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Given that leptin, ghrelin and thyrotropin play a major role in the regulation of resting energy expenditure (REE) and that the FTO rs9939609 and the MC4R rs17782313 polymorphisms have been proposed to affect energy homeostasis, we hypothesized that both polymorphisms are associated with REE and that these relationships can be mediated by leptin, ghrelin and thyrotropin in obesity. Therefore, the present study aimed to examine the relationships between FTO rs9939609 and the MC4R rs17782313 with REE, leptin, ghrelin and thyrotropin levels in obese women. The study comprised 77 obese (body mass index 34.0 ± 2.8 kg/m2) women (age 36.7 ± 7 years). We measured body composition by dual-energy X-ray absorptiometry and REE by indirect calorimetry. We analysed fasting leptin, ghrelin and thyrotropin levels and the ratio of leptin to fat mass was calculated. Genotype distributions of the polymorphisms did not deviate from Hardy–Weinberg expectations (P values >0.2). Women carrying the A allele of the FTO rs9939609 had lower REE (1,580 ± 22 vs. 1,739 ± 35 kcal/day, P

The aim of the present study was to examine the effects of green tea epigallocatechin-3-gallate (EGCG) on changes in body composition, energy and substrate metabolism, cardiometabolic risk factors and liver function enzymes after an energy-restricted diet intervention in obese women. In the present randomised, double-blind, placebo-controlled study, eighty-three obese (30 kg/m2>BMI 2) pre-menopausal women consumed 300 mg/d of EGCG or placebo (lactose). We measured body weight and adiposity (dual-energy X-ray absorptiometry), energy expenditure and fat oxidation rates (indirect calorimetry), blood lipid levels (TAG, total cholesterol, LDL-cholesterol and HDL-cholesterol), insulin resistance, C-reactive protein and liver function markers (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyltransferase, urea, bilirubin and 2-keto[1-13C]isocaproate oxidation) before and after the intervention in the EGCG and control groups. We did not find any significant difference in the changes in body weight ( − 0·3 kg, 95 % CI − 5·0, 4·3), fat mass ( − 0·7 kg, 95 % CI − 3·5, 2·1), energy (0·3 kJ/kg per d, 95 % CI − 3·1, 2·7) and fat ( − 0·1 g/min, 95 % CI − 0·03, 0·01) metabolism, homeostasis assessment model for insulin resistance (0·2, 95 % CI − 0·2, 0·7), total cholesterol ( − 0·21 mmol/l, 95 % CI − 0·55, 0·13), LDL-cholesterol ( − 0·15 mmol/l, 95 % CI − 0·50, 0·20), TAG ( − 0·14 mmol/l, 95 % CI − 0·56, 0·29) and liver function markers between the EGCG and control groups. In conclusion, the present results suggest that dietary supplementation with 300 mg/d of EGCG for 12 weeks did not enhance energy-restricted diet-induced adiposity reductions, and did not improve weight-loss-induced changes in cardiometabolic risk factors in obese Caucasian women. The intake of 300 mg/d of EGCG for 12 weeks did not cause any adverse effect on liver function biomarkers.

Background: The global pandemic of obesity has led to an increased risk for prediabetes and type-2 diabetes (T2D). The aims of the current project are: (1) to evaluate the effect of a 22-week family based intervention program, including supervised exercise, on insulin resistance syndrome (IRS) risk in children with a high risk of developing T2D and (2) to identify the profile of microRNA in circulating exosomes and in peripheral blood mononuclear cells in children with a high risk of developing T2D and its response to a multidisciplinary intervention program including exercise. Methods: A total of 84 children, aged 8–12 years, with a high risk of T2D will be included and randomly assigned to control (N = 42) or intervention (N = 42) groups. The control group will receive a family based lifestyle education and psycho-educational program (2 days/month), while the intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program (3 days/week, 90 min per session including warm-up, moderate to vigorous aerobic activities, and strength exercises). The following measurements will be evaluated at baseline prior to randomization and after the intervention: fasting insulin, glucose and hemoglobin A1c; body composition (dual-energy X-ray absorptiometry); ectopic fat (magnetic resonance imaging); microRNA expression in circulating exosomes and in peripheral blood mononuclear cells (MiSeq; Illumina); cardiorespiratory fitness (cardiopulmonary exercise testing); dietary habits and physical activity (accelerometry). Discussion: Prevention and identification of children with a high risk of developing T2D could help to improve their cardiovascular health and to reduce the comorbidities associated with obesity. The current project was supported by the Spanish Ministry of Industry and Competitiveness (DEP2016-78377-R), by “Fondos Estructurales de la Unión Europea (FEDER), Una manera de hacer Europa.” and by the University of the Basque Country (GIU14/21). This work was also supported by grants from Spanish Ministry of Economy and Competitiveness (RYC-2010-05957, RYC-2011-09011), Spanish Ministry of Education, Culture and Sports (FPU14/ 03329) and by the Education, Linguistic Policy and Culture Department of the Government of the Basque Country (PRE_2016_1_0057).

OBJECTIVES Menopause increases the risk of several pathologies, probably due to enlarged levels of visceral fat. Apart from morphological and endocrine changes, a cluster of genes, still not fully defined, may be involved in these alterations. The objectives of the present study, therefore, were to analyze differences in adipose tissue gene expression between premenopausal and postmenopausal women and to ascertain whether any differences were depot specific. METHODS Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) biopsies were taken from 7 premenopausal and 7 postmenopausal women undergoing surgery because of morbid obesity. RNA was extracted, and the overall gene expression profile was analyzed by microarray analysis. RESULTS In general, SAT genes were overexpressed, whereas VAT genes were down-regulated in premenopausal compared with postmenopausal women. We found 724 differentially expressed genes in SAT and 327 in VAT. These differences suggest that several biological processes, such as the immune system and other metabolic processes, were altered based on menopause status. Regarding individual genes, neurexin 3, metallothionein 1E, and keratyn 7 showed the most pronounced differences. Interestingly, the expression of these genes was related to body fat distribution. CONCLUSIONS Our results reveal that menopause influences the adipose tissue expression of many genes, especially of neurexin 3, metallothionein 1E, and keratyn 7, which are associated with the alteration of several key biological processes, such as the immune system and cell metabolism. Gene expression in adipose tissue could be used for diagnosis and the development of new therapeutic strategies against obesity and related alterations, depending on menopause status.

The aim of the present study was to investigate the association ofPLIN111482G>A (rs894160) andPLIN113041A>G (rs2304795) polymorphisms with body composition, energy and substrate metabolism, and the metabolic response to a 12-week energy-restricted diet in obese women. The study comprised a total of seventy-eight obese (BMI 34·0 (sd2·8) kg/m2) women (age 36·7 (sd7) years). We measured weight, height and waist circumference before and after a 12-week controlled energy-restricted diet intervention. Body fat mass and lean mass were measured by dual-energy X-ray absorptiometry. RMR and lipid oxidation rate were measured by indirect calorimetry. We also analysed fasting plasma glucose, insulin, cholesterol and leptin. Women carrying the 11482A allele had a lower reduction in waist circumference than non-A allele carriers (3·2 (sd0·5)v.4·6 (sd0·6) %, respectively,P = 0·047;Pfor gene–diet interaction = 0·064). Moreover, women with the 11482A allele had a higher decrease in lipid oxidation rate than non-A allele carriers (58·9 (sd6·7)v. 31·3 (sd8·2) %, respectively,P = 0·012;Pfor gene–diet interaction = 0·004). There was no interaction effect between the 13041A>G polymorphism and diet-induced changes on the outcome variables (allP>0·1). These results confirm and extend previous findings suggesting that thePLIN111482G>A polymorphism plays a modulating role on diet-induced changes in body fat and energy metabolism in obese women.

We investigated the role of common β2-adrenergic receptor (ADRB2) rs1042714 (Gln27Glu) and rs1042713 (Arg16Gly) polymorphisms on body weight and body composition response to 12-week energy-restricted diet in women. The study comprised 78 Spanish obese (BMI: 34.0 ± 2.8 kg/m²) women (age: 36.7 ± 7 years). We measured (before and after the dietary intervention) weight and height, and BMI calculated. Moreover, body fat mass and lean mass (LM) were measured by dual energy X-ray absorptiometry. We observed an interaction effect between the Gln27Glu polymorphism and diet-induced changes on body weight (P = 0.006), BMI (P = 0.004), and LM (P = 0.001). Women carrying the Glu allele had a greater reduction in body weight than non-Glu allele carriers (9.5 ± 2.9 vs. 7.0 ± 3.5%, respectively, P = 0.002). Moreover, women with the Glu allele lost more LM than the Gln27Gln group (5.9 ± 2.7 vs. 4.0 ± 2.7%, respectively, P = 0.001). We did not find any significant interaction effect between the Arg16Gly polymorphism and diet-induced changes on the outcome variables (all P > 0.1). The results suggest that the ADRB2 Gln27Glu polymorphism has a modulating effect on diet-induced changes on body weight and body composition, and should be considered in future obesity treatments. These findings should be taken as preliminary and be replicated in further energy restriction studies with larger sample sizes.

Klebsiella pneumoniae is an important cause of community-acquired and nosocomial pneumonia. Subversion of inflammation is essential for pathogen survival during infection. Evidence indicates that K. pneumoniae infections are characterized by lacking an early inflammatory response although the molecular bases are currently unknown. Here we unveil a novel strategy employed by a pathogen to counteract the activation of inflammatory responses. K. pneumoniae attenuates pro-inflammatory mediators-induced IL-8 secretion. Klebsiella antagonizes the activation of NF-κB via the deubiquitinase CYLD and blocks the phosphorylation of mitogen-activated protein kinases (MAPKs) via the MAPK phosphatase MKP-1. Our studies demonstrate that K. pneumoniae has evolved the capacity to manipulate host systems dedicated to control the immune balance. To exert this anti-inflammatory effect, Klebsiella engages NOD1. In NOD1 knock-down cells, Klebsiella neither induces the expression of CYLD and MKP-1 nor blocks the activation of NF-κB and MAPKs. Klebsiella inhibits Rac1 activation; and inhibition of Rac1 activity triggers a NOD1-mediated CYLD and MKP-1 expression which in turn attenuates IL-1β-induced IL-8 secretion. A capsule (CPS) mutant does not attenuate the inflammatory response. However, purified CPS neither reduces IL-1β-induced IL-8 secretion nor induces the expression of CYLD and MKP-1 thereby indicating that CPS is necessary but not sufficient to attenuate inflammation.

To understand the pathogenesis of glioblastoma multiforme (GBM) we used high-resolution comparative genomic hybridization arrays and gene expression microarrays to identify DNA copy number alterations and gene expression changes in comparable sets of GBM samples. Gains were detected at chromosomes 1, 2, 7, 9, 12, 19, and 20 and losses at 6, 9, and 10. Gene expression analyses identified specific genes overexpressed in GBM mapping at amplified chromosomal regions. Among these genes we found genes involved in angiogenesis, extracellular matrix remodeling and several oncogenes. DNA copy number analysis along with gene expression profiles provides a powerful strategy to understand tumor progression and identification of genes involved in GBM pathogenesis.

To examine the independent and combined influence of the FTOrs9939609 and the MC4Rrs17782313 polymorphisms on changes in fat mass (FM), resting energy expenditure (REE), leptin, and thyrotropin (TSH) levels, after a 12-week energy-restricted diet intervention in non-morbid premenopausal obese women.Fat mass (dual X-ray absorptiometry), REE (indirect calorimetry) and plasma leptin and thyrotropin levels were measured (before and after the intervention) in 77 obese (BMI: 33.9 ± 2.8 kg/m(2)) women (age: 36.8 ± 7.0y).There were no significant differences across FTOrs9939609 genotype groups (TT vs. A allele carriers, Ps0.1) on changes in body mass (-8.6 ± 3.2% vs. -8.7 ± 3.3 %), FM (12.8 ± 4.7% vs. -12.9 ± 6.3%), REE (-11.3 ± 4.7 vs. -9.4 ± 8.1%), leptin (-34.1 ± 25.1% vs. -43.5 ± 24.1%) or TSH (5.2 ± 34.5% vs. -1.7 ± 27.1%) levels. Moreover, it was not observed any significant difference on changes in body mass (-8.6 ± 3.6% vs. -8.9 ± 2.6%), FM (-12.7 ± 6.1% vs. -13.4 ± 5.3%), REE (-9.8 ± 7.4% -9.4 ± 9.4%), leptin (-39.0 ± 26.9% vs. -44.8 ± 18.4%) or TSH (-1.0 ± 30.0% vs. 1.5 ± 26.5%) levels between non-C allele carriers and C allele carriers of the MC4Rrs17782313 (Ps0.3). Finally, there were no significant difference on changes in body mass and composition, REE, leptin or TSH levels among non-risk allele carriers, carriers of the C allele risk of the MC4Rrs17782313, carriers of the A allele of the FTOrs9939609 and carriers of both risk alleles after the 12-week energy-restricted diet intervention (Ps0.1).Carrying the A risk allele of the FTOrs9939609 and/or the C risk allele of the MC4Rrs17782313 did not influence body mass and FM loss, or REE decrease in obese women after a 12-week energy-restricted diet intervention.Objetivo: Examinar la influencia individual y combinada de los polimorfismos genéticos FTO rs9939609 y MC4R rs17782313 en los cambios en la masa grasa (MG), gasto energético en reposo (GER), leptina y tirotropina (TSH) tras una intervención de 12 semanas de duración con dieta hipocalórica en mujeres pre-menopáusicas con obesidad no mórbida. Métodos: Se evaluaron al inicio y al final de la intervención la MG (absorciometría dual de rayos X), el GER (calorimetría indirecta) y los niveles de leptina y TSH en sangre en 77 mujeres (edad: 36.8±7.0 años) obesas (IMC: 33.9±2.8kg/m2). Resultados: No se observaron diferencias estadísticamente significativas (Ps0.1) entre las portadores y las no portadoras del alelo A del FTOrs9939609 (TT vs. portadores del alelo) en los cambios en la masa corporal (-8.6±3.2% vs. -8.7±3.3 %), MG (12.8±4.7% vs. –12.9±6.3%), GER (-11.3±4.7 vs. -9.4±8.1%), leptina (-34.1±25.1% vs. -43.5±24.1%) y TSH (5.2±34.5% vs. -1.7±27.1%). Tampoco se observaron diferencias estadísticamente significativas en los cambios en la masa corporal (-8.6±3.6% vs. -8.9±2.6%), MG (-12.7±6.1% vs. -13.4±5.3%), GER (-9.8±7.4% -9.4±9.4%), leptina (-39.0±26.9% vs. -44.8±18.4%) y TSH (-1.0±30.0% vs. 1.5±26.5%) entre las participantes portadoras y no portadoras del alelo C del MC4Rrs17782313 (Ps0.3). Finalmente, no se encontraron diferencias estadísticamente significativas en los cambios en la masa y composición corporal, el GER, o los niveles de leptina y TSH entre mujeres no portadoras de alelos de riesgo, portadoras del alelo C del MC4Rrs17782313, portadoras del alelo A del FTOrs9939609 y portadoras de los dos alelos de riesgo (A y C) al final de las 12 semanas de intervención con dieta hipocalórica (Ps0.1). Conclusión: Ser portador del alelo de riesgo A del FTOrs9939609 y/o del alelo de riesgo C del MC4Rrs17782313 no influye en la pérdida de masa grasa o en el descenso del GER en mujeres obesas tras 12 semanas de intervención con dieta hipocalórica.

Mitochondrial uncoupling protein 1 (UCP1) mediates the thermogenic transport of protons through the inner mitochondrial membrane. This proton leak uncouples respiration from ATP synthesis. The current study assessed the possible contribution of UCP1 muscle gene transfer to impair mitochondrial respiration in a tissue lacking UCP1 gene expression. Rats received an intramuscular injection of plasmid pXC1 containing UCP1 cDNA in the right tibialis muscles, while left tibialis muscles were injected with empty plasmid as control. Ten days after DNA injection, mitochondria from tibialis anterior muscles were isolated and analyzed. UCP1 gene transfer resulted in protein expression as analyzed by inmunoblotting. Mitochondria isolated from UCP1-injected muscles showed a significant increase in state 2 and state 4 oxygen consumption rates and a decreased respiration control ratio in comparison to mitochondria from control muscles. Furthermore, UCP1-containing mitochondria had a lower membrane potential in those states (2 and 4) when compared with control mitochondria. Our results revealed that UCP1 muscle gene transfer is associated with an induced mitochondrial proton leak, which could contribute to increase energy expenditure.

A number of experiments have demonstrated the antiobesity effects of b3-adrenergic receptor stimulation by promoting thermogenesis and/or lipolysis. While many studies have been performed in order to develop b3-adrenergic agonists as a novel strategy in the management of obesity, more information is needed about the mechanisms involved in thermogenesis and the actions of these drugs on adipocyte differentiation. To address this, the possible thermogenic and antiadipogenic properties of Tertatolol, a b3-adrenergic agonist, in a diet-induced obesity model has been tested. Animals fed on a high-fat diet gained more weight and fat mass as compared with control and high-fat fed animals treated with Tertatolol. A RT-PCR was carried out in white adipose tissue specific genes involved in thermogenesis such as uncoupling proteins (UCPs) and adipogenesis such as peroxisome proliferator-activated receptor (PPARg2), retinoid receptors (RXRa/RARa), and fatty acid binding protein (aP2). Levels of UCP1 mRNA were augmented in the Tertatolol-treated group as compared to non-treated high-fat fed animals, while the b3-adrenergic agonist treatment significantly decreased the expression levels of aP2 and transcription factors such as PPARg2 and the ratio RXRa/RARa as compared to obese rats. Altogether these data suggest that the antiobesity effects of b3-adrenergic agonists are not limited to the promotion of thermogenesis and/or lipolysis and support the implication that these b3-adrenergic agonists also affect fat deposition by impairing adipogenesis in white adipose tissue (WAT). © 2001 Elsevier Science Inc. All rights reserved.

The aim of this study was to evaluate the effects of Eminol®, the polyphenol-rich grape extract supplement (700 mg), on cardiovascular risk and oxidant stress indicators in a sample of volunteers. A randomized, double-blind, placebo-controlled clinical trial was performed over 56 days and included 60 volunteers. Thirty volunteers took 700 mg of the grape extract, Eminol® (E), and 30 took the placebo (P). On comparison of the results, a decrease in total cholesterol (E: 213.77 ± 4.1 mg/dl and P: 245.57 ± 4.1 mg/dl; p = 0.01) and LDL cholesterol (E: 142.17 ± 3.1 mg/dl and P: 165.13 ± 3.1 mg/dl; p = 0.02) levels as well as an increase in antioxidant capacity (E: 65.63 ± 5.8 μmol TE/mg and P: 57.80 ± 7.7 μmol TE/mg; p < 0.01) and vitamin E (E: 11.46 ± 0.5 μg/ml and P: 9.06 ± 0.5 μg/ml; p = 0.018) was observed. This result indicates that the grape extract Eminol® modulated the lipid profile in terms of cardiovascular risk indicators, lowering total blood cholesterol and LDL cholesterol levels.

The objective of this study was to examine the association of birth weight (BW) with body composition, resting metabolic rate (RMR), nonprotein respiratory quotient (NPRQ), and insulin sensitivity changes after a 12-week diet intervention program.A total of 78 obese (body mass index [BMI] 34.0 ± 2.8) women aged 36.7 ± 7 years volunteered to participate in a 12-week diet intervention program. We assessed body fat mass (FM), lean mass (LM), and bone mass (BM; measured by dual energy x-ray absorptiometry), RMR (measured by indirect calorimetry), fasting plasma glucose, and insulin before and after the intervention. We calculated BMI, FM to LM ratio (FM/LM), and HOMA-IR. BW and gestational age were self-reported, and the BW Z-score was calculated.At baseline, the BW Z-score was positively associated with LM (p0.01) and RMR (p0.05). The BW Z-score was significantly associated with diet-induced FM (p0.05) and FM/LM ratio changes (p0.01) independently of potential confounders including weight loss. The BW Z-score was not associated with diet-induced RMR or insulin resistance changes.Lower birth weight is associated with lower LM and RMR in obese women and could program a lower FM loss achievement after an energy-restriction diet intervention.

Klebsiella pneumoniae is an important cause of community-acquired and nosocomial pneumonia. Subversion of inflammation is essential for pathogen survival during infection. Evidence indicates that K. pneumoniae infections are characterized by lacking an early inflammatory response although the molecular bases are currently unknown. Here we unveil a novel strategy employed by a pathogen to counteract the activation of inflammatory responses. K. pneumoniae attenuates pro-inflammatory mediators-induced IL-8 secretion. Klebsiella antagonizes the activation of NF-κB via the deubiquitinase CYLD and blocks the phosphorylation of mitogen-activated protein kinases (MAPKs) via the MAPK phosphatase MKP-1. Our studies demonstrate that K. pneumoniae has evolved the capacity to manipulate host systems dedicated to control the immune balance. To exert this anti-inflammatory effect, Klebsiella engages NOD1. In NOD1 knock-down cells, Klebsiella neither induces the expression of CYLD and MKP-1 nor blocks the activation of NF-κB and MAPKs. Klebsiella inhibits Rac1 activation; and inhibition of Rac1 activity triggers a NOD1-mediated CYLD and MKP-1 expression which in turn attenuates IL-1β-induced IL-8 secretion. A capsule (CPS) mutant does not attenuate the inflammatory response. However, purified CPS neither reduces IL-1β-induced IL-8 secretion nor induces the expression of CYLD and MKP-1 thereby indicating that CPS is necessary but not sufficient to attenuate inflammation.

We investigated the role of common β2-adrenergic receptor (ADRB2) rs1042714 (Gln27Glu) and rs1042713 (Arg16Gly) polymorphisms on body weight and body composition response to 12-week energy-restricted diet in women. The study comprised 78 Spanish obese (BMI: 34.0 ± 2.8 kg/m²) women (age: 36.7 ± 7 years). We measured (before and after the dietary intervention) weight and height, and BMI calculated. Moreover, body fat mass and lean mass (LM) were measured by dual energy X-ray absorptiometry. We observed an interaction effect between the Gln27Glu polymorphism and diet-induced changes on body weight (P = 0.006), BMI (P = 0.004), and LM (P = 0.001). Women carrying the Glu allele had a greater reduction in body weight than non-Glu allele carriers (9.5 ± 2.9 vs. 7.0 ± 3.5%, respectively, P = 0.002). Moreover, women with the Glu allele lost more LM than the Gln27Gln group (5.9 ± 2.7 vs. 4.0 ± 2.7%, respectively, P = 0.001). We did not find any significant interaction effect between the Arg16Gly polymorphism and diet-induced changes on the outcome variables (all P0.1). The results suggest that the ADRB2 Gln27Glu polymorphism has a modulating effect on diet-induced changes on body weight and body composition, and should be considered in future obesity treatments. These findings should be taken as preliminary and be replicated in further energy restriction studies with larger sample sizes.

To assess the influence of body composition changes on circulating serum visfatin after following 12 weeks of energy restricted diet intervention. We also examined the possible role of visfatin in glucose metabolism and in obesity-associated low-grade inflammation.A total of 78 obese (BMI 34.0 ± 2.8 kg/m²) women aged 36.7±7 y volunteered to participate in the study. We measured by DXA body fat mass (FM) and lean mass (LM). Fasting serum visfatin, glucose, insulin, adiponectin, leptin, IL-1β, IL-6, IL-8, TNF-α and CRP concentrations were analyzed before and after the intervention and HOMA and QUIKI indexes were calculated. Mean weight loss 7.7 ± 3.0 kg and HOMA decreased in 24 ± 35%. Serum visfatin concentration change was negatively associated with LM difference (P0.05), whereas no significant relationship was observed with FM changes after energy restricted diet intervention. Changes in circulating serum visfatin levels were significantly and inversely associated with HOMA-IR (P0.01) and positively with QUICKI index (P0.02) after energy restricted diet intervention, regardless of achieved body weight loss. We did not find any significant association between changes in visfatin levels and IL-1β, IL-6, IL-8, TNF-α and CRP levels after dietary intervention (all P0.2).Circulating visfatin concentration is associated with sensitivity improvement achieved after energy restricted diet intervention induced weight loss. Furthermore, LM changes could be an influencing factor on visfatin concentrations and consequently, on the improvement of insulin sensitivity after weight loss in obese non-diabetic women. Our findings did not provide any evidence for a role of visfatin increase on low-grade inflammation after weight loss.

Human β-defensins (hBDs) contribute to the protection of the respiratory tract against pathogens. It is reasonable to postulate that pathogens have developed countermeasures to resist them. Klebsiella pneumoniae capsule polysaccharide (CPS), but not the lipopolysaccharide O antigen, mediated resistance against hBD1 and hBD2. hBD3 was the most potent hBD against Klebsiella. We investigated the possibility that as a strategy for survival in the lung, K. pneumoniae may not activate the expression of hBDs. Infection of A549 and normal human bronchial cells with 52145-ΔwcaK2, a CPS mutant, increased the expression of hBD2 and hBD3. Neither the wild type nor the lipopolysaccharide O antigen mutant increased the expression of hBDs. In vivo, 52145-ΔwcaK2 induced higher levels of mBD4 and mBD14, possible mouse orthologues of hBD2 and hBD3, respectively, than the wild type. 52145-ΔwcaK2-dependent upregulation of hBD2 occurred via NF-κB and mitogen-activated protein kinases (MAPKs) p44/42, Jun N-terminal protein kinase (JNK)-dependent pathways. The increase in hBD3 expression was dependent on the MAPK JNK. 52145-ΔwcaK2 engaged Toll-like receptors 2 and 4 (TLR2 and TLR4) to activate hBD2, whereas hBD3 expression was dependent on NOD1. K. pneumoniae induced the expression of CYLD and MKP-1, which act as negative regulators for 52145-ΔwcaK2-induced expression of hBDs. Bacterial engagement of pattern recognition receptors induced CYLD and MKP-1, which may initiate the attenuation of proinflammatory pathways. The results of this study indicate that K. pneumoniae CPS not only protects the pathogen from the bactericidal action of defensins but also impedes their expression. These features of K. pneumoniae CPS may facilitate pathogen survival in the hostile environment of the lung. Copyright © 2010, American Society for Microbiology. All Rights Reserved., This work has been funded by grants from the Instituto de Salud Carlos III (PI05/2311 and PI06/1629) and ERA-NET Pathogenomics (GEN2006-27776-C2-2-E/PAT and SAF2008-04353-E) to J.A.B. CibeRes is an initiative of the Instituto de Salud Carlos III.

Nutrigenomics is a new application of omics technologies in nutritional science. Nutrigenomics aims to identify molecular markers of diet-related diseases and mechanisms of interindividual variability in response to food. The aim of this study was to evaluate peripheral blood mononuclear cells (PBMC) as a model system and readily available source of RNA to discern gene expression signatures in relation to personalized therapy of obesity. PBMC were collected from obese men before and after an 8-week low-calorie diet (LCD) to lose weight. Changes in gene expression before and after the LCD were initially screened using a DNA-microarray platform and validated by qRT-PCR. Global gene expression analysis identified 385 differentially expressed transcripts after the LCD. Further analyses showed a decrease in some specific oxidative stress and inflammation genes. Interestingly, expression of these genes was directly related to body weight, while a lower IL8 gene expression was associated with higher fat mass decrease. Collectively, these observations suggest that PBMCs are a suitable RNA source and model system to perform nutrigenomics studies related to obesity and development of personalized dietary treatments. IL8 gene expression warrant further research as a putative novel biomarker of changes in body fat percentage in response to an LCD.

Human malignant astrocytic tumors are the most common primary brain malignancies. Human gliomas are classified according to the extent of anaplasia or ‘de-differentiation’ appearance. Although this type of histological classification is widely accepted, the extensive heterogeneity of astrocytic tumors has made their pathological classification rather difficult. New genome-scale high throughput technologies for gene expression profiling, such as DNA microarrays, are emerging as new tools to allow a more accurate identification and characterization of different tumor degrees by discovering new specific markers and pathways of each stage. Present work reports interesting results that might be useful to differentiate between tumor grades. Data presented here provides new evidences about the molecular basis underlying different tumor stages. In this sense, we identified key metabolic pathways, crucial for tumor progression, as being differentially regulated in different tumor stages. On the other hand, remarkable findings regarding Notch pathway are reported, as some members of this receptor family were found to be differentially expressed depending on the malignancy degree. Our results clearly point out important molecular differences between different tumor stages and suggest that more studies are needed to understand specific molecular events characteristic of each stage. These types of studies represent a first step to deepen into the tumor physiology, which may potentially help for better and a more precise diagnosis of gliomas.

The aim of this work was to evaluate the effect of uncoupling protein 2 (UCP2) muscle gene transfer on mitochondrial activity.Five week-old male Wistar rats received an intramuscular injection of plasmid pXU1 containing UCP2 cDNA in the right tibialis anterior muscles. Left tibialis anterior muscles were injected with vehicle as control. Ten days after DNA injection, tibialis anterior muscles were dissected and muscle mitochondria isolated and analyzed.There were two mitochondrial populations in the muscle after UCP2 gene transfer, one of low fluorescence and complexity and the other, showing high fluorescence and complexity. UCP2 gene transfer resulted in a 3.6 fold increase in muscle UCP2 protein levels compared to control muscles assessed by Western blotting. Furthermore, a significant reduction in mitochondria membrane potential assessed by spectrofluorometry and flow cytometry was observed. The mitochondria membrane potential reduction might account for a decrease in fluorescence of the low fluorescence mitochondrial subpopulation.It has been demonstrated that UCP2 muscle gene transfer in vivo is associated with a lower mitochondria membrane potential. Our results suggest the potential involvement of UCP2 in uncoupling respiration. International Journal of Obesity (2001) 25, 68-74

Resistin has been suggested as a hormone involved in insulin resistance, which may link obesity with type-2 diabetes. The aim of this work was to evaluate adipocyte resistin mRNA level in high-fat fed animals (cafeteria diet) and the influence of the treatment with the b3-adrenergic agonist tertratolol in overweight animals. Thus, female rats were assigned to three groups, which received control or cafeteria diet and intraperitoneal placebo or cafeteria diet and tertratolol administration for 30 days. Resistin mRNA levels were determined by RT-PCR. The results demonstrate that tertratolol treatment significantly prevented the excessive weight gain induced by the cafeteria regime In the same way, fat depots (perirenal, periovaric and abdominal regions) were similarly influenced by the dietary and pharmacological conditions. Interestingly, the resistin mRNA levels (arbitrary units) in adipose tissue, which remained unaffected in control and overweight animals receiving the cafeteria diet, were doubled by the b3 agonist administration. These data seem to indicate that tertratolol, in diet-related overweightiness, induces overexpression of resistin, which suggests a potential implication of the hormone in the energy balance regulation