Association of increased Visfatin/PBEF/NAMPT circulating concentrations and gene expression levels in peripheral blood cells with lipid metabolism and fatty liver in human morbid obesity

BACKGROUND AND AIMS: Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine with physiological effects on the control of glucose homeostasis as well as potentially involved in inflammation. The association of circulating NAMPT concentrations with obesity has not been clearly established. The aim of the present work was to evaluate the effect of obesity on circulating concentrations and gene expression levels of NAMPT in human peripheral blood cells (PBCs) as well as its involvement in inflammation, glucose and lipid metabolism. METHODS AND RESULTS: Forty-four serum samples obtained from 14 lean and 30 obese volunteers were used to analyse the circulating concentrations of NAMPT. In addition, PBC, omental adipose tissue (OM) and liver biopsy samples obtained from a subgroup of subjects were used to determine transcript levels of NAMPT by Real-time PCR. Glucose and lipid profile as well as several inflammatory factors and hepatic enzymes were analysed. NAMPT circulating concentrations (P<0.01) and gene expression levels in PBC (P<0.05) were significantly increased in obese patients as compared to lean subjects. Total-cholesterol (P=0.016), HDL-cholesterol (P=0.036) and triglycerides (P=0.050) were significant and independent determinants of circulating concentrations of NAMPT (P<0.01). Moreover, a positive correlation (P<0.01) was found with the hepatic enzymes alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase after BMI adjustment. CONCLUSION: Our work shows that NAMPT circulating concentrations and mRNA expression levels in PBC are increased in obese patients and that plasma NAMPT levels are related to inflammation, lipid metabolism and hepatic enzymes suggesting a potential involvement in fatty liver disease and in the obesity-associated inflammatory stat

The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus

The G protein-coupled receptor 39 (GPR39) has recently been identified as the receptor for obestatin, a peptidic hormone involved in energy homeostasis. However, the expression levels of this receptor in human adipose tissue in obesity and obesity-associated type 2 diabetes mellitus (T2DM) remain unknown. Therefore, we evaluated the actual presence of GPR39 mRNA in human adipose tissue and whether GPR39 expression levels are altered in obesity and obesity-associated T2DM. DESIGN: Omental adipose tissue biopsies obtained from 15 women were used in the study. Patients were classified as lean (body mass index 20.8 +/- 1.0 kg/m(2)), obese normoglycaemic (body mass index 48.4 +/- 2.1 kg/m(2)) and obese T2DM patients (body mass index 52.6 +/- 4.9 kg/m(2)). Anthropometric measurements and biochemical profiles were assessed for each subject. Real-time RT-PCR analyses were performed to quantify transcript levels of GPR39 and adiponectin. RESULTS: Obese T2DM patients exhibited significantly lower GPR39 expression levels compared to lean (P = 0.016) and obese normoglycaemic subjects (P = 0.008), while no differences between lean and obese normoglycaemic patients were observed. The mRNA expression levels of GPR39 were negatively correlated to fasting glucose concentrations (r = -0.581, P = 0.023), while exhibiting a positive correlation to adiponectin mRNA expression levels (r = 0.674, P = 0.006). CONCLUSION: GPR39 is expressed in human adipose tissue. The reduced expression levels of GPR39 in omental adipose tissue observed in obese patients with T2DM suggest an involvement of obestatin signalling in glucose homeostasis and T2DM development

Expression of caveolin-1 in human adipose tissue is upregulated in obesity and obesity-associated type 2 diabetes mellitus and related to inflammation

Caveolin-1 (CAV-1) plays important roles in many aspects of cellular biology, including vesicular transport, cholesterol homeostasis and signal transduction. The aim of the present study was to explore gene expression levels of CAV-1 in human adipose tissue in obesity and obesity-associated type 2 diabetes mellitus (T2DM) and to analyse its potential implication in the inflammatory state associated with obesity. DESIGN AND METHODS: Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) obtained from 15 females were used in the study. Patients were classified as lean (BMI 20.8 +/- 1.0 kg/m(2)) or obese (BMI 50.5 +/- 2.6 kg/m(2)). The obese group was further subclassified as normoglycaemic (NG) or patients with T2DM. Anthropometric measurements as well as circulating metabolites, hormones and adipokines were determined. Real-time polymerase chain reaction (PCR) analyses were performed to quantify transcript levels of CAV-1 and monocyte chemoattractant protein (MCP-1). RESULTS: The presence of CAV-1 protein was detected in VAT and SAT by immunohistochemistry. Both obese NG and with T2DM patients exhibited significantly higher CAV-1 expression levels in VAT and SAT compared with lean subjects (P < 0.05). No differences between obese NG and T2DM patients were observed in VAT. However, obese T2DM patients were found to have higher CAV-1 expression levels in SAT (P < 0.05) compared with obese NG patients. A significant correlation was found between CAV-1 mRNA expression levels in VAT and different circulating inflammatory markers such as sialic acid (SA) (P < 0.001) and fibrinogen (P < 0.001) as well as with MCP1 mRNA expression (P < 0.05). CONCLUSION: Our findings show for the first time the upregulation of mRNA CAV-1 expression levels in VAT and SAT of obese NG and obese T2DM patients compared with lean controls, suggesting a role for CAV-1 in obesity and T2DM development. The association with different inflammatory markers further suggests an implication of CAV-1 in the low-grade inflammation accompanying obesity

Plasma osteopontin levels and expression in adipose tissue are increased in obesity

Obesity acts as a cardiovascular risk factor by mechanisms that are not fully understood. Osteopontin (OPN) is a proinflammatory mediator involved in tissue remodeling that plays a role in atherosclerosis and diabetes. OBJECTIVE: The aim of the present study was to compare the circulating concentrations of OPN and its mRNA expression in omental adipose tissue of lean, overweight, and obese individuals and to analyze the effect of weight loss. SUBJECTS AND METHODS: Plasma concentrations of OPN were measured in 77 volunteers. OPN mRNA expression in omental adipose tissue obtained from 12 women was quantified by real-time PCR. In addition, the concentrations of OPN in 12 obese men were measured before and after weight loss following a dietetic program. SETTING: The study was conducted at a University Hospital. RESULTS: Obese and overweight patients exhibited significantly increased circulating OPN concentrations as compared with lean subjects (obese 72.6 +/- 28.5, overweight 68.2 +/- 20.8, lean 42.7 +/- 27.9 ng/ml; P < 0.001). A significant positive correlation was found between OPN levels and body fat (r = 0.45; P < 0.0001). Obese individuals showed significantly increased (P < 0.05) mRNA expression of OPN in omental adipose tissue as compared with lean volunteers, which was further increased in obese diabetic patients. Diet-induced weight loss significantly decreased OPN concentrations from 64.7 +/- 22.1 to 36.6 +/- 20.1 ng/ml (P = 0.006). CONCLUSIONS: These findings represent the first observation that plasma OPN and mRNA expression of OPN in omental adipose tissue are increased in overweight/obese patients with the latter being further elevated in obesity-associated diabetes. Moreover, weight loss reduces OPN concentrations, which may contribute to the beneficial effects accompanying weight reduction. Measurement of OPN might be useful for evaluating the outcomes of various clinical interventions for obesity-related cardiovascular disease

Increased circulating and visceral adipose tissue expression levels of YKL-40 in obesity-associated type 2 diabetes are related to inflammation: impact of conventional weight loss and gastric bypass

Context: Plasma YKL-40 is elevated in patients with type 2 diabetes. The potential role of visceral adipose tissue (VAT) as a significant source of YKL-40 is unknown. Objective: In the study circulating and expression levels of YKL-40 were examined in VAT analyzing the contribution of adipocytes and stromovascular fraction cells (SVFCs).Wealso explored YKL-40’s implication in insulin resistance and inflammation and the effect of weight loss on plasma YKL-40 concentrations. PatientsandMethods: Samples obtained from 53 subjects were used in the study.Geneandprotein expression levels of YKL-40 were analyzed in VAT as well as in both adipocytes and SVFCs. In addition, circulating YKL-40 concentrations were measured before and after weight loss achieved either by Roux-en-Y gastric bypass (n 26) or after a conventional dietetic program (n 20). Results: Circulating concentrations and VAT expression of YKL-40 were increased in obese patients with type 2 diabetes (P 0.01) as well as associated with variables of insulin resistance and inflammation. No differences in YKL-40 expression levels between adipocytes and SVFCs were detected. Monocyte chemoattractant protein-1 and homeostasis model assessment emerged (P 0.01) as independent factors predicting circulating YKL-40. Elevated levels of YKL-40 in obese patients decreased after weight loss following a conventional hypocaloric diet (P 0.05) but not via a surgery-induced negative energy balance mediated by the Roux-en-Y gastric bypass. Conclusions: The association of increased YKL-40 mRNA and protein levels in VAT with its circulating concentrations indicates an important contribution of VAT in YKL-40 regulation. Furthermore, our data suggest a relevant role of glucose metabolism and inflammation on YKL-40 regulation

Perpendicular magnetic anisotropy in granular multilayers of CoPd alloyed nanoparticles

Under the terms of the Creative Commons Attribution license.-- et al.Co-Pd multilayers obtained by Pd capping of pre-deposited Co nanoparticles on amorphous alumina are systematically studied by means of high-resolution transmission electron microscopy, x-ray diffraction, extended x-ray absorption fine structure, SQUID-based magnetometry, and x-ray magnetic circular dichroism. The films are formed by COPD alloyed nanoparticles self-organized across the layers, with the interspace between the nanoparticles filled by the non-alloyed Pd metal. The nanoparticles show atomic arrangements compatible with short-range chemical order of L10 strucure type. The collective magnetic behavior is that of ferromagnetically coupled particles with perpendicular magnetic anisotropy, irrespective of the amount of deposited Pd. For increasing temperature three magnetic phases are identified: hard ferromagnetic with strong coercive field, soft-ferromagnetic as in an amorphous asperomagnet, and superparamagnetic. Increasing the amount of Pd in the system leads to both magnetic hardness increment and higher transition temperatures. Magnetic total moments of 1.77(4) μB and 0.45(4) μB are found at Co and Pd sites, respectively, where the orbital moment of Co, 0.40(2) μB, is high, while that of Pd is negligible. The effective magnetic anisotropy is the largest in the capping metal series (Pd, Pt, W, Cu, Ag, Au), which is attributed to the interparticle interaction between de nanoparticles, in addition to the intraparticle anisotropy arising from hybridization between the 3d-4d bands associated to the Co and Pd chemical arrangement in a L10 structure type.The financial support of the Spanish Ministerio de Economía MAT2014-53921-R and Aragonese DGA-IMANA E34 projects is acknowledged.Peer Reviewe

Profiling of chemonaive osteosarcoma and paired-normal cells identifies EBF2 as a mediator of osteoprotegerin inhibition to tumor necrosis factor–related apoptosis-inducing ligand–induced apoptosis

Osteosarcoma is the most prevalent bone tumor in children and adolescents. At present, the mechanisms of initiation, maintenance, and metastasis are poorly understood. The purpose of this study was to identify relevant molecular targets in the pathogenesis of osteosarcoma. EXPERIMENTAL DESIGN: Tumor chemonaive osteoblastic populations and paired control normal osteoblasts were isolated and characterized phenotypically from seven osteosarcoma patients. Global transcriptomic profiling was analyzed by robust microarray analysis. Candidate genes were confirmed by real-time PCR and organized in molecular pathways. EBF2 and osteoprotegerin (OPG) levels were determined by real-time PCR and OPG protein levels were assessed by ELISA. Immunohistochemical analysis was done in a panel of 46 osteosarcoma samples. Silencing of EBF2 was achieved by lentiviral transduction of short hairpin RNA. Apoptosis was determined by caspase-3/7 activity. RESULTS: A robust clustered transcriptomic signature was obtained in osteosarcoma. Transcription factor EBF2, a known functional bone regulator, was among the most significantly overexpressed genes. Immunohistochemical analysis showed that osteosarcoma is expressed in approximately 70% of tumors analyzed. Because EBF2 was shown previously to act as a transcriptional activator of OPG, elevated levels of EBF2 were associated with high OPG protein levels in osteosarcoma samples compared with normal osteoblastic cells. Knockdown of EBF2 led to stunted abrogation of OPG levels and increased sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. CONCLUSIONS: These findings suggest that EBF2 represents a novel marker of osteosarcoma. EBF2 up-regulation may be one of the mechanisms involved in the high levels of OPG in osteosarcoma, contributing to decrease TRAIL-induced apoptosis and leading to TRAIL resistance

Cortactin (CTTN) overexpression in osteosarcoma correlates with advanced stage and reduced survival

The cortactin (CTTN) gene has been found, by transcriptomic profiling, to be overexpressed in pediatric osteosarcoma. The location of CTTN at 11q13 and the role of cortactin in cytoskeleton restructuring make CTTN of interest as a potential biomarker for osteosarcoma. MATERIALS AND METHODS: Osteoblasts were isolated from 20 high-grade osteosarcomas before chemotherapy, and paired with cell samples from normal tissue, prior to RNA expression analysis on HG-U133A chips (Affymetrix). Semiquantitative CTTN mRNA expression was analyzed by real-time PCR. An osteosarcoma tissue microarray (TMA) containing 233 tissue spots from 48 patients was used for an immunohistochemical (IHC) study of cortactin. RESULTS: Transcriptomic profiling and real-time PCR analysis indicated increased CTTN expression in osteosarcomas (p = 0.001, Student's T test). TMA IHC showed cortactin to be present more frequently and in greater abundance in osteosarcomas than non-tumoral osteoblastic samples (p< 0.006, Mann-Withney test). Analysis of clinical outcomes indicated that overall survival for patients with primary tumors positive for cortactin was significantly lower than that for patients with cortactin negative (or only weakly staining) tumors (p = 0.0278, Log-rank test). CONCLUSIONS: Our preliminary data support the hypothesis that over-expression of cortactin, contained in the 11q13 amplicon, is involved in osteosarcoma carcinogenesis. The potential of cortactin overexpression as a biomarker for osteosarcoma is consolidated

Structural and magnetic properties of granular CoPd multilayers

Multilayers of bimetallic CoPd alloyed and assembled nanoparticles, prepared by room temperature sequential sputtering deposition on amorphous alumina, were studied by means of high-resolution transmission electron microscopy, x-ray diffraction, SQUID-based magnetometry and x-ray magnetic circular dichroism. Alloying between Co and Pd in these nanoparticles gives rise to a high perpendicular magnetic anisotropy. Their magnetic properties are temperature dependent: at low temperature, the multilayers are ferromagnetic with a high coercive field; at intermediate temperature the behavior is of a soft-ferromagnet, and at higher temperature, the perpendicular magnetic anisotropy in the nanoparticles disappears. The magnetic orbital moment to spin moment ratio is enhanced compared with Co bare nanoparticles and Co fcc bulk.The financial support of the Spanish MINECO MAT2011-23791, MAT2014-53921-R and Aragonese DGA-IMANA E34 projects is acknowledged.Peer Reviewe

Z boson production in p+Pb collisions at sNN√=5.02 TeV measured with the ATLAS detector

The ATLAS Collaboration has measured the inclusive production of Z bosons via their decays into electron and muon pairs in p+Pb collisions at √ sNN = 5.02 TeV at the Large Hadron Collider. The measurements are made using data corresponding to integrated luminosities of 29.4 nb−1 and 28.1 nb−1 for Z → ee and Z → µµ, respectively. The results from the two channels are consistent and combined to obtain a cross section times the Z → `` branching ratio, integrated over the rapidity region |y ∗ Z | < 3.5, of 139.8 ± 4.8 (stat.) ± 6.2 (syst.) ± 3.8 (lumi.) nb. Differential cross sections are presented as functions of the Z boson rapidity and transverse momentum, and compared with models based on parton distributions both with and without nuclear corrections. The centrality dependence of Z boson production in p+Pb collisions is measured and analyzed within the framework of a standard Glauber model and the model’s extension for fluctuations of the underlying nucleon-nucleon scattering cross sectionFil: Aad, G.. Aix-Marseille Université; FranciaFil: Abbott, B.. Oklahoma State University; Estados UnidosFil: Abdallah, J.. Academia Sinica; ChinaFil: Abdinov, O.. Azerbaijan Academy of Sciences; AzerbaiyánFil: Aben, R.. University of Amsterdam; Países BajosFil: Alconada Verzini, María Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Alonso, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Arduh, Francisco Anuar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Dova, Maria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Monticelli, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Wahlberg, Hernan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Otero y Garzon, Gustavo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Piegaia, Ricardo Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Reisin, Hernan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Sacerdoti, Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Zieminska, D.. Indiana University; Estados UnidosFil: Zimine, N. I.. Joint Institute for Nuclear Research ; RusiaFil: Zimmermann, C.. Universität Mainz; AlemaniaFil: Zimmermann, S.. Albert-Ludwigs-Universität; AlemaniaFil: Zinonos, Z.. Georg-August-Universität; AlemaniaFil: Zinser, M.. Universität Mainz; AlemaniaFil: Ziolkowski, M.. Universität Siegen ; AlemaniaFil: Živković, L.. University of Belgrade; SerbiaFil: Zobernig, G.. University of Wisconsin; Estados UnidosFil: Zoccoli, A.. Università di Bologna; ItaliaFil: Nedden, M. zur. Humboldt University; AlemaniaFil: Zurzolo, G.. Università di Napoli; ItaliaFil: Zwalinski, L.. Cern - European Organization For Nuclear Research; SuizaFil: The ATLAS Collaboration. No especifica