Cardiovascular risk biomarkers and metabolically unhealthy status in prepubertal children: Comparison of definitions.

BACKGROUND AND AIMS: The early onset of cardio-metabolic abnormalities, known as metabolically unhealthy (MU) status, is highly associated with obesity and cardiovascular disease (CVD), as well as with increased morbidity and mortality later in life. Given the lack of a consensus MU classification for prepubertal children, we aimed to compare available MU definitions in terms of their association with CVD risk biomarkers. METHODS AND RESULTS: A total of 930 prepubertal children (622 with overweight/obesity, 462 males) aged 5-10.9 years were recruited, anthropometric measures were taken and biomarkers were analyzed. Children were classified using eight MU definitions based on different cut-offs for blood pressure, triacylglycerides, high-density lipoprotein cholesterol, glucose and homeostasis model assessment for insulin resistance (HOMA-IR). MU prevalence in children with overweight/obesity ranged between 30% and 60% across definitions. Plasma concentrations of resistin, leptin, myeloperoxidase (MPO) and total plasminogen activator inhibitor 1 (tPAI-1) were higher, and those of adiponectin were lower, in MU compared to MH children with overweight/obesity. Linear regression analyses confirmed the contribution of MPO and tPAI-1 concentrations to MU status, with most significant results derived from definitions that use age and sex-specific criteria and that account for HOMA-IR. CONCLUSION: Plasma concentrations of MPO and tPAI-1 are increased in prepubertal MU children irrespective of having normal-weight or overweight/obesity. Inclusion of age and sex-specific cut-offs for cardio-metabolic components as well as insulin resistance criteria increases the quality of MU definitions as seen by their stronger association with CVD biomarkers concentrations.

Effect of two bakery products on short-term food intake and gut-hormones in young adults: a pilot study.

The aim of this study is to compare the effect of conventional bread and a whole grain bread on appetite and energy intake, satiety and satiety gut-hormones. A randomized controlled crossover pilot study was carried out in 11 university students (age: 18.7 ± 0.9 years; body mass index: 22.7 ± 2.7 kg/m(2)). Participants consumed two different mid-morning cereal-based snacks, including a conventional or whole grain bread. Two testing days were completed, including satiety questionnaires, blood sampling and consumption of standardized breakfast, mid-morning test-snacks and ad libitum lunch. Several gut-hormones were analysed and satiation was assessed using Visual Analogue Scale scores. The consumption of whole grain bread increased satiety perception, decreased the remained energy intake during the testing day, and decreased the postprandial response of peptide YY, compared with conventional bread (p < 0.005). These data suggest that the consumption of whole grain bread might be a useful strategy to improve satiety.

Paraoxonase 1 activities and genetic variation in childhood obesity.

Changes in paraoxonase 1 (PON1) activities have been observed in a variety of diseases involving oxidative stress, such as CVD. However, its role in obesity has not been fully established. In the present study, we aimed (1) to genotype sixteen PON1 SNP, (2) to measure serum PON1 activities and (3) to correlate these findings with the incidence of childhood obesity and related traits. We conducted a case-control study of 189 normal-weight and 179 obese prepubertal children, and we measured four different PON1 activities: lactonase; paraoxonase; arylesterase; diazoxonase. Although none of these activities was significantly different between the obese and normal-weight children, lactonase activity was found to be positively correlated with HDL-cholesterol and ApoA1 levels and negatively correlated with myeloperoxidase and fatty acid-binding protein 4 levels. Among the sixteen genotyped PON1 SNP, only the intronic SNP rs854566 exhibited a significant association with obesity (OR 0·61, 95 % CI 0·41, 0·91; P= 0·016). This genetic variant was also associated with increased diazoxonase, lactonase and arylesterase activities and decreased paraoxonase activity. Other genetic variants exhibited different association patterns with serum activities based on their location within the PON1 gene, and SNP that were located within the promoter were strongly associated with lactonase, arylesterase and diazoxonase activities. The functional variant Q192R exhibited the greatest effect on paraoxonase activity (P= 5·88 × 10(-42)). In conclusion, SNP rs854566 was negatively associated with childhood obesity and with increased serum PON1 activities in prepubertal children. We determined that lactonase is a reliable indicator of PON1 activities and should be included in future studies of PON1 function.

A gene variant of 11ß-hydroxysteroid dehydrogenase type 1 is associated with obesity in children.

BACKGROUND: The 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) enzyme catalyses the regeneration of active cortisol from inert cortisone and plays a critical role in tissue-specific corticosteroid reactions; therefore, 11ß-HSD1 is a key molecule associated with the development of obesity. Despite evidence for its role in obesity, no genetic polymorphisms have been significantly associated with the disease per se. OBJECTIVE: The aim of this study was to evaluate whether HSD11B1 gene variants, which have never been studied before, are associated with obesity and its related traits, as well as its relation to biomarkers of inflammation, liver damage and cardiovascular disease in a cohort of Spanish children. DESIGN: We performed a prospective case-control study. SUBJECTS: A total of 534 children were examined and classified as being obese (n=292) or normal weight (n=242). Anthropometric and biochemical measurements related to obesity, including inflammation, liver damage and cardiovascular disease, were determined. Genomic DNA was extracted and 10 HSD11B1 gene single-nucleotide polymorphisms (SNPs) were genotyped. RESULTS: A novel SNP, rs3753519, was strongly associated with obesity and this SNP was the only statistically significant HSD11B1 gene SNP remaining after a Bonferroni correction (odds ratio=1.97 for allelic effect, 95% confidence interval 1.23-3.16; P=0.004 and Bonferroni corrected P=0.046). In addition, this SNP was significantly and positively associated with increased body mass index (BMI), BMI z-score, weight, waist circumference, plasma γ-glutamyl transpeptidase and plasma active plasminogen activator inhibitor 1. The SNP was negatively associated with plasma adiponectin and cortisol after adjusting for sex and age. None of the inflammation biomarkers tested were associated with the risk allele. CONCLUSION: These data, which link an HSD11B1 genotype with both disease prevalence and its related phenotypes, strongly support a role for the rs3753519 polymorphism in the pathogenesis of pediatric-onset obesity.

Fasting and postprandial adiponectin alterations anticipate NEFA and TNF-α changes in prepubertal obese children.

BACKGROUND AND AIMS: It has been suggested that adipokine changes might precede changes in plasma non-esterified fatty acids and other obesity metabolic biomarkers. The aim of the present study was to evaluate changes in fasting and postprandial plasma levels of adiponectin, non-esterified fatty acids, and tumor necrosis factor-alpha in prepubertal obese children and age-matched normal-weight children. METHODS AND RESULTS: Fifty-four children of prepubertal age (34 obese, comprising 23 males and 11 females, and 20 normal-weight comprising 11 males and 9 females) were studied. A standard 438 kcal breakfast was given to both groups. Baseline measurements included anthropometry and plasma lipids. The following parameters were determined in plasma before and after breakfast: glucose, insulin, and C-peptide at baseline and 2h and non-esterified fatty acids, adiponectin, and tumor necrosis factor-alpha at baseline and 1, 2, and 3h. Fasting plasma non-esterified fatty acid levels were lower in the obese versus normal-weight children (P=0.021). Both at baseline and postprandially, plasma adiponectin levels were lower in the obese versus normal-weight children (P<0.001). A trend was observed (P=0.06) that levels of tumor necrosis factor-alpha were lower in the obese versus normal-weight children. Adiponectin was inversely associated with insulin in the obese children after adjustment for BMI and sex (r=-0.401, P=0.025). CONCLUSION: At prepubertal age, obese children show lower fasting and postprandial plasma adiponectin levels in comparison to normal-weight children, whereas non-esterified fatty acids and tumor necrosis factor-alpha were not yet increased. Therefore, adiponectin appears to be a good marker of early metabolic alterations associated with childhood obesity.

Presence of the metabolic syndrome in obese children at prepubertal age.

BACKGROUND/AIMS: There is a strong debate on the diagnosis and early phenotypic expression of the metabolic syndrome in children. The aim of the present study was to examine the frequency of the metabolic syndrome using various definitions in obese prepubertal and pubertal children. METHODS: 478 (213 females and 265 males) obese children were recruited in three provinces of Spain. Blood pressure (BP), waist circumference, and weight and height were measured, and body mass index was calculated. Glucose, insulin, high-density lipoprotein cholesterol and triacylglycerols were determined. We classified the children according to seven different proposed definitions of the metabolic syndrome. RESULTS: Regardless of the definition used, the prevalence of the metabolic syndrome (8.3-34.2%) was relatively high in obese children in the prepubertal period as well as in pubertal children (9.7-41.2%). We performed a principal-factor analysis to explain correlations among features of the metabolic syndrome and found that glucose metabolism (factor 1), dyslipidemia (factor 2) and obesity/BP (factor 3) explained 72% of the total variance. CONCLUSION: Irrespective of the classification used, the metabolic syndrome is not only present in pubertal but also in prepubertal children. International definitions of the metabolic syndrome should also consider criteria specific for children in the prepubertal period, i.e. children aged <10 years.

Uric acid is associated with features of insulin resistance syndrome in obese children at prepubertal stage.

Elevated plasma uric acid levels are associated with obesity and could be an expression of insulin-resistant state. The aim of the present study was to evaluate plasma uric acid in obese and normal-weight children exclusively at prepubertal stage and its relationship with anthropometric measurements, intake, and features of the insulin resistance syndrome. A study was performed in 34 obese and 20 normal-weight prepubertal children. Nutrient intake was determined using a 72 h recall questionnaire and a consumption food frequency questionnaire. Anthropometric parameters and fasting plasma lipids, glucose, insulin, leptin, adiponectin, tumour necrosis factor (TNF-alpha) and uric acid were measured. Multiple regression analysis was used to identify association of anthropometric parameters, nutrient intake and insulin resistance syndrome variables (arterial blood pressure, plasma glucose, insulin, homeostasis model assessment of insulin resistance index- HOMA- triacylglycerols and, HDL-cholesterol) with uric acid. Plasma uric concentration was significantly higher in the obese group than in the control group and when adjusted by sex, age and BMI was positively associated with tricipital skinfold and insulin resistance, and negatively with adiponectin. In multiple regression analysis, BMI, HDL-cholesterol and adiponectin were independent predictors of plasma uric acid. In conclusion, elevated levels of uric acid in obese children, compared with lean subjects, at the prepubertal period, seems to be an early metabolic alteration that is associated with other features of insulin resistance syndrome.

Sunflower, virgin-olive and fish oils differentially affect the progression of aortic lesions in rabbits with experimental atherosclerosis.

In this study we report the effects of sunflower, virgin olive and fish oils on the progression of aortic lesions. A total of 24 male New Zealand rabbits (six per each group) were fed for 50 days on a diet containing 3% lard and 1.3% cholesterol, to induce atherosclerosis. An atherogenic control group (A) was killed after this period and three groups were fed for an additional period of 30 days with a diet composed of (1.75 g of supplemented oil and 98.25 of standard chow): sunflower oil (S), virgin olive oil (O) and fish oil (F). A control group (n=6) was fed with a standard chow diet for 80 days. LDL lipid composition and histological analysis of aortic atherosclerotic lesions were assayed. The atherogenic diet caused a significant increase of cholesterol levels in LDL and aorta tissue. Cholesterol ester content rose significantly in the aortic arch of groups S, O and F. Fatty streaks were found in all aortic sections, although only group S showed a significant progression of the lesion compared with group A. We conclude that the replacement of a high cholesterol-saturated fat diet by another cholesterol free-unsaturated fat diet does not regress atherosclerosis in rabbit. However, sunflower oil provokes a significant progression in lesion development, whereas diet enrichment with extra virgin olive oil and, to a lesser extent, fish oil, stops this progression.

Virgin olive and fish oils enhance the hepatic antioxidant defence system in atherosclerotic rabbits.

BACKGROUND & AIMS: In this study we report the effects of sunflower, virgin olive and fish oils on the lipid profile and antioxidant defence system in liver mitochondria from rabbits with experimental atherosclerosis. METHOD: An atherogenic control group were fed for 50 days on a diet containing 3% lard and 1.3% cholesterol. Four groups were fed for an additional period of 30 days with a diet enriched in different oils: sunflower oil, virgin olive oil, refined olive oil and fish oil. A control group was fed with a standard chow. RESULTS: The atherogenic diet caused important changes in the hepatic mitochondria lipid profile and in the enzymatic and non-enzymatic antioxidant defence system accompanied with an increase in the content of hydroperoxides in liver mitochondria. The administration of virgin olive and fish oils showed a better profile in the antioxidant system as well as decrease in the content of hydroperoxides. CONCLUSIONS: The intake of cholesterol- and lard-enriched diet leads to a high impairment in the hepatic antioxidant defence system. However, the replacement of that diet by other unsaturated fat-enriched diets using virgin olive, sunflower and fish oil enhances hepatic antioxidant defence system, virgin olive and fish oil diet provide the best results.

Sunflower oil does not protect against LDL oxidation as virgin olive oil does in patients with peripheral vascular disease.

BACKGROUND & AIMS: The aim of this study was to compare the in vivo effects of a diet rich in virgin olive oil or sunflower oil on the lipid profile and on LDL susceptibility to oxidative modification in free-living Spanish male patients with peripheral vascular disease. METHODS: A total of 20 Spanish male subjects diagnosed with peripheral vascular disease were randomly divided into two groups (n = 10) receiving different supplements, virgin olive oil and sunflower oil for 4 months. RESULTS: The adaptation of patients to the experimental supplements was demonstrated since plasma and LDL fatty acids composition reflected dietary fatty acids. No differences in triglycerides, total cholesterol, LDL-cholesterol or HDL-cholesterol concentrations were found between the groups of patients. A significantly higher LDL susceptibility to oxidation was observed after sunflower oil intake in comparison with virgin olive oil, in spite of an increase in LDL alpha-tocopherol concentration in sunflower oil group. CONCLUSIONS: The results of the present study provide further evidence that sunflower-oil-enriched diets does not protect LDL against oxidation as virgin olive oil does in patients with peripheral vascular disease.

Influence of dietary lipids on lipoprotein composition and LDL Cu(2+)-induced oxidation in rabbits with experimental atherosclerosis.

The aim of this study was to investigate the composition of plasma lipoproteins and their susceptibility to oxidation in rabbits with experimental atherosclerosis provoked by the intake of a diet rich in cholesterol and saturated fat as well as the influence of the intake of four diets differing in their lipid profiles (fish (F), refined olive (R), virgin olive (V) and sunflower (S) oils) on plasma lipoprotein composition and susceptibility to oxidation of these atherosclerotic rabbits. Plasma and lipoproteins concentrations of cholesterol, phospholipids and triglycerides were markedly higher in atherosclerotic rabbits but decreased with the experimental diets. LDL oxidation damage increased in atherosclerotic rabbits; the F diet led to a higher LDL oxidation susceptibility whereas groups fed either S, R, or V showed LDL oxidation values close to those of the control group. Diets rich in monounsaturated and n-3 polyunsaturated oils showed efficacy in restoring the normal lipid profiles in atherosclerotic rabbits provided in fish oil is adequately stabilized with antioxidants.

[Protective effect of monounsaturated and polyunsaturated fatty acids on the development of cardiovascular disease]. / Efectos protectores de los ácidos grasos monoinsaturados y poliinsaturados sobre el desarrollo de la enfermedad cardiovascular.

Cardiovascular disease has a multifactorial aetiology, as is illustrated by the existence of numerous risk indicators, many of which can be influenced by dietary means. In this article, the effects of unsaturated fatty acids on cardiovascular disease are reviewed, with special emphasis on the modifications of the lipoprotein profile and the mechanism by which fatty acids may affect the immune response on the development of the atherosclerotic lesion. Atherosclerosis occurs fundamentally in three stages: dysfunction of the vascular endothelium, fatty streak and fibrous cap formation. Each of the three stages is regulated by the action of vasoactive molecules, growth factors and cytokines, mediators of the immune response. Dietary lipid quality can affect the lipoprotein metabolism, altering their concentrations in the blood, permitting a greater or lesser recruitment of them in the artery wall. The replacement of dietary saturated fat by mono- or polyunsaturated fats significantly lowers the plasma-cholesterol and LDL-cholesterol levels. Likewise, an enriched monounsaturated fatty acid diet prevents LDL oxidative modifications more than an enriched polyunsaturated diet, and the oxidation of LDL in patients with peripheral vascular disease mediated by n-3 fatty acids can be reduced by the simultaneous consumption of olive oil. However, strong controversy surrounds the effect of the different unsaturated fatty acids. The type of dietary fat can directly or indirectly influence some of the mediating factors of the immune response; n-3 fatty acids have powerful antiinflammatory properties. Dietary fatty acids strongly determine the susceptibility of lipoproteins to oxidation, which also has an impact on the activation of molecules of adhesion and other inflammatory factors. Moreover, several works have demonstrated a direct effect of fatty acids on the genetic expression of many of those factors. Finally, certain aspects of blood platelet function, blood coagulability, and fibrinolytic activity associated with cardiovascular risk, are modulated by dietary fatty acids; n-3 fatty acids strongly inhibits platelet aggregation and activate thrombolytic processes.

Fasting and postprandial relationships among plasma leptin, ghrelin, and insulin in prepubertal obese children.

BACKGROUND: Leptin is involved in the long-term regulation of body weight and dietary intake, while ghrelin plays an essential role in appetite control. High levels of leptin have been associated with adiposity and the suppression of ghrelin levels with increased dietary intake. AIMS: To evaluate fasting and postprandial concentrations of plasma leptin and ghrelin after intake of a standardised breakfast and to study the relationship of these hormones with adiposity and insulin resistance in obese prepubertal children. METHODS: 34 obese and 20 normal-weight prepubertal children aged 6-12 years were selected. Plasma leptin and ghrelin were measured by ELISA and radioimmunoassay, respectively. The general linear model of variance, principal-component factor, and Pearson's analyses correlation were performed. RESULTS: Baseline and postprandial leptin levels were higher in obese versus normal-weight children. In obese, ghrelin showed an altered pattern during the postprandial period, recovering to baseline levels at 3h after the intake. Insulin resistance was associated with leptin and independently with ghrelin. CONCLUSION: The association of ghrelin with insulin resistance provides further evidence on the regulation of ghrelin in glucose homeostasis in childhood obesity at the prepubertal age. Changes in ghrelin after dietary intake may be related to an earlier recovery of appetite in prepubertal obese children.

Efectos farmacológicos y nutricionalesde los extractos de Curcuma longa L.y de los cucuminoides / Pharmacological and nutritional effects of Curcuma longa L. extracts and curcuminoids

La Curcuma longa L., es una planta de origen asiático muy usada comúnmente como una especia en la cultura asiática. El principal componente es la curcumina, uno de los ingredientes activos responsables de su actividad biológica. Se sabe que esta sustancia es estable en el estómago y en el intestino delgado; su elevada lipofilia le permite una rápida absorción gastrointestinal por difusión pasiva. Tras su administración, es metabolizada y excretada principalmente por bilis y heces, y también por orina. Sus principales metabolitos también son bioactivos. Desde antiguo, se han descrito muchas propiedades para los extractos de Curcuma longa y para la curcumina. Se conoce su actividad antibacteriana, antifúngica y antiparasitaria, y recientemente se ha demostrado su capacidad para inhibir la integrasa del HIV-1. También se han demostrado efectos específicos en otros tejidos y órganos, como la piel, el sistema gastrointestinal y respiratorio y en el hígado. Todas estas propiedades son debidas a distintos mecanismos de acción. Se ha demostrado que la cúrcuma posee efectos antiinflamatorios, a través de la modulación del metabolismo de los eicosanoides, tiene capacidad inmunomoduladora, principalmente alterando el perfil de las citoquinas Thl de los linfocitos T helper, y actividad hipolipidémica, disminuyendo el colesterol, los triglicéridos y los fosfolípidos plasmáticos así como en las LDL. Hay muchos estudios que demuestran la capacidad de la cúrcuma para estabilizar membranas y para prevenir la peroxidación lipídica, un proceso fundamental en el establecimiento, la progresión y las complicaciones de muchas patologías como las enfermedades hepáticas, renales, cardiovasculares, neurodegenerativas, en la diabetes y en las cataratas. Las últimas investigaciones sobre los efectos biológicos de los extractos de cúrcuma y de los curcuminoides están encaminados a estudiar su actividad anticancerosa, principalmente frente al cáncer de piel, colon y duodeno (AU)