline sUA, and ΔBMI% were independent predictors of sUA reduction, explaining 77% of data variability. In males, sUA reduction was significant in the metformin group only, and negatively correlated with ΔWHR (waist-to-hip ratio), ΔWHtR, Δleptin, baseline sUA, and waist circumference. Of these, baseline sUA and ΔBMI% were independent predictors of sUA reduction, explaining 69% of data variability. Except for sUA, females reduced their BMI%, waist circumference, triglycerides, triglycerides/HDL and increased HDL, while males reduced total cholesterol. A longitudinal weight reduction program encompassing diet/exercise with or without metformin was more efficient in reducing sUA than weight and its effect on sUA and other metabolic parameters differed between genders. Weight loss did not condition sUA reduction, which was strongly dependent on baseline levels. The sUA reducing effects of metformin may contribute to its effects on blood pressure-lowering and endothelial function-improving properties in females.
Article
Hyperuricemia has been implicated in the pathogenesis of obesity and related metabolic abnormalities. Studies on the association between serum uric acid (sUA) and metabolic syndrome (MetS) in juvenile obesity are scant. The effect of gender has not been evaluated. sUA (uricase method), anthropometric and biochemical indices were measured in gender-stratified children/adolescents consisting of 113 overweight/obese and 71 lean individuals. In males, sUA was significantly elevated in overweight as well as obese patients. sUA was strongly associated with obesity indices and reflected sexual development, decreases in high density lipoprotein-cholesterol, and moderately, the number of MetS components. Waist circumference (WC) and Tanner stage explained 40% of sUA variability. Controlling for body mass index (BMI) and other MetS components, sUA was associated with abdominal obesity, explaining 30% of variability in WC. In females, sUA was significantly increased in obesity, high blood pressure (BP), and MetS and corresponded with the number of MetS components, indices of glucose metabolism, triglycerides (TG), and the atherogenecity index. Insulin-resistance (IR) (homeostasis model assessment; HOMA) and high BP explained 29% of sUA variability, whereas sUA, while controlling for BMI, age, and other MetS components, was associated with hypertriglyceridemia, hyperglycemia, high BP, and abdominal obesity. IR mediated the associations with high TG and glucose. The association between sUA and MetS components in juvenile obesity is gender-specific, with females being related more closely and to more metabolic abnormalities. It may explain why, despite its lower concentrations, sUA is an independent predictor of mortality from all causes and from vascular diseases exclusively in females. Our findings may help in identifying metabolic abnormalities which may possibly be targeted by reducing sUA in males and females.
Article
Childhood obesity is a predisposing factor for adult cardiovascular diseases. Human serum paraoxonase (PON1) may protect against atherosclerosis by hydrolyzing lipid peroxides in oxidized LDL. Alterations and potential correlations of PON1 activities, leptin and adiponectin levels in childhood obesity were studied. We measured PON1 paraoxonase and arylesterase activities, anthropometric parameters, leptin and adiponectin levels in 59 white, obese (obese group-OB: BMI corrected for age: 95.1 +/- 3.5 percentile, age: 11.9 +/- 1.6 y) and 51 normal-weight children (control group-C: BMI corrected for age: 64.1 +/- 8.4 percentile, age: 12.0 +/- 3.9 y). Obese children had significantly lower PON1 paraoxonase (OB: 84.80 (64.33/144.74) U/L versus. C: 99.42 (83.33/152.05) U/L; p < 0.05) and arylesterase activities (OB: 94.40 (82.20/108.70) U/L versus. C: 115.20 (93.70/126.00) U/L; p < 0.01), higher leptin (OB: 37.05 (24.33/53.87) ng/mL versus. C: 4.62 (2.52/17.6) ng/mL; p < 0.0001) and lower adiponectin levels (OB: 7.56 (5.69/12.06) microg/mL versus. C: 11.51 (8.84/14.49) microg/mL; p < 0.001) compared with the normal-weight group. PON1 arylesterase activity showed inverse univariate correlation with leptin (r = -0.29; p < 0.05) and positive correlation with adiponectin levels (r = 0.39; p < 0.01). In multiple regression analysis adiponectin was strongly associated with PON1 arylesterase activity in obese children (beta = 0.45, p < 0.02). Our results emphasize the importance of the investigated metabolic alterations which may have further effects on cardiovascular morbidity and mortality in later adulthood. Altered levels of leptin, adiponectin and PON1 activities may be useful markers beside the general risk factors in childhood obesity.
Article
A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, de- pending on the patient population compared. Additional Keyph rases hyperlipoproteinemia classifi- cation #{149} determination of plasma total cholesterol, tri- glyceride, high-density lipoprotein cholesterol #{149} beta lipo proteins
Article
Numerous epidemiological studies have suggested an association between the acute phase response and atherosclerosis. Paraoxonase (PON) is an HDL associated enzyme that protects LDL from oxidative stress. Here we demonstrate that serum PON activity decreases following endotoxin (LPS) administration in Syrian hamsters. This decrease is seen within 24 h following LPS treatment and doses as low as 100 ng/100 g body weight of LPS elicit a reduction in serum PON activity. LPS also induces a marked decrease in PON1 mRNA in the liver (80% decrease). The decrease in mRNA levels is observed as early as 4 h and is sustained for at least 48 h after a single LPS treatment. Moreover, TNF and IL-1, cytokines which mediate the acute phase response, also decrease serum PON activity and PON mRNA levels in the liver. Additionally, TNF and IL-1 treatment of HepG2 cells results in a decrease in PON mRNA levels indicating that these cytokines are capable of directly affecting liver cells. Along with other changes in lipid metabolism that occur during the acute phase response, the decrease in PON could be another factor linking the acute phase response with increased atherogenesis.
In adults the metabolic syndrome imposes a substantial risk for type 2 diabetes mellitus and premature coronary heart disease. Even so, no national estimate is currently available of the prevalence of this syndrome in adolescents. To estimate the prevalence and distribution of a metabolic syndrome among adolescents in the United States. Analyses of cross-sectional data obtained from the Third National Health and Nutrition Examination Survey (1988-1994), which was administered to a representative sample of the noninstitutionalized civilian population of the United States. Male and female respondents aged 12 to 19 years (n = 2430). The prevalence and distribution of a metabolic syndrome among US adolescents, using the National Cholesterol Education Program (Adult Treatment Panel III) definition modified for age. The overall prevalence of the metabolic syndrome among adolescents aged 12 to 19 years was 4.2%; 6.1% of males and 2.1% of females were affected (P=.01). The syndrome was present in 28.7% of overweight adolescents (body mass index [BMI], >/=95th percentile) compared with 6.8% of at-risk adolescents (BMI, 85th to <95th percentile) and 0.1% of those with a BMI below the 85th percentile (P<.001). Based on population-weighted estimates, approximately 910 000 US adolescents have the metabolic syndrome. Perhaps 4% of adolescents and nearly 30% of overweight adolescents in the United States meet these criteria for a metabolic syndrome, a constellation of metabolic derangements associated with obesity. These findings may have significant implications for both public health and clinical interventions directed at this high-risk group of mostly overweight young people.
Article
Although there have been suggestions that serum paraoxonase is important in protecting against coronary heart disease (CHD), a large number of studies of genetic determinants of serum paraoxonase have reported apparently conflicting results about their association with CHD. We conducted a meta-analysis of 43 studies of the Q192R, L55M, and T(-107)C polymorphisms in the paraoxonase PON1 gene and the S311C polymorphism in the PON2 gene (all of which are in moderately strong linkage disequilibrium with one another), involving a total of 11212 CHD cases and 12786 controls. We explored potential sources of heterogeneity. In a combined analysis of all studies, the per-allele relative risk of R192 for CHD was 1.12 (95% CI 1.07-1.16), but in the five largest studies it was only 1.05 (0.98-1.13). Combined analyses of studies of the M55, (-107)T, and C311 variants showed no significant overall associations with CHD, yielding per-allele relative risks of 1.00 (0.95-1.06), 1.02 (0.92-1.14), and 1.04 (0.93-1.17), respectively. In contrast to previous suggestions, this meta-analysis shows no significant association of CHD with the L55M or T(-107)C polymorphism in PON1 or with the S311C polymorphism in PON2. The weak overall association between the Q192R polymorphism and CHD is of uncertain relevance, particularly since there was no significant association among the larger studies which should be less prone to selective publication. These findings reinforce the need for much larger and more rigorous investigations of the genetic determinants of complex diseases than is now customary, as well as for regularly updated systematic appraisals of such studies to help improve interpretation and prioritise hypotheses.
Article
Paraoxonase, an enzyme associated with high-density lipoprotein (HDL-PON), exerts a protective effect against oxidative damage of circulating cells and lipoproteins, modulates the susceptibility of HDL to atherogenic modifications such as glycation and homocysteinylation, and even exerts an antiinflammatory role. The aim of the present study was to investigate the relationship between lipoprotein oxidative stress and the activity of HDL-PON in healthy and obese subjects. Therefore, the activity of HDL-PON and the levels of lipid hydroperoxides in HDL and low-density lipoprotein (LDL) isolated from plasma of obese females (n = 12) and age-sex-matched controls (n = 31) were compared. Our results demonstrated for the first time that the activity of HDL-PON in obese subjects was significantly lower compared with that in controls (P < 0.001). Moreover, our results showed a significant increase in the levels of lipid hydroperoxides in HDL and LDL isolated from obese subjects (P < 0.001). The negative correlations established between HDL-PON activity and the levels of lipid hydroperoxides associated with HDL and LDL confirm the relationship between paraoxonase activity and lipid peroxidation of lipoproteins. Plasma levels of leptin correlated negatively with HDL-PON activity and positively with levels of lipid hydroperoxides in HDL and LDL of obese subjects, suggesting a relationship between leptin and oxidative damage of lipoproteins. In conclusion, our study demonstrated that the increase in oxidative stress in LDL and HDL of obese subjects is associated with a decrease in HDL-PON activity. The lower paraoxonase activity and the compositional changes in HDL and LDL could contribute to the greater risk of cardiovascular disease associated with obesity.
Article
Weight control programs for obese children monitor change in body mass index (BMI) adjusted for age. However, change can be measured in several ways: raw (kg/m2) units, percentage, z-scores or centiles. The suitability of the different measures is not known. To identify the optimal BMI measure for change, whose short-term variability is most consistent for children across the spectrum of adiposity. An Italian kindergarten. A total of 135 (66 female) children aged 29-68 months at baseline, with BMI measured three times over a 9-month period. Each child's short-term variability in adiposity was summarized by the standard deviation (s.d.) of BMI and BMI % adjusted for age, and BMI z-score and BMI centile. The s.d.'s were then compared in obese and nonobese children, and also correlated with each child's baseline BMI z-score. The within-child s.d.s of BMI z-score and BMI centile were significantly smaller in obese than nonobese children, while the s.d.s of BMI and BMI % were similar in the two groups. Also, the within-child s.d.s of z-score and centile, and to a lesser extent BMI %, were significantly inversely correlated with baseline z-score, whereas the s.d. of BMI was not. The changes in adiposity over time, as assessed by the four measures, were very highly correlated with each other, particularly for BMI with BMI %. Even though BMI z-score is optimal for assessing adiposity on a single occasion, it is not necessarily the best scale for measuring change in adiposity, as the within-child variability over time depends on the child's level of adiposity. Better alternatives are BMI itself or BMI %. Our results underscore the importance of using a relatively stable method to assess adiposity change when following children at risk of obesity.
Article
Adipocyte fatty acid-binding protein (A-FABP) has been reported to be increased in obese adults and to be related to metabolic syndrome. Because studies concerning A-FABP in weight loss are limited and studies in obese children are missing, we analyzed A-FABP in obese children before and after weight loss. Fasting serum A-FABP, leptin, insulin, glucose, triglycerides, low-and high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and tumor necrosis factor alpha concentrations as markers of the metabolic syndrome, and weight status (body mass index and percentage body fat based on skinfold measurements) were determined in 30 obese children (median age, 11.9 years) before and after participating in a 1-year obesity intervention. Furthermore, A-FABP levels were measured in 10 nonobese children of similar age, sex, and pubertal stage. Obese children had significantly (P < .001) higher A-FABP concentrations compared with nonobese children. In backward multivariate linear regression analysis, A-FABP correlated significantly (P < .05) with percentage body fat and leptin, but not with any of the markers of the metabolic syndrome. Changes of A-FABP concentrations correlated significantly with changes of percentage body fat (r = 0.53, P = .001) and leptin (r = 0.55, P < .001), but not with any changes of parameters of the metabolic syndrome. Substantial weight loss in 10 children led to a significant (P < .05) decrease in A-FABP levels in contrast to the 20 children without change of weight status. In cross-sectional as well as longitudinal analyses, A-FABP levels were related to weight status and leptin levels. Further longitudinal studies are necessary to study the relationship between A-FABP concentrations and parameters of the metabolic syndrome.
Article
To evaluate the formation of advanced oxidation protein products (AOPPs) in juvenile overweight/obesity and obesity-related disorders and to investigate the effect of weight reduction on AOPPs. AOPPs were determined in 114 overweight/obese children and adolescents without/with insulin resistance and metabolic syndrome and compared with 53 lean controls. Measurements were repeated following weight reduction program (diet/exercise, bran-enriched diet/exercise, and diet/exercise plus metformin). Overweight/obese subjects had higher AOPPs than lean controls, more elevated in patients with co-occurring metabolic syndrome. AOPPs positively correlated with central obesity, triglycerides, lipid peroxidation and insulin, and negatively with glucose to insulin ratio. AOPPs decreased following obesity intervention and DeltaAOPPs correlated with DeltaBMI%. AOPPs reduction was more pronounced in subjects on bran-enriched diet. Baseline AOPPs were a better predictor of clinically significant weight reduction than BMI%. Juvenile overweight/obesity was associated with AOPPs accumulation, more pronounced in metabolic syndrome. Body mass reduction decreased oxidative stress, with bran-enriched diet being more effective than diet/exercise alone.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents: The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents: The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004, 114, 555-576.
Wolne rodniki w przyrodzie
  • G Bartosz
Bartosz G: Druga twarz tlenu. Wolne rodniki w przyrodzie. Wydawnictwo Naukowe PWN, Warszawa 2004, 2nd ed.