Prognostic value of serum resistin levels in patients with acute myocardial infarction.

PubMed

Erer, Hatice Betul; Sayar, Nurten; Guvenc, Tolga Sinan; Aksaray, Sebahat; Yilmaz, Hale; Altay, Servet; Turer, Ayca; Oz, Tugba Kemaloglu; Karadeniz, Fatma Ozpamuk; Oz, Dilaver; Ekmekci, Ahmet; Zencirci, Aycan Esen; Eren, Mehmet

2014-01-01

Resistin is a novel adipokine that is suggested to be involved in inflammatory conditions and atherosclerosis. To investigate the prognostic importance of resistin in acute myocardial infarction (AMI) patients. Resistin levels were measured in a population of 132 patients with AMI, of whom 72 (54%) had a diagnosis of ST elevation myocardial infarction (STEMI), and 60 (46%) had non-ST elevation myocardial infarction (NSTEMI). Thirty-three consecutive subjects who were referred to elective coronary angiography due to chest pain evaluation with normal coronary angiograms served as controls. All patients were followed-up for the occurrence of major adverse cardiac events (MACE). There was a significant increase in serum resistin levels in patients with AMI compared to controls (3.71 ± 4.20 vs. 2.00 ± 1.05, p = 0.001, respectively). However, serum resistin levels were similar in patients with STEMI and NSTEMI. (4.26 ± 5.11 vs. 3.06 ± 2.64, p = 0.49, respectively). The patients with MACE had significantly higher levels of serum resistin levels compared to either the AMI or the control group (6.35 ± 5.47, p = 0.005, respectively). Logistic regression analysis revealed that resistin, left ventricular ejection fraction, and coronary artery bypass graft were independent predictors of MACE in AMI patients (OR = 1.11, 95% CI 1.01-1.22, p = 0.03 and OR = 3.84, 95% CI 1.26-11.71, p = 0.018, respectively). Serum resistin level was increased in patients with AMI and constituted a risk factor for MACE in this group.

Assessment of Salivary Adipokines Resistin, Visfatin, and Ghrelin as Type 2 Diabetes Mellitus Biomarkers

PubMed Central

Meadows, Melinda L.; Maxwell, Lisa

2018-01-01

Type 2 diabetes mellitus (T2DM) is emerging as a metabolic epidemic worldwide. Pathologically, dysregulation of many biological pathways precedes hyperglycemia and the clinical diagnosis of T2DM. Changing trajectories along the process of T2DM development necessitates frequent measurement of biomarkers for early identification of at-risk individuals and successful prevention. Increase in circulating inflammatory adipokines has been suggested as predictive of T2DM. Human saliva is an easily accessible biospecimen amenable for painless frequent collection and possesses nearly 50% of serum proteome. In this study, we measured the adipokines resistin, visfatin, TNF-α, and ghrelin as markers for T2DM in unstimulated whole saliva (UWS) using specific assay kits. Resistin and visfatin concentrations were significantly higher in T2DM saliva. Although the concentration of acylated or unacylated ghrelin was lower in diabetic saliva, the decrease was not significant. Since resistin and visfatin are biomarkers integral to T2DM pathology, their salivary assessments may receive clinical acceptance. PMID:29487749

Neutrophil-derived resistin release induced by Aggregatibacter actinomycetemcomitans.

PubMed

Furugen, Reiko; Hayashida, Hideaki; Yoshii, Yumiko; Saito, Toshiyuki

2011-08-01

Resistin is an adipokine that induces insulin resistance in mice. In humans, resistin is not produced in adipocytes, but in various leukocytes instead, and it acts as a proinflammatory molecule. The present investigation demonstrated high levels of resistin in culture supernatants of neutrophils that are stimulated by a highly leukotoxic strain of Aggregatibacter actinomycetemcomitans. In contrast, the level of resistin was remarkably low when neutrophils were exposed to two other strains that produce minimal levels of leukotoxin and a further isogenic mutant strain incapable of producing leukotoxin. Pretreatment of neutrophils with a monoclonal antibody to CD18, β chain of lymphocyte function-associated molecule 1 (LFA-1), or an Src family tyrosine kinase inhibitor before incubation with the highly leukotoxic strain inhibited the release of resistin. These results show that A. actinomycetemcomitans-expressed leukotoxin induces extracellular release of human neutrophil-derived resistin by interacting with LFA-1 on the surface of neutrophils and, consequently, activating Src family tyrosine kinases. 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal-weight individuals.

PubMed

Jonas, Marta Izabela; Kurylowicz, Alina; Bartoszewicz, Zbigniew; Lisik, Wojciech; Jonas, Maurycy; Domienik-Karlowicz, Justyna; Puzianowska-Kuznicka, Monika

2017-01-01

The interplay between adiponectin and resistin, the two adipokines of opposite effects, may determine the metabolic profile of obese individuals and development of obesity-related complications. The current study was conducted to assess how adiponectin/resistin interplay in sera and adipose tissues may influence the metabolic profile of obese and normal-weight subjects. Concentrations of adiponectin and resistin were measured on protein level by immunoassay in visceral and subcutaneous adipose tissues from 50 obese (body mass index > 40 kg/m 2 ) and 28 normal-weight (body mass index 20-24.9 kg/m 2 ) individuals. Simultaneously expression of ADIPOQ and RETN (encoding adiponectin and resistin, respectively) was assessed on mRNA level by real-time PCR. ADIPOQ mRNA (P = 0.0001) and adiponectin protein (P = 0.0013) levels were lower, while RETN mRNA (P = 0.0338) and resistin (P < 0.0001)-higher in subcutaneous adipose tissues of obese subjects. ADIPOQ and RETN mRNA levels did not correlate with protein concentrations in the investigated adipose tissues. In obesity adiponectin serum concentrations correlated positively with ADIPOQ mRNA in subcutaneous adipose tissue (P = 0.005) and negatively with protein levels in visceral adipose tissue (P = 0.001). Obesity was associated with higher adiponectin-resistin index value in sera (P < 0.0001) and decreased in subcutaneous adipose tissue (P < 0.001), but only adiponectin-resistin index measured in sera was significantly higher in obese with the metabolic syndrome (P = 0.04). Obesity affects synthesis of adiponectin and resistin mainly in subcutaneous adipose tissue. The adiponectin-resistin index assessed in the adipose tissues has a different prognostic value compared to the adiponectin-resistin index in serum and does not reflect a metabolic risk in obese individuals.

The relation of obesity with serum resistin levels in smoker and nonsmokers

PubMed Central

Gürsoy, Gül; Eşbah, Onur; Kirnap, Nazli Gülsoy; Çetiner, Hacer; Acar, Yaşar; Demirbaş, Berrin; Öztürk, Abidin; Kiliç, Zuhal

2012-01-01

Background: The demonstration that adipose tissue produces numerous cytokines increases interest of investigators in their role in the pathogenesis of obesity. Resistin is one of those cytokines. There are conflicing reports as cigarette smoking impairs insulin secretion, augments insulin resistance, or has no effect on glucose metabolism. In our study, we intended to examine the relationship of obesity with resistin levels in smokers and nonsmokers. Patients and Methods: The study included 52 male smokers and 34 age matched nonsmoker male control subjects. We classified smoker and nonsmoker groups according to their body mass index as BMI < 27 and ≥27. As well as making physical and anthropometric examinations, fasting plasma glucose and insulin, postprandial plasma glucose, lipid profile, and resistin levels were measured in all male subjects. We compared all parameters in smoker and nonsmokers either having BMI < 27 or ≥27. Results: In both BMI levels, resistin levels were higher in smoker groups than nonsmoker ones (P<0.01 all), we did not find any difference in other parameters. Conclusion: in conclusion we may speculate that if someone smokes resistin levels increase. PMID:23264782

The associations between the growth hormone/insulin-like growth factor-1 axis, adiponectin, resistin and metabolic profile in children with growth hormone deficiency before and during growth hormone treatment.

PubMed

Witkowska-Sędek, Ewelina; Rumińska, Małgorzata; Stelmaszczyk-Emmel, Anna; Majcher, Anna; Pyrżak, Beata

2018-01-01

This study investigated associations between the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, adiponectin, resistin and metabolic profile in 47 GH-deficient children before and during 12 months of GH treatment. 23 short age-matched children without growth hormone deficiency (GHD) or any genetic or chronic disorders were recruited as controls at baseline. Metabolic evaluation included measurements of adiponectin, resistin, IGF-1, total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, glycated haemoglobin (HbA1c), thyroid stimulating hormone (TSH) and free thyroxine (free T4) concentrations. The GH-deficient children had significantly higher adiponectin (p<0.05) and total cholesterol (p<0.05) levels, and a significantly lower level of resistin (p<0.05) than the controls. Resistin at 6 months of GH treatment significantly correlated with changes in height SDS in that period (r=0.35) and with the level of fasting insulin (r=0.50), the HOMA-IR (r=0.56) and the QUICKI (r=-0.53) at 12 months of therapy. Adiponectin level at 12 months of GH treatment was significantly associated with changes in HDL-C within the first 6 (r=0.73) and within 12 (r=0.56) months of therapy, while resistin significantly correlated with an increment in IGF-1 within 12 months of treatment (r=0.49) and with total-C at 12 months (r=0.56). Untreated GH-deficient children had higher adiponectin and lower resistin levels than healthy short children without GHD. Adiponectin and resistin levels did not change significantly during the first 12 months of GH therapy. Good responders to GH treatment had a tendency for higher resistin level during GH therapy, which positively correlates with the insulin resistance parameters.

Adipocyte resistin mRNA levels are down-regulated by laparoscopic ovarian electrocautery in both obese and lean women with polycystic ovary syndrome.

PubMed

Seow, Kok-Min; Juan, Chi-Chang; Ho, Low-Tone; Hsu, Yung-Pei; Lin, Yu-Hung; Huang, Lee-Wen; Hwang, Jiann-Loung

2007-04-01

The aim of this study was to investigate serum and adipocyte mRNA expression of resistin in lean and obese women with polycystic ovary syndrome (PCOS) before and 3 months after laparoscopic ovarian electrocauterization (LOE). Adipose tissue obtained from 12 women with PCOS (six obese and six lean, body mass index > 27 kg m(-1) as threshold point) before and after LOE was analysed. Gene expression of resistin was measured by semi-quantitative RT-PCR. Ten lean, age-matched healthy women served as controls. Both lean and obese women with PCOS had significantly higher fasting and 2 h insulin and homeostasis model insulin resistance index (HOMA(IR)) values and lower fasting glucose-to-insulin ratios (G(0)/I(0)) than did the controls. The serum levels of glucose and insulin and HOMA(IR) were significantly decreased, and the G(0)/I(0) ratio was significantly increased 3 months after LOE. No difference was found in serum resistin levels between controls and either obese or lean women with PCOS before LOE, nor between PCOS patients before and after LOE. However, resistin mRNA expression levels in both lean and obese women with PCOS before LOE were significantly higher than that in controls and were decreased significantly after LOE back to control levels. Local resistin activity may be actively involved in the pathogenesis of PCOS. LOE reduces insulin resistance and down-regulates resistin mRNA expression in lean and obese women with PCOS.

Measurement of salivary resistin, visfatin and adiponectin levels.

PubMed

Mamali, Irene; Roupas, Nikolaos D; Armeni, Anastasia K; Theodoropoulou, Anastasia; Markou, Kostas B; Georgopoulos, Neoklis A

2012-01-01

Hormonal determination in saliva offers several advantages. Peptides enter the salivary glands either by active transport mechanisms or are expressed and secreted by the salivary glands themselves. The collection of saliva is a noninvasive, easily repeatable and less stressful technique than blood withdrawal. The purpose of the present study was to introduce a method for measuring salivary resistin, visfatin and adiponectin levels and to evaluate their associations with serum levels. Resistin, visfatin and adiponectin levels were measured in serum and saliva of 50 healthy adult volunteers (17 male and 33 female) using commercial enzyme immunoassay kits for serum with minor modifications. The present study documented the determination of resistin and adiponectin levels in saliva and the significant correlation of salivary levels with serum levels (r=0.441, p<0.01 and r=0.347, p<0.05, respectively). Moreover, the identification of visfatin in saliva was achieved, but no significant correlation with serum visfatin levels was observed. To our knowledge, this is the first study to report the determination of resistin and visfatin in saliva and the significant correlation of salivary resistin with serum levels, while it confirmed the significant association between salivary and serum adiponectin. The introduction of salivary determinations of adipokines could contribute to the elucidation of the physiology and the role of the specific adipokines in various clinical conditions (obesity, insulin resistance, inflammation, reproduction, energy imbalance and stress response). Copyright © 2011 Elsevier Inc. All rights reserved.

Elevated resistin levels induce central leptin resistance and increased atherosclerotic progression in mice

USDA-ARS?s Scientific Manuscript database

Resistin was originally identified as an adipocyte-derived factor upregulated during obesity and as a contributor to obesity-associated insulin resistance. Clinically, resistin has also been implicated in cardiovascular disease in a number of different patient populations. Our aim was to simultaneou...

Loxin polymorphism is associated with increased resistin levels and with oxidative status.

PubMed

Gambino, Roberto; Bo, Simona; Musso, Giovanni; Pagano, Gianfranco; Cassader, Maurizio

2011-08-01

We hypothesized that LOX-1 polymorphism may impact on inflammation and cardiovascular risk by modulating systemic resistin expression. 276 men were randomly selected from a population-based cohort. Metabolic and inflammatory markers were evaluated at baseline and after 6-years follow-up, OLR1 (loxin) IVS4-14 A>G polymorphism was assessed. Mean plasma resistin and nitrotyrosine values were significantly higher, and TAS was significantly lowered in homozygous for the G allele. The G allele was significantly and directly associated with resistin and nitrotyrosine values. Enhanced oxidized-LDL uptake by LOX-1 G-allele carriers is associated with increased pro-oxidant status and resistin levels, suggesting a major uptake of ox-LDL by macrophages, smooth muscle cells, and monocytes. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Role of resistin in the inflammatory response induced by nicotine plus lipopolysaccharide in human periodontal ligament cells in vitro.

PubMed

Kang, S K; Park, Y D; Kang, S I; Kim, D K; Kang, K L; Lee, S Y; Lee, H J; Kim, E C

2015-10-01

Resistin was recently reported to play a role in inflammation-related diseases such as arthritis. However, the precise role of resistin in chronic inflammatory diseases, such as periodontal disease, remains unclear. The aim of this study was to investigate the combined effects of nicotine and lipopolysaccharide (LPS) on the expression of resistin and to assess whether resistin expression influences the levels of inflammatory cytokines, extracellular matrix (ECM) molecules and MMPs in human periodontal ligament cells (PDLCs) stimulated with both nicotine and LPS. PDLCs were pretreated with isoproterenol or resistin-specific small interfering RNA (siRNA), stimulated with LPS plus nicotine for 24 h, and then monitored for the production of inflammatory mediators. The concentrations of prostaglandin E2 (PGE2) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method, respectively. RT-PCR and western blot analysis were used to measure the levels of mRNA and protein, respectively. Western blot analysis was also used to assess the activation of various signal-transduction pathways. Treatment with nicotine plus LPS up-regulated the expression of resistin mRNA and the production of resistin protein in PDLCs in a time- and concentration-dependent manner. Isoproterenol-mediated interference with the function of resistin, or siRNA-mediated knockdown of resistin expression, markedly attenuated the LPS plus nicotine-mediated stimulation of PGE2 and NO production, the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase proteins and the expression of proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-12] and MMPs (MMP-1, MMP-2 and MMP-9); however, these treatments restored the expression of ECM molecules. Furthermore, pretreatment with isoproterenol or resistin-specific siRNA blocked nicotine plus LPS-induced activation of phosphoinositide-3-kinase, glycogen synthase kinase-3 beta, β-catenin, p38, ERK, JNK and nuclear factor-κB. This is the first study to show that the inhibition of resistin, by either a pharmacological or a genetic silencing approach, has anti-inflammatory effects. These effects include decreased levels of inflammatory cytokines and the prevention of ECM breakdown in a nicotine plus LPS-stimulated PDLC model. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A family of tissue-specific resistin-like molecules

PubMed Central

Steppan, Claire M.; Brown, Elizabeth J.; Wright, Christopher M.; Bhat, Savitha; Banerjee, Ronadip R.; Dai, Charlotte Y.; Enders, Gregory H.; Silberg, Debra G.; Wen, Xiaoming; Wu, Gary D.; Lazar, Mitchell A.

2001-01-01

We have identified a family of resistin-like molecules (RELMs) in rodents and humans. Resistin is a hormone produced by fat cells. RELMα is a secreted protein that has a restricted tissue distribution with highest levels in adipose tissue. Another family member, RELMβ, is a secreted protein expressed only in the gastrointestinal tract, particularly the colon, in both mouse and human. RELMβ gene expression is highest in proliferative epithelial cells and is markedly increased in tumors, suggesting a role in intestinal proliferation. Resistin and the RELMs share a cysteine composition and other signature features. Thus, the RELMs together with resistin comprise a class of tissue-specific signaling molecules. PMID:11209052

A family of tissue-specific resistin-like molecules.

PubMed

Steppan, C M; Brown, E J; Wright, C M; Bhat, S; Banerjee, R R; Dai, C Y; Enders, G H; Silberg, D G; Wen, X; Wu, G D; Lazar, M A

2001-01-16

We have identified a family of resistin-like molecules (RELMs) in rodents and humans. Resistin is a hormone produced by fat cells. RELMalpha is a secreted protein that has a restricted tissue distribution with highest levels in adipose tissue. Another family member, RELMbeta, is a secreted protein expressed only in the gastrointestinal tract, particularly the colon, in both mouse and human. RELMbeta gene expression is highest in proliferative epithelial cells and is markedly increased in tumors, suggesting a role in intestinal proliferation. Resistin and the RELMs share a cysteine composition and other signature features. Thus, the RELMs together with resistin comprise a class of tissue-specific signaling molecules.

Maternal Serum Resistin Is Reduced in First Trimester Preeclampsia Pregnancies and Is a Marker of Clinical Severity.

PubMed

Christiansen, Michael; Hedley, Paula L; Placing, Sophie; Wøjdemann, Karen R; Carlsen, Anting L; Jørgensen, Jennifer M; Gjerris, Anne-Cathrine; Shalmi, Anne-Cathrine; Rode, Line; Sundberg, Karin; Tabor, Ann

2015-11-01

To examine whether resistin levels in first trimester maternal serum are associated with insulin resistance or preeclampsia (PE). A case-control study of maternal serum resistin concentration conducted using 285 normal pregnancies and 123 PE pregnancies matched for gestational age, parity and maternal age. Samples were taken in gestational weeks 10 +0 -13 +6 . There was a negative correlation between resistin and clinical severity of PE, but no correlation with IS, TNF-α, body mass index, birth weight and pregnancy length. Resistin is reduced in first trimester of PE pregnancies, particularly in severe PE. Inflammation and IS cannot explain this phenomenon.

Correlation between Resistin, Tuberculosis and Khat Addiction: A Study from South Western Province of Saudi Arabia

PubMed Central

Alvi, Ayesha; Fatima, Nuzhath; Jerah, Ahmed Ali; Rizwan, Mohammed; Hobani, Yahya Hasan; Sunosi, Rashad Al; Taha, Manal Mohamed El Hassan; Habiballah, Eldaw Mohamed; Agarwal, Pradeep Kumar; Abdulwahab, Siddig Ibrahim

2015-01-01

Tuberculosis(TB) is a disease of global significance, which accounts for a death in every 15 seconds. Recent studies shows TB is rising in certain parts of the world, and Saudi Arabia is one of them. Several factor contribute in predisposing the subjects for infection including but not limited to addiction to various compounds which have immune modulation properties, such as amphetamines and Heroin etc. Khat a plant whose leaves are chewed for its euphoric effect in east Africa and Arabian Peninsula including Saudi Arabia, is considered as mildly addictive, and its principle compound, Cathinone shares structural and functional similarity with amphetamine a known immunomodulator. Tuberculosis being a disease of immune modulation has a varied spectrum of complex interplay of proinflammatory molecules, resistin is one of them. In the present study, we try to explore the trinity of khat addiction, serum resistin level and tuberculosis by correlating the serum resistin level in non khat addicted healthy subjects, khat addicted healthy subjects, and in patients, both khat addicted and non khat addicted, with active tuberculosis. We observed significantly higher resistin level among the apparently healthy khat addicted subjects as compared to non addicted healthy controls. Thereafter, when we compare the resistin levels between khat addicted and non khat addicted TB patients we did not found significant difference between the two groups. However bacillary load was observe to be significantly higher among the khat addicted TB patient as compare to non addicted one. Validation of above results in animal model revealed dose dependant increase in bacillary growth in the Wistar rats treated with khat. Taken together these results suggest the role of khat in immune modulation albeit in the limited frame of resistin level. PMID:26448186

Resistin polymorphims, plasma resistin levels and obesity in Tunisian volunteers.

PubMed

Zayani, Nesrine; Hamdouni, Haithem; Boumaiza, Imen; Achour, Ons; Neffati, Fadoua; Omezzine, Asma; Najjar, Mohamed Fadhel; Bouslama, Ali

2018-02-01

Adipose tissue is an important endocrine organ that secretes a number of adipokines, like Resistin (RETN); it's an adipocytes-secreted cytokine and has been proposed as a link between obesity and diabetes. Many resistin gene polymorphisms were described and their implication in obesity was controversial. This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in RETN gene 420C/G; 44G/A; 62G/A; 394C/G and 299 G/A and their association with Resistin level and obesity in Tunisian volunteers. We recruited 169 nonobese (mean age=42.16-14.26 years; mean body mass index [BMI]=24.51-3.69 kg/m 2 ) and 160 obese (mean age=47.86-11.17 years; mean BMI=36-4.78 kg/m 2 ). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. Anthropometric parameters, lipid levels, Glycemia and insulinemia were measured, BMI was calculated and insulinresistance was evaluated with the homeostasis model assessment insulin resistance (HOMA-IR) and resistin level was measured by ELISA. Statistical analyses were performed by SPSS19.0. After adjustment for confounding parameters; the Odds Ratio (OR) of obesity associated with mutated genotypes at 420C/G compared with normal genotype was as: OR=2.17; 95% CI [1.28-3.68], P=.004. The serum Resistin levels present no significant association with all RETN polymorphisms and it was significantly associated with BMI (P=.047). In our haplotype analysis, one haplotype seems to be protective and one other seems to be the highest risk to obesity. The 420 C/G Polymorphism were associated with obesity and Leptin concentration in our population. © 2017 Wiley Periodicals, Inc.

Serum adipokines and HIV viral replication in patients undergoing antiretroviral therapy

PubMed Central

Aramă, Victoria; Tilişcan, Cătălin; Ion, Daniela Adriana; Mihăilescu, Raluca; Munteanu, Daniela; Streinu-Cercel, Anca; Tudor, Ana Maria; Hristea, Adriana; Leoveanu, Viorica; Olaru, Ioana; Aramă, Ştefan Sorin

2012-01-01

Introduction Several studies have reported that cytokines secreted by adipose tissue (adipokines) may be linked to HIV replication. The aim of the study was to evaluate the relationship between HIV replication and serum levels of adipokines, in a Caucasian HIV-infected population of men and women undergoing complex antiretroviral therapy. Methods A cross-sectional study was conducted in an unselected sample of 77 HIV-1-positive patients. Serum adipokines levels were measured including circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Patients were divided into two groups: Group 1 - with undetectable viral load and Group 2 - with persistent HIV viral replication. Differences between groups ? were tested using independent-sample t-test for Gaussian variables and Mann–Whitney–Wilcoxon test for non-parametric variables. Pearson's chi-squared test was used for correlation analysis. Results A total of 77 patients (age range: 17-65, mean: 32.5 years) including 44 men (57.1% men, age range: 17–63 years, mean: 34.1 years) and 33 women (42.9% women age range: 19–65 years, mean: 30.3 years) were included in the study. TNF-alpha had significantly higher serum levels in patients with detectable viral load (16.89 vs. 9.35 pg/mL), (p=0.043), but correlation analysis lacked statistical significance. Adiponectin had median serum levels of 9.22 ìg/mL in Group 1 vs. 16.50 ìg/mL in Group 2 but the results lacked statistical significance (p=0.059). Higher leptin, IL-6 and resistin serum levels were noted in patients with undetectable HIV viral load, without statistical significance. Conclusions The present study reported higher TNF-alpha serum levels in patients with persistent HIV viral load. We found no statistically significant correlations between adiponectin, leptin, resistin and IL-6 and HIV viral load in our Caucasian HIV-positive study population, undergoing antiretroviral therapy. PMID:24432258

Running a marathon induces changes in adipokine levels and in markers of cartilage degradation--novel role for resistin.

PubMed

Vuolteenaho, Katriina; Leppänen, Tiina; Kekkonen, Riina; Korpela, Riitta; Moilanen, Eeva

2014-01-01

Running a marathon causes strenuous joint loading and increased energy expenditure. Adipokines regulate energy metabolism, but recent studies have indicated that they also exert a role in cartilage degradation in arthritis. Our aim was to investigate the effects of running a marathon on the levels of adipokines and indices of cartilage metabolism. Blood samples were obtained from 46 male marathoners before and after a marathon run. We measured levels of matrix metalloproteinase-3 (MMP-3), cartilage oligomeric protein (COMP) and chitinase 3-like protein 1 (YKL-40) as biomarkers of cartilage turnover and/or damage and plasma concentrations of adipokines adiponectin, leptin and resistin. Mean marathon time was 3:30:46±0:02:46 (h:min:sec). The exertion more than doubled MMP-3 levels and this change correlated negatively with the marathon time (r = -0.448, p = 0.002). YKL-40 levels increased by 56% and the effect on COMP release was variable. Running a marathon increased the levels of resistin and adiponectin, while leptin levels remained unchanged. The marathon-induced changes in resistin levels were positively associated with the changes in MMP-3 (r = 0.382, p = 0.009) and YKL-40 (r = 0.588, p<0.001) and the pre-marathon resistin levels correlated positively with the marathon induced change in YKL-40 (r = 0.386, p = 0.008). The present results show the impact of running a marathon, and possible load frequency, on cartilage metabolism: the faster the marathon was run, the greater was the increase in MMP-3 levels. Further, the results introduce pro-inflammatory adipocytokine resistin as a novel factor, which enhances during marathon race and associates with markers of cartilage degradation.

Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats.

PubMed

Lee, Tsung-Ming; Chen, Wei-Ting; Chang, Nen-Chung

2016-01-25

Myocardial infarction (MI) was associated with insulin resistance, in which resistin acts as a critical mediator. We aimed to determine whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can attenuate arrhythmias by regulating resistin-dependent nerve growth factor (NGF) expression in postinfarcted rats. Normoglycaemic male Wistar rats after ligating coronary artery were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after operation. Post-infarction was associated with increased myocardial noradrenaline [norepinephrine (NE)] levels and sympathetic hyperinnervation. Compared with vehicle, sympathetic innervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Furthermore, sitagliptin was associated with reduced resistin expression and increased Akt activity. Ex vivo studies showed that glucose-dependent insulinotropic polypeptide (GIP) infusion, but not glucagon-like peptide-1 (GLP-1), produced similar reduction in resistin levels to sitagliptin in postinfarcted rats. Furthermore, the attenuated effects of sitagliptin on NGF levels can be reversed by wortmannin (a phosphatidylinositol 3-kinase antagonist) and exogenous resistin infusion. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation in the non-diabetic infarcted rats. Sitagliptin attenuated resistin expression via the GIP-dependent pathway, which inhibited sympathetic innervation through a signalling pathway involving phosphatidylinositol 3-kinase (PI3K) and Akt protein. © 2016 Authors.

Resistin modulates glucose uptake and glucose transporter-1 (GLUT-1) expression in trophoblast cells.

PubMed

Di Simone, Nicoletta; Di Nicuolo, Fiorella; Marzioni, Daniela; Castellucci, Mario; Sanguinetti, Maurizio; D'lppolito, Silvia; Caruso, Alessandro

2009-02-01

The adipocytokine resistin impairs glucose tolerance and insulin sensitivity. Here, we examine the effect of resistin on glucose uptake in human trophoblast cells and we demonstrate that transplacental glucose transport is mediated by glucose transporter (GLUT)-1. Furthermore, we evaluate the type of signal transduction induced by resistin in GLUT-1 regulation. BeWo choriocarcinoma cells and primary cytotrophoblast cells were cultured with increasing resistin concentrations for 24 hrs. The main outcome measures include glucose transport assay using [(3)H]-2-deoxy glucose, GLUT-1 protein expression by Western blot analysis and GLUT-1 mRNA detection by quantitative real-time RT-PCR. Quantitative determination of phospho(p)-ERK1/2 in cell lysates was performed by an Enzyme Immunometric Assay and Western blot analysis. Our data demonstrate a direct effect of resistin on normal cytotrophoblastic and on BeWo cells: resistin modulates glucose uptake, GLUT-1 messenger ribonucleic acid (mRNA) and protein expression in placental cells. We suggest that ERK1/2 phosphorylation is involved in the GLUT-1 regulation induced by resistin. In conclusion, resistin causes activation of both the ERK1 and 2 pathway in trophoblast cells. ERK1 and 2 activation stimulated GLUT-1 synthesis and resulted in increase of placental glucose uptake. High resistin levels (50-100 ng/ml) seem able to affect glucose-uptake, presumably by decreasing the cell surface glucose transporter.

Roles of leptin, adiponectin and resistin in the transcriptional regulation of steroidogenic genes contributing to decreased Leydig cells function in obesity.

PubMed

Roumaud, Pauline; Martin, Luc J

2015-10-01

The increase in obesity rate is a major public health issue associated with increased pathological conditions such as type 2 diabetes or cardiovascular diseases. Obesity also contributes to decreased testosterone levels in men. Indeed, the adipose tissue is an endocrine organ which produces hormones such as leptin, adiponectin and resistin. Obesity results in pathological accumulations of leptin and resistin, whereas adiponectin plasma levels are markedly reduced, all having a negative impact on testosterone synthesis. This review focuses on current knowledge related to transcriptional regulation of Leydig cells' steroidogenesis by leptin, adiponectin and resistin. We show that there are crosstalks between the regulatory mechanisms of these hormones and androgen production which may result in a dramatic negative influence on testosterone plasma levels. Indeed leptin, adiponectin and resistin can impact expression of different steroidogenic genes such as Star, Cyp11a1 or Sf1. Further investigations will be required to better define the implications of adipose derived hormones on regulation of steroidogenic genes expression within Leydig cells under physiological as well as pathological conditions.

Quantification and regulation of the adipokines resistin and progranulin in human cerebrospinal fluid.

PubMed

Berghoff, Martin; Hochberg, Alexandra; Schmid, Andreas; Schlegel, Jutta; Karrasch, Thomas; Kaps, Manfred; Schäffler, Andreas

2016-01-01

Adipokines bearing the potential to cross the blood-brain barrier (BBB) are promising candidates for the endocrine regulation of central nervous processes and of a postulated fat-brain axis. Resistin and progranulin concentrations in paired serum and cerebrospinal fluid (CSF) samples of patients undergoing neurological evaluation and spinal puncture were investigated. Samples of n = 270 consecutive patients with various neurological diseases were collected without prior selection. Adipokine serum and CSF concentrations were measured by enzyme-linked immunosorbent assay and serum and CSF routine parameters by standard procedures. Anthropometric data, medication and patient history were available. Serum levels of resistin and progranulin were positively correlated among each other, with respective CSF levels, low-density lipoprotein cholesterol levels and markers of systemic inflammation. CSF resistin concentrations were generally low. Progranulin CSF concentrations and CSF/serum progranulin ratio were significantly higher in patients with infectious diseases, with disturbed BBB function and with elevated CSF cell count and presence of oligoclonal bands. Both adipokines are able to cross the BBB depending on a differing patency that increases with increasing grade of barrier dysfunction. Whereas resistin represents a systemic marker of inflammation, CSF progranulin levels strongly depend on the underlying disease and dysfunction of blood-CSF barrier. Resistin and progranulin represent novel and putative regulators of the fat-brain axis by their ability to cross the BBB under physiological and pathophysiological conditions. The presented data provide insight into the characteristics of BBB function regarding progranulin and resistin and the basis for future establishment of normal values for CSF concentrations and CSF/serum ratios. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Immunometabolic biomarkers of inflammation in Behçet's disease: relationship with epidemiological profile, disease activity and therapeutic regimens

PubMed Central

Pucino, V.; Vitale, A.; Talarico, R.; M. Lucherini, O.; Magnotti, F.; De Rosa, V.; Galgani, M.; Alviggi, C.; Marone, G.; Galeazzi, M.

2016-01-01

Summary Behcet's disease (BD) is a systemic inflammatory disease with a still unclear pathogenesis. Although several inflammatory molecules have been studied, current biomarkers are largely insensitive in BD and unable to predict disease progression and response to treatment. Our primary aim was to explore serum levels of soluble CD40 L (sCD40L), soluble intracellular adhesion molecule (sICAM‐1), monocyte chemoattractant protein‐1 (MCP‐1), myeloperoxidase (MPO), leptin, resistin, osteoprotegerin (OPG), soluble type 1 tumour necrosis factor receptor (sTNFR), interleukin (IL)−6 and serum amyloid A (SAA) serum concentration in a cohort of 27 BD patients. The secondary aim was to evaluate potential correlations between the putative circulating biomarkers, demographic profile of patients, the status of disease activity, the specific organ involvement at the time of sample collection and different therapeutic regimens. Serum concentrations of sTNFR (P = 0·008), leptin (P = 0·0011), sCD40L (P < 0·0001) and IL‐6 (P = 0·0154) were significantly higher in BD patients than in HC, while no difference was found in MCP‐1, MPO and resistin serum levels. Moreover, we observed significantly higher sTNFR serum concentrations in BD patients presenting inactive disease than HC (P = 0·0108). A correlation between sTNFR and age was also found, with higher levels in patients over 40 years than HC (P = 0·0329). Although further research is warranted to elucidate the role of circulating biomarkers, some of that may contribute to the understanding of the physiopathology processes underlying BD activity and damage as well as to provide useful tools for prognostic purposes and a personalized treatment approach. PMID:26756979

Cytokine Response to Diet and Exercise Affects Atheromatous Matrix Metalloproteinase-2/9 Activity in Mice.

PubMed

Shon, Soo-Min; Jang, Hee Jeong; Schellingerhout, Dawid; Kim, Jeong-Yeon; Ryu, Wi-Sun; Lee, Su-Kyoung; Kim, Jiwon; Park, Jin-Yong; Oh, Ji Hye; Kang, Jeong Wook; Je, Kang-Hoon; Park, Jung E; Kim, Kwangmeyung; Kwon, Ick Chan; Lee, Juneyoung; Nahrendorf, Matthias; Park, Jong-Ho; Kim, Dong-Eog

2017-09-25

The aim of this study is to identify the principal circulating factors that modulate atheromatous matrix metalloproteinase (MMP) activity in response to diet and exercise.Methods and Results:Apolipoprotein-E knock-out (ApoE -/- ) mice (n=56) with pre-existing plaque, fed either a Western diet (WD) or normal diet (ND), underwent either 10 weeks of treadmill exercise or had no treatment. Atheromatous MMP activity was visualized using molecular imaging with a MMP-2/9 activatable near-infrared fluorescent (NIRF) probe. Exercise did not significantly reduce body weight, visceral fat, and plaque size in either WD-fed animals or ND-fed animals. However, atheromatous MMP-activity was different; ND animals that did or did not exercise had similarly low MMP activities, WD animals that did not exercise had high MMP activity, and WD animals that did exercise had reduced levels of MMP activity, close to the levels of ND animals. Factor analysis and path analysis showed that soluble vascular cell adhesion molecule (sVCAM)-1 was directly positively correlated to atheromatous MMP activity. Adiponectin was indirectly negatively related to atheromatous MMP activity by way of sVCAM-1. Resistin was indirectly positively related to atheromatous MMP activity by way of sVCAM-1. Visceral fat amount was indirectly positively associated with atheromatous MMP activity, by way of adiponectin reduction and resistin elevation. MMP-2/9 imaging of additional mice (n=18) supported the diet/exercise-related anti-atherosclerotic roles for sVCAM-1. Diet and exercise affect atheromatous MMP activity by modulating the systemic inflammatory milieu, with sVCAM-1, resistin, and adiponectin closely interacting with each other and with visceral fat.

Resistin is linked to inflammation, and leptin to metabolic syndrome, in women with inflammatory arthritis.

PubMed

Kontunen, P; Vuolteenaho, K; Nieminen, R; Lehtimäki, L; Kautiainen, H; Kesäniemi, Ya; Ukkola, O; Kauppi, M; Hakala, M; Moilanen, E

2011-01-01

To investigate how inflammation and metabolic syndrome (MetS) are associated with adipokine levels in patients with inflammatory arthritis. Fifty-four female patients with arthritis were enrolled in the study. Twenty (37%) of these patients had MetS, which was diagnosed according to the definition of the International Diabetes Federation (IDF). Interleukin (IL)-6 and four adipokines (resistin, leptin, adiponectin, and adipsin) were determined by immunoassay. Healthy women with body mass index (BMI) between 22 and 25 kg/m(2) served as controls. The patients with arthritis had higher levels of resistin than the healthy controls. This difference was clear in patients without MetS (17.4 in patients vs. 10.8 ng/mL in controls, p < 0.001), and even higher resistin levels were found in the patients with MetS (20.7 ng/mL; p < 0.001 vs. healthy controls; and p = 0.095 vs. patients without MetS). In the patients with arthritis and MetS, resistin correlated positively with IL-6 (Pearson's r = 0.5, p = 0.03). Leptin levels were increased in arthritis patients with MetS as compared to healthy controls, but not in patients without MetS. The statistically significant difference between patients with MetS and controls remained when leptin was adjusted with BMI. Accordingly, adiponectin levels were lower in patients with MetS than in healthy controls (p < 0.05). Leptin, adiponectin, and adipsin did not correlate with the inflammatory cytokine IL-6 or with C-reactive protein (CRP). The results show that high resistin levels are associated with arthritis independently of MetS, whereas leptin is increased only in arthritis patients with MetS.

[Effects of telmisartan on resistin expression in a rat model of nonalcoholic steatohepatitis and insulin resistance].

PubMed

Zhang, Qiuzan; Wang, Yanrong; Liu, Yingli; Yang, Qian; Wang, Xiuru; Wang, Qiang; Zhang, Chenming; Wang, Bangmao

2015-04-01

To investigate the effects of telmisartan on expression of resistin in serum and liver under conditions of nonalcoholic steatohepatitis (NASH) and insulin resistance using a rat model system. Forty-five male Sprague-Dawley rats were randomly divided into a normal control group (NC, n=10), a model control group (MC, n=15), a polyene phosphatidylcholine prevention group (PP, n=10), and a telmisartan prevention group (TP, n=10). The NC group was given a standard diet and the other groups were given a high-fat diet for 16 weeks in order to induce NASH. At the end of week 12, 5 rats in the MC group were sacrificed for pathology confirmation of the NASH model. At the end of week 12, the TP group was given telmisartan (8.0 mg/kg/d) and the PP group was given polyene phosphatidylcholine (8.4 mg/kg/d) for an additional 4 weeks by intragastric administration. At the end of week 16, all rats were sacrificed and body weights recorded. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), resistin, insulin and fasting blood glucose were measured. The insulin resistance value, HOMA-IR, was assessed by homeostasis mode assessment. Liver expression of the resistin protein was detected by western blotting and of the resistin mRNA was detected by RT-PCR. The F test and LSD test were used for statistical analyses. Compared to the NC group, the body weight and HOMA-IR of rats in the MC group were significantly increased (P<0.01). The levels of serum resistin, and of resistin protein and mRNA in liver, were significantly higher in the MC group than in the NC group of rats (all P less than 0.01). The body weight of rats in the TP group was significantly lower than those in the MC group (P<0.05). The levels of serrn resistin, resistin protein and mRNA in the liver, and insulin resistance were significantly lower in the TP group than in the MC group of rats (all P<0.01). The PP group did not show significant differences in any of these measures, except for loss of body weight (P<0.05). Telmisartan elicits preventive and protective effects in a NASH rat model.Telmisartan may improve insulin resistance in NASH rats by decreasing the expression of serum resistin, and liver resistin protein and mRNA.

Running a Marathon Induces Changes in Adipokine Levels and in Markers of Cartilage Degradation – Novel Role for Resistin

PubMed Central

Vuolteenaho, Katriina; Leppänen, Tiina; Kekkonen, Riina; Korpela, Riitta; Moilanen, Eeva

2014-01-01

Running a marathon causes strenuous joint loading and increased energy expenditure. Adipokines regulate energy metabolism, but recent studies have indicated that they also exert a role in cartilage degradation in arthritis. Our aim was to investigate the effects of running a marathon on the levels of adipokines and indices of cartilage metabolism. Blood samples were obtained from 46 male marathoners before and after a marathon run. We measured levels of matrix metalloproteinase-3 (MMP-3), cartilage oligomeric protein (COMP) and chitinase 3-like protein 1 (YKL-40) as biomarkers of cartilage turnover and/or damage and plasma concentrations of adipokines adiponectin, leptin and resistin. Mean marathon time was 3∶30∶46±0∶02∶46 (h:min:sec). The exertion more than doubled MMP-3 levels and this change correlated negatively with the marathon time (r = –0.448, p = 0.002). YKL-40 levels increased by 56% and the effect on COMP release was variable. Running a marathon increased the levels of resistin and adiponectin, while leptin levels remained unchanged. The marathon-induced changes in resistin levels were positively associated with the changes in MMP-3 (r = 0.382, p = 0.009) and YKL-40 (r = 0.588, p<0.001) and the pre-marathon resistin levels correlated positively with the marathon induced change in YKL-40 (r = 0.386, p = 0.008). The present results show the impact of running a marathon, and possible load frequency, on cartilage metabolism: the faster the marathon was run, the greater was the increase in MMP-3 levels. Further, the results introduce pro-inflammatory adipocytokine resistin as a novel factor, which enhances during marathon race and associates with markers of cartilage degradation. PMID:25333960

Changes in profile of lipids and adipokines in patients with newly diagnosed hypothyroidism and hyperthyroidism

PubMed Central

Chen, Yanyan; Wu, Xiafang; Wu, Ruirui; Sun, Xiance; Yang, Boyi; Wang, Yi; Xu, Yuanyuan

2016-01-01

Changes in profile of lipids and adipokines have been reported in patients with thyroid dysfunction. But the evidence is controversial. The present study aimed to explore the relationships between thyroid function and the profile of lipids and adipokines. A cross-sectional study was conducted in 197 newly diagnosed hypothyroid patients, 230 newly diagnosed hyperthyroid patients and 355 control subjects. Hypothyroid patients presented with significantly higher serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDLC), fasting insulin, resistin and leptin than control (p < 0.05). Hyperthyroid patients presented with significantly lower serum levels of high-density lipoprotein cholesterol, LDLC and leptin, as well as higher levels of fasting insulin, resistin, adiponectin and homeostasis model insulin resistance index (HOMA-IR) than control (p < 0.05). Nonlinear regression and multivariable linear regression models all showed significant associations of resistin or adiponectin with free thyroxine and association of leptin with thyroid-stimulating hormone (p < 0.001). Furthermore, significant correlation between resistin and HOMA-IR was observed in the patients (p < 0.001). Thus, thyroid dysfunction affects the profile of lipids and adipokines. Resistin may serve as a link between thyroid dysfunction and insulin resistance. PMID:27193069

Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.

PubMed

Deshmukh, Sachin K; Srivastava, Sanjeev K; Bhardwaj, Arun; Singh, Ajay P; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L; Dal Zotto, Valeria; Carter, James E; Singh, Seema

2015-05-10

African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity.

Resistin facilitates VEGF-C-associated lymphangiogenesis by inhibiting miR-186 in human chondrosarcoma cells.

PubMed

Su, Chen-Ming; Tang, Chih-Hsin; Chi, Meng-Ju; Lin, Chih-Yang; Fong, Yi-Chin; Liu, Yueh-Ching; Chen, Wei-Cheng; Wang, Shih-Wei

2018-05-03

Chondrosarcoma is a common primary malignant tumor of the bone that can metastasize through the vascular system to other organs. A key step in the metastatic process, lymphangiogenesis, involves vascular endothelial growth factor-C (VEGF-C). However, the effects of lymphangiogenesis in chondrosarcoma metastasis remain to be clarified. Accumulating evidence shows that resistin, a cytokine secreted from adipocytes and monocytes, also promotes tumor pathogenesis. Notably, chondrosarcoma can easily metastasize. In this study, we demonstrate that resistin enhances VEGF-C expression and lymphatic endothelial cells (LECs)-associated lymphangiogenesis in human chondrosarcoma cells. We also show that resistin triggers VEGF-C-dependent lymphangiogenesis via the c-Src signaling pathway and down-regulating micro RNA (miR)-186. Overexpression of resistin in chondrosarcoma cells significantly enhanced VEGF-C production and LECs-associated lymphangiogenesis in vitro and tumor-related lymphangiogenesis in vivo. Resistin levels were positively correlated with VEGF-C-dependent lymphangiogenesis via the down-regulation of miR-186 expression in clinical samples from chondrosarcoma tissue. This study is the first to evaluate the mechanism underlying resistin-induced promotion of LECs-associated lymphangiogenesis via the upregulation of VEGF-C expression in human chondrosarcomas. We suggest that resistin may represent a molecular target in VEGF-C-associated tumor lymphangiogenesis in chondrosarcoma metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Increased resistin in brain dead organ donors is associated with delayed graft function after kidney transplantation

PubMed Central

2013-01-01

Introduction Resistin increases during several inflammatory diseases and after intracerebral bleeding or head trauma. Resistin activates the endothelium and may initiate an inflammatory response. No data are available on resistin in brain dead donors (DBD) that regularly manifest a pronounced inflammatory state. Methods We analyzed plasma resistin in 63 DBDs and correlated results with donor variables and the postoperative course following kidney transplantation using organs from these donors. Endocan and monocyte chemotactic protein (MCP)-1 were also studied. Twenty-six live kidney donors (LD) and the corresponding kidney transplantations were used as controls. Results DBDs had higher resistin (median/range 30.75 ng/ml, 5.41–173.6) than LD (7.71 ng/ml, 2.41–15.74, p < 0.0001). Resistin in DBD correlated with delayed graft function (DGF) in the kidney recipients (r = 0.321, p < 0.01); receiver operating characteristic curve revealed an area under the curve of 0.765 (95% confidence interval [CI] 0.648–0.881, p < 0.01) and a cut-off value for resistin of 25 ng/ml; MCP-1 and endocan were higher in DBDs (p < 0.0001) but did not correlate with DGF or acute rejection. No relationship was found between the studied molecules and the postoperative course of LD kidney transplants. Conclusions High resistin levels in the DBD before organ retrieval are associated with DGF after kidney transplantation. The resistin increase seems related to the inflammatory state after brain death but not to the cause of death. PMID:24070260

Chromium picolinate inhibits resistin secretion in insulin-resistant 3T3-L1 adipocytes via activation of amp-activated protein kinase.

PubMed

Wang, Yi-Qun; Dong, Yi; Yao, Ming-Hui

2009-08-01

1. Chromium picolinate (CrPic) has been recommended as an alternative therapeutic regimen for Type 2 diabetes mellitus (T2DM). However, the molecular mechanism underlying the action of CrPic is poorly understood. 2. Using normal and insulin-resistant 3T3-L1 adipocytes, we examined the effects of CrPic on the gene transcription and secretion of adiponectin and resistin. In addition, using immunoblotting, ELISA and real-time reverse transcription-polymerase chain reaction (RT-PCR), we investigated the effects of 10 nmol/L CrPic for 24 h on AMP-activated protein kinase (AMPK) to determine whether this pathway contributed to the regulation of adiponectin and resistin expression and secretion. 3. Chromium picolinate did not modulate the expression of adiponectin and resistin; however, it did significantly inhibit the secretion of resistin, but not adiponectin, by normal and insulin-resistant 3T3-L1 adipocytes in vitro. Furthermore, although CrPic markedly elevated levels of phosphorylated AMPK and acetyl CoA carboxylase in 3T3-L1 adipocytes, it had no effect on the levels of AMPK alpha-1 and alpha-2 mRNA transcripts. Importantly, inhibition of AMPK by 2 h pretreatment of cells with 20 micromol/L compound C completely abolished the CrPic-induced suppression of resistin secretion. 4. In conclusion, the data suggest that CrPic inhibits resistin secretion via activation of AMPK in normal and insulin-resistant 3T3-L1 adipocytes.

Chemotherapy and plasma adipokines level in patients with colorectal cancer.

PubMed

Słomian, Grzegorz; Świętochowska, Elżbieta; Nowak, Grzegorz; Pawlas, Krystyna; Żelazko, Aleksandra; Nowak, Przemysław

2017-04-12

Adipokines are molecules produced and secreted by adipose tissue and are linked to multiple malignancies. Adipokines can suppress or promote particular cell behaviors in different types of cancer. The aim of this study was to investigate the impact of chemotherapy on select adipokines in patients with colorectal cancer (CRC). Blood samples were collected from 42 patients with pathologically documented advanced CRC, who required palliative chemotherapy. Leptin, adiponectin, resistin and visfatin levels were measured by ELISA before and 3 months after the administration of chemotherapy. Among the 42 patients evaluated, 18 achieved a partial response (PR), 16 achieved stable disease (SD) and 8 patients experienced disease progression (PD). We found that 5-fluorouracil-based chemotherapy regimens significantly increased plasma levels of leptin and adiponectin and decreased plasma levels of resistin and visfatin in PR and SD patients, whereas the plasma levels of these molecules were not affected in PD patients. Furthermore, the mean plasma levels of leptin were significantly lower, and the mean plasma levels of resistin and visfatin were significantly greater in patients with PD compared with PR and SD both before and after chemotherapy treatment. We conclude that palliative chemotherapy in CRC patients, in addition to providing clinical benefits, positively affects cytokine production and secretion in PR and SD patients. Specifically, we found that palliative chemotherapy increased plasma levels of the anti-inflammatory adipokine adiponectin and decreased the plasma levels of visfatin and resistin, molecules known to promote angiogenesis and cancer cell proliferation in PR and SD patients. Moreover, the baseline values of leptin, visfatin and resistin might serve as prognostic indicators of a poor response to chemotherapy.

Adiponectin, Resistin, and Visfatin in Childhood Obesity and Exercise.

PubMed

Jamurtas, Athanasios Z; Stavropoulos-Kalinoglou, Antonios; Koutsias, Stilianos; Koutedakis, Yiannis; Fatouros, Ioannis

2015-11-01

Childhood obesity is increasing alarmingly, and a strong association with chronic diseases has been established. Specific adipokines are released from the adipose tissue and relate with chronic diseases even in the pediatric population. Adiponectin levels are lower in obesity and increase with decreasing body weight. A few pediatric studies examining a possible relationship between resistin and obesity do not provide a clear picture. Most studies agree that visfatin levels appear elevated in childhood obesity. Exercise seems to increase adiponectin levels whereas resistin levels are reduced. The lack of data on the effects of acute and chronic exercise on visfatin levels precludes us from making safe conclusions as to what the effects of exercise (acute or chronic) would be on visfatin levels in children. Clearly, exercise has an impact on the adipose tissue and the release of adiponectin, resistin, and visfatin. However, other factors affect the secretion rate of these adipokines from the adipose tissue; these factors should also be taken into consideration when examining the effects of exercise on adipokines. Gender, age, body composition, physical activity levels, mode and intensity of exercise are some of the factors that should be looked into in future studies.

Serum adipokine levels in chronic liver diseases: association of resistin levels with fibrosis severity.

PubMed

Tsochatzis, Emmanuel; Papatheodoridis, George V; Hadziyannis, Emilia; Georgiou, Anastasia; Kafiri, Georgia; Tiniakos, Dina G; Manesis, Emanuel K; Archimandritis, Athanasios J

2008-01-01

Leptin and adiponectin have been implicated in the pathogenesis and progression of non-alcoholic steatohepatitis (NASH) and chronic hepatitis C (CHC), but little is known about the role of resistin in chronic liver diseases. The objective of this study was to investigate serum levels of the above three adipokines in relation to the etiology of liver disease and to determine their associations with histological severity. We prospectively evaluated 146 patients (HBeAg-negative chronic hepatitis B (CHB): 52, CHC: 70, NASH: 24) who consecutively underwent liver biopsy. Detailed epidemiological, anthropometric and laboratory data were recorded. Histological lesions were evaluated blindly according to the Ishak and the Brunt classifications for CHB/CHC and NASH, respectively. Serum adipokine levels were similar between CHB and CHC patients, while CHB/CHC patients had significantly lower leptin levels compared with NASH patients (8.3+/-7.3 versus 17.6+/-16.6 ng/ml, p=0.012) and higher adiponectin (10.2+/-5.1 versus 7.5+/-4 microg/ml, p=0.018) and resistin levels (7.1+/-2.5 versus 5.7+/-2.8 ng/ml, p=0.016). In CHB/CHC, there was no significant association between steatosis or necroinflammation and levels of adipokines, while the presence of moderate/severe fibrosis (stages 4-6) was associated with higher leptin and adiponectin levels in male but not in female patients and with lower resistin levels irrespective of gender or other factors (adjusted odds ratio=0.788, p=0.035). Serum adipokine levels depend on the etiology of liver disease differing between chronic viral hepatitis and NASH, but not between CHB and CHC. In CHB/CHC, resistin levels are independently associated with fibrosis severity, whereas in the association of leptin and adiponectin levels with fibrosis, it seems to be a gender effect.

Association of RETN and CAP1 SNPs, Expression and Serum Resistin Levels with Breast Cancer in Mexican Women.

PubMed

Muñoz-Palomeque, Alejandrina; Guerrero-Ramirez, Miguel Angel; Rubio-Chavez, Lidia Ariadna; Rosales-Gomez, Roberto Carlos; Lopez-Cardona, Maria Guadalupe; Barajas-Avila, Victor Hugo; Delgadillo-Barrera, Alfredo; Canton-Romero, Juan Carlos; Montoya-Fuentes, Hector; Garcia-Cobian, Teresa Arcelia; Gutierrez-Rubio, Susan Andrea

2018-04-01

Breast cancer is the most common cancer in women worldwide. Approximately 70% of female breast cancer patients have a body mass index (BMI) >25. In obesity, adipose tissue secretes additional resistin, which prompts a proinflammatory effect through its action on adenylate cyclase-associated protein 1 (CAP1). Several studies have associated the RETN gene single nucleotide polymorphism (SNP) rs1862513 (-420C

Adipokines, insulin resistance and hyperandrogenemia in obese patients with polycystic ovary syndrome: cross-sectional correlations and the effects of weight loss.

PubMed

Spanos, Nikolaos; Tziomalos, Konstantinos; Macut, Djuro; Koiou, Ekaterini; Kandaraki, Eleni A; Delkos, Dimitrios; Tsourdi, Elena; Panidis, Dimitrios

2012-01-01

To assess the effects of weight loss on serum adipokine levels in polycystic ovary syndrome (PCOS). We determined serum leptin, adiponectin, resistin, and visfatin levels in 60 overweight/obese women with PCOS and 48 BMI-matched female volunteers. Measurements were repeated after 24 weeks of treatment with orlistat 120 mg 3 times per day along with an energy-restricted diet. At baseline, serum visfatin concentration was higher in patients with PCOS than in controls (p = 0.036); serum levels of leptin, adiponectin, and resistin did not differ between the two groups. After 24 weeks, a significant reduction in BMI and waist circumference was observed in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). Also serum leptin levels decreased in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). The reduction in serum leptin levels did not differ between groups. Serum adiponectin, resistin, and visfatin levels did not change in either group. Leptin, adiponectin, and resistin do not appear to play major pathogenetic roles in overweight/obese patients with PCOS. In contrast, visfatin emerges as a potentially important mediator of the endocrine abnormalities of these patients. However, serum visfatin levels are not substantially affected by weight loss.

Resistin increases the expression of NOD2 in mouse monocytes.

PubMed

Ren, Yi; Wan, Taomei; Zuo, Zhicai; Cui, Hengmin; Peng, Xi; Fang, Jing; Deng, Junliang; Hu, Yanchun; Yu, Shuming; Shen, Liuhong; Ma, Xiaoping; Wang, Ya; Ren, Zhihua

2017-05-01

Previous studies have indicated that resistin, a type of adipokine, contributes to the development of insulin resistance and type 2 diabetes mellitus, and mediates inflammatory reactions. However, a specific receptor for resistin has not yet been identified. In this study, the relationship between resistin and nucleotide-binding oligomerization domain-like receptors, as well as resistin signal transduction, was examined through transfection, quantitative polymerase chain reaction, western blot analysis and ELISA. The mRNA expression of nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a key immune receptor related to insulin resistance, was significantly increased by resistin treatment at concentrations of 100, 150 and 200 ng/ml (P<0.05, P<0.01 and P<0.01, respectively). The mRNA expression of downstream signaling molecules in the NOD2 signaling pathway, receptor-interacting serine/threonine-protein kinase 2 (RIP2; P<0.01 at 6, 12 and 24 h) and inhibitor of NF-κB kinase subunit beta (P<0.01 at 3, 6, 12 and 24 h) were significantly increased by resistin treatment compared with the control. The mRNA expression of key proinflammatory cytokines, tumor necrosis factor α, IL (interleukin)-6 and IL-1β, were also significantly increased by resistin treatment compared with the control (P<0.01). NOD2 knockdown by small interfering RNA (siRNA) significantly decreased the expression of NOD2 and RIP2 (P<0.01), and there was no significant increase in the levels of cytokines, as compared with treatment with control siRNA. These findings indicate that the inflammatory reaction induced by resistin involves the NOD2-nuclear factor (NF)-κB signaling pathway. The inhibition of NF-κB significantly decreased the secretion of key inflammatory cytokines (P<0.01), suggesting that NF-κB signaling mechanisms are essential to the resistin-induced inflammatory response.

Experimental hyperthyroidism decreases gene expression and serum levels of adipokines in obesity.

PubMed

Luvizotto, Renata de Azevedo Melo; do Nascimento, André Ferreira; de Síbio, Maria Teresa; Olímpio, Regiane Marques Castro; Conde, Sandro José; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; Cicogna, Antonio Carlos; Nogueira, Célia Regina

2012-01-01

To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Male Wistar rats were randomly divided into two groups: control (C)-fed with commercial chow ad libitum-and obese (OB)-fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T(3))/100 BW (OT). The T(3) dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. T(3) treatment was effective, increasing fT(3) levels and decreasing fT(4) and TSH serum concentration. Administration of T(3) promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Our results suggest that T(3) modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T(3) and adipokines in obesity.

Serum adiponectin and resistin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome.

PubMed

Pangaribuan, Bertha; Yusuf, Irawan; Mansyur, Muchtaruddin; Wijaya, Andi

2011-12-01

The role of insulin resistance in polycystic ovary syndrome (PCOS) has been established. However the role of adiponectin and resistin in the relationship between insulin resistance as markers of obesity and PCOS has not been conclusive. This study aims to determine the influence of the serum levels of adiponectin and resistin on PCOS, and assess possible correlations with the hormonal and metabolic parameters of the syndrome and obesity. This study continued a case control study that had finished recruiting 24 subjects of reproductive women with PCOS as a case group, and 24 subjects of normal ovulatory reproductive women without hyperandrogenism as a control group. Further, only 18 subjects of the control group had a body mass index (BMI) <25 kg/m(2) and were included the data analysis, whereas others were excluded. Therefore, these study data were divided into three groups. Twenty-four PCOS patients from the case group were allocated to two groups, A (n = 14) patients had PCOS + BMI ≥25 kg/m(2); B (n = 10) patients had PCOS + BMI <25 kg/m(2). Group C was the control group of 18 reproductive women without PCOS + BMI <25 kg/m(2). Blood samples were collected between day 3 and 5 of a spontaneous menstrual cycle, at 07:00 to 09:00, after overnight fasting. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, prolactin, sex hormone-binding globulin (SHBG), glucose, insulin, adiponectin and resistin were measured. Serum adiponectin levels were significantly decreased in group A compared with group B and group C. No significant difference existed in adiponectin between group B and group C. Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR) value in group A was found to be significantly higher than group C, but no significant differences were found between group B and group C or between group A and group B. There was no significant difference in serum resistin between all groups, nevertheless the resistin-to-adiponectin (R:A) ratio was significantly decreased in group A compared with groups B and C. In a multiple regression model, BMI, testosterone and insulin resistance were the major determinants of hypoadiponectinemia. However, only BMI was the major determinant of the resistin represented by the R:A ratio. Serum adiponectin levels and the ratio of resistin to adiponectin levels are reduced in obese women with PCOS. These results suggest that, by reducing adiponectin serum level, hyperandrogenemia, together with nutritional status of obesity, might contribute to insulin resistance in the pathogenesis of PCOS.

Effects of SCFA on the DNA methylation pattern of adiponectin and resistin in high-fat-diet-induced obese male mice.

PubMed

Lu, Yuanyuan; Fan, Chaonan; Liang, Aimin; Fan, Xiuqin; Wang, Rui; Li, Ping; Qi, Kemin

2018-06-21

Specific adipokines, such as adiponectin and resistin, are secreted from adipose tissue and are associated with the development of obesity. Supplementation of dietary SCFA can prevent and reverse high-fat-diet (HFD)-induced obesity. However, it is not clear whether SCFA ameliorate abnormal expression of adiponectin and resistin in the obese state. The aim of this study was to investigate the effects of SCFA on adiponectin and resistin's expressions in diet-induced obese mice, as well as the potential mechanisms associated with DNA methylation. C57BL/6J male mice were fed for 16 weeks with five types of HFD (34·9 % fat by wt., 60 % kJ) - a control HFD and four HFD with acetate (HFD-A), propionate (HFD-P), butyrate (HFD-B) and their admixture (HFD-SCFA). Meanwhile, a low-fat diet (4·3 % fat by wt., 10 % kJ) was used as the control group. The reduced mRNA levels of adiponectin and resistin in the adipose tissue of the HFD-fed mice were significantly reversed by dietary supplementation of acetate, propionate, butyrate or their admixture to the HFD. Moreover, the expressional changes of adiponectin and resistin induced by SCFA were associated with alterations in DNA methylation at their promoters, which was mediated by reducing the expressions of enzyme-catalysed DNA methyltransferase (DNMT1, 3a, 3b) and the methyl-CpG-binding domain protein 2 (MBD2) and suppressing the binding of these enzymes to the promoters of adiponectin and resistin. Our results indicate that SCFA may correct aberrant expressions of adiponectin and resistin in obesity by epigenetic regulation.

Experimental Hyperthyroidism Decreases Gene Expression and Serum Levels of Adipokines in Obesity

PubMed Central

Luvizotto, Renata de Azevedo Melo; do Nascimento, André Ferreira; de Síbio, Maria Teresa; Olímpio, Regiane Marques Castro; Conde, Sandro José; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; Cicogna, Antonio Carlos; Nogueira, Célia Regina

2012-01-01

Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Main Methods. Male Wistar rats were randomly divided into two groups: control (C)—fed with commercial chow ad libitum—and obese (OB)—fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T3)/100 BW (OT). The T3 dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. Results. T3 treatment was effective, increasing fT3 levels and decreasing fT4 and TSH serum concentration. Administration of T3 promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Conclusions. Our results suggest that T3 modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3 and adipokines in obesity. PMID:22645452

Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.

PubMed

Yuan, Hong; Weng, Chunyan; Yang, Youbo; Huang, Lihua; Xing, Xiaowei

2013-12-01

The metabolic syndrome (MS) is a cluster of metabolic disorders arising from insulin resistance, characterized by the presence of central obesity, impaired fasting glucose level, dyslipidemia and hypertension. As the first-line medication, metformin is commonly used for MS to reduce insulin resistance. Comparing with rosiglitazone, metformin does not increase cardiovascular mortality risk in patients with MS. However, metformin is not good enough in improving insulin sensitivity. Its molecular mechanism is still not clear. Recent studies have demonstrated that resistin, an adipokine, could induce IR by both AMPK-dependent and AMPK-independent pathways. Though there were conflicting findings of resistin in metabolic syndrome or type 2 diabetes mellitus in different studies, resistin was significant decreased in the rosiglitazone treated patients than in the metformin-treated patients in most of studies. Here, we hypothesized that resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin. This hypothesis could explain why rosiglitazone is superior to metformin in enhancement of insulin sensitivity. Copyright © 2013. Published by Elsevier Ltd.

Aspirin prevents resistin-induced endothelial dysfunction by modulating AMPK, ROS, and Akt/eNOS signaling.

PubMed

Ou, Hsiu-Chung; Lee, Wen-Jane; Wu, Ching-Mei; Chen, Judy Fuh-Meei; Sheu, Wayne Huey-Herng

2012-04-01

Resistin, an adipocytokine, plays a potential role in cardiovascular disease and may contribute to increased atherosclerotic risk by modulating the activity of endothelial cells. A growing body of evidence suggests that aspirin is a potent antioxidant. We investigated whether aspirin mitigates resistin-induced endothelial dysfunction via modulation of reactive oxygen species (ROS) generation and explored the role that AMP-activated protein kinase (AMPK), a negative regulator of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, plays in the suppressive effects of aspirin on resistin-induced endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) were pretreated with various doses of aspirin (10-500 μg/mL) for 2 hours and then incubated with resistin (100 ng/mL) for an additional 48 hours. Fluorescence produced by the oxidation of dihydroethidium (DHE) was used to quantify the production of superoxide in situ; superoxide dismutase (SOD) and catalase activities were determined by an enzymatic assay; and protein levels of AMPK-mediated downstream signaling were investigated by Western blot. Treatment of HUVECs with resistin for 48 hours resulted in a 2.9-fold increase in superoxide production; however, pretreatment with aspirin resulted in a dose-dependent decrease in production of superoxide (10-500 μg/mL; n = 3 experiments; all P < .05). Resistin also suppressed the activity of superoxide dismutase and catalase by nearly 50%; that result, however, was not observed in HUVECs that had been pretreated with aspirin at a concentration of 500 μg/mL. The membrane translocation assay showed that the levels of NADPH oxidase subunits p47(phox)and Rac-1 in membrane fractions of HUVECs were threefold to fourfold higher in cells that had been treated with resistin for 1 hour than in untreated cells; however, pretreatment with aspirin markedly inhibited resistin-induced membrane assembly of NADPH oxidase via modulating AMPK-suppressed PKC-α activation. Application of AMPKα1-specific siRNA resulted in increased activation of PKC-α and p47(phox). In addition, resistin significantly decreased AMPK-mediated downstream Akt/endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling and induced the phosphorylation of p38 mitogen-activated protein kinases, which in turn activated NF-κB-mediated inflammatory responses such as the release of interleukin (IL)-6 and IL-8, the overexpression of adhesion molecules, and stimulation of monocytic THP-1 cell attachment to HUVECs (2.5-fold vs control; n = 3 experiments). Furthermore, resistin downregulated eNOS and upregulated inducible NO synthase (iNOS) expression, thereby augmenting the formation of NO and protein nitrosylation. Pretreatment with aspirin, however, exerted significant cytoprotective effects in a dose-dependent manner (P < .05). Our findings suggest a direct connection between adipocytokines and endothelial dysfunction and provide further insight into the protective effects of aspirin in obese individuals with endothelial dysfunction. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance.

PubMed

Baranova, Ancha; Gowder, Shobha J; Schlauch, Karen; Elariny, Hazem; Collantes, Rochelle; Afendy, Arian; Ong, Janus P; Goodman, Zachary; Chandhoke, Vikas; Younossi, Zobair M

2006-09-01

Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin 3.431 +/- 1.162 microU/mL). Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.

Inflammatory Cytokines as Uremic Toxins: "Ni Son Todos Los Que Estan, Ni Estan Todos Los Que Son".

PubMed

Castillo-Rodríguez, Esmeralda; Pizarro-Sánchez, Soledad; Sanz, Ana B; Ramos, Adrian M; Sanchez-Niño, Maria Dolores; Martin-Cleary, Catalina; Fernandez-Fernandez, Beatriz; Ortiz, Alberto

2017-03-23

Chronic kidney disease is among the fastest growing causes of death worldwide. An increased risk of all-cause and cardiovascular death is thought to depend on the accumulation of uremic toxins when glomerular filtration rate falls. In addition, the circulating levels of several markers of inflammation predict mortality in patients with chronic kidney disease. Indeed, a number of cytokines are listed in databases of uremic toxins and uremic retention solutes. They include inflammatory cytokines (IL-1β, IL-18, IL-6, TNFα), chemokines (IL-8), and adipokines (adiponectin, leptin and resistin), as well as anti-inflammatory cytokines (IL-10). We now critically review the cytokines that may be considered uremic toxins. We discuss the rationale to consider them uremic toxins (mechanisms underlying the increased serum levels and evidence supporting their contribution to CKD manifestations), identify gaps in knowledge, discuss potential therapeutic implications to be tested in clinical trials in order to make this knowledge useful for the practicing physician, and identify additional cytokines, cytokine receptors and chemokines that may fulfill the criteria to be considered uremic toxins, such as sIL-6R, sTNFR1, sTNFR2, IL-2, CXCL12, CX3CL1 and others. In addition, we suggest that IL-10, leptin, adiponectin and resistin should not be considered uremic toxins toxins based on insufficient or contradictory evidence of an association with adverse outcomes in humans or preclinical data not consistent with a causal association.

Hemoadsorption corrects hyperresistinemia and restores anti-bacterial neutrophil function.

PubMed

Bonavia, Anthony; Miller, Lauren; Kellum, John A; Singbartl, Kai

2017-12-01

Mounting evidence suggests that sepsis-induced morbidity and mortality are due to both immune activation and immunosuppression. Resistin is an inflammatory cytokine and uremic toxin. Septic hyperresistinemia (plasma resistin >20 ng/ml) has been associated with greater disease severity and worse outcomes, and it is further exacerbated by concomitant acute kidney injury (AKI). Septic hyperresistinemia disturbs actin polymerization in neutrophils leading to impaired neutrophil migration, a crucial first-line mechanism in host defense to bacterial infection. Our experimental objective was to study the effects of hyperresistinemia on other F-actin-dependent neutrophil defense mechanisms, in particular intracellular bacterial clearance and generation of reactive oxygen species (ROS). We also sought to examine the effects of hemoadsorption on hyperresistinemia and neutrophil dysfunction. Thirteen patients with septic shock and six control patients were analyzed for serum resistin levels and their effects on neutrophil migration. In vitro, following incubation with resistin-spiked serum samples, Pseudomonas aeruginosa clearance and ROS generation in neutrophils were measured. Phosphorylation of 3-phosphoinositide-dependent protein kinase-1 (PDPK1) was assessed using flow cytometry. In vitro hemoadsorption with both Amberchrome™ columns (AC) and CytoSorb® cartridges (CC) were used to test correction of hyperresistinemia. We further tested AC for their effect on cell migration and ROS generation and CC for their effect on bacterial clearance. Patients with septic shock had higher serum resistin levels than control ICU patients and showed a strong, negative correlation between hyperresistinemia and neutrophil transwell migration (ρ= - 0.915, p < 0.001). In vitro, neutrophils exposed to hyperresistinemia exhibited twofold lower intracellular bacterial clearance rates compared to controls. Resistin impaired intracellular signaling and ROS production in a dose-dependent manner. Hemoadsorption with AC reduced serum concentrations of resistin and restored neutrophil migration and generation of ROS to normal levels. Hemoadsorption with CC also corrected hyperresistinemia and reconstituted normal intracellular bacterial clearance. Septic hyperresistinemia strongly correlates with inhibition of neutrophil migration in vitro. Hyperresistinemia itself reversibly impairs neutrophil intracellular bacterial clearance and ROS generation. Hemoadsorption therapy with a clinically approved device corrects hyperresistinemia and neutrophil dysfunction. It may therefore provide a therapeutic option to improve neutrophil function during septic hyperresistinemia and ultimately alleviate immunosuppression in this disease state.

Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

PubMed Central

2011-01-01

Background Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to povide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IRAR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity. Methods In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables. Results The AR index was formulated as 1+log10(R0)-log10(A0). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IRAR index was formulated as log10(I0G0)+log10(I0G0)log10(R0/A0). The normal reference range of the IRAR index for insulin sensitive individuals was between 3.265 and 3.538. The minimum cut-off values of the IRAR index for insulin resistance assessment were between 3.538 and 3.955. Conclusions The novel AR and IRAR indexes are cost-effective, precise, reproducible and reliable integrated diagnostic biomarkers of insulin sensitivity for screening subjects with increased risk of future development of T2DM and MS. PMID:21251282

Adiponectin and resistin in acute and chronic graft-vs-host disease patients undergoing allogeneic hematopoietic stem cell transplantation.

PubMed

Robak, Oliver; Kuzmina, Zoya; Winkler, Andreas; Kalhs, Peter; Rabitsch, Werner; Greinix, Hildegard

2016-06-30

To investigate the association of adiponectin and resistin levels in patients undergoing hematopoietic stem cell transplantation (HSCT) with the clinical outcome, including the occurrence of acute and chronic graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. We prospectively collected serum samples from 40 patients undergoing either autologous (n=12; 10 male) or allogeneic (n=28; 11 male) HSCT for up to 12 months post HSCT and determined adiponectin and resistin serum concentrations using enzyme-linked immunosorbent assay. There were no significant differences in adiponectin levels (18.5 vs 9.3 μg/mL, P=0.071) and adiponectin/BMI ratio (0.82 vs 0.39, P=0.068) between patients with acute GVHD grades 2-4 and autologous controls. However, resistin values were significantly lower in patients with acute GVHD grades 2-4 than in autologous controls (4.6 vs 7.3 ng/mL, P=0.030). Adiponectin levels were higher in patients with chronic GVHD (n=17) than in autologous controls (13.5 vs 7.6 μg/mL, P=0.051), but the difference was not significant. Adiponectin/BMI ratio was significantly higher in patients with chronic GVHD than in autologous controls (0.59 vs 0.25, P=0.006). Patients dying from relapse also had significantly lower adiponectin levels (8.2 μg/mL) and adiponectin/BMI ratio (0.3) on admission than surviving allogeneic (15.8 µg/mL, P=0.030 and 0.7, P=0.004) and surviving autologous patients (19.2 μg/mL, P=0.031 and 0.7, P=0.021). Adiponectin and resistin levels were altered in patients with acute and chronic GVHD compared to autologous controls and were associated with overall survival and relapse mortality in patients undergoing allogeneic HSCT.

Adiponectin and resistin in acute and chronic graft-vs-host disease patients undergoing allogeneic hematopoietic stem cell transplantation

PubMed Central

Robak, Oliver; Kuzmina, Zoya; Winkler, Andreas; Kalhs, Peter; Rabitsch, Werner; Greinix, Hildegard

2016-01-01

Aim To investigate the association of adiponectin and resistin levels in patients undergoing hematopoietic stem cell transplantation (HSCT) with the clinical outcome, including the occurrence of acute and chronic graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. Methods We prospectively collected serum samples from 40 patients undergoing either autologous (n = 12; 10 male) or allogeneic (n = 28; 11 male) HSCT for up to 12 months post HSCT and determined adiponectin and resistin serum concentrations using enzyme-linked immunosorbent assay. Results There were no significant differences in adiponectin levels (18.5 vs 9.3 µg/mL, P = 0.071) and adiponectin/BMI ratio (0.82 vs 0.39, P = 0.068) between patients with acute GVHD grades 2-4 and autologous controls. However, resistin values were significantly lower in patients with acute GVHD grades 2-4 than in autologous controls (4.6 vs 7.3 ng/mL, P = 0.030). Adiponectin levels were higher in patients with chronic GVHD (n = 17) than in autologous controls (13.5 vs 7.6 µg/mL, P = 0.051), but the difference was not significant. Adiponectin/BMI ratio was significantly higher in patients with chronic GVHD than in autologous controls (0.59 vs 0.25, P = 0.006). Patients dying from relapse also had significantly lower adiponectin levels (8.2 µg/mL) and adiponectin/BMI ratio (0.3) on admission than surviving allogeneic (15.8 µg/mL, P = 0.030 and 0.7, P = 0.004) and surviving autologous patients (19.2 µg/mL, P = 0.031 and 0.7, P = 0.021). Conclusion Adiponectin and resistin levels were altered in patients with acute and chronic GVHD compared to autologous controls and were associated with overall survival and relapse mortality in patients undergoing allogeneic HSCT. PMID:27374827

Effects of 17β-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase.

PubMed

Pektaş, Mehtap; Kurt, Akif Hakan; Ün, İsmail; Tiftik, Rukiye Nalan; Büyükafşar, Kansu

2015-04-01

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10(-8)-10(-7)M), progesterone (10(-6)-10(-5)M), the Rho-kinase inhibitor, Y-27632 (10(-5)M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Resistin promotes tumor metastasis by down-regulation of miR-519d through the AMPK/p38 signaling pathway in human chondrosarcoma cells

PubMed Central

Huang, Ho-Ning; Hung, Chih-Hung; Hsu, Chin-Jung; Fong, Yi-Chin; Hsu, Horng-Chaung; Huang, Yuan-Li; Tang, Chih-Hsin

2015-01-01

Resistin is a recently discovered adipocyte-secreting adipokine, which may play a critical role in modulating cancer pathogenesis. Chondrosarcoma is a highly malignant tumor known to frequently metastasize; however, the role of resistin in the metastasis of human chondrosarcoma is largely unknown. Here, we found that the expression of resistin was higher in chondrosarcoma biopsy tissues than in normal cartilage. Moreover, treatment with resistin increased matrix metalloproteinase (MMP)-2 expression and promoted cell migration in human chondrosarcoma cells. Co-transfection with microRNA (miR)-519d mimic resulted in reversed resistin-mediated cell migration and MMP-2 expression. Additionally, AMP-activated protein kinase (AMPK) and p38 inhibitors or siRNAs reduced the resistin-increased cell migration and miR-519d suppression, and inhibition of resistin expression resulted in suppression of MMP-2 expression and lung metastasis in vivo. Taken together, our results indicate that resistin promotes chondrosarcoma metastasis and MMP-2 expression through activation of the AMPK/p38 signaling pathway and down-regulation of miR-519d expression. Therefore, resistin may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis. PMID:25404641

Anti-TNF-alpha therapy does not modulate leptin in patients with severe rheumatoid arthritis.

PubMed

Gonzalez-Gay, M A; Garcia-Unzueta, M T; Berja, A; Gonzalez-Juanatey, C; Miranda-Filloy, J A; Vazquez-Rodriguez, T R; de Matias, J M; Martin, J; Dessein, P H; Llorca, J

2009-01-01

The adipocytokine leptin regulates weight centrally and participates in the regulation of the immune and inflammatory responses. Chronic systemic inflammation is of major importance in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study we investigated whether inflammation, obesity or both of these characteristics are potential determinants of circulating leptin concentrations in a group of RA patients on periodical treatment with the TNF-alpha-blocker-infliximab due to severe disease. We also assessed whether the infusion of infliximab may alter circulating leptin concentrations in patients with severe RA. We investigated 33 patients with RA on periodical treatment with infliximab. Serum leptin levels were determined immediately prior to and after infliximab infusion. There was a positive correlation between body mass index of RA patients and baseline serum level of leptin (rho=0.665, p<0.001). Apart from a significant correlation with VCAM-1 (rho=0.349, p=0.04), no significant correlations between baseline leptin levels and the age at the time of the study or at the onset of the disease, disease duration, ESR and CRP levels, DAS28, lipids, insulin sensitivity, adhesion molecules, resistin, adiponectin, ghrelin or the cumulative prednisone dose at the time of the study were found. Leptin levels did not change upon infliximab infusion (p=0.48). In RA patients on TNF-alpha blocker treatment, circulating leptin levels are unrelated to disease activity but constitute a manifestation of adiposity. The beneficial effect of anti-TNF-alpha therapy on cardiovascular mortality in RA does not seem to be mediated by reduction in serum levels of leptin.

Adiponectin is partially associated with exosomes in mouse serum.

PubMed

Phoonsawat, Worrawalan; Aoki-Yoshida, Ayako; Tsuruta, Takeshi; Sonoyama, Kei

2014-06-06

Exosomes are membrane vesicles 30-120 nm in diameter that are released by many cell types and carry a cargo of proteins, lipids, mRNA, and microRNA. Cultured adipocytes reportedly release exosomes that may play a role in cell-to-cell communication during the development of metabolic diseases. However, the characteristics and function of exosomes released from adipocytes in vivo remain to be elucidated. Clearly, adipocyte-derived exosomes could exist in the circulation and may be associated with adipocyte-specific proteins such as adipocytokines. We isolated exosomes from serum of mice by differential centrifugation and analyzed adiponectin, leptin, and resistin in the exosome fraction. Western blotting detected adiponectin but no leptin and only trace amounts of resistin in the exosome fraction. The adiponectin signal in the exosome fraction was decreased by proteinase K treatment and completely quenched by a combination of proteinase K and Triton X-100. Quantitative ELISA showed that the exosome fraction contains considerable amounts of adiponectin, but not leptin or resistin. The concentration of adiponectin in the serum and the ratio of adiponectin to total protein in the exosome fraction were lower in obese mice than in lean mice. These results suggest that a portion of adiponectin exists as a transmembrane protein in the exosomes in mouse serum. We propose adiponectin as a marker of exosomes released from adipocytes in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice.

PubMed

Seto, Sai Wang; Lam, Tsz Yan; Or, Penelope Mei Yu; Lee, Wayne Yuk Wai; Au, Alice Lai Shan; Poon, Christina Chui Wa; Li, Rachel Wai Sum; Chan, Shun Wan; Yeung, John Hok Keung; Leung, George Pak Heng; Lee, Simon Ming Yuen; Ngai, Sai Ming; Kwan, Yiu Wa

2010-09-01

Folic acid supplementation provides beneficial effects on endothelial functions in patients with hyperhomocysteinemia. However, its effects on vascular functions under diabetic conditions are largely unknown. Therefore, the effect(s) of folic acid (5.7 and 71 microg/kg/day for 4 weeks) on aortic relaxation was investigated using obese/diabetic (+db/+db) mice and lean littermate (+db/+m) mice. Acetylcholine-induced relaxation in +db/+db mice was less than that observed in +db/+m mice. The reduced relaxation in +db/+db mice was restored by consumption of 71 microg/kg folic acid. Acetylcholine-induced relaxation (with and without folic acid treatment) was sensitive to N(G)-nitro-L-arginine methyl ester, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, geldanamycin and triciribine. In addition, acetylcholine-induced relaxation was attenuated by resistin. The plasma level of resistin in +db/+db mice was sevenfold higher than that measured in +db/+m mice, and the elevated plasma level of resistin in +db/+db mice was reduced by 25% after treatment with 71 microg/kg folic acid. Folic acid slightly increased the ratio of reduced glutathione to oxidized glutathione in +db/+db mice. Moreover, folic acid caused a reduction in PTEN (phosphatase and tensin homolog deleted on chromosome 10) expression, an increase in the phosphorylation of endothelial nitric oxide synthase (eNOS(Ser1177)) and Akt(Ser473), and an enhanced interaction of heat shock protein 90 (HSP90) with eNOS in both strains, with greater magnitude observed in +db/+db mice. In conclusion, folic acid consumption improved blunted acetylcholine-induced relaxation in +db/+db mice. The mechanism may be, at least partly, attributed to enhancement of PI3K/HSP90/eNOS/Akt cascade, reduction in plasma resistin level, down-regulation of PTEN and slight modification of oxidative state. Copyright 2010 Elsevier Inc. All rights reserved.

Adipokines induce catabolism of newly synthesized matrix in cartilage and meniscus tissues.

PubMed

Nishimuta, James F; Levenston, Marc E

Altered synovial levels of various adipokines (factors secreted by fat as well as other tissues) have been associated with osteoarthritis (OA) onset and progression. However, the metabolic effects of adipokines on joint tissues, in particular the fibrocartilaginous menisci, are not well understood. This study investigated effects of several adipokines on release of recently synthesized extracellular matrix in bovine cartilage and meniscus tissue explants. After labeling newly synthesized proteins and sulfated glycosaminoglycans (sGAGs) with 3 H-proline and 35 S-sulfate, respectively; bovine cartilage and meniscus tissue explants were cultured for 6 days in basal medium (control) or media supplemented with adipokines (1 µg/ml of leptin, visfatin, adiponectin, or resistin) or 20 ng/ml interleukin-1 (IL-1). Release of radiolabel and sGAG to the media during culture and the final explant water, DNA, sGAG, and retained radiolabel were measured. Matrix metalloproteinase (MMP-2) and MMP-3 activities were assessed using gelatin and casein zymography, respectively. Water and DNA contents were not significantly altered by any treatment. Visfatin, adiponectin, resistin, and IL-1 stimulated sGAG release from meniscus, whereas only IL-1 stimulated sGAG release from cartilage. Release of 3 H and 35 S was stimulated not only by resistin and IL-1 in meniscus but also by IL-1 in cartilage. Retained 3 H was unaltered by any treatment, while retained 35 S was reduced by visfatin, resistin, and IL-1 in meniscus and by only IL-1 in cartilage. Resistin and IL-1 elevated active MMP-2 and total MMP-3 in meniscus, whereas cartilage MMP-3 activity was elevated by only IL-1. Resistin stimulated rapid and extensive catabolism of meniscus tissue, similar to IL-1, whereas adipokines minimally affected cartilage. Release of newly synthesized matrix was similar to overall release in both tissues. These observations provide further indications that meniscal tissue is more sensitive to pro-inflammatory factors than cartilage and also suggest further study of resistin's role in OA.

Serum resistin is associated with the severity of microangiopathies in type 2 diabetes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osawa, Haruhiko; Ochi, Masaaki; Kato, Kenichi

2007-04-06

Resistin, secreted from adipocytes, causes insulin resistance and diabetes in rodents. To determine the relation between serum resistin and diabetic microangiopathies in humans, we analyzed 238 Japanese T2DM subjects. Mean serum resistin was higher in subjects with either advanced retinopathy (preproliferative or proliferative) (P = 0.0130), advanced nephropathy (stage III or IV) (P = 0.0151), or neuropathy (P = 0.0013). Simple regression analysis showed that serum resistin was positively correlated with retinopathy stage (P = 0.0212), nephropathy stage (P = 0.0052), and neuropathy (P = 0.0013). Multiple regression analysis adjusted for age, gender, and BMI, revealed that serum resistin wasmore » correlated with retinopathy stage (P = 0.0144), nephropathy stage (P = 0.0111), and neuropathy (P = 0.0053). Serum resistin was positively correlated with the number of advanced microangiopathies, independent of age, gender, BMI, and either the duration of T2DM (P = 0.0318) or serum creatinine (P = 0.0092). Therefore, serum resistin was positively correlated with the severity of microangiopathies in T2DM.« less

Resistin Regulates Fatty Acid Β Oxidation by Suppressing Expression of Peroxisome Proliferator Activator Receptor Gamma-Coactivator 1α (PGC-1α).

PubMed

He, Fang; Jin, Jie-Qiong; Qin, Qing-Qing; Zheng, Yong-Qin; Li, Ting-Ting; Zhang, Yun; He, Jun-Dong

2018-01-01

Abnormal fatty acid β oxidation has been associated with obesity and type 2 diabetes. Resistin is an adipokine that has been considered as a potential factor in obesity-mediated insulin resistance and type 2 diabetes. However, the effect of resistin on fatty acid β oxidation needs to be elucidated. We detected the effects of resistin on the expression of fatty acid oxidation (FAO) transcriptional regulatory genes, the fatty acid transport gene, and mitochondrial β-oxidation genes using real-time PCR. The rate of FAO was measured using 14C-palmitate. Immunofluorescence assay and western blot analysis were used to explore the underlying molecular mechanisms. Resistin leads to a reduction in expression of the FAO transcriptional regulatory genes ERRα and NOR1, the fatty acid transport gene CD36, and the mitochondrial β-oxidation genes CPT1, MCAD, and ACO. Importantly, treatment with resistin led to a reduction in the rate of cellular fatty acid oxidation. In addition, treatment with resistin reduced phosphorylation of acetyl CoA carboxylase (ACC) (inhibitory). Mechanistically, resistin inhibited the activation of CREB, resulting in suppression of PGC-1α. Importantly, overexpressing PGC-1α can rescue the inhibitory effects of resistin on fatty acid β oxidation. Activating the transcriptional activity of CREB using small molecular chemicals is a potential pharmacological strategy for preventing the inhibitory effects of resistin on fatty acid β oxidation. © 2018 The Author(s). Published by S. Karger AG, Basel.

Effects of central administration of resistin on renal sympathetic nerve activity in rats fed a high-fat diet: a comparison with leptin.

PubMed

Habeeballah, H; Alsuhaymi, N; Stebbing, M J; Badoer, E

2017-08-01

Similar to leptin, resistin acts centrally to increase renal sympathetic nerve activity (RSNA). In high-fat fed animals, the sympatho-excitatory effects of leptin are retained, in contrast to the reduced actions of leptin on dietary intake. In the present study, we investigated whether the sympatho-excitatory actions of resistin were influenced by a high-fat diet. Further, because resistin and leptin combined can induce a greater sympatho-excitatory response than each alone in rats fed a normal chow diet, we investigated whether a high-fat diet (22%) could influence this centrally-mediated interaction. Mean arterial pressure (MAP), heart rate (HR) and RSNA were recorded before and for 3 hours after i.c.v. saline (control; n=5), leptin (7 μg; n=4), resistin (7 μg; n=5) and leptin and resistin combined (n=6). Leptin alone and resistin alone significantly increased RSNA (71±16%, 62±4%, respectively). When leptin and resistin were combined, there was a significantly greater increase in RSNA (195±41%) compared to either hormone alone. MAP and HR responses were not significantly different between hormones. When the responses in high-fat fed rats were compared to normal chow fed rats, there were no significant differences in the maximum RSNA responses. The findings indicate that sympatho-excitatory effects of resistin on RSNA are not altered by high-fat feeding, including the greater increase in RSNA observed when resistin and leptin are combined. Our results suggest that diets rich in fat do not induce resistance to the increase in RSNA induced by resistin alone or in combination with leptin. © 2017 British Society for Neuroendocrinology.

Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure

PubMed Central

Razvi, Shehla S.; Richards, Jeremy B.; Malik, Farhan; Cromar, Kevin R.; Price, Roger E.; Bell, Cynthia S.; Weng, Tingting; Atkins, Constance L.; Spencer, Chantal Y.; Cockerill, Katherine J.; Alexander, Amy L.; Blackburn, Michael R.; Alcorn, Joseph L.; Haque, Ikram U.

2015-01-01

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines—including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)—promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology. PMID:26386120

Liver-specific GH receptor gene-disrupted (LiGHRKO) mice have decreased endocrine IGF-I, increased local IGF-I, and altered body size, body composition, and adipokine profiles.

PubMed

List, Edward O; Berryman, Darlene E; Funk, Kevin; Jara, Adam; Kelder, Bruce; Wang, Feiya; Stout, Michael B; Zhi, Xu; Sun, Liou; White, Thomas A; LeBrasseur, Nathan K; Pirtskhalava, Tamara; Tchkonia, Tamara; Jensen, Elizabeth A; Zhang, Wenjuan; Masternak, Michal M; Kirkland, James L; Miller, Richard A; Bartke, Andrzej; Kopchick, John J

2014-05-01

GH is an important regulator of body growth and composition as well as numerous other metabolic processes. In particular, liver plays a key role in the GH/IGF-I axis, because the majority of circulating "endocrine" IGF-I results from GH-stimulated liver IGF-I production. To develop a better understanding of the role of liver in the overall function of GH, we generated a strain of mice with liver-specific GH receptor (GHR) gene knockout (LiGHRKO mice). LiGHRKO mice had a 90% decrease in circulating IGF-I levels, a 300% increase in circulating GH, and significant changes in IGF binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, IGFBP-5, and IGFBP-7. LiGHRKO mice were smaller than controls, with body length and body weight being significantly decreased in both sexes. Analysis of body composition over time revealed a pattern similar to those found in GH transgenic mice; that is, LiGHRKO mice had a higher percentage of body fat at early ages followed by lower percentage of body fat in adulthood. Local IGF-I mRNA levels were significantly increased in skeletal muscle and select adipose tissue depots. Grip strength was increased in LiGHRKO mice. Finally, circulating levels of leptin, resistin, and adiponectin were increased in LiGHRKO mice. In conclusion, LiGHRKO mice are smaller despite increased local mRNA expression of IGF-I in several tissues, suggesting that liver-derived IGF-I is indeed important for normal body growth. Furthermore, our data suggest that novel GH-dependent cross talk between liver and adipose is important for regulation of adipokines in vivo.

Exercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin?

PubMed

Bjersing, Jan L; Erlandsson, Malin; Bokarewa, Maria I; Mannerkorpi, Kaisa

2013-02-27

Severe fatigue is a major health problem in fibromyalgia (FM). Obesity is common in FM, but the influence of adipokines and growth factors is not clear. The aim was to examine effects of exercise on fatigue, in lean, overweight and obese FM patients. In a longitudinal study, 48 FM patients (median 52 years) exercised for 15 weeks. Nine patients were lean (body mass index, BMI 18.5 to 24.9), 26 overweight (BMI 25 to 29.9) and 13 obese. Fatigue was rated on a 0 to 100 mm scale (fibromyalgia impact questionnaire [FIQ] fatigue) and multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF). Higher levels in FIQ fatigue and MFIGF indicate greater degree of fatigue. Free and total IGF-1, neuropeptides, adipokines were determined in serum and cerebrospinal fluid (CSF). Baseline FIQ fatigue correlated negatively with serum leptin (r=-0.345; P=0.016) and nerve growth factor (NGF; r=-0.412; P=0.037). In lean patients, baseline MFIGF associated negatively with serum resistin (r=-0.694; P=0.038). FIQ Fatigue associated negatively with CSF resistin (r=-0.365; P=0.073). Similarly, FIQ fatigue (r=-0.444; P=0.026) and MFIGF correlated negatively with CSF adiponectin (r=-0.508; P=0.01). In lean patients, FIQ fatigue (P=0.046) decreased after 15 weeks. After 30 weeks, MFIGF decreased significantly in lean (MFIGF: P=0.017), overweight (MFIGF: P=0.001), and obese patients (MFIGF: P=0.016). After 15 weeks, total IGF-1 increased in lean (P=0.043) patients. ∆Total IGF-1 differed significantly between lean and obese patients (P=0.010). ∆Total IGF-1 related negatively with ∆MFIGF after 15 weeks (r=-0.329; P=0.050). After 30 weeks, ∆FIQ fatigue negatively correlated with ∆NGF (r=-0.463; P=0.034) and positively with ∆neuropeptide Y (NPY) (r=0.469; P=0.032). Resistin increased after 30 weeks (P=0.034). ∆MFIGF correlated negatively with ∆resistin (r=-0.346; P=0.031), being strongest in obese patients (r=-0.815; P=0.007). In obese patients, ∆FIQ fatigue after 30 weeks correlated negatively with ∆free IGF-1 (r=-0.711; P=0.032). Exercise reduced fatigue in all FM patients, this effect was achieved earlier in lean patients. Baseline levels of resistin in both serum and CSF associated negatively with fatigue. Resistin was increased after the exercise period which correlated with decreased fatigue. Changes in IGF-1 indicate similar long-term effects in obese patients. This study shows reduced fatigue after moderate exercise in FM and indicates the involvement of IGF-1 and resistin in these beneficial effects. ClinicalTrials.gov: NCT00643006.

Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.

PubMed

Villarroya, Joan; Dorado, Beatriz; Vilà, Maya R; Garcia-Arumí, Elena; Domingo, Pere; Giralt, Marta; Hirano, Michio; Villarroya, Francesc

2011-01-01

Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues. © 2011 Villarroya et al.

Thymidine Kinase 2 Deficiency-Induced Mitochondrial DNA Depletion Causes Abnormal Development of Adipose Tissues and Adipokine Levels in Mice

PubMed Central

Villarroya, Joan; Dorado, Beatriz; Vilà, Maya R.; Garcia-Arumí, Elena; Domingo, Pere; Giralt, Marta; Hirano, Michio; Villarroya, Francesc

2011-01-01

Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues. PMID:22216345

New insights into adipokines as potential biomarkers for type-2 diabetes mellitus.

PubMed

Olivera Santa-Catalina, Marta; Redondo, Pedro C; Cantonero, C; Granados, Maria P; Sanchez-Collado, Jose; Albarran, Letizia; Lopez, Jose Javier

2017-12-05

A large number of studies have been focused on investigating serum biomarkers associated with risk or diagnosis of type-2 diabetes mellitus. In the last decade, promising studies have shown that circulating levels of adipokines could be used as a relevant biomarker for diabetes mellitus progression as well as therapeutic future targets. Here we discuss the possible use of recent described adipokines, including apelin, omentin-1, resistin, FGF-21, neuregulin-4 and visfatin, as early biomarkers for diabetes. In addition, we also include recent findings of other well know adipokines such as leptin and adiponectin. In conclusion, further studies are needed to clarify the pathophysiological significance and clinical value of these biological factors as potential biomarkers in type-2 diabetes and related dysfunctions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Weight and metabolic effects of CPAP in obstructive sleep apnea patients with obesity.

PubMed

Garcia, Jose M; Sharafkhaneh, Hossein; Hirshkowitz, Max; Elkhatib, Rania; Sharafkhaneh, Amir

2011-06-15

Obstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting. In a pre- and post-treatment, within-subject design, insulin and appetite-regulating hormones were assayed in 20 obese subjects with OSA before and after 6 months of CPAP use. Primary outcome measures included glucose, insulin, and IR levels. Other measures included ghrelin, leptin, adiponectin and resistin levels. Body weight change were recorded and used to examine the relationship between glucose regulation and appetite-regulating hormones. CPAP effectively improved hypoxia. However, subjects had increased insulin and IR. Fasting ghrelin decreased significantly while leptin, adiponectin and resistin remained unchanged. Forty percent of patients gained weight significantly. Changes in body weight directly correlated with changes in insulin and IR. Ghrelin changes inversely correlated with changes in IR but did not change as a function of weight. Weight change rather than elimination of hypoxia modulated alterations in IR in obese patients with OSA during the first six months of CPAP therapy.

Exercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin?

PubMed Central

2013-01-01

Introduction Severe fatigue is a major health problem in fibromyalgia (FM). Obesity is common in FM, but the influence of adipokines and growth factors is not clear. The aim was to examine effects of exercise on fatigue, in lean, overweight and obese FM patients. Methods In a longitudinal study, 48 FM patients (median 52 years) exercised for 15 weeks. Nine patients were lean (body mass index, BMI 18.5 to 24.9), 26 overweight (BMI 25 to 29.9) and 13 obese. Fatigue was rated on a 0 to 100 mm scale (fibromyalgia impact questionnaire [FIQ] fatigue) and multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF). Higher levels in FIQ fatigue and MFIGF indicate greater degree of fatigue. Free and total IGF-1, neuropeptides, adipokines were determined in serum and cerebrospinal fluid (CSF). Results Baseline FIQ fatigue correlated negatively with serum leptin (r = -0.345; P = 0.016) and nerve growth factor (NGF; r = -0.412; P = 0.037). In lean patients, baseline MFIGF associated negatively with serum resistin (r = -0.694; P = 0.038). FIQ Fatigue associated negatively with CSF resistin (r = -0.365; P = 0.073). Similarly, FIQ fatigue (r = -0.444; P = 0.026) and MFIGF correlated negatively with CSF adiponectin (r = -0.508; P = 0.01). In lean patients, FIQ fatigue (P = 0.046) decreased after 15 weeks. After 30 weeks, MFIGF decreased significantly in lean (MFIGF: P = 0.017), overweight (MFIGF: P = 0.001), and obese patients (MFIGF: P = 0.016). After 15 weeks, total IGF-1 increased in lean (P = 0.043) patients. ∆Total IGF-1 differed significantly between lean and obese patients (P = 0.010). ∆Total IGF-1 related negatively with ∆MFIGF after 15 weeks (r = -0.329; P = 0.050). After 30 weeks, ∆FIQ fatigue negatively correlated with ∆NGF (r = -0.463; P = 0.034) and positively with ∆neuropeptide Y (NPY) (r = 0.469; P = 0.032). Resistin increased after 30 weeks (P = 0.034). ∆MFIGF correlated negatively with ∆resistin (r = -0.346; P = 0.031), being strongest in obese patients (r = -0.815; P = 0.007). In obese patients, ∆FIQ fatigue after 30 weeks correlated negatively with ∆free IGF-1 (r = -0.711; P = 0.032). Conclusions Exercise reduced fatigue in all FM patients, this effect was achieved earlier in lean patients. Baseline levels of resistin in both serum and CSF associated negatively with fatigue. Resistin was increased after the exercise period which correlated with decreased fatigue. Changes in IGF-1 indicate similar long-term effects in obese patients. This study shows reduced fatigue after moderate exercise in FM and indicates the involvement of IGF-1 and resistin in these beneficial effects. Trial registration ClinicalTrials.gov: NCT00643006 PMID:23446104

The Adipose Renin-Angiotensin System Modulates Systemic Markers of Insulin Sensitivity and Activates the Intrarenal Renin-Angiotensin System

DOE PAGES

Kim, Suyeon; Soltani-Bejnood, Morvarid; Quignard-Boulange, Annie; ...

2006-01-01

Background . The adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass and may also impact systemic functions such as blood pressure and metabolism. Methods and results . A panel of mouse models including mice lacking angiotensinogen, Agt ( Agt -KO), mice expressing Agt solely in adipose tissue (aP2- Agt/Agt -KO), and mice overexpressing Agt in adipose tissue (aP2- Agt ) was studied. Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin, and resistin were significantly decreased in Agt -KO mice, while plasma adiponectin levels were increased. aP2- Agt mice exhibited increased adiposity andmore » plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also elevated in kidney of aP2- Agt mice. Conclusion . These findings demonstrate that alterations in adipose RAS activity significantly impact both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.« less

Cognitive patterns in relation to biomarkers of cerebrovascular disease and vascular risk factors.

PubMed

Miralbell, Júlia; López-Cancio, Elena; López-Oloriz, Jorge; Arenillas, Juan Francisco; Barrios, Maite; Soriano-Raya, Juan José; Galán, Amparo; Cáceres, Cynthia; Alzamora, Maite; Pera, Guillem; Toran, Pere; Dávalos, Antoni; Mataró, Maria

2013-01-01

Risk factors for vascular cognitive impairment (VCI) are the same as traditional risk factors for cerebrovascular disease (CVD). Early identification of subjects at higher risk of VCI is important for the development of effective preventive strategies. In addition to traditional vascular risk factors (VRF), circulating biomarkers have emerged as potential tools for early diagnoses, as they could provide in vivo measures of the underlying pathophysiology. While VRF have been consistently linked to a VCI profile (i.e., deficits in executive functions and processing speed), the cognitive correlates of CVD biomarkers remain unclear. In this population-based study, the aim was to study and compare cognitive patterns in relation to VRF and circulating biomarkers of CVD. The Barcelona-AsIA Neuropsychology Study included 747 subjects older than 50, without a prior history of stroke or coronary disease and with a moderate to high vascular risk (mean age, 66 years; 34.1% women). Three cognitive domains were derived from factoral analysis: visuospatial skills/speed, verbal memory and verbal fluency. Multiple linear regression was used to assess relationships between cognitive performance (multiple domains) and a panel of circulating biomarkers, including indicators of inflammation, C-reactive protein (CRP) and resistin, endothelial dysfunction, asymmetric dimethylarginine (ADMA), thrombosis, plasminogen activator inhibitor 1 (PAI-1), as well as traditional VRF, metabolic syndrome and insulin resistance (homeostatic model assessment for insulin resistance index). Analyses were adjusted for age, gender, years of education and depressive symptoms. Traditional VRF were related to lower performance in verbal fluency, insulin resistance accounted for lower performance in visuospatial skills/speed and the metabolic syndrome predicted lower performance in both cognitive domains. From the biomarkers of CVD, CRP was negatively related to verbal fluency performance and increasing ADMA levels were associated with lower performance in verbal memory. Resistin and PAI-1 did not relate to cognitive function performance. Vascular risk factors, and markers of inflammation and endothelial dysfunction predicted lower performance in several cognitive domains. Specifically, cognitive functions associated with CRP are typically affected in VCI and overlap those related to VRF. ADMA indicated a dissociation in the cognitive profile involving verbal memory. These findings suggest that inflammation and endothelial dysfunction might play a role in the predementia cognitive impairment stages. Copyright © 2013 S. Karger AG, Basel.

Low-birth-weight, but not catch-up growth, correlates with insulin resistance and resistin level in SGA infants at 12 months.

PubMed

Giapros, Vasileios; Vavva, Efthymia; Siomou, Ekaterini; Kolios, Georgios; Tsabouri, Sofia; Cholevas, Vasileios; Bairaktari, Eleni; Tzoufi, Meropi; Challa, Anna

2017-08-01

To investigate the insulin resistance status in SGA infants at 12 months and its relationship with auxological and metabolic parameters. One group of 45 SGA and one of 50 appropriate for gestational age infants were followed from birth to the end of the first year of life. At 12 months, skinfold thickness, waist circumference, and blood levels of glucose, insulin, adiponectin, leptin, resistin, visfatin, retinol-binding protein 4, IGFs, lipids profile were determined, and the HOMA-IR index was calculated. The SGAs had increased insulin (5.2 ± 2.7 versus 2.9 ± 2.4 μIU/ml, p = 0.012) and HOMA-IR (1.09 ± 0.9 versus 0.59 ± 0.55, p = 0.016). In multiple regression, insulin resistance indices were independently correlated with low-birth-weight (β = -2.92, p = 0.015 for insulin, β = -2.98, p = 0.011 for HOMA-IR) but not with catch-up growth in either height or weight or any other metabolic parameter. Resistin was higher in the SGAs (5.1 ± 2.1 versus 3.9 ± 2.1 ng/ml, p = 0.03) and independently correlated with low-birth-weight but not insulin resistance. Resistin was negatively correlated with total cholesterol (R = -0.33, p = 0.007) and positively with lipoprotein(a) (R = 0.49, p = 0.001). Low-birth-weight, but not catch-up growth or adiposity tissue hormones, was correlated with insulin resistance at 12 months in non-obese SGA infants. The higher resistin in SGA infants and its correlation with total cholesterol and lipoprotein(a) need further clarification.

Adiponectin-resistin index and its strong association with acute coronary syndrome in South Indian men.

PubMed

Singh, Prerna; Sridhar, M G; Rajappa, Medha; Balachander, J; Kadhiravan, Tamilarasu

2014-11-01

India has the highest burden of acute coronary syndromes worldwide. Apart from certain lipid alterations that have been established to be definite risk factors, low level of adiponectin, high levels of resistin, and IL-6 have been shown to be risk factors for cardiovascular events. Insulin resistance is also a significant predictor of poor outcome in patients admitted with ACS. 69 male patients with ACS and 70 age-matched healthy males were recruited in the study. Insulin, total adiponectin, resistin, and IL-6 levels were assayed in all study subjects. Indices of insulin resistance and novel adipokine indices were calculated using standard formulae. Multiple logistic regression analysis was done to find out the best predictor of ACS. Resistin, IL-6, insulin resistance indices, AR index, and IRAR index were found to be significantly higher, while insulin sensitivity indices and total adiponectin were found to be lower in cases, as compared with controls (p < 0.001). Insulin resistance was found to be higher in the admission sample, when compared to the fasting sample in patients with ACS (p = 0.01). On multivariate logistic regression analysis, HOMA-IR and AR index were found to be significantly associated with ACS. AR index was the best independent predictor of ACS, with the highest odds ratio (AR index: adjusted OR 17.528, p < 0.0001 versus HOMA-IR: adjusted OR 1.146, p = 0.001). The present results implicate that adipokines are significantly associated with pathogenesis of ACS, warranting adequate and early appropriate treatment to reverse this metabolic dysregulation. In our study, AR index was the best predictor of ACS. Hence, the novel AR index might be useful in routine clinical practice for screening persons with increased risk of future development of ACS.

Inflammatory Cytokine Profile Associated with Metabolic Syndrome in Adult Patients with Type 1 Diabetes.

PubMed

Ferreira-Hermosillo, Aldo; Molina-Ayala, Mario; Ramírez-Rentería, Claudia; Vargas, Guadalupe; Gonzalez, Baldomero; Isibasi, Armando; Archundia-Riveros, Irma; Mendoza, Victoria

2015-01-01

To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (n = 61), 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. . We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance.

Type 2 diabetes and metabolic syndrome - adipokine levels and effect of drugs.

PubMed

Farooq, Rabia; Amin, Shajrul; Hayat Bhat, M; Malik, Rawoof; Wani, Hilal Ahmad; Majid, Sabhiya

2017-01-01

Type 2 diabetes mellitus (T2DM) is a consequence of complex interactions among multiple genetic variants and environmental risk factors. This complex disorder is also characterized by changes in various adipokines. In this study, our objective was to estimate the levels of adiponectin, leptin, and resistin (ALR) in T2DM patients, besides studying the effect of various drugs on their levels. Study participants included 400 diabetic and 300 normal patients from the Department of Endocrinology and Department of Biochemistry, Govt Medical College Srinagar. Subjects were categorized under various groups, i.e., Group 1 (metformin treated) and Group 2 (glimepiride treated), and cases were also categorized as obese with T2DM (Group A), obese without T2DM (Group B), and T2DM only (Group C). The serum ALR levels were estimated by ELISA (Alere), and biochemical parameters were also evaluated before and after treatment. Adiponectin levels were found to be significantly lower in T2DM cases as compared to controls (12 ± 5.5 versus 22.5 ± 7.9 μg/ml), while leptin and resistin levels were found to be significantly higher than controls (14.3 ± 7.4 versus 7.36 ± 3.73 ng/ml) (13.4 ± 1.56 versus 7.236 ± 2.129 pg/ml). Taking the effect of drugs into consideration, the effect on adiponectin and resistin levels was found to be highly significant in Group 2 before and after treatment (11 ± 5 versus 19.2 ± 4.5 μg/ml) (13.6 ± 2.5 versus 7.3 ± 2.9 pg/ml), while more effect was observed in leptin among Group 1 (metformin)-treated cases (27 ± 15 ng/ml versus 15 ± 15 ng/ml). Further the adiponectin levels were found to be significantly lower in Group B, while leptin and resistin levels were found to be significantly higher among obese cases when compared to T2DM cases only. Glimepiride also shows more effect on FBG, HbA1c% levels, while metformin shows more effect on Lipid profile levels. From the study, it can be concluded that ALR levels are affected by use of antidiabetic drugs among which glimepiride shows more effect on adiponectin and resistin levels, while leptin gets affected more by metformin. It can also be proposed that ALR levels are not affected by diabetes only, suggesting that their alterations in T2DM may be due to obesity as we observed more ALR changes in obese cases when compared to T2DM cases, and so there might be an important link between adiposity and insulin resistance.

The role of adipokines in the rapid antidepressant effects of ketamine.

PubMed

Machado-Vieira, R; Gold, P W; Luckenbaugh, D A; Ballard, E D; Richards, E M; Henter, I D; De Sousa, R T; Niciu, M J; Yuan, P; Zarate, C A

2017-01-01

We previously found that body mass index (BMI) strongly predicted response to ketamine. Adipokines have a key role in metabolism (including BMI). They directly regulate inflammation and neuroplasticity pathways and also influence insulin sensitivity, bone metabolism and sympathetic outflow; all of these have been implicated in mood disorders. Here, we sought to examine the role of three key adipokines-adiponectin, resistin and leptin-as potential predictors of response to ketamine or as possible transducers of its therapeutic effects. Eighty treatment-resistant subjects who met DSM-IV criteria for either major depressive disorder (MDD) or bipolar disorder I/II and who were currently experiencing a major depressive episode received a single ketamine infusion (0.5 mg kg -1 for 40 min). Plasma adipokine levels were measured at three time points (pre-infusion baseline, 230 min post infusion and day 1 post infusion). Overall improvement and response were assessed using percent change from baseline on the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. Lower baseline levels of adiponectin significantly predicted ketamine's antidepressant efficacy, suggesting an adverse metabolic state. Because adiponectin significantly improves insulin sensitivity and has potent anti-inflammatory effects, this finding suggests that specific systemic abnormalities might predict positive response to ketamine. A ketamine-induced decrease in resistin was also observed; because resistin is a potent pro-inflammatory compound, this decrease suggests that ketamine's anti-inflammatory effects may be transduced, in part, by its impact on resistin. Overall, the findings suggest that adipokines may either predict response to ketamine or have a role in its possible therapeutic effects.

[Effects of the body fat mass and blood sugar and plasma resistin to slim exercise prescription for overweight and obesity students].

PubMed

Bai, Youping; Zhang, Jing; Jiang, Shuangshuang; Sun, Jun; Zheng, Chenfei; Wang, Ke; Qian, Jingjing; Nie, Liuwang

2013-07-01

To explore the influences of slim exercise prescription on body fat mass, blood sugar and plasma resistin for overweight and obesity students. Subjects were 9 males and 13 females for simple overweight and obesity students of freshman and junior. The function capacity (FC) were defined after examine of body shape, physical function and exercise capacity. The slim goals and exercise projects were determined according to different objects. The exercise intensity was 60%-70% of FC and 13-15 levels of RPE. Exercise with each time was 60 min, exercise frequency was 5 times perweek, energy metabolism was 500-600 kcal at a time. The relative indexes were detected after 8 weeks. Implementing programmes of slim exercise prescription for 8 weeks, before and after the experiment in the males and females group. The weight, BMI, percentage of body fat (FAT%), waist and hip circumference ratio (WHR), body surface area (BS), fat indexes, the density of body for overweight and obesity the male and female students were significantly decreased (P < 0.01). Body fat mass (FM) and blood sugar were significantly decreased (P < 0.01). Plasma resistin of the male students were significant different (P < 0.01), but the female students were significant different (P < 0.05). Analysis of Bivariate Correlation was Pearson Correlation, plasma resistin and BMI, WHR the male students had correlation, but the female had no correlation. The exercise prescription was safe and sure, and could improve weight, BMI, FAT%, FM, WHR, BS, fat indexes, the density of body, blood sugar, plasma resistin in obesity without the diet control.

Molecular signature of adipose tissue in patients with both Non-Alcoholic Fatty Liver Disease (NAFLD) and Polycystic Ovarian Syndrome (PCOS)

PubMed Central

2013-01-01

Background Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only. Methods We included patients with biopsy-proven NAFLD and PCOS (N = 12) and BMI-matched biopsy-proven NAFLD patients without PCOS (N = 12). Expression levels of individual mRNAs and soluble serum biomarkers were compared by non-parametric Mann–Whitney test. The analysis also included Spearman rank correlation tests and multiple regression analysis. For co-correlated genes, the factor analysis was performed. Results The total serum levels of apoptotic biomarker M30 were significantly elevated in PCOS patients with liver steatosis as compared to non-PCOS NAFLD controls (P < 0.02), pointing that androgen-dependent proapoptotic PCOS environment that may directly contribute to NAFLD progression in these patients. Similarly, hyperandrogenism may explain the observed PCOS-specific decrease (P < 0.04) in adipose LDLR mRNA expression that may be connected to the proneness of PCOS patients to NAFLD. The levels of mRNA encoding angiogenesis-associated GSK-3B interacting protein ninein were also significantly increased in the adipose tissue of NAFLD patients with PCOS (P < 0.007). Furthermore, the levels of resistin positively correlated with expression levels of LDLR and prothrombin time (PT). Conclusion An androgen-dependent proapoptotic PCOS environment may directly contribute to NAFLD progression in these patients. Hyperandrogenism may explain an observed decrease in adipose LDLR mRNA expression. An inflammation-associated increase in the release of resistin into circulation might contribute to the prothrombotic state observed under conditions associated with insulin resistance, including PCOS. The studies of larger cohorts of NAFLD with and without PCOS patients are needed to further assess these potential interactions. PMID:23721173

Molecular signature of adipose tissue in patients with both non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS).

PubMed

Baranova, Ancha; Tran, Thuy Phuong; Afendy, Arian; Wang, Lei; Shamsaddini, Amirhossein; Mehta, Rohini; Chandhoke, Vikas; Birerdinc, Aybike; Younossi, Zobair M

2013-05-31

Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only. We included patients with biopsy-proven NAFLD and PCOS (N = 12) and BMI-matched biopsy-proven NAFLD patients without PCOS (N = 12). Expression levels of individual mRNAs and soluble serum biomarkers were compared by non-parametric Mann-Whitney test. The analysis also included Spearman rank correlation tests and multiple regression analysis. For co-correlated genes, the factor analysis was performed. The total serum levels of apoptotic biomarker M30 were significantly elevated in PCOS patients with liver steatosis as compared to non-PCOS NAFLD controls (P < 0.02), pointing that androgen-dependent proapoptotic PCOS environment that may directly contribute to NAFLD progression in these patients. Similarly, hyperandrogenism may explain the observed PCOS-specific decrease (P < 0.04) in adipose LDLR mRNA expression that may be connected to the proneness of PCOS patients to NAFLD. The levels of mRNA encoding angiogenesis-associated GSK-3B interacting protein ninein were also significantly increased in the adipose tissue of NAFLD patients with PCOS (P < 0.007). Furthermore, the levels of resistin positively correlated with expression levels of LDLR and prothrombin time (PT). An androgen-dependent proapoptotic PCOS environment may directly contribute to NAFLD progression in these patients. Hyperandrogenism may explain an observed decrease in adipose LDLR mRNA expression. An inflammation-associated increase in the release of resistin into circulation might contribute to the prothrombotic state observed under conditions associated with insulin resistance, including PCOS. The studies of larger cohorts of NAFLD with and without PCOS patients are needed to further assess these potential interactions.

Impact of Treatment with Metformin on Adipocytokines in Patients with Polycystic Ovary Syndrome: A Meta-Analysis.

PubMed

Kong, Wen; Niu, Xun; Zeng, Tianshu; Lu, Meixia; Chen, Lulu

2015-01-01

Metformin is effective for the treatment of polycystic ovary syndrome, but conflicting results regarding its effect on adipocytokine levels (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving metformin treatment have been reported. To provide high-quality evidence about the effect of metformin treatment on adipocytokines in patients with polycystic ovary syndrome, relevant studies that assessed the levels of adipocytokines (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving treatment with metformin administration were reviewed and analyzed. A literature search was conducted in the SCI, PUBMED, EMBASE, and Elsevier databases, and personal contact was made with the authors. Standard mean differences and 95% confidence intervals were calculated and combined appropriately. To ensure synthesis of the best available evidence, sensitivity analyses were performed. A total of 34 data sets were included in 4 different outcomes, involving 744 women with polycystic ovary syndrome and adipocytokine levels measured both before and after metformin administration. Metformin treatment was associated with significantly elevated serum adiponectin concentrations (standard mean differences [95% confidence interval], -0.43 [-0.75 to -0.11]) and decreased serum leptin concentrations (0.65 [0.26 to 1.04]), whereas no significant difference in resistin level (-0.01 [-0.49 to 0.45]) or visfatin level (-0.04 [-1.55 to 1.46]) was found. Metformin administration was associated with increased serum adiponectin concentrations and decreased serum leptin levels. Further study is needed to elucidate whether this apparent effect decreases the incidence of type 2 diabetes and other metabolic diseases in patients with polycystic ovary syndrome later in life.

Impact of Treatment with Metformin on Adipocytokines in Patients with Polycystic Ovary Syndrome: A Meta-Analysis

PubMed Central

Kong, Wen; Niu, Xun; Zeng, Tianshu; Lu, Meixia; Chen, Lulu

2015-01-01

Background Metformin is effective for the treatment of polycystic ovary syndrome, but conflicting results regarding its effect on adipocytokine levels (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving metformin treatment have been reported. To provide high-quality evidence about the effect of metformin treatment on adipocytokines in patients with polycystic ovary syndrome, relevant studies that assessed the levels of adipocytokines (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving treatment with metformin administration were reviewed and analyzed. Methods A literature search was conducted in the SCI, PUBMED, EMBASE, and Elsevier databases, and personal contact was made with the authors. Standard mean differences and 95% confidence intervals were calculated and combined appropriately. To ensure synthesis of the best available evidence, sensitivity analyses were performed. Results A total of 34 data sets were included in 4 different outcomes, involving 744 women with polycystic ovary syndrome and adipocytokine levels measured both before and after metformin administration. Metformin treatment was associated with significantly elevated serum adiponectin concentrations (standard mean differences [95% confidence interval], −0.43 [−0.75 to −0.11]) and decreased serum leptin concentrations (0.65 [0.26 to 1.04]), whereas no significant difference in resistin level (−0.01 [−0.49 to 0.45]) or visfatin level (−0.04 [−1.55 to 1.46]) was found. Conclusions Metformin administration was associated with increased serum adiponectin concentrations and decreased serum leptin levels. Further study is needed to elucidate whether this apparent effect decreases the incidence of type 2 diabetes and other metabolic diseases in patients with polycystic ovary syndrome later in life. PMID:26473366

Serum adipokine concentrations in dogs with diabetes mellitus: a pilot study

PubMed Central

Kim, Ah Young; Kim, Hye-Sun; Yang, Mhan-Pyo

2015-01-01

This study was conducted to determine whether serum adipokine concentrations differed between healthy dogs and dogs with diabetes mellitus (DM). To accomplish this, 19 dogs with newly diagnosed DM were compared to 20 otherwise healthy dogs. The serum concentrations of visfatin, leptin, IL-1β, IL-6, IL-18, and TNF-α were significantly higher in diabetic dogs than in healthy dogs, whereas the serum adiponectin concentrations were lower in diabetic dogs. However, there were no significant differences in the IL-10 and resistin levels between groups. The serum leptin concentrations in diabetic dogs with and without concurrent disorders differed significantly. Treatment with insulin induced a significant decrease in IL-6 in diabetic dogs without concurrent disorders. These results show that the clinical diabetic state of dogs could modulate the circulating visfatin and adiponectin concentrations directly, while upregulation of leptin was probably a result of concurrent disorders rather than an effect of persistent hyperglycemia as a result of DM. PMID:25643799

The concentrations of adipokines in goat milk: relation to plasma levels, inflammatory status, milk quality and composition.

PubMed

Guzel, Saime; Yibar, Artun; Belenli, Deniz; Cetin, Ismail; Tanriverdi, Meltem

2017-03-23

The main objectives of our study were to measure the major adipokines adiponectin, leptin and resistin in goat milk, to assess their interrelationships and to assess their relationships with the plasma and serum concentrations of total protein, cholesterol, total lipids, plasma C-reactive protein (CRP), milk somatic cell count (SCC), milk total aerobic colony and lactobacillus count, and milk components in lactating Saanen goats. The study was performed on eighteen lactating Saanen goats. Milk and blood samples were collected on days 20, 35, 50, 65 and 80 of lactation postpartum. The milk and plasma adiponectin levels on days 50, 65 and 80 postpartum were significantly higher than those on day 20. The milk and plasma leptin levels were lower on day 20 than on days 35, 50, 65 and 80. The milk concentrations of these major adipokines were positively intercorrelated. The milk and plasma concentrations of these three adipokines were also positively correlated. The plasma CRP concentrations correlated positively with milk leptin and resistin concentrations and inversely with milk adiponectin concentration. Milk adiponectin concentration was inversely related with its SCC. These data confirm that adiponectin, leptin and resistin are present in goat milk. The milk concentrations of these three adipokines were interrelated and interacted with the general inflammatory marker, CRP. The inverse relationship between milk adiponectin concentrations and its SCC suggests that variations in milk adiponectin might be involved in the udder health of lactating goats, but clinical trials are needed to support this hypothesis.

Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

PubMed Central

López-Mejías, Raquel; Rueda-Gotor, Javier; Miranda-Filloy, José A.; Ubilla, Begoña; Carnero-López, Beatriz; Palmou-Fontana, Natalia; Gómez-Acebo, Inés; Blanco, Ricardo; Pina, Trinitario; Ochoa, Rodrigo; González-Juanatey, Carlos; González-Gay, Miguel A.

2014-01-01

Objective. TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients. PMID:24976690

Effect of 6-gingerol on AMPK- NF-κB axis in high fat diet fed rats.

PubMed

Hashem, Reem M; Rashed, Laila A; Hassanin, Kamel M A; Hetta, Mona H; Ahmed, Asmaa O

2017-04-01

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in metabolic homeostasis and regulation of inflammatory responses through attenuation of nuclear factor kappa-B (NF-κB), Thus AMPK may be a promising pharmacologic target for the treatment of various chronic inflammatory diseases. We examined the effect of 6-gingerol, an active ingredient of ginger on AMPK-NF-κB pathway in high fat diet (HFD) rats in comparison to fish oil. Protein levels of AMPK-α1 and phosphorylated AMPK-α1 were measured by western blot while Sirtuin 6 (Sirt-6), resistin and P65 were estimated by RT-PCR, TNF-α was determined by ELISA, FFAs were estimated chemically as well as the enzymatic determination of the metabolic parameters. 6-Gingerol substantially enhanced phosphorylated AMPK-α1 more than fish oil and reduced the P65 via upregulation of Sirt-6 and downregulation of resistin, and resulted in attenuation of the inflammatory molecules P65, FFAs and TNF-α more than fish oil treated groups but in an insignificant statistical manner, those effects were accompanied by a substantial hypoglycemic effect. Gingerol treatment effectively modulated the state of inflammatory privilege in HFD group and the metabolic disorders via targeting the AMPK-NF-κB pathway, through an increment in the SIRT-6 and substantial decrement in resistin levels. Copyright © 2017. Published by Elsevier Masson SAS.

Metabolic status and resistin in chronic schizophrenia over a 2-year period with continuous atypical antipsychotics

PubMed Central

Kawabe, Kentaro; Ochi, Shinichiro; Yoshino, Yuta; Mori, Yoko; Onuma, Hiroshi; Osawa, Haruhiko; Hosoda, Yoshiki; Ueno, Shu-ichi

2015-01-01

Background: Common adverse effects of atypical antipsychotic treatments for schizophrenia are weight gain and lipid metabolism abnormality. We aimed to identify the signs of metabolic problems with continuous atypical antipsychotic treatment for schizophrenia over a 2-year period. Methods: The participants were 68 schizophrenic patients (29 males, 39 females; ages 53.4 ± 13.5 years old). Changes in carbohydrate metabolism and changes in physical characteristics were studied over a 2-year period. In addition, functional single nucleotide polymorphisms in the transcriptional regulatory region of the resistin gene were examined. Results: We found no changes in the mental state of the participants over a 2-year period. Patients did show a significant decrease in total cholesterol and hemoglobin A1c levels, although physical changes such as body mass index and abdominal girth, were not observed. The amount of resistin may not be associated with mental states and physical parameters. Conclusions: We could not find physical factors related to metabolic changes of antipsychotics in this 2-year study. However, several psychological factors, such as health-related thoughts and behaviors, should be studied in the future. PMID:26557983

Protective effects and mechanisms of total alkaloids of Rubus alceaefolius Poir on non‑alcoholic fatty liver disease in rats.

PubMed

Zheng, Haiyin; Zhao, Jinyan; Zheng, Yuqing; Wu, Juan; Liu, Yan; Peng, Jun; Hong, Zhenfeng

2014-10-01

The plant Rubus alceaefolius Poir is used as a hepatic protectant in Traditional Chinese Medicine. The aim of the present study was to confirm the protective effect of the total alkaloids of Rubus alceaefolius Poir (TARAP) on the liver and to evaluate the potential molecular mechanisms associated with adipocytokines underlying non-alcoholic fatty liver disease (NAFLD) in rats. To generate the NAFLD model, Sprague-Dawley rats were administered a high‑fat diet and following 12 weeks of model construction, rats were orally treated with a positive control drug and different doses of TARAP daily for 28 days. The rats were then sacrificed and the livers were collected to evaluate the liver index (LI) and observe histological changes by hematoxylin and eosin (H&E) staining. The secretion levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were examined by ELISA. Finally, the expression levels of leptin (LEP), resistin and adiponectin (APN) in liver tissues were determined by immunohistochemistry (IHC). The results demonstrated that, in the group treated with methionine and choline bitartrate tablets and in the groups treated with different doses of TARAP, there was a significant reduction in the LI (P<0.05 or P<0.01), a downregulation of the secretion levels of ALT and AST, reduced levels of LEP and resistin and an increased expression of APN in the liver of NAFLD rats compared with the model group. Furthermore, the effect of TARAP treatment of NAFLD rats was dose dependent. In conclusion, TARAP is a potential agent for downregulating LEP and resistin and upregulating APN expression in rats with NAFLD. Furthermore, TARAP may be a potential candidate for improving treatment responses in patients with NAFLD.

Increased Ghrelin Levels and Unchanged Adipocytokine Levels in Major Depressive Disorder.

PubMed

Tunçel, Özgür Korhan; Akbaş, Seher; Bilgici, Birşen

2016-10-01

One of the hypotheses of the pathophysiology of major depressive disorder (MDD) proposes that there is a relationship between adipocytokine and ghrelin levels and depression. Patients with major depression with a BMI ≤25 kg/m 2 between the ages of 11 and 18 years (n = 30) were compared with a healthy control group (n = 30). Both groups were evaluated across a pretreatment period (MD-PT) and an improved period (MD-I). We measured serum leptin, adiponectin, resistin, and ghrelin levels and other parameters related to metabolic syndrome, such as glucose, insulin, insulin resistance (homeostasis model assessment [HOMA]), triglycerides (TG), and total cholesterol (TCHOL). Leptin, adiponectin, and resistin levels did not differ across groups; however, ghrelin levels were increased in the MD-I group compared with the control and MD-PT groups (p < 0.05). HOMA levels were also higher in the MD-PT group than in the control group (p < 0.05). After treatment, there was no difference in this measurement. The relationship between adipocytokines and major depression may be dependent on ghrelin levels as a result of antidepressant treatment and subsequent obesity.

Adipocytokine concentrations in children with different types of beta-thalassemia.

PubMed

Enli, Yaşar; Balci, Yasemin I; Gönen, Cafer; Uzun, Ebru; Polat, Aziz

2014-06-01

Beta-thalassemia is an inherited blood disorder. It results from the impaired production of β-globin chains, leading to a relative excess of alpha-globin chains. Clinical severity separates this disease into three main subtypes: β- thalassemia major, β-thalassemia intermedia and β-thalassemia minor, the former two being clinically more significant. Inflammatory processes may play an important role in some of the complications of thalassemia. Adipose tissue is one of the most important endocrine and secretory organs that release adipocytokines like adiponectin, resistin and visfatin. The aim of our study was to analyze adipocytokine concentrations (adiponectin, resistin and visfatin) in different types of β-thalassemia patients and determine any possible correlations with disease severity. We recruited 29 patients who were transfusion-dependent β-thalassemia-major patients, 17 patients with β-thalassemia intermedia, 30 β-thalassemia minor patients. The control group consisted of 30 healthy children. Anthropometric measurements, complete blood count, biochemical parameters, serum concentrations of adiponectin, resistin, visfatin were performed for all subjects. Resistin and visfatin concentrations were significantly higher in β-thalassemia minor patients than in controls. Adiponetin, resistin and visfatin concentrations were significantly higher in both β-thalassemia intermedia and major patients than in controls. The concentrations of adiponectin, resistin and visfatin were significantly higher in both β-thalassemia intermedia and major patients than in β-thalassemia minor patients. There was no significant difference between β-thalassemia intermedia and β-thalassemia major patients for adipocytokines concentrations. We speculate that these adipocytokines may play a role in the development of complications in β-thalassaemia.

Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children.

PubMed

Shaikh, M Guftar; Grundy, Richard G; Kirk, Jeremy M W

2008-12-01

Obesity following hypothalamic damage is often severe and resistant to lifestyle changes. Disruption of hypothalamic feedback mechanisms that maintain energy homeostasis may be responsible for this intractable obesity. Adipocytokines including insulin and leptin are also known to be important regulators of appetite and weight. To investigate the role of insulin, leptin, adiponectin and resistin in the aetiology of hypothalamic obesity (HO). This was a cross-sectional study of three groups of children, those with HO, congenital hypopituitarism (CH) and simple obesity (SO). A total of 69 children (HO=28, CH=18, SO=23) had leptin, resistin, adiponectin and insulin measured. Although fasting hyperinsulinaemia and insulin resistance were demonstrated, no differences in insulin or insulin resistance were seen between the groups. The HO group, however, had higher levels of leptin, adiponectin and resistin, which persisted even after adjusting for fat mass, compared with the other groups (P<0.05). No differences in fasting hyperinsulinaemia or insulin resistance were seen between the groups; however, leptin levels are elevated, even after adjusting for fat mass, suggesting that an element of leptin resistance is associated with HO. This is consistent with the inability of leptin to act on the hypothalamus, either due to transport across the blood-brain barrier or dysfunctional receptors. The lack of response to leptin may be more important in the development of obesity in these individuals, and the fasting hyperinsulinaemia is a result of the increased adipose tissue rather than the cause of the weight gain.

Effect of telmisartan on selected adipokines, insulin sensitivity, and substrate utilization during insulin-stimulated conditions in patients with metabolic syndrome and impaired fasting glucose.

PubMed

Wohl, Petr; Krusinová, Eva; Hill, Martin; Kratochvílová, Simona; Zídková, Katerina; Kopecký, Jan; Neskudla, Tomás; Pravenec, Michal; Klementová, Marta; Vrbíková, Jana; Wohl, Pavel; Mlejnek, Petr; Pelikánová, Terezie

2010-10-01

Telmisartan improves glucose and lipid metabolism in rodents. This study evaluated the effect of telmisartan on insulin sensitivity, substrate utilization, selected plasma adipokines and their expressions in subcutaneous adipose tissue (SAT) in metabolic syndrome. Twelve patients with impaired fasting glucose completed the double-blind, randomized, crossover trial. Patients received telmisartan (160 mg/day) or placebo for 3 weeks and vice versa with a 2-week washout period. At the end of each period, a hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry was performed. During HEC (0, 30, and 120 min), plasma levels of adipokines were measured and a needle biopsy (0 and 30 min) of SAT was performed. Fasting plasma glucose was lower after telmisartan compared with placebo (P<0.05). There were no differences in insulin sensitivity and substrate utilization. We found no differences in basal plasma adiponectin, resistin and tumour necrosis factor α (TNFα), but an increase was found in basal leptin, after telmisartan treatment. Insulin-stimulated plasma adiponectin (P<0.05), leptin and resistin (P<0.001) were increased, whereas TNFα was decreased (P<0.05) after telmisartan treatment. Expression of resistin, but not adiponectin, TNFα and leptin was increased after telmisartan treatment. Despite the decrease in fasting plasma glucose, telmisartan does not improve insulin sensitivity and substrate utilization. Telmisartan increases plasma leptin as well as insulin-stimulated plasma adiponectin, leptin and resistin, and decreases plasma TNFα during HEC. Changes in plasma adipokines cannot be explained by their expressions in SAT. The changes in plasma adipokines might be involved in the metabolic effects of telmisartan in metabolic syndrome.

Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock.

PubMed

Kaplan, Jennifer M; Denenberg, Alvin; Monaco, Marie; Nowell, Marchele; Wong, Hector; Zingarelli, Basilia

2010-01-01

To assess changes in peroxisome proliferator-activated receptor-gamma (PPARgamma) in peripheral blood mononuclear cells (PBMC) from critically ill children with sepsis. Additionally, to investigate the effects of sepsis on the endogenous activator of PPARgamma, 15-deoxy-(12,14)-PGJ(2) (15d-PGJ(2)), and the downstream targets of PPARgamma activity, adiponectin and resistin. Single-center, prospective case-control study in critically ill children with systemic inflammatory response syndrome, sepsis or septic shock. PPARgamma nuclear protein expression was decreased but PPARgamma activity was increased in PBMC from children with septic shock compared with controls. PPARgamma activity on day 1 was significantly higher in patients with higher pediatric risk of mortality (PRISM) score compared with controls [mean 0.22 optical density (OD) +/- standard error of the mean (SEM) 0.03 versus 0.12 OD +/- 0.02; p < 0.001]. Patients with resolved sepsis had increased levels of the endogenous PPARgamma ligand, 15d-PGJ(2), compared with patients with systemic inflammatory response syndrome (SIRS) and septic shock (77.7 +/- 21.7 versus 58 +/- 16.5 pg/ml; p = 0.03). Plasma high-molecular-weight adiponectin (HMWA) and resistin levels were increased in patients with septic shock on day 1 and were significantly higher in patients with higher PRISM scores. Nonsurvivors from sepsis had higher resistin levels on the first day of hospitalization compared with survivors from septic shock [660 ng/ml, interquartile range (IQR) 585-833 ng/ml versus 143 ng/ml, IQR 66-342 ng/ml; p < 0.05]. Sepsis is associated with altered PPARgamma expression and activity in PBMC. Plasma adipokines correlate with risk of mortality scores in sepsis and may be useful biomarkers. Further studies are needed to understand the mechanisms underlying changes in PPARgamma in sepsis.

Cytokine Profile in Chronic Periodontitis Patients with and without Obesity: A Systematic Review and Meta-Analysis

PubMed Central

Abduljabbar, Tariq; Abu Hassan, Mohamed Ibrahim; Vohra, Fahim

2016-01-01

To investigate the cytokine profile as biomarkers in the gingival crevicular fluid (GCF) of chronic periodontitis (CP) patients with and without obesity, MEDLINE/PubMed, EMBASE, ScienceDirect, and SCOPUS databases were combined with handsearching of articles published from 1977 up to May 2016 using relevant MeSH terms. Meta-analyses were conducted separately for each of the cytokines: resistin, adiponectin, TNF-α, leptin, IL-6, IL-8, and IL-1β. Forest plots were produced reporting standardized mean difference of outcomes and 95% confidence intervals. Eleven studies were included. Three studies showed comparable levels of leptin among obese and nonobese patients with CP. Four studies reported comparable levels of interleukin- (IL-) 6 and resistin whereas five studies reported comparable levels of adiponectin. Two studies reported similar levels of CRP in patients with periodontitis with and without obesity. One study showed higher levels of tumor necrosis factor-alpha in obese patients with CP. One study showed higher levels of IL-1β and IL-8 in obese patients with CP. The level of localized periodontal inflammation may have a greater influence on the GCF proinflammatory biomarker levels as compared to systemic obesity. Whether patients having chronic periodontitis with obesity have elevated proinflammatory GCF biomarkers levels compared to nonobese individuals remains debatable. PMID:27795608

Adiposity and insulin resistance correlate with telomere length in middle-aged Arabs: the influence of circulating adiponectin.

PubMed

Al-Attas, Omar S; Al-Daghri, Nasser M; Alokail, Majed S; Alfadda, Assim; Bamakhramah, Ahmed; Sabico, Shaun; Pritlove, Dave; Harte, Alison; Tripathi, Gyanendra; McTernan, Philip G; Kumar, Sudhesh; Chrousos, George

2010-10-01

Studies in obesity have implicated adipocytokines in the development of insulin resistance, which in turn may lead to accelerated aging. In this study, we determined associations of chromosomal telomere length (TL) to markers of obesity and insulin resistance in middle-aged adult male and female Arabs with and without diabetes mellitus type 2 (DMT2). One hundred and ninety-three non-diabetic and DMT2 subjects without complications (97 males and 96 females) participated in this cross-sectional study. Clinical data, as well as fasting blood samples, were collected. Serum glucose and lipid profile were determined using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumor necrosis factor-α, and PAI-1 were quantified using customized multiplex assay kits. High sensitive C-reactive protein (hsCRP) and angiotensin II (ANG II) were measured using ELISAs. Circulating leukocyte TL was examined by quantitative real-time PCR. Circulating chromosomal leukocyte TL had significant inverse associations with body mass index (BMI), systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein (LDL)- and total cholesterol, ANG II and hsCRP levels. Adiponectin, BMI, systolic blood pressure, and LDL cholesterol predicted 47% of the variance in TL (P<0.0001). HOMA-IR was the most significant predictor for TL in males, explaining 35% of the variance (P=0.01). In females, adiponectin accounted for 28% of the variance in TL (P=0.01). Obesity and insulin resistance are associated with chromosomal TL among adult Arabs. Evidence of causal relations needs further investigation. The positive association of adiponectin to TL has clinical implications as to the possible protective effects of this hormone from accelerated aging.

Adiposity and insulin resistance correlate with telomere length in middle-aged Arabs: the influence of circulating adiponectin

PubMed Central

Al-Attas, Omar S; Al-Daghri, Nasser M; Alokail, Majed S; Alfadda, Assim; Bamakhramah, Ahmed; Sabico, Shaun; Pritlove, Dave; Harte, Alison; Tripathi, Gyanendra; McTernan, Philip G; Kumar, Sudhesh; Chrousos, George

2010-01-01

Objective Studies in obesity have implicated adipocytokines in the development of insulin resistance, which in turn may lead to accelerated aging. In this study, we determined associations of chromosomal telomere length (TL) to markers of obesity and insulin resistance in middle-aged adult male and female Arabs with and without diabetes mellitus type 2 (DMT2). Design and methods One hundred and ninety-three non-diabetic and DMT2 subjects without complications (97 males and 96 females) participated in this cross-sectional study. Clinical data, as well as fasting blood samples, were collected. Serum glucose and lipid profile were determined using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumor necrosis factor-α, and PAI-1 were quantified using customized multiplex assay kits. High sensitive C-reactive protein (hsCRP) and angiotensin II (ANG II) were measured using ELISAs. Circulating leukocyte TL was examined by quantitative real-time PCR. Results Circulating chromosomal leukocyte TL had significant inverse associations with body mass index (BMI), systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein (LDL)- and total cholesterol, ANG II and hsCRP levels. Adiponectin, BMI, systolic blood pressure, and LDL cholesterol predicted 47% of the variance in TL (P<0.0001). HOMA-IR was the most significant predictor for TL in males, explaining 35% of the variance (P=0.01). In females, adiponectin accounted for 28% of the variance in TL (P=0.01). Conclusion Obesity and insulin resistance are associated with chromosomal TL among adult Arabs. Evidence of causal relations needs further investigation. The positive association of adiponectin to TL has clinical implications as to the possible protective effects of this hormone from accelerated aging. PMID:20679357

Exercise, adipokines and pediatric obesity: a meta-analysis of randomized controlled trials.

PubMed

García-Hermoso, A; Ceballos-Ceballos, R J M; Poblete-Aro, C E; Hackney, A C; Mota, J; Ramírez-Vélez, R

2017-04-01

Adipokines are involved in the etiology of diabetes, insulin resistance, and the development of atherosclerosis and other latent-onset complications. The objective of this meta-analysis was to determine the effectiveness of exercise interventions on adipokines in pediatric obesity. A computerized search was made using three databases. The analysis was restricted to studies that examined the effect of exercise interventions on adipokines (adiponectin, leptin, resistin and visfatin) in pediatric obesity (6-18 years old). Fourteen randomized controlled trials (347 youths) were included. Weighted mean difference (WMD) and 95% confidence intervals were calculated. Exercise was associated with a significant increase in adiponectin (WMD=0.882 μg ml -1 , 95% CI, 0.271-1.493) but did not alter leptin and resistin level. Likewise, exercise intensity and change in body fat; as well as total exercise program duration, duration of the sessions, and change in body fat all significantly influenced the effect of exercise on adiponectin and leptin, respectively. Exercise seems to increase adiponectin levels in childhood obesity. Our results also suggested that exercise on its own, without the concomitant presence of changes in body composition levels, does not affect leptin levels.

Pathological Type-2 Immune Response, Enhanced Tumor Growth, and Glucose Intolerance in Retnlβ (RELMβ) Null Mice: A Model of Intestinal Immune System Dysfunction in Disease Susceptibility.

PubMed

Wernstedt Asterholm, Ingrid; Kim-Muller, Ja Young; Rutkowski, Joseph M; Crewe, Clair; Tao, Caroline; Scherer, Philipp E

2016-09-01

Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicated in metabolic dysregulation, inflammation, and cancer. Specifically, RELMβ, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both the intestinal lumen in the mucosal layer as well as in the circulation. RELMβ has been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELMβ plays a complex role in immune system regulation, and the impact of loss of function of RELMβ on colon cancer and metabolic regulation has not been fully elucidated. We therefore tested whether Retnlβ (mouse ortholog of human RETNLβ) null mice have an enhanced or reduced susceptibility for colon cancer as well as metabolic dysfunction. We found that the lack of RELMβ leads to increased colonic expression of T helper cell type-2 cytokines and IL-17, associated with a reduced ability to maintain intestinal homeostasis. This defect leads to an enhanced susceptibility to the development of inflammation, colorectal cancer, and glucose intolerance. In conclusion, the phenotype of the Retnlβ null mice unravels new aspects of inflammation-mediated diseases and strengthens the notion that a proper intestinal barrier function is essential to sustain a healthy phenotype. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Antidiabetic activity of Ganoderma lucidum polysaccharides F31 down-regulated hepatic glucose regulatory enzymes in diabetic mice.

PubMed

Xiao, Chun; Wu, Qingping; Zhang, Jumei; Xie, Yizhen; Cai, Wen; Tan, Jianbin

2017-01-20

Ganoderma lucidum (Lin Zhi) has been used to treat diabetes in Chinese folk for centuries. Our laboratory previously demonstrated that Ganoderma lucidum polysaccharides (GLPs) had hypoglycemic effects in diabetic mice. Our aim was to identify the main bioactives in GLPs and corresponding mechanism of action. Four polysaccharide-enriched fraction were isolated from GLPs and the antidiabetic activities were evaluated by type 2 diabetic mice. Fasting serum glucose (FSG), fasting serum insulin (FSI) and epididymal fat/BW ratio were measured at the end of the experiment. In liver, the mRNA levels of hepatic glucose regulatory enzymes were determined by quantitative polymerase chain reaction (qPCR) and the protein levels of phospho-AMP-activated protein kinase (p-AMPK)/AMPK were determined by western blotting test. In epididymal fat tissue, the mRNA and protein levels GLUT4, resistin, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC1) were determined by qPCR and immuno-histochemistry. The structure of polysaccharide F31 was obtained from GPC, FTIR NMR and GC-MS spectroscopy, RESULTS: F31 significantly decreased FSG (P<0.05), FSI and epididymal fat/BW ratio (P<0.01). In liver, F31 decreased the mRNA levels of hepatic glucose regulatory enzymes, and up-regulated the ratio of phospho-AMP-activated protein kinase (p-AMPK)/AMPK. In epididymal fat tissue, F31 increased the mRNA levels of GLUT4 but decreased fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC1) and resistin. Immuno-histochemistry results revealed F31 increased the protein levels of GLUT4 and decreased resistin. Data suggested that the main bioactives in GLPs was F31, which was determined to be a β-heteropolysaccharide with the weight-average molecular weight of 15.9kDa. The possible action mechanism of F31 may be associated with down-regulation of the hepatic glucose regulated enzyme mRNA levels via AMPK activation, improvement of insulin resistance and decrease of epididymal fat/BW ratio. These results strongly suggest that F31 has antidiabetic potential. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs.

PubMed

Abu-Farha, Mohamed; Behbehani, Kazem; Elkum, Naser

2014-04-09

Cardiovascular diseases (CVD) are a leading cause of death worldwide including the Middle East. This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin. Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines. In this study, for the first time, the relationship between traditional cardiovascular risk factors, Metabolic Syndrome (MetS) and circulating level of adipokines in Arab ethnicity was investigated. We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait. Traditional cardiovascular risk factors such as blood pressure (BP), low density lipoprotein (LDL) and triglyceride (TG) were measured. Plasma levels of circulating Leptin, Plasminogen Activator Inhibitor (PAI-1) visfatin, adiponectin, resistin and adipsin were assessed using the multiplexing immunobead-based assay. Circulating levels of High sensitivity C-Reactive Protein (hsCRP), Leptin, PAI-1 and adiponectin were significantly higher in Arab women than men (p < 0.0001). In multi-variate analysis, the homeostasis model assessment-insulin resistance (HOMA-IR) and body mass index (BMI) showed strong association with most of the biomarkers (p < 0.05). HsCRP showed significant association with all risk factors (p < 0.05). Leptin, PAI-1 and adipsin showed significant positive correlation with BMI, unlike adiponectin which showed inverse correlation (p < 0.05). Subjects in the highest tertile of leptin, PAI-1 and hsCRP had higher odds of having Metabolic Syndrome (MetS) (odd ratio [OR] = 3.02, 95% confidence interval [CI] = 1.47-6.19) and (OR = 2.52, 95% CI = 1.45-4.35), (OR = 4.26, 95% CI = 2.39-7.59) respectively. On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS (OR = 0.22, 95% CI = 0.12-0.40). Leptin, PAI-1 and hsCRP showed significant positive association with increased MetS components (P-trend <0.05), while adiponectin was negatively associated with increased MetS components (P-trend <0.0001). Our results show positive association between hsCRP, leptin, PAI-1 with increased MetS components and increase the odds of having MetS. Adiponectin on the other hand showed inverse correlation with MetS components and associated with reduction in MetS. Overall, our data highlights the significant clinical value these markers have in MetS especially hsCRP which can be used as good marker of low grade inflammation in Arabs.

Relationship between adiponectin levels, acylated ghrelin levels, and short-term body mass index changes in children with diabetes mellitus type 1 at diagnosis and after insulin therapy.

PubMed

Martos-Moreno, Gabriel A; Barrios, Vicente; Soriano-Guillén, Leandro; Argente, Jesús

2006-11-01

To determine the effect of the initial metabolic imbalance and its restoration after insulin therapy on adiponectin and acylated ghrelin levels in children with type 1 diabetes mellitus (T1DM). Twenty prepubertal children with newly diagnosed T1DM were prospectively studied at diagnosis and after 1 and 4 months of therapy. Body mass index (BMI) and serum levels of adiponectin, resistin, total and acylated ghrelin, leptin, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) were determined. The control group comprised 40 healthy prepubertal children. BMI was decreased at diagnosis, normalized at 1 month, and remained so thereafter. Adiponectin levels at diagnosis were similar to controls, increasing significantly after 1 month and normalizing at 4 months. Acylated ghrelin levels were lower at diagnosis, with a significant increase at 1 month and normalizing at 4 months. Resistin levels were normal at all time points. Leptin levels were decreased, while TNF-alpha and IL-6 were increased at diagnosis and normalized at 1 month. These findings suggest that BMI is not the main predictor of acylated ghrelin or adiponectin levels in newly diagnosed T1DM subjects and that these peptides may play an important role in the metabolic adaptation in this disease.

The orphan nuclear receptor small heterodimer partner is required for thiazolidinedione effects in leptin-deficient mice.

PubMed

Tseng, Hsiu-Ting; Park, Young Joo; Lee, Yoon Kwang; Moore, David D

2015-05-08

Small heterodimer partner (SHP, NR0B2) is involved in diverse metabolic pathways, including hepatic bile acid, lipid and glucose homeostasis, and has been implicated in effects on the peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and the receptor for antidiabetic drugs thiazolidinediones (TZDs). In this study, we aim to investigate the role of SHP in TZD response by comparing TZD-treated leptin-deficient (ob/ob) and leptin-, SHP-deficient (ob/ob;Shp(-/-)) double mutant mice. Both ob/ob and double mutant ob/ob;Shp(-/-) mice developed hyperglycemia, insulin resistance, and hyperlipidemia, but hepatic fat accumulation was decreased in the double mutant ob/ob;Shp(-/-) mice. PPARγ2 mRNA levels were markedly lower in ob/ob;Shp(-/-) liver and decreased to a lesser extent in adipose tissue. The TZD troglitazone did not reduce glucose or circulating triglyceride levels in ob/ob;Shp(-/-) mice. Expression of the adipocytokines, such as adiponectin and resistin, was not stimulated by troglitazone treatment. Expression of hepatic lipogenic genes was also reduced in ob/ob;Shp(-/-) mice. Moreover, overexpression of SHP by adenovirus infection increased PPARγ2 mRNA levels in mouse primary hepatocytes. Our results suggest that SHP is required for both antidiabetic and hypolipidemic effects of TZDs in ob/ob mice through regulation of PPARγ expression.

Here, there and everywhere: Resistin-like molecules in infection, inflammation, and metabolic disorders.

PubMed

Pine, Gabrielle M; Batugedara, Hashini M; Nair, Meera G

2018-06-01

The Resistin-Like Molecules (RELM) α, β, and γ and their namesake, resistin, share structural and sequence homology but exhibit significant diversity in expression and function within their mammalian host. RELM proteins are expressed in a wide range of diseases, such as: microbial infections (eg. bacterial and helminth), inflammatory diseases (eg. asthma, fibrosis) and metabolic disorders (eg. diabetes). While the expression pattern and molecular regulation of RELM proteins are well characterized, much controversy remains over their proposed functions, with evidence of host-protective and pathogenic roles. Moreover, the receptors for RELM proteins are unclear, although three receptors for resistin, decorin, adenylyl cyclase-associated protein 1 (CAP1), and Toll-like Receptor 4 (TLR4) have recently been proposed. In this review, we will first summarize the molecular regulation of the RELM gene family, including transcription regulation and tissue expression in humans and mouse disease models. Second, we will outline the function and receptor-mediated signaling associated with RELM proteins. Finally, we will discuss recent studies suggesting that, despite early misconceptions that these proteins are pathogenic, RELM proteins have a more nuanced and potentially beneficial role for the host in certain disease settings. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adipokines and nutritional status for patients on maintenance hemodialysis.

PubMed

Małgorzewicz, S; Aleksandrowicz-Wrona, E; Owczarzak, A; Debska-Slizień, A; Rutkowski, B; Łysiak-Szydłowska, W

2010-09-01

The aim of this study was to investigate the serum concentration of adipokines, such as leptin, adiponectin, and resistin, and assess its relation to nutritional and inflammatory parameters in both overweight and normal weight patients on maintenance hemodialysis. A total of 36 hemodialysis patients (27 M, 9 F; mean age 55.3 +/- 12 yr.) were examined and 23 additional healthy volunteers were recruited as the control group. The concentrations of leptin, leptin receptor, adiponectin, resistin, IL-6, TNFa and CRP were measured by ELISA. Assessment of nutritional status was determined by the levels of albumin, BMI, percentage of body fat (%F), lean body mass (LBM), and Subjective Global Assessment Score (SGA). According to the SGA 7-points score and the albumin level, 20 patients were of good nutritional status (6-7 points), while 16 patients were mildly malnourished (4-5 points). The concentrations of CRP, resistin, adiponectin, and TNFa were statistically higher in hemodialysis patients than in the control group (p pound 0.05). The adiponectin level was inversely correlated with %F (R Spearman=-0.3; p pound 0.05). The level of leptin was positively correlated with %F as well as with BMI and SGA scores (R Spearman=0.4; p pound 0.05). Although there was no significant difference in the nutritional status between the nonoverweight (BMI 18.5-24.99) and overweight (BMI (3)25.0) groups of patients, in the nonoverweight group there were 12 patients (54.5%) with signs of mild malnutrition compared to 4 malnourished patients (28.5%) in the overweight group. Nonoverweight patients presented significantly lower leptin concentration (12.7 vs 27.8 ug/l) and higher adiponectin level (38.9 vs 32.5 ng/ml) when compared to overweight patients. The levels of IL-6 and TNFa were higher in the nonoverweight group of patients. Overweight patients also had shorter durations of stay in the hemodialysis program (30.5 vs. 87.6 months). The results of our study indicate that lean hemodialysis patients are more prone to malnutrition and inflammation. The increased levels of leptin and decreased levels of adiponectin in the overweight hemodialysis patients support the idea of a reverse epidemiology phenomenon in this group of patients. (c) 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Long-Term Dietary Supplementation with Yerba Mate Ameliorates Diet-Induced Obesity and Metabolic Disorders in Mice by Regulating Energy Expenditure and Lipid Metabolism.

PubMed

Choi, Myung-Sook; Park, Hyo Jin; Kim, Sang Ryong; Kim, Do Yeon; Jung, Un Ju

2017-12-01

This study evaluated whether long-term supplementation with dietary yerba mate has beneficial effects on adiposity and its related metabolic dysfunctions in diet-induced obese mice. C57BL/6J mice were randomly divided into two groups and fed their respective experimental diets for 16 weeks as follows: (1) control group fed with high-fat diet (HFD) and (2) mate group fed with HFD plus yerba mate. Dietary yerba mate increased energy expenditure and thermogenic gene mRNA expression in white adipose tissue (WAT) and decreased fatty acid synthase (FAS) mRNA expression in WAT, which may be linked to observed decreases in body weight, WAT weight, epididymal adipocyte size, and plasma leptin level. Yerba mate also decreased levels of plasma lipids (free fatty acids, triglycerides, and total cholesterol) and liver aminotransferase enzymes, as well as the accumulation of hepatic lipid droplets and lipid content by inhibiting the activities of hepatic lipogenic enzymes, such as FAS and phosphatidate phosphohydrolase, and increasing fecal lipid excretion. Moreover, yerba mate decreased the levels of plasma insulin as well as the homeostasis model assessment of insulin resistance, and improved glucose tolerance. Circulating levels of gastric inhibitory polypeptide and resistin were also decreased in the mate group. These findings suggest that long-term supplementation of dietary yerba mate may be beneficial for improving diet-induced adiposity, insulin resistance, dyslipidemia, and hepatic steatosis.

Chronic benzylamine administration in the drinking water improves glucose tolerance, reduces body weight gain and circulating cholesterol in high-fat diet-fed mice.

PubMed

Iffiú-Soltész, Zsuzsa; Wanecq, Estelle; Lomba, Almudena; Portillo, Maria P; Pellati, Federica; Szöko, Eva; Bour, Sandy; Woodley, John; Milagro, Fermin I; Alfredo Martinez, J; Valet, Philippe; Carpéné, Christian

2010-04-01

Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in traditional medicine. In mammals, benzylamine is metabolized by semicarbazide-sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter product has insulin-mimicking action, and is involved in the effects of benzylamine on human adipocytes: stimulation of glucose transport and inhibition of lipolysis. This study examined whether chronic, oral administration of benzylamine could improve glucose tolerance and the circulating lipid profile without increasing oxidative stress in overweight and pre-diabetic mice. The benzylamine diffusion across the intestine was verified using everted gut sacs. Then, glucose handling and metabolic markers were measured in mice rendered insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine in their drinking water (3600micromol/(kgday)) for 17 weeks. HFD-benzylamine mice showed lower body weight gain, fasting blood glucose, total plasma cholesterol and hyperglycaemic response to glucose load when compared to HFD control. In adipocytes, insulin-induced activation of glucose transport and inhibition of lipolysis remained unchanged. In aorta, benzylamine treatment partially restored the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers were reduced. Resistin and uric acid, surrogate plasma markers of metabolic syndrome, were decreased. In spite of the putative deleterious nature of the hydrogen peroxide generated during amine oxidation, and in agreement with its in vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine could be considered as a potential oral agent to treat metabolic syndrome. Copyright 2010 Elsevier Ltd. All rights reserved.

Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice.

PubMed

Okubo, Hirofumi; Kushiyama, Akifumi; Sakoda, Hideyuki; Nakatsu, Yusuke; Iizuka, Masaki; Taki, Naoyuki; Fujishiro, Midori; Fukushima, Toshiaki; Kamata, Hideaki; Nagamachi, Akiko; Inaba, Toshiya; Nishimura, Fusanori; Katagiri, Hideki; Asahara, Takashi; Yoshida, Yasuto; Chonan, Osamu; Encinas, Jeffery; Asano, Tomoichiro

2016-01-28

Resistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMβ-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH.

Resistin role in development of gestational diabetes mellitus.

PubMed

Siddiqui, Khalid; George, Teena P

2017-07-01

Diabetes is estimated to be one of the major causes of deaths in most countries due to its high prevalence rate, which was 8.8% in 2015. Hyperglycemia detected during pregnancy is known as gestational diabetes mellitus and it increases the potential risk of development of Type 2 diabetes in mothers with its varying prevalence rate of 1-14% in different populations. It also leads to the higher risk of developing abnormal glucose tolerance and obesity in their child at an early age. Recent studies show that potential mediators of insulin resistance such as adipokines - adiponectin, leptin and resistin are important for glucose and lipid metabolism. Adipokines are directly involved in the regulation of insulin secretion and insulin sensitivity in the liver, muscle and adipose tissue. It is also involved in inflammation, adipose tissue accumulation, adverse fat distribution and subsequently affects glucose metabolism. This review highlights the role of resistin (an adipokine) in the development of gestational diabetes mellitus.

Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs

PubMed Central

2014-01-01

Background Cardiovascular diseases (CVD) are a leading cause of death worldwide including the Middle East. This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin. Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines. In this study, for the first time, the relationship between traditional cardiovascular risk factors, Metabolic Syndrome (MetS) and circulating level of adipokines in Arab ethnicity was investigated. Methods We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait. Traditional cardiovascular risk factors such as blood pressure (BP), low density lipoprotein (LDL) and triglyceride (TG) were measured. Plasma levels of circulating Leptin, Plasminogen Activator Inhibitor (PAI-1) visfatin, adiponectin, resistin and adipsin were assessed using the multiplexing immunobead-based assay. Results Circulating levels of High sensitivity C-Reactive Protein (hsCRP), Leptin, PAI-1 and adiponectin were significantly higher in Arab women than men (p < 0.0001). In multi-variate analysis, the homeostasis model assessment-insulin resistance (HOMA-IR) and body mass index (BMI) showed strong association with most of the biomarkers (p < 0.05). HsCRP showed significant association with all risk factors (p < 0.05). Leptin, PAI-1 and adipsin showed significant positive correlation with BMI, unlike adiponectin which showed inverse correlation (p < 0.05). Subjects in the highest tertile of leptin, PAI-1 and hsCRP had higher odds of having Metabolic Syndrome (MetS) (odd ratio [OR] = 3.02, 95% confidence interval [CI] = 1.47 – 6.19) and (OR = 2.52, 95% CI = 1.45 – 4.35), (OR = 4.26, 95% CI = 2.39 – 7.59) respectively. On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS (OR = 0.22, 95% CI = 0.12 – 0.40). Leptin, PAI-1 and hsCRP showed significant positive association with increased MetS components (P-trend <0.05), while adiponectin was negatively associated with increased MetS components (P-trend <0.0001). Conclusion Our results show positive association between hsCRP, leptin, PAI-1 with increased MetS components and increase the odds of having MetS. Adiponectin on the other hand showed inverse correlation with MetS components and associated with reduction in MetS. Overall, our data highlights the significant clinical value these markers have in MetS especially hsCRP which can be used as good marker of low grade inflammation in Arabs. PMID:24716628

Post-partum plasma C-peptide and ghrelin concentrations are predictive of type 2 diabetes in women with previous gestational diabetes mellitus.

PubMed

Lappas, Martha; Jinks, Debra; Ugoni, Antony; Louizos, Connie C J; Permezel, Michael; Georgiou, Harry M

2015-07-01

Women with previous gestational diabetes mellitus (pGDM) are at increased risk of developing type 2 diabetes later in life. The aim of this study was to determine if circulating levels of metabolic hormones 12 weeks following a GDM pregnancy are associated with an increased risk of type 2 diabetes 8-10 years later. Fasting plasma concentrations of glucose, insulin, C-peptide, ghrelin, GIP, GLP-1, glucagon, leptin, PAI-1, resistin and visfatin were measured in 98 normal glucose tolerant women, 12 weeks following an index GDM pregnancy. Women were assessed every 2 years for up to 10 years for development of overt type 2 diabetes. After a median follow-up period of 8.7 years, 22.5% of women with a pGDM pregnancy developed type 2 diabetes. Significant risk factors for the development of type 2 diabetes were fasting plasma glucose levels >5 mmol/L during pregnancy and at 12 weeks post-pregnancy. In addition, higher C-peptide levels and lower ghrelin levels at 12 weeks post-pregnancy were also significant risk factors for the development of type 2 diabetes. Fasting plasma glucose during pregnancy and post-partum, and post-partum C-peptide and ghrelin levels were significant risk factors for the development of type 2 diabetes in women with pGDM. This is the first report that identifies C-peptide and ghrelin as potential biomarkers for the prediction of type 2 diabetes in women with a history of GDM. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

[Effects of berberine on mRNA expression levels of PPARγ and adipocytokines in insulin-resistant adipocytes].

PubMed

Tu, Jun; Luo, Xin-Xin; Li, Bing-Tao; Li, Yu; Xu, Guo-Liang

2016-06-01

Adipocytokines are closely associated with insulin resistance (IR) in adipose tissues, and they are more and more seriously taken in the study of the development of diabetes. This experiment was mainly to study the effect of berberine on mRNA expression levels of PPARγ and adipocytokines in insulin resistant adipocytes, and investigate the molecular mechanism of berberine in enhancing insulin sensitization and application advantages of droplet digital PCR (ddPCR). ddPCR absolute quantification analysis was taken in this experiment to simply and intuitively determine the appropriate reference genes. ddPCR and quantitative Real-time PCR (qPCR) were used to compare the effect of different doses of berberine (10, 20, 50, 100 μmol•L⁻¹) on mRNA expression levels of PPARγ, adiponectin, resistin and leptin in IR 3T3-L1adipocytes. Antagonist GW9662 was added to study the inherent correlation between PPARγ and adiponectin mRNA expression levels. ddPCR results showed that the expression level of β-actin in adipocytes was stable, and suitable as reference gene for normalization of quantitative PCR data. Both of ddPCR and qPCR results showed that, as compared with IR models, the mRNA expression levels of adiponectin were decreased in the treatment with berberine (10, 20, 50, 100 μmol•L⁻¹) in a dose-dependent manner (P<0.01); the expression of PPARγ was decreased by 20, 50, 100 μmol•L⁻¹ berberine in a dose-dependent manner in qPCR assay (P<0.01) and decreased only by 50 and 100 μmol•L⁻¹ berberine in ddPCR assay (P<0.05). PPARγ specific antagonist GW9662 intervention experiment showed that adiponectin gene expression was directly relevant with PPARγ (P<0.05). ddPCR probe assay showed that various doses of berberine could significantly reduce mRNA expression levels of resistin and leptin (P<0.01) in a dose-dependent manner. In conclusion, berberine enhanced insulin sensitization effect not by up-regulating adiponect in expression of transcriptional level in PPARγ-dependent manner, but may by the elevated multimerization of adiponectin in the posttranslational regulation level. Berberine down-regulated the resistin and leptin expression levels, which could alleviate lipolysis and improve IR in adipocytes. ddPCR provided better sensitivity and linear range than qPCR, with obvious technical advantages for the detection of low abundance expression of target genes. Copyright© by the Chinese Pharmaceutical Association.

Obesity-related adipokines predict patient-reported shoulder pain.

PubMed

Gandhi, Rajiv; Perruccio, Anthony V; Rizek, Randy; Dessouki, Omar; Evans, Heather M K; Mahomed, Nizar N

2013-01-01

Increasingly, an inflammatory modulating effect of adipokines within synovial joints is being recognized. To date, there has been no work examining a potential association between the presence of adipokines in the shoulder and patient-reported outcomes. This study undertakes an investigation assessing these potential links. 50 osteoarthritis patients scheduled for shoulder surgery completed a pre-surgery questionnaire capturing demographic information including validated, patient-reported function (Disabilities of the Arm, Shoulder, and Hand questionnaire) and pain (Short Form McGill Pain Questionnaire) measures. Synovial fluid (SF) samples were analyzed for leptin, adiponectin, and resistin levels using Milliplex MAP assays. Linear regression modeling was used to assess the association between adipokine levels and patient-reported outcomes, adjusted for age, sex, BMI, and disease severity. 54% of the cohort was female (n = 27). The mean age (SD) of the sample was 62.9 (9.9) years and the mean BMI (SD) was 28.1 (5.4) kg/m(2). From regression analyses, greater SF leptin and adiponectin levels, but not regarding resistin, were found to be associated with greater pain (p < 0.05). Adipokine levels were not associated with functional outcome scores. The identified association between shoulder-derived SF leptin and adiponectin and shoulder pain is likely explained by the pro-inflammatory characteristics of the adipokines and represents potentially important therapeutic targets. © 2013 S. Karger GmbH, Freiburg.

Antidiabetic Effect of Brain-Derived Neurotrophic Factor and Its Association with Inflammation in Type 2 Diabetes Mellitus

PubMed Central

Kaplon-Cieslicka, Agnieszka; Malek, Lukasz; Postula, Marek

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which plays an important role in the central nervous system, and systemic or peripheral inflammatory conditions, such as acute coronary syndrome and type 2 diabetes mellitus (T2DM). BDNF is also expressed in several nonneuronal tissues, and platelets are the major source of peripheral BDNF. Here, we reviewed the potential role of BDNF in platelet reactivity in T2DM and its association with selected inflammatory and platelet activation mediators. Besides that, we focused on adipocytokines such as leptin, resistin, and adiponectin which are considered to take part in inflammation and both lipid and glucose metabolism in diabetic patients as previous studies showed the relation between adipocytokines and BDNF. We also reviewed the evidences of the antidiabetic effect of BDNF and the association with circulating inflammatory cytokines in T2DM. PMID:29062839

The adipose renin-angiotensin system modulates sysemic markers of insulin sensitivity activates the intrarenal renin-angiotensin system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Suyeon; Soltani-Bejnood, Morvarid; Quignard-Boulange, Annie

2006-07-01

BACKGROUND: A growing body of data provides increasing evidence that the adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass. Beyond its paracrine actions within adipose tissue, adipocyte-derived angiotensin II (Ang II) may also impact systemic functions such as blood pressure and metabolism. METHODS AND RESULTS: We used a genetic approach to manipulate adipose RAS activity in mice and then study the consequences on metabolic parameters and on feedback regulation of the RAS. The models included deletion of the angiotensinogen (Agt) gene (Agt-KO), its expression solely in adipose tissue under the control of an adipocyte-specific promoter (aP2-Agt/ Agt-KO),more » and overexpression in adipose tissue of wild type mice (aP2-Agt). Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. Overexpression of Agt in adipose tissue resulted in increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also markedly elevated in kidney of aP2-Agt mice, suggesting that hypertension in these animals may be in part due to stimulation of the intrarenal RAS. CONCLUSIONS: Taken together, the results from this study demonstrate that alterations in adipose RAS activity significantly alter both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.« less

Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice

PubMed Central

Okubo, Hirofumi; Kushiyama, Akifumi; Sakoda, Hideyuki; Nakatsu, Yusuke; Iizuka, Masaki; Taki, Naoyuki; Fujishiro, Midori; Fukushima, Toshiaki; Kamata, Hideaki; Nagamachi, Akiko; Inaba, Toshiya; Nishimura, Fusanori; Katagiri, Hideki; Asahara, Takashi; Yoshida, Yasuto; Chonan, Osamu; Encinas, Jeffery; Asano, Tomoichiro

2016-01-01

Resistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMβ-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH. PMID:26818807

[The role of single nucleotide polymorphisms in GIPR gene in the changes of secretion in hormones and adipokines in patients with obesity with type 2 diabetes].

PubMed

Skuratovskaia, D A; Vulf, M A; Kirienkova, E V; Mironyuk, N I; Zatolokin, P A; Litvinova, L S

2018-03-01

The relationship between the rs2302382, rs8111428 and Glu354Gln (rs1800437) polymorphisms in GIPR (glucosedependent insulinotropic polypeptide receptor) gene and plasma levels of mediators involved in the regulation of carbohydrate metabolism in obese patients with type 2 diabetes (before and after a test breakfast) was investigated. The contribution of polymorphic variants of rs2302382, rs8111428 in GIPR gene in the predisposition to type 2 diabetes in individuals belonging to the Slavic population of Russia was found. Polymorphisms rs2302382 and rs8111428 in the GIPR gene were characterized by the nonequilibrium cohesion. The decrease in the level of expression of the GIPR gene in adipose tissue of the small intestine mesentery in the carriers of the CC genotype rs2302382 and AA rs8111428 was associated with the increase in the plasma leptin level, whereas during normal expression, the plasma content of insulin, and GIP (in persons with the genotype of the polymorphism rs2302382 and AG polymorphism rs8111428), resistin and ghrelin (in individuals with the genotype of the polymorphism rs2302382) increased. We propose the stimulating effect of GIP on the secretion of resistin, leptin and ghrelin, with an increase in insulin production in obese patients with type 2 diabetes.

Effect of OSA on hypoxic and inflammatory markers during CPAP withdrawal: Further evidence from three randomized control trials.

PubMed

Turnbull, Chris D; Rossi, Valentina A; Santer, Peter; Schwarz, Esther I; Stradling, John R; Petousi, Nayia; Kohler, Malcolm

2017-05-01

Obstructive sleep apnoea (OSA) is associated with cardiovascular disease. Intermittent hypoxia, endothelial dysfunction and adipose tissue-mediated inflammation have all been linked to cardiovascular disease in OSA. We therefore explored the effect of OSA on relevant associated blood markers: adrenomedullin (ADM), endocan, endothelin-1 (ET-1), resistin and vascular endothelial growth factor (VEGF). Patients with OSA, established on and compliant with continuous positive airways pressure (CPAP) therapy for >1 year were included from three randomized controlled trials, conducted at two centres. Patients were randomized to either continued therapeutic CPAP or sham CPAP (CPAP withdrawal) for 2 weeks. Blood markers were measured at baseline and at 14 days and the treatment effect between sham CPAP and therapeutic CPAP was analysed. A total of 109 patients were studied (therapeutic CPAP n = 54, sham CPAP n = 55). Sham CPAP was associated with a return of OSA (between-group difference in oxygen desaturation index (ODI) 36.0/h, 95% CI 29.9-42.2, P < 0.001). Sham CPAP was associated with a reduction in ADM levels at 14 days (-26.0 pg/mL, 95% CI -47.8 to -4.3, P = 0.02), compared to therapeutic CPAP. Return of OSA was not associated with changes in endocan, ET-1, resistin or VEGF. Whilst CPAP withdrawal was associated with return of OSA, it was associated with an unexpected significant reduction in the vasodilator ADM and not with expected increases in hypoxia-induced markers, markers of endothelial function or resistin. We propose that the vascular effects occurring in OSA may be brought about by other mechanisms, perhaps partly through a reduction in ADM. © 2016 Asian Pacific Society of Respirology.

Pathological Fingerprints, Systems Biology and Biomarkers of Blast Brain Injury

DTIC Science & Technology

2010-06-01

in triplicate. *=pɘ.05 vs. sham ( noise exposed rats) according unpaired t-test analysis. NS- Not significant. E-selectin and L-selectin are adhesion...an energy balance, food intake, wakefulness . We measured serum Resistin and Orexin A levels after blast exposure using 2 different methods...penetrating flesh wounds (Belanger et al., 2005; Lew, 2005). However, even mild and moderate brain injuries can produce significant deficits , and when repeated

Adipokines, cytokines and body fat stores in hepatitis C virus liver steatosis

PubMed Central

González-Reimers, Emilio; López-Prieto, Javier; Quintero-Platt, Geraldine; Pelazas-González, Ricardo; Alemán-Valls, M Remedios; Pérez-Hernández, Onán; de-la-Vega-Prieto, M José; Gómez-Rodríguez, M Angeles; Martín-González, Candelaria; Santolaria-Fernández, Francisco

2016-01-01

AIM: To identify patients with or without liver steatosis and its severity in treatment-naïve patients affected by hepatitis C virus (HCV) infection. METHODS: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body (by densitometry), hormones [insulin, homeostatic model assessment (HOMA)], adipokines (resistin, adiponectin, leptin), and cytokines (tumor necrosis factor α, interleukin-6). RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunk fat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin. CONCLUSION: Steatosis in HCV infection is common (67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines. PMID:26783423

Adipokines, cytokines and body fat stores in hepatitis C virus liver steatosis.

PubMed

González-Reimers, Emilio; López-Prieto, Javier; Quintero-Platt, Geraldine; Pelazas-González, Ricardo; Alemán-Valls, M Remedios; Pérez-Hernández, Onán; de-la-Vega-Prieto, M José; Gómez-Rodríguez, M Angeles; Martín-González, Candelaria; Santolaria-Fernández, Francisco

2016-01-08

To identify patients with or without liver steatosis and its severity in treatment-naïve patients affected by hepatitis C virus (HCV) infection. We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body (by densitometry), hormones [insulin, homeostatic model assessment (HOMA)], adipokines (resistin, adiponectin, leptin), and cytokines (tumor necrosis factor α, interleukin-6). Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunk fat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin. Steatosis in HCV infection is common (67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

Correlation between PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients.

PubMed

Dragović, Gordana; Sumarac-Dumanovic, Mirjana; Khawla, Al Musalhi; Soldatović, Ivan; Andjić, Mladen; Jevtović, Djordje; Nair, Devaki

2018-06-22

Data about correlation of interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), adipocytokines (leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFα), ferritin, C reactive protein (CRP) and vascular endothelial growth factor (VEGF) with homeostasis model assessment (HOMA) in HIV/AIDS patients are still limited. Therefore the aim of this study was to evaluate the possible correlations of serum levels of PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients treated with combined antiretroviral therapy (cART). This cross-sectional study included 64 HIV/AIDS patients, all Caucasians, receiving cART at the HIV/AIDS Centre, Belgrade, Serbia. PAI-1, leptin, ferritin and insulin levels were measured using the Metabolic Syndrome Array I (Randox Laboratories Ltd., London, UK), while adiponectin and resistin levels were measured using Metabolic Syndrome Array II (Randox Laboratories Ltd., London, UK), interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), MCP-1, TNF-α as well as VEGF was measured using Cytokine Array I (Randox Laboratories Ltd., London, UK). Insulin resistance was determined using the homeostasis model assessment index (HOMA). Multicollinearity of independent variables in multivariate model was analyzed using Variance Inflation Factor. Correlation analysis revealed significant correlations between HOMA and waist circumference, body mass index, patients' age, number of cART combinations and triglycerides (p = 0.001, p = 0.001, p = 0.050, p = 0.044, p = 0.002, respectively). HOMA negatively correlated with levels of high density lipoprotein (HDL) (Rho = -0.282; p = 0.025). PAI-1 (Rho = 0.334; p = 0.007) and leptin (Rho = 0.492; p = 0.001) together with ferritin (Rho = 0.396, p = 0.001) positively and significantly correlated with HOMA. Levels of IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10, adiponectin, MCP-1, resistin, TNF-α, CRP and VEGF did not significantly correlate with HOMA. Further, multiple logistic regression showed that there is a statistically significant correlation between PAI, leptin and ferritin with HOMA levels (p = 0.042; p < 0.001, p = 0.009). We showed significant correlation between PAI-1, leptin and ferritin, independently of each other with HOMA, in HIV/AIDS patients on cART. Copyright © 2018. Published by Elsevier Inc.

Serum visfatin and vaspin levels in prepubertal children: effect of obesity and weight loss after behavior modifications on their secretion and relationship with glucose metabolism.

PubMed

Martos-Moreno, G Á; Kratzsch, J; Körner, A; Barrios, V; Hawkins, F; Kiess, W; Argente, J

2011-10-01

To investigate the impact of obesity, weight loss and oral glucose ingestion on serum visfatin and vaspin levels in prepubertal children. A total of 100 prepubertal obese Caucasian children (OB) and 42 controls (C) were studied. The OB group was studied at baseline and after moderate (n=46) and extensive (n=14) body mass index (BMI) reduction by conservative treatment, undergoing body composition studies (dual-energy X-ray absorptiometry) and oral glucose tolerance tests (OGTTs). Serum visfatin and vaspin levels were studied throughout the OGTT, as were their relationships with insulin, leptin, leptin soluble receptor (sOB-R), adiponectin (total and high molecular weight), resistin, interleukin-6 (IL-6) and tumor necrosis factor-α levels at every time point. OB had higher visfatin (P<0.001), but similar vaspin than C. BMI reduction decreased visfatin levels (P<0.001), with BMI, waist circumference and the surrogate markers of body fat (leptin and sOB-R) showing significant correlations (P<0.05) with this peptide, but not with vaspin. Visfatin and vaspin decreased during the OGTT (P<0.001). Weight reduction did not alter visfatin dynamics in the OGTT, but decreased the area under the curve (AUC) for vaspin (P<0.001), with a correlation between the AUCs for vaspin and insulin after weight loss (P<0.05). Visfatin levels were positively correlated with resistin and IL-6, after controlling for BMI and HOMA (homeostatic model assessment) index at every time point in the study. Serum visfatin, but not vaspin, levels are influenced by body fat content in obese children, whereas both adipokines are modulated by glucose intake in a BMI-dependent manner.

Gene expression of placental hormones regulating energy balance in small for gestational age neonates.

PubMed

Struwe, Ellen; Berzl, Gabriele M; Schild, Ralf L; Dötsch, Jörg

2009-01-01

Fetal growth restriction is associated with an increased risk for metabolic and cardiovascular disease in later life. To further elucidate mechanisms that might be involved in the process of prenatal programming, we measured the adipokines leptin, resistin, and adiponectin and the GH-releasing hormone ghrelin in the placenta of small for gestational age (SGA) neonates. The control group included 24 placentas of appropriate for gestational age (AGA) newborns, in the study group were 16 placentas of SGA neonates. Gene expression of leptin, resistin, adiponectin, and ghrelin was examined. For hormones showing alterations in gene regulation placental protein expression was measured by Western blot. Placental mRNA expression of leptin was significantly increased in SGA placentas (p=0.0035, related to beta-actin). Protein concentration was increased, as well. There were no differences in placental resistin, adiponectin, or ghrelin gene expressions between SGA neonates and controls. Leptin was the only hormone to demonstrate a significant inverse correlation with birth weight (r=-0.44, p=0.01). Adiponectin correlated significantly with leptin (r=0.53, p=0.0023) and ghrelin (r=0.50, p=0.0045). Placental leptin gene expression and protein concentration showed the expected increase in the SGA group. Leptin was inversely correlated with birth weight. Positive correlation of adiponectin with leptin and ghrelin expression suggests an interaction between these hormones in the placenta. However, the unchanged expression of resistin, adiponectin, and ghrelin in SGA placentas and the absence of correlation with birth weight cast doubt whether these hormones produced in the placenta play a key role in fetal programming.

Molecular aspects of diabetes mellitus: Resistin, microRNA, and exosome.

PubMed

Saeedi Borujeni, Mohammad Javad; Esfandiary, Ebrahim; Taheripak, Gholamreza; Codoñer-Franch, Pilar; Alonso-Iglesias, Eulalia; Mirzaei, Hamed

2018-02-01

Diabetes mellitus (DM) is known as one of important common endocrine disorders which could due to deregulation of a variety of cellular and molecular pathways. A large numbers studies indicated that various pathogenesis events including mutation, serin phosphorylation, and increasing/decreasing expression of many genes could contribute to initiation and progression of DM. Insulin resistance is one of important factors which could play critical roles in DM pathogenesis. It has been showed that insulin resistance via targeting a sequence of cellular and molecular pathways (eg, PI3 kinases, PPARγ co-activator-1, microRNAs, serine/threonine kinase Akt, and serin phosphorylation) could induce DM. Among of various factors involved in DM pathogenesis, microRNAs, and exosomes have been emerged as effective factors in initiation and progression of DM. A variety of studies indicated that deregulation of these molecules could change behavior of various types of cells and contribute to progression of DM. Resistin is other main factor which is known as signal molecule involved in insulin resistance. Multiple lines evidence indicated that resistin exerts its effects via affecting on glucose metabolism, inhibition of fatty acid uptake and metabolism with affecting on a variety of targets such as CD36, fatty acid transport protein 1, Acetyl-CoA carboxylase, and AMP-activated protein kinase. Here, we summarized various molecular aspects are associated with DM particularly the molecular pathways involved in insulin resistance and resistin in DM. Moreover, we highlighted exosomes and microRNAs as effective players in initiation and progression of DM. © 2017 Wiley Periodicals, Inc.

Different protein composition of low-calorie diet differently impacts adipokine profile irrespective of weight loss in overweight and obese women.

PubMed

Mateo-Gallego, R; Lamiquiz-Moneo, I; Perez-Calahorra, S; Marco-Benedí, V; Bea, A M; Baila-Rueda, L; Laclaustra, M; Peñalvo, J L; Civeira, F; Cenarro, A

2018-02-01

High-protein (HP) diets have shown benefits in cardiometabolic markers such as insulin or triglycerides but the responsible mechanisms are not known. We aimed to assess the effect of three energy-restricted diets with different protein contents (20%, 27%, and 35%; ∼80% coming from animal source) on plasma adipokine concentration and its association with changes in cardiometabolic markers. Seventy-six women (BMI 32.8 ± 2.93) were randomized to one of three calorie-reduced diets, with protein, 20%, 27%, or 35%; carbohydrates, 50%, 43%, or 35%; and fat, 30%, for 3 months. Plasma adipokine (leptin, resistin, adiponectin, and retinol-binding protein 4; RBP4) levels were assessed. After 3 months, leptin concentration decreased in all groups without differences among them, while resistin levels remained unchanged. Adiponectin concentration heterogeneously changed in all groups (P for trend = 0.165) and resistin concentration did not significantly change. RPB4 significantly decreased by -17.5% (-31.7, -3.22) in 35%-protein diet (P for trend = 0.024 among diets). Triglycerides improved in women following the 35%-protein diet regardless of weight loss; RBP4 variation significantly influenced triglyceride concentration change by 24.9% and 25.9% when comparing 27%- and 35%- with 20%-protein diet, respectively. A 35%-protein diet induced a decrease in RBP4 regardless of weight loss, which was directly associated with triglyceride concentration improvement. These findings suggest that HP diets improve the cardiometabolic profile, at least in part, through changes in adipokine secretion. Whether this beneficial effect of HP diet is due to improvements in hepatic or adipose tissue functionality should be elucidated. The clinical trial has been registered in ClinicalTrials.gov (Identifier: NCT02160496). Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Changes of serum adipocytokines and body weight following Zingiber officinale supplementation in obese women: a RCT.

PubMed

Ebrahimzadeh Attari, Vahideh; Ostadrahimi, Alireza; Asghari Jafarabadi, Mohammad; Mehralizadeh, Sajjad; Mahluji, Sepideh

2016-09-01

The present randomized, double-blind, placebo-controlled study aimed to evaluate the effect of Zingiber officinale (ginger) consumption on some metabolic and clinical features of obesity. Eighty eligible obese women (aged 18-45 years) were randomly assigned to either ginger or placebo groups (receiving 2 g/day of ginger powder or corn starch as two 1 g tablets) for 12 weeks. Body mass index (BMI) and body composition were assessed every 4 weeks, and serum levels of leptin, adiponectin, resistin, insulin and glucose were determined before and after intervention. The homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were also calculated. Ginger consumption significantly decreased BMI, serum insulin and HOMA-IR index, along with increasing QUICKIs as compared to the placebo. Moreover, significant reductions in serum leptin, resistin and glucose were observed in both groups, especially in ginger group with nonsignificant differences between groups. The body composition and serum levels of adiponectin were not significantly changed in study groups. In conclusion, our findings demonstrate a minor beneficial effect of 2 g ginger powder supplementation for 12 weeks on weight loss and some metabolic features of obesity. However, given the lack of data in this area, ongoing clinical trials are needed to further explore ginger's effectiveness.

Allergen-induced resistin-like molecule-α promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis

PubMed Central

Mavi, Parm; Niranjan, Rituraj; Dutt, Parmesh; Zaidi, Asifa; Shukla, Jai Shankar; Korfhagen, Thomas

2014-01-01

Resistin-like molecule (Relm)-α is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-α in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-α is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-α, we generated Relm-α gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA-Relm-α). We found Relm-α protein is significantly induced in the esophagus of CC10-rtTA-Relm-α bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-α is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4+ and CD4− T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-α promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-α induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4+ and CD4− T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE. PMID:24994859

Allergen-induced resistin-like molecule-α promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis.

PubMed

Mavi, Parm; Niranjan, Rituraj; Dutt, Parmesh; Zaidi, Asifa; Shukla, Jai Shankar; Korfhagen, Thomas; Mishra, Anil

2014-09-01

Resistin-like molecule (Relm)-α is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-α in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-α is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-α, we generated Relm-α gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA-Relm-α). We found Relm-α protein is significantly induced in the esophagus of CC10-rtTA-Relm-α bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-α is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4(+) and CD4(-) T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-α promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-α induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4(+) and CD4(-) T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE. Copyright © 2014 the American Physiological Society.

Genetic variation may influence obesity only under conditions of diet: analysis of three candidate genes.

PubMed

Aberle, Jens; Flitsch, Jörg; Beck, Nicola Alessia; Mann, Oliver; Busch, Philipp; Peitsmeier, Philipp; Beil, Frank Ulrich

2008-11-01

Under the hypothesis of obesity as a polygenetic disease numerous genes have been associated with an obese phenotype and metabolic co-morbidities. The cannabinoid receptor 1 (CB 1) is part of an underinvestigated system that participates in appetite control. Previous publications suggest that the endocannabinoid systems interact with the better understood leptin-melanocortin axis. Neuropeptide Y (NPY) is a player in the latter. Finally resistin has been shown to influence NPY expression in the brain. In a cohort of 1721 caucasion men and women with a BMI of 25kg/m(2) or more we therefore investigated three candidate polymorphisms at baseline and following 3 months low fat caloric restriction diet by polymerase chain reaction and restriction digestion: the 1359 G/A variant of the cannabinoid receptor 1 (CB1), the L7P variation in neuropeptide Y (NPY) and the -420C>G polymorphism in resistin. Comparing groups according to genotype for each gene separately revealed significant results at baseline only for the CB1 gene. However, upon dieting significant data was found for all 3 genes. Carriers of at least one A allele in CB1 lost more weight and reduced LDL cholesterol more than wildtype patients. LL homocygotes in NPY had a greater reduction in glucose, triglycerides, and LDL cholesterol whereas in resistin carriers of the G allele had a greater reduction in weight and triglycerides. Creating two groups defined by NPY and resistin genotype, respectively, with similar BMI values resulted in significant differences concerning weight loss and metabolic improvement. In conclusion, genetic polymorphisms associated with obesity may become relevant only under the condition of a low calory diet. The presence of a certain genotype may then be beneficial for obesity treatment.

Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome.

PubMed

Yilmaz, Murat; Bukan, Neslihan; Ersoy, Reyhan; Karakoç, Ayhan; Yetkin, Ilhan; Ayvaz, Göksun; Cakir, Nuri; Arslan, Metin

2005-09-01

The aim of the present study was to evaluate insulin resistance (IR), glucose tolerance status and cardiovascular risk factors in first degree relatives of patients with polycystic ovary syndrome (PCOS). A total of 120 family members [Mothers(PCOS) (n = 40), Fathers(PCOS) (n = 38), Sisters(PCOS) (n = 25) and Brothers(PCOS) (n = 17)] of 55 patients with PCOS and 75 unrelated healthy control subjects without a family history of diabetes or PCOS (four age- and weight-matched subgroups, i.e. Control(Mothers), Control(Fathers), Control(Sisters) and Control(Brothers)) were studied. IR was assessed by homeostatic model assessment (HOMA IR), log HOMA, insulin sensivity index (ISI), the quantitative insulin sensitivity check index (QUICKI) and area under the curve for insulin during the oral glucose tolerance test (AUCI, AUCG) in with normal glucose tolerance (NGT) subjects and controls. Serum adiponectin, resistin, homocysteine and lipid levels were measured. The prevalence of any degree of glucose intolerance was 40% in Mothers(PCOS) and 52% in Fathers(PCOS). In total, six (15%) glucose tolerance disorders were identified in the Control(Mothers) and Control(Fathers) in first degree relatives of control subjects. The first degree relatives of PCOS patients had significantly higher serum fasting insulin, HOMA-IR, Log HOMA and AUCI levels in all subgroups than the control subjects. The control subjects had significantly elevated QUCKI, ISI levels and serum adiponectin levels compared to the first degree relatives of PCOS subjects in all subgroups. The serum Hcy and resistin levels increased significantly in both Fathers(PCOS) and Mothers(PCOS) groups but not Brothers(PCOS) and Sister(PCOS). The results of the present study support the finding that the first degree relatives of PCOS patients carry an increased risk of cardiovascular disease, as do PCOS patients.

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

PubMed

Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

2016-09-01

Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Resistin, visfatin, leptin and omentin are differently related to hormonal and metabolic parameters in growth hormone-deficient children.

PubMed

Ciresi, A; Pizzolanti, G; Leotta, M; Guarnotta, V; Teresi, G; Giordano, C

2016-09-01

The effect of growth hormone (GH) on adipose tissue and the role of adipokines in modulating metabolism are documented, but with discordant data. Our aim was to evaluate the impact of GH treatment on a series of selected adipokines known to have a metabolic role and poorly investigated in this setting. This is a prospective study. Thirty-one prepubertal children (25 M, 6 F; aged 8.5 ± 1.6 years) with isolated GH deficiency treated with GH for at least 12 months and 30 matched controls were evaluated. Auxological and metabolic parameters, insulin sensitivity indexes, leptin, soluble leptin receptor, adiponectin, visfatin, resistin, omentin, adipocyte fatty acid-binding protein and retinol-binding protein-4 were evaluated before and after 12 months of treatment. At baseline, no significant difference in metabolic parameters was found between GHD children and controls, except for higher LDL cholesterol (p = 0.004) in the first group. At multivariate analysis, LDL cholesterol was independently associated with resistin (B 0.531; p = 0.002), while IGF-I was the only variable independently associated with visfatin (B 0.688; p < 0.001). After 12 months, a significant increase in fasting insulin (p = 0.008), Homa-IR (p = 0.007) and visfatin (p < 0.001) was found, with a concomitant decrease in LDL cholesterol (p = 0.015), QUICKI (p = 0.001), ISI Matsuda (p = 0.006), leptin (p = 0.015) and omentin (p = 0.003)]. At multivariate analysis, BMI was the only variable independently associated with leptin (B 0.485; p = 0.040). GH treatment modifies adipokine secretion and the perturbation of some adipokine levels could contribute to the clinical and metabolic changes observed during the follow-up.

High prevalence of metabolic syndrome in antisynthetase syndrome.

PubMed

Araujo, Paula A O; Silva, Marilda Guimarães; Borba, Eduardo Ferreira; Shinjo, Samuel K

2018-01-01

A high frequency of metabolic syndrome (MetS) has been recently described in different idiopathic inflammatory myopathies, but not in antisynthetase syndrome (ASS). Therefore, the aim of the present study was to determine the prevalence of MetS in ASS and also its possible association with cardiovascular the risk factors and ASS-related disease characteristics. A cross-sectional single centre study of 42 consecutive ASS patients was conducted from 2012 to 2015 and compared to 84 healthy individuals matched for gender, age, ethnicity and body mass index-matched (control group). MetS was defined according to the 2009 Join Interim Statement. Clinical and laboratory data were assessed according to a standardised protocol. ASS patients had a median age of 41.1 years with a predominance of female gender and white race. ASS patients had a higher frequency of MetS (42.9% vs. 13.1%; p<0.001) as well as of insulin resistance than controls. Moreover, ASS patients had higher resistin, lower leptin and similar adiponectin levels in serum than controls. Further analysis of ASS patients with (n=18) and without (n=24) MetS revealed that older age at disease onset (48.7 vs. 35.4 years; p<0.001) was identified in those with the syndrome but were similar regarding disease duration, disease status, treatment, insulin resistance and serum adipocytokine levels. The prevalence of MetS was high in ASS patients that also had serum resistin and low leptin levels. As also identified in other idiopathic inflammatory myopathies, MetS in ASS is more prevalent in older patients.

Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk.

PubMed

Bonfante, Ivan Luiz Padilha; Chacon-Mikahil, Mara Patricia Traina; Brunelli, Diego Trevisan; Gáspari, Arthur Fernandes; Duft, Renata Garbellini; Oliveira, Alexandre Gabarra; Araujo, Tiago Gomes; Saad, Mario Jose Abdalla; Cavaglieri, Cláudia Regina

2017-12-01

Thus, the aim of this study was to compare if higher or smaller fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin levels are associated with inflammatory and metabolic markers, caloric/macronutrient intake, physical fitness and type 2 diabetes mellitus (T2DM) risk in obese middle-aged men, and also to correlate all variables analyzed with FNDC5/irisin. On the basis of a cluster study, middle-aged obese men (IMC: 31.01 ± 1.64 kg/m2) were divided into groups of higher and smaller levels of FNDC5/irisin. The levels of leptin, resistin, adiponectin, tumor necrosis factor alpha (TNFα), interleukin 6 and 10 (IL6, IL10), lipopolysaccharide (LPS), glucose, insulin, glycated hemoglobin, insulin resistance and sensibility, lipid profile, risk of T2DM development, body composition, rest energy expenditure, caloric/macronutrient intake and physical fitness were measured. The higher FNDC5/ irisin group presented improved insulin sensibility (homeostasis model assessment - sensibility (HOMA-S) (p = 0.01) and QUICKI index (p < 0.01)), insulin (p = 0.02) and triglyceride levels (p = 0.01), lower insulin resistance (homeostasis model assessment - insulin resistance (HOMA-IR) (p = 0.01), triglycerides/glucose (TYG index) (p = 0.02), neck circumference (p = 0.02), risk of T2DM development (p = 0.02), tendency to decrease serum resistin (p = 0.08) and significant lower LPS levels (p = 0.02). Inverse correlations between FNDC5/irisin and body weight (r -0.46, p = 0.04), neck circumference (r -0.51, p = 0.02), free fat mass (r -0.49, p = 0.02), triglycerides (r -0.43, p = 0.05) and risk of developing T2DM (r -0.61, p = 0.04) were observed. These results suggest that higher FNDC5/irisin levels in obese middle-aged men are related to a better metabolic profile and lower risk of T2DM development and serum LPS, a potential inducer of insulin resistance.

FABP4 blocker attenuates colonic hypomotility and modulates white adipose tissue-derived hormone levels in mouse models mimicking constipation-predominant IBS.

PubMed

Mosińska, P; Jacenik, D; Sałaga, M; Wasilewski, A; Cygankiewicz, A; Sibaev, A; Mokrowiecka, A; Małecka-Panas, E; Pintelon, I; Storr, M; Timmermans, J P; Krajewska, W M; Fichna, J

2018-05-01

The role of fatty acid binding protein 4 (FABP4) in lower gastrointestinal (GI) motility is unknown. We aimed to verify the effect of inhibition of FABP4 on GI transit in vivo, and to determine the expression of FABP4 in mouse and human tissues. Fatty acid binding protein 4 inhibitor, BMS309403, was administered acutely or chronically for 6 and 13 consecutive days and its effect on GI transit was assessed in physiological conditions and in loperamide-induced constipation. Intracellular recordings were made to examine the effects of BMS309403 on colonic excitatory and inhibitory junction potentials. Abdominal pain was evaluated using behavioral pain response. Localization and expression of selected adipokines were determined in the mouse colon and serum using immunohistochemistry and Enzyme-Linked ImmunoSorbent Assay respectively. mRNA expression of FABP4 and selected adipokines in colonic and serum samples from irritable bowel syndrome (IBS) patients and control group were assessed. Acute injection of BMS309403 significantly increased GI motility and reversed inhibitory effect of loperamide. BMS309403 did not change colonic membrane potentials. Chronic treatment with BMS309403 increased the number of pain-induced behaviors. In the mouse serum, level of resistin was significantly decreased after acute administration; no changes in adiponectin level were detected. In the human serum, level of adiponectin and resistin, but not of FABP4, were significantly elevated in patients with constipation-IBS (IBS-C). FABP4 mRNA expression was significantly downregulated in the human colon in IBS-C. Fatty acid binding protein 4 may be involved in IBS pathogenesis and become a novel target in the treatment of constipation-related diseases. © 2017 John Wiley & Sons Ltd.

Visfatin Is Regulated by Rosiglitazone in Type 2 Diabetes Mellitus and Influenced by NFκB and JNK in Human Abdominal Subcutaneous Adipocytes

PubMed Central

da Silva, Nancy F.; Al-Daghri, Nasser; Creely, Steven J.; Kusminski, Christine M.; Tripathi, Gyanendra; Levick, Paul L.; Khanolkar, Manish; Evans, Marc; Chittari, Madhu V.; Patel, Vinod; Kumar, Sudhesh; McTernan, Philip G.

2011-01-01

Visfatin has been proposed as an insulin-mimicking adipocytokine, predominantly secreted from adipose tissue and correlated with obesity. However, recent studies suggest visfatin may act as a proinflammatory cytokine. Our studies sought to determine the significance of this adipocytokine and its potential role in the pathogenesis of T2DM. Firstly, we examined the effects of diabetic status on circulating visfatin levels, and several other adipocytokines, demonstrating that diabetic status increased visfatin*, TNF-α*** and IL-6*** compared with non-diabetic subjects (*p<0.05, **p<0.01, ***p<0.001, respectively). We then assessed the effects of an insulin sensitizer, rosiglitazone (RSG), in treatment naïve T2DM subjects, on circulating visfatin levels. Our findings showed that visfatin was reduced post-RSG treatment [vs. pre-treatment (*p<0.05)] accompanied by a reduction in HOMA-IR**, thus implicating a role for insulin in visfatin regulation. Further studies addressed the intracellular mechanisms by which visfatin may be regulated, and may exert pro-inflammatory effects, in human abdominal subcutaneous (Abd Sc) adipocytes. Following insulin (Ins) and RSG treatment, our in vitro findings highlighted that insulin (100 nM), alone, upregulated visfatin protein expression whereas, in combination with RSG (10 nM), it reduced visfatin*, IKKβ** and p-JNK1/2*. Furthermore, inhibition of JNK protein exacted a significant reduction in visfatin expression (**p<0.01), whilst NF-κB blockade increased visfatin (*p<0.05), thus identifying JNK as the more influential factor in visfatin regulation. Additional in vitro analysis on adipokines regulating visfatin showed that only Abd Sc adipocytes treated with recombinant human (rh)IL-6 increased visfatin protein (*p<0.05), whilst rh visfatin treatment, itself, had no influence on TNF-α, IL-6 or resistin secretion from Sc adipocytes. These data highlight visfatin's regulation by insulin and RSG, potentially acting through NF-κB and JNK mechanisms, with only rh IL-6 modestly affecting visfatin regulation. Taken together, these findings suggest that visfatin may represent a pro-inflammatory cytokine that is influenced by insulin/insulin sensitivity via the NF-κB and JNK pathways. PMID:21694775

[Performance of entero-insular axis in an athletic population: diet and exercise influence].

PubMed

Rodriguez, Carmen; Quezada-Feijoo, Maribel; Toro, Carmen; Barón-Esquivias, Gonzalo; Segura, Eduardo; Mangas, Alipio; Toro, Rocio

2015-05-01

The relationship between physical exercise and appetite regulation can lead to improved competitive performance of athletes. Mediators of the entero-insular axis generate neurohumoral signals that influence on the appetite regulation and energy homeostasis. Determine the influence of diet and prolonged exercise on intestinal peptide, ghrelin, resistin, leptin, and incretins (GLP-1 and GIP) in an athlete population. It is a prospective intervention study, conducted from October 2012 to March 2013. 32 healthy semiprofessional rugby players, aged 13-39 years were included. Anthropometric measurements and blood samples were taken at time 0 and after six months of study. Athletes were randomized to a protein diet (PD) or Mediterranean diet (MD) and plasma levels of intestinal peptide, ghrelin, resistin, leptin, and incretins were calculated. In the PD group, GLP-1 and GIP plasmatic levels showed a significant decrease (p <0.03; p <0.01 respectively). GLP-1 and ghrelin plasmatic concentration demonstrated a significant decrease (p <0.03 respectively) in those who experienced gain of muscle mass (MM). Finally, the athletes related to the PD who showed increased total weight and muscle mass presented significantly decreased GLP-1 concentration (p <0.03 and p<0.002, respectively). GLP-1 plasmatic concentration was decreased, with the PD suggesting to be more beneficial for the athletes in order to avoid hypoglycemia. Furthermore, muscle mass and total weight gain, linked to the PD, could enhance athletic performance in certain sport modalities. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Adipocytokines, neuropeptide Y and insulin resistance in overweight women with gynoid and android type of adipose tissue distribution.

PubMed

Orbetzova, Maria M; Koleva, Daniela I; Mitkov, Mitko D; Atanassova, Iliana B; Nikolova, Julia G; Atanassova, Pepa K; Genchev, Gencho D

2012-01-01

The AIM of the study was to compare the levels of certain adipose tissue hormones in women with the two main morphological types of obesity - android and gynoid obesity. The study included 2 groups of age- and weight-matched women with android (n = 32) and gynoid (n = 27) type of obesity, and a group of age-matched healthy women (n = 24) with normal weight and body constitution. Leptin, resistin, tumour necrosis factor alpha (TNFalpha), neuropeptide Y (NPY), glucose and insulin were measured. HOMA index was calculated. Leptin levels in the women with gynoid obesity did not differ significantly from those in the controls and the women with android obesity. The controls had significantly lower leptin levels compared with the android obesity women. NPY was significantly higher in the control women compared to the women with android obesity and did not differ significantly between the two groups of obese women. TNFalpha levels in all groups were very similar. Resistin did not show significant differences between all groups but tended to have the lowest levels in the controls. In the women with android obesity, insulin was significantly higher than that in the women with gynoid obesity and the controls. Insulin resistance was found in the women with android obesity only. Basal insulin and HOMA index in the women with gynoid obesity did not differ significantly from the values in the control group. The results from this study contribute to understanding the association of adipose tissue hormones and insulin resistance in obesity. When adipose tissue is predominantly distributed in the abdominal area at similar amount and percentage of body fats, leptin production is higher and insulin resistance develops. In the gynoid type of adipose tissue predisposition, overt insulin resistance is not found, leptin levels does not differ significantly from those in the control group.

Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 1: The adipokines apelin and resistin and their relationship to receptors linked with lipolysis.

PubMed

Weber, M; Locher, L; Huber, K; Kenéz, Á; Rehage, J; Tienken, R; Meyer, U; Dänicke, S; Sauerwein, H; Mielenz, M

2016-02-01

The transition from pregnancy to lactation is characterized by major changes in glucose and adipose tissue metabolism. Anti- and prolipolytic pathways mediated via the hydroxycarboxylic acid receptors 1 (HCAR1) and 2 (HCAR2) and tumor necrosis factor-α receptor 1 (TNFR1), as well as the adipokines apelin and resistin, are likely involved in regulating these processes. This study aimed to determine the mRNA abundance of the aforementioned receptors in both subcutaneous and visceral adipose tissue, to characterize the adipokine concentrations in serum, and to test the effects of feeding diets with either high or low portions of concentrate and a concomitant niacin supplementation from late gestation to early lactation. Twenty pluriparous German Holstein cows were all kept on the same silage-based diet until d 42 antepartum, when they were allocated to 2 feeding groups: until d 1 antepartum, 10 animals each were assigned to either a high-concentrate (60:40 concentrate-to-roughage ratio) or a low-concentrate diet (30:70). Both groups were further subdivided into a control and a niacin group, the latter receiving 24 g/d of nicotinic acid from d -42 until 24. From d 1 to 24 postpartum, the concentrate portion was increased from 30 to 50% for all cows. Biopsies of subcutaneous (SCAT) and retroperitoneal adipose tissue (RPAT) were taken at d -42, 1, 21, and 100 relative to parturition. Blood samples were drawn along with the biopsies and on d -14, 3, 7, 14, and 42. The concentrations of the adipokines apelin and resistin in serum were measured via ELISA. The mRNA of the 3 receptors in AT was quantified as well as the protein abundance of HCAR2 by Western blot. The feeding regimen did not affect the variables examined. The concentrations of apelin remained fairly constant during the observation period, whereas the resistin concentrations increased toward parturition and decreased to precalving levels within 1 wk after calving. The mRNA abundance of HCAR1, HCAR2, and TNFR1 changed in SCAT and RPAT during the considered time period. For the HCAR2 protein, time-dependent changes were restricted to SCAT. The mRNA abundance of all receptors was greater in RPAT than in SCAT. The tissue-specific correlations observed between the receptors point to a link between these factors and may indicate different regulatory roles in the respective tissues. This study provides insight into the complex metabolic adaptations during the transition period and supports a differential regulation of lipolysis among SCAT and RPAT in dairy cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Insulin resistance, adipokine profile and hepatic expression of SOCS-3 gene in chronic hepatitis C.

PubMed

Wójcik, Kamila; Jabłonowska, Elżbieta; Omulecka, Aleksandra; Piekarska, Anna

2014-08-14

To analyze adipokine concentrations, insulin resistance and hepatic expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with chronic hepatitis C genotype 1 with normal body weight, glucose and lipid profile. The study group consisted of 31 patients with chronic hepatitis C and 9 healthy subjects. Total levels of adiponectin, leptin, resistin, visfatin, omentin, osteopontin and insulin were measured using an ELISA kit. The hepatic expression of SOCS-3 was determined by the use of the reverse transcription polymerase chain reaction method. Homeostasis model assessment for insulin resistance (HOMA-IR) values were significantly higher in hepatitis C virus (HCV) infected patients without metabolic disorders compared to healthy controls (2.24 vs 0.59, P = 0.0003). Hepatic steatosis was observed in 32.2% of patients with HCV infection and was found in patients with increased HOMA-IR index (2.81 vs 1.99, P = 0.05) and reduced adiponectin level (5.96 vs 8.37, P = 0.04). Inflammatory activity (G ≥ 2) was related to increased osteopontin concentration (34.04 vs 23.35, P = 0.03). Advanced liver fibrosis (S ≥ 2) was associated with increased levels of omentin and osteopontin (436.94 vs 360.09, P = 0.03 and 32.84 vs 20.29, P = 0.03) and reduced resistin concentration (1.40 vs 1.74, P = 0.047). No correlations were reported between adipokine profile, HOMA-IR values and hepatic expression of the SOCS-3 gene. We speculated that no relationship between adipokines and HOMA-IR values may indicate that HCV can induce insulin resistance itself. Some adipokines appear to be biochemical markers of steatosis, inflammation and fibrosis in patients with chronic HCV infection. © 2014 Baishideng Publishing Group Inc. All rights reserved.

Effect of marine collagen peptides on markers of metabolic nuclear receptors in type 2 diabetic patients with/without hypertension.

PubMed

Zhu, Cui-Feng; Li, Guan-Zhi; Peng, Hong-Bin; Zhang, Fan; Chen, Yun; Li, Yong

2010-04-01

To explore Effects of marine collagen peptides (MCPs) on markers of metablic nuclear receptors, i.e peroxisome proliferator-activated receptor (PPARs), liver X receptor (LXRs) and farnesoid X receptor (FXRs) in type 2 diabetic patients with/without hypertension. METHOD Study population consisted of 200 type 2 diabetic patients with/without hypertension and 50 healthy subjects, all of whom were randomly assigned to MCPs-treated diabetics (n = 50), placebo-treated diabetics (n = 50), MCPs-treated diabetics with hypertension (n=50), placebo-treated diabetics with hypertension (n = 50), and healthy controls (n = 50). MCPs or placebo (water-soluble starch) were given daily before breakfast and bedtime over three months. Levels of free fatty acid, cytochrome P450, leptin, resistin, adiponectin, bradykinin, NO, and Prostacyclin were determined before intervention, and 1.5 months, and 3 months after intervention. Hypoglycemia and the endpoint events during the study were recorded and compared among the study groups. At the end of the study period, MCPs-treated patients showed marked improvement compared with patients receiving placebo. The protection exerted by MCPs seemed more profound in diabetics than in diabetics with hypertension. In particular, after MCPs intervention, levels of free fatty acid, hs-CRP, resistin, Prostacyclin decreased significantly in diabetics and tended to decrease in diabetic and hypertensive patients whereas levels of cytochrome P450, leptin, NO tended to decrease in diabetics with/without hypertension. Meanwhile, levels of adiponectin and bradykinin rose markedly in diabetics following MCPs administration. MCPs could offer protection against diabetes and hypertension by affecting levels of molecules involved in diabetic and hypertensive pathogenesis. Regulation on metabolic nuclear receptors by MCPs may be the possible underlying mechanism for its observed effects in the study. Further study into its action may shed light on development of new drugs based on bioactive peptides from marine sources.

Serum adipokines, adipose tissue measurements and metabolic parameters in patients with advanced radiographic knee osteoarthritis.

PubMed

Toussirot, Eric; Michel, Fabrice; Béreau, Matthieu; Dehecq, Barbara; Gaugler, Béatrice; Wendling, Daniel; Grandclément, Emilie; Saas, Philippe; Dumoulin, Gilles

2017-11-01

We conducted the present study to evaluate the serum levels of adipokines (leptin, total and high molecular adiponectin, resistin), a marker of cartilage breakdown (C2C), and ghrelin together with body composition in patients with knee osteoarthritis (OA). Fifty patients and 50 sex-matched healthy subjects (HS) were evaluated. Knee OA was scored according to the Kellgren-Lawrence (KL) grade. Body composition parameters including lean mass and measurements of fat mass (total fat, adiposity, fat in the android and gynoid regions, visceral fat and trunk/legs fat ratio) were obtained using dual energy X-ray absorptiometry. Most of the recruited patients (88%) had advanced knee OA with KL grade 3 or 4. The patients had higher body mass index than HS (p < 0.0001). Serum leptin, high molecular adiponectin, resistin and ghrelin levels did not differ between patients and HS. Total adiponectin was higher in women with OA compared to women from the HS group (p = 0.004). Total fat mass, adiposity and measurements of central adiposity (fat in the android region, trunk/lower limbs fat ratio and visceral fat) were increased in patients with knee OA (all p < 0.05). Total adiponectin was borderline associated with the severity of OA. Our results show that total adiponectin is significantly increased in women with advanced knee OA. Independently of gender, patients with severe knee OA were characterized by a significant excess of fat with a distribution toward the visceral region. This abnormal body composition may contribute to the cardiometabolic profile that is described in patients with knee OA.

Chitosan oligosaccharide improves the therapeutic efficacy of sitagliptin for the therapy of Chinese elderly patients with type 2 diabetes mellitus.

PubMed

Zhao, Lijie; Sun, Tingli; Wang, Lina

2017-01-01

Sitagliptin improves glycemic control in type 2 diabetes mellitus (T2DM) patients but its side effects are undesirable. Chitosan oligosaccharide (COS) is expected to improve the therapeutic result as a natural product. A total of 200 elderly T2DM patients were evenly assigned into four groups: sitagliptin group (SG), receiving sitagliptin 100 mg/day; COS group (CG), receiving COS 100 mg/day; combination therapy of sitagliptin and COS group (SCG), receiving both sitagliptin and COS 100 mg/day; and placebo group (PG), receiving placebo 100 mg/day. After 42-week therapy, biochemical indices and clinical parameters for the alterations from start points were analyzed. The related molecular mechanism was tested by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot at cell level. Lower risk of hypoglycemia was found in the SCG group when compared with SG and other groups ( P <0.05). More patients from the SCG group than other groups attained hemoglobin A1c (HbA1c) reduction >2.5% ( P <0.05). Weight reduction of 1.2±0.9, 2.6±0.8, 4.7±1.3, and 0.9±0.6 kg was observed in the patients from SG, CG, SCG, and PG groups, respectively ( P <0.05). The combined treatment of COS and sitagliptin presented better therapeutic results by improving insulin sensitivity, lipid profile, adiponectin levels, and glucagon-like peptide 1 and reducing side effects, insulin resistance, HbA1c, body mass index, resistin, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) ( P <0.05). qRT-PCR and Western blot analysis also showed that COS treatment reduced the levels of resistin, TNF-α, and CRP, and increased the level of adiponectin. The combination of COS and sitagliptin provided better glycemic control with fewer side effects and with more weight reduction in the elderly participants with T2DM.

A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH).

PubMed

Younossi, Zobair M; Jarrar, Mohammed; Nugent, Clare; Randhawa, Manpreet; Afendy, Mariam; Stepanova, Maria; Rafiq, Nila; Goodman, Zachary; Chandhoke, Vikas; Baranova, Ancha

2008-11-01

Within the spectrum of nonalcoholic fatty liver disease (NAFLD), only patients with nonalcoholic steatohepatitis (NASH) show convincing evidence for progression. To date, liver biopsy remains the gold standard for the diagnosis of NASH; however, liver biopsy is expensive and associated with a small risk, emphasizing the urgent need for noninvasive diagnostic biomarkers. Recent findings suggest a role for apoptosis and adipocytokines in the pathogenesis of NASH. The aim of this study was to develop a noninvasive diagnostic biomarker for NASH. The study included 101 patients with liver biopsies who were tested with enzyme-linked immunosorbent assay (ELISA)-based assays. Of these, 69 were included in the biomarker development set and 32 were included in the biomarker validation set. Clinical data and serum samples were collected at the time of biopsy. Fasting serum samples were assayed for adiponectin, resistin, insulin, glucose, TNF-alpha, IL-6, IL-8, cytokeratin CK-18 (M65 antigen), and caspase-cleaved CK-18 (M30 antigen). Data analysis revealed that the levels of M30 antigen (cleaved CK-18) predicted histological NASH with 70% sensitivity and 83.7% specificity and area under the curve (AUC) = 0.711, p < 10(-4), whereas the predictive value of the levels of intact CK-18 (M65) was higher (63.6% sensitivity and 89.4% specificity and AUC = 0.814, p < 10(-4)). Histological NASH could be predicted by a combination of Cleaved CK-18, a product of the subtraction of Cleaved CK-18 level from intact CK-18 level, serum adiponectin, and serum resistin with a sensitivity of 95.45% sensitivity, specificity of 70.21%, and AUC of 0.908 (p < 10(-4)). Blinded validation of this model confirmed its reliability for separating NASH from simple steatosis. Four ELISA-based tests were combined to form a simple diagnostic biomarker for NASH.

The rs1862513 Variant in Resistin Gene-Modified Insulin Resistance and Insulin Levels after Weight Loss Secondary to Hypocaloric Diet.

PubMed

de Luis, Daniel Antonio; Izaola, Olatz; Primo, David; de la Fuente, Beatriz; Mulero, Ines; Aller, Rocío

2016-01-01

Polymorphisms of a single nucleotide in RETN have been associated with indexes of insulin resistance. Our aim was to analyze the effects of the rs1862513 RETN gene polymorphism on insulin resistance, insulin levels, and resistin levels changes after 3 months of a low-fat hypocaloric diet. A Caucasian population of 133 obese patients was analyzed before and after 3 months on a low-fat hypocaloric diet. Fifty-six patients (42.1%) had the genotype GG (wild group) and 77 (57.9%) patients had the other genotypes; GC (59 patients, 44.4%) or CC (18 patients, 13.5%; mutant group). In wild and mutant genotype groups, weight, body mass index, fat mass, waist circumference, and systolic blood pressure decreased. In the wild genotype group, the decrease in total cholesterol was -13.1 ± 25.3 mg/dL (vs. -4.4 ± 13.7 mg/dL in mutant group: p = 0.004 for group deltas), low density lipoprotein (LDL)-cholesterol was -13.0 ± 21.5 mg/dL (-4.3 ± 10.5 mg/dL: p = 0.007), glucose -7.2 ± 3.5 mg/dL (-0.8 ± 0.2 mg/dL: p = 0.01), insulin -5.6 ± 2.5 mUI/L (-2.9 ± 1.2 mUI/L: p = 0.03) and homeostasis model assessment-insulin resistance (HOMA-IR) -2.5 ± 1.1 (-0.6 ± 1.4: p = 0.02). Leptin levels decreased in both genotypes (-10.1 ± 9.5 ng/dL in wild type group vs. -13.1 ± 0.2 ng/dL in mutant type group: p > 0.05). The present study suggests that the G/G genotype of RETN rs1862513 could be a predictor of the reduction of HOMA-IR, insulin, fasting glucose and LDL cholesterol secondary to a hypocaloric diet in obese subjects. © 2016 S. Karger AG, Basel.

Chitosan oligosaccharide improves the therapeutic efficacy of sitagliptin for the therapy of Chinese elderly patients with type 2 diabetes mellitus

PubMed Central

Zhao, Lijie; Sun, Tingli; Wang, Lina

2017-01-01

Sitagliptin improves glycemic control in type 2 diabetes mellitus (T2DM) patients but its side effects are undesirable. Chitosan oligosaccharide (COS) is expected to improve the therapeutic result as a natural product. A total of 200 elderly T2DM patients were evenly assigned into four groups: sitagliptin group (SG), receiving sitagliptin 100 mg/day; COS group (CG), receiving COS 100 mg/day; combination therapy of sitagliptin and COS group (SCG), receiving both sitagliptin and COS 100 mg/day; and placebo group (PG), receiving placebo 100 mg/day. After 42-week therapy, biochemical indices and clinical parameters for the alterations from start points were analyzed. The related molecular mechanism was tested by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot at cell level. Lower risk of hypoglycemia was found in the SCG group when compared with SG and other groups (P<0.05). More patients from the SCG group than other groups attained hemoglobin A1c (HbA1c) reduction >2.5% (P<0.05). Weight reduction of 1.2±0.9, 2.6±0.8, 4.7±1.3, and 0.9±0.6 kg was observed in the patients from SG, CG, SCG, and PG groups, respectively (P<0.05). The combined treatment of COS and sitagliptin presented better therapeutic results by improving insulin sensitivity, lipid profile, adiponectin levels, and glucagon-like peptide 1 and reducing side effects, insulin resistance, HbA1c, body mass index, resistin, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) (P<0.05). qRT-PCR and Western blot analysis also showed that COS treatment reduced the levels of resistin, TNF-α, and CRP, and increased the level of adiponectin. The combination of COS and sitagliptin provided better glycemic control with fewer side effects and with more weight reduction in the elderly participants with T2DM. PMID:28721055

Impact of maternal BMI and sampling strategy on the concentration of leptin, insulin, ghrelin and resistin in breast milk across a single feed: a longitudinal cohort study.

PubMed

Andreas, Nicholas J; Hyde, Matthew J; Herbert, Bronwen R; Jeffries, Suzan; Santhakumaran, Shalini; Mandalia, Sundhiya; Holmes, Elaine; Modi, Neena

2016-07-07

We tested the hypothesis that there is a positive association between maternal body mass index (BMI) and the concentration of appetite-regulating hormones leptin, insulin, ghrelin and resistin in breast milk. We also aimed to describe the change in breast milk hormone concentration within each feed, and over time. Mothers were recruited from the postpartum ward at a university hospital in London. Breast milk samples were collected at the participants' homes. We recruited 120 healthy, primiparous, breastfeeding mothers, aged over 18 years. Mothers who smoked, had multiple births or had diabetes were excluded. Foremilk and hindmilk samples were collected from 105 women at 1 week postpartum and 92 women at 3 months postpartum. We recorded maternal and infant anthropometric measurements at each sample collection and measured hormone concentrations using a multiplex assay. The concentration of leptin in foremilk correlated with maternal BMI at the time of sample collection, at 7 days (r=0.31, p=0.02) and 3 months postpartum (r=0.30, p=<0.00). Foremilk insulin correlated with maternal BMI at 3 months postpartum (r=0.22, p=0.04). Breast milk ghrelin and resistin were not correlated with maternal BMI. Ghrelin concentrations at 3 months postpartum were increased in foremilk compared with hindmilk (p=0.01). Concentrations of ghrelin were increased in hindmilk collected at 1  week postpartum compared with samples collected at 3 months postpartum (p=0.03). A trend towards decreased insulin concentrations in hindmilk was noted. Concentrations of leptin and resistin were not seen to alter over a feed. A positive correlation between maternal BMI and foremilk leptin concentration at both time points studied, and foremilk insulin at 3 months postpartum was observed. This may have implications for infant appetite regulation and obesity risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Similar Metabolic, Innate Immunity, and Adipokine Profiles in Adult and Pediatric Sepsis Versus Systemic Inflammatory Response Syndrome-A Pilot Study.

PubMed

Tavladaki, Theonymfi; Spanaki, Anna Maria; Dimitriou, Helen; Kondili, Efmorfia; Choulaki, Christianna; Georgopoulos, Dimitris; Briassoulis, George

2017-11-01

To examine whether the septic profiles of heat shock protein 72, heat shock protein 90α, resistin, adiponectin, oxygen consumption, CO2 production, energy expenditure, and metabolic pattern, along with illness severity, nutritional, and inflammatory indices, differ between adult and pediatric patients compared with systemic inflammatory response syndrome and healthy controls. To evaluate whether these biomolecules may discriminate sepsis from systemic inflammatory response syndrome in adult and pediatric patients. Prospective cohort study. University ICU and PICU. Seventy-eight adults (sepsis/23; systemic inflammatory response syndrome/23; healthy controls/33), 67 children (sepsis/18; systemic inflammatory response syndrome/23; controls/27), mechanically ventilated. None. Flow cytometry determined mean fluorescence intensity for monocyte or neutrophil heat shock protein expression. Resistin, adiponectin, and extracellular heat shock proteins were measured using enzyme-linked immunosorbent assay; energy expenditure by E-COVX (GE Healthcare). Genomic DNA was extracted with PureLink Genomic DNA kit (Invitrogen, Carlsbad, CA) to detect heat shock protein 72 single nucleotide polymorphisms. Similarly, in adult and pediatric patients, Acute Physiology and Chronic Evaluation-II/Acute Physiology and Pediatric Risk of Mortality-III, Simplified Acute Physiology Score-III, C-reactive protein, lactate, and resistin were higher and myocardial contractility, monocyte heat shock protein 72, oxygen consumption, CO2 production, energy expenditure, metabolic pattern, glucose, and albumin lower in sepsis compared with systemic inflammatory response syndrome or controls (p < 0.05). For discriminating sepsis from systemic inflammatory response syndrome, resistin, extracellular heat shock protein 90α, and lactate achieved a receiver operating characteristic curve greater than 0.80 in children and greater than 0.75 in adults (p < 0.05). In both, adults and children, genotype heat shock protein 72 analysis did not disclose any diagnosis or mortality group differences regarding either rs6457452 or rs1061581 haplotypes. Sepsis presents with similar profiles in adult and pediatric patients, characterized by enhanced inflammatory hormonal response and by repressed innate immunity, metabolism, and myocardial contractility. These features early distinguish sepsis from systemic inflammatory response syndrome across all age groups.

Serum Concentrations of Leptin and Adiponectin in Dogs with Myxomatous Mitral Valve Disease.

PubMed

Kim, H-S; Kang, J-H; Jeung, E-B; Yang, M-P

2016-09-01

The concentrations of circulating adipokines in dogs with myxomatous mitral valve disease (MMVD) have not been investigated in detail. To determine whether serum concentrations of adipokines differ between healthy dogs and dogs with MMVD and whether circulating concentrations depend on the severity of heart failure resulting from MMVD. In the preliminary study, 30 healthy dogs and 17 client-owned dogs with MMVD, and in the subsequent study, 30 healthy dogs and 46 client-owned dogs with MMVD. Prospective case-controlled observational study. In the preliminary study, serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)-1β, IL-6, IL-10, IL-18, and tumor necrosis factor-α were measured. In the subsequent study, MMVD dogs were divided into three groups according to the International Small Animal Cardiac Health Council (ISACHC) classification, and serum concentrations of leptin and adiponectin were measured. In the preliminary study, serum leptin and adiponectin concentrations differed significantly between dogs with MMVD and healthy dogs. Serum leptin (P = .0013) concentrations were significantly higher in dogs with MMVD than in healthy dogs, whereas adiponectin (P = .0009) concentrations were significantly lower in dogs with MMVD. However, we observed no significant differences in the other variables. In the subsequent study, dogs classified as ISACHC class 3 had higher serum concentrations of leptin (P = .0022) than healthy dogs but ISACHC class 1 or 2 dogs did not. Serum adiponectin concentrations were significantly lower in ISACHC class 1 (P < .0001) dogs than in healthy dogs, whereas adiponectin concentrations in ISACHC class 3 dogs were significantly higher than in ISACHC class 1 dogs (P = .0081). Circulating concentrations of leptin and adiponectin might be altered in dogs with MMVD. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Adipokine Profile in Patients with Type 2 Diabetes Depends on Degree of Obesity

PubMed Central

Kocot, Joanna; Dziemidok, Piotr; Kiełczykowska, Małgorzata; Hordyjewska, Anna; Szcześniak, Grzegorz; Musik, Irena

2017-01-01

Background The fast pace of life, promoting fast food consumption and low physical activity, has resulted in obesity and/or diabetes as being serious social problems. The aim of the present study was to evaluate concentrations of selected adipokines (leptin, adiponectin, resistin, and visfatin) and to assess the leptin/adiponectin ratio in plasma of type 2 diabetes (T2D) patients in relation to degree of obesity. Material/Methods The study comprised 92 T2D subjects divided into 4 groups according to BMI value – I (normal body weight), II (overweight), III (obesity), and IV (severe obesity) – and 20 healthy volunteers (control group). Each group was divided into male and female subgroups. Plasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. Results In women, leptin concentration was significantly higher in group IV, whereas in men it was higher in groups III and IV than in the control group and groups I and II. Irrespective of sex, a significant decrease in adiponectin level was observed in group III vs. control. There was no significant difference in resistin levels. In women visfatin was markedly enhanced in group III, whereas in men in groups II, III and IV vs. control. Leptin/adiponectin ratio was increased in groups III and IV vs. control in women, whereas in men vs. both control and group I. Conclusions The obese type 2 diabetic patients presented a disturbed adipokine profile, which seems to be an important link between obesity and T2D. The future studies concerning the question if regulating of adipokines’ concentrations could be a promising approach for managing metabolic disorders seem to be well-grounded. PMID:29049270

The clinical value of adipokines in predicting the severity and outcome of acute pancreatitis.

PubMed

Karpavicius, Andrius; Dambrauskas, Zilvinas; Gradauskas, Audrius; Samuilis, Arturas; Zviniene, Kristina; Kupcinskas, Juozas; Brimas, Gintautas; Meckovski, Artur; Sileikis, Audrius; Strupas, Kestutis

2016-08-22

Recent data shows that patients with severe acute pancreatic might benefit from early intensive therapy, enteral nutrition and timely transfer to specialized centers. The early prophylactic use of antibiotics in AP remains controversial. The role and need for new markers in stratification of acute pancreatitis is also uncertain. This study aims to evaluate the prognostic usefulness of adipokines in prediction of the severity and outcome of acute pancreatitis (AP). Prospective study was conducted in four clinical centers. The diagnosis and severity assessment of AP was established according to the revised 2012 Atlanta classification. Adipokines, IL-6 and CRP levels were measured at admission and on 3rd day of hospital stay and compared with the control group. The predictive accuracy of each marker was measured by area under the receiver operating curve. Forty healthy controls and 102 patients were enrolled in to the study. Twenty seven (26.5 %) patients had mild, 55 (53.9 %) - moderate and 20 (19.6 %) - severe AP. Only resistin (cut-off value 13.7 ng/ml) and IL-6 (cut-off value 473.4 pg/ml) were reliable early markers of SAP. IL-6 with cut-off value of 157.0 pg/ml was a predictor of necrosis. The peripancreatic necrosis volume of 112.5 ml was a marker of SAP and 433.0 ml cut-off value could be used to predict the need of interventions. The prognostic value of adipokines in AP is limited. Only admission resistin levels could serve as an early predictor for SAP. The Lithuanian Regional Ethics Committee approved the study protocol (permission No. L-12-02/1/2/3/4) and all the patients and the control group provided written informed consent.

Regularly consuming a green/roasted coffee blend reduces the risk of metabolic syndrome.

PubMed

Sarriá, Beatriz; Martínez-López, Sara; Sierra-Cinos, José Luis; García-Diz, Luis; Mateos, Raquel; Bravo-Clemente, Laura

2018-02-01

Preventive health effects of coffee could have a widespread impact on public health. Green coffee has more phenols than roasted, and thus is healthier, although with less acceptable organoleptic properties. Therefore, the effects of regularly consuming a green/roasted coffee blend (35/65) on the main components of MetS in humans were evaluated. A crossover, randomized, controlled study was performed in 25 normocholesterolaemic and 27 hypercholesterolaemic men and women aged 18-45 years with BMI 18-25 kg/m 2 . Three servings/day of the blend, providing 510.6 mg hydroxycinnamic acids and 121.2 mg caffeine/day, were consumed versus a control drink, during 8 weeks each. Polyphenol and methylxanthine-rich foods were restricted along the study. At the beginning (baseline) and end of the control and coffee interventions, blood samples were collected and glucose, HDL-cholesterol, triglycerides, insulin, leptin, plasminogen activator inhibitor-1 (PAI-1), resistin and visfatin were analysed; waist circumference, %body fat, and blood pressure were measured and dietary records and physical activity questionnaires completed. Systolic and diastolic blood pressure decreased (p = 0.001 and p < 0.001, respectively) in both groups as well as %body fat (p = 0.001) which may be related to the lower leptin (p = 0.001), PAI-1 (p < 0.001) and resistin (p = 0.034) levels in the two groups after coffee consumption. Glucose concentration (p = 0.030) and insulin resistance (p = 0.011; HOMA-IR) also decreased, as well as triglyceride levels (p = 0.017), so that the reduction was much greater in the hypercholesterolaemics (group effect, p = 0.027). Regular consumption of the green/roasted coffee blend may be recommended to healthy and hypercholesterolaemic subjects to prevent MetS, as it produces positive effects on blood pressure, glucose and triglyceride levels.

Less favorable body composition and adipokines in South Asians compared with other US ethnic groups: results from the MASALA and MESA studies.

PubMed

Shah, A D; Kandula, N R; Lin, F; Allison, M A; Carr, J; Herrington, D; Liu, K; Kanaya, A M

2016-04-01

Small studies have shown that South Asians (SAs) have more total body, subcutaneous, visceral and hepatic fat and abnormal adipokine levels compared with Whites. However, comprehensive studies of body composition and adipokines in SAs compared with other ethnic groups are lacking. Using harmonized data, we performed a cross-sectional analysis of two community-based cohorts: Mediators of Atherosclerosis of South Asians Living in America (MASALA, n=906) and Multi-Ethnic Study of Atherosclerosis (MESA which included 2622 Whites, 803 Chinese Americans, 1893 African Americans and 1496 Latinos). General linear models were developed to assess the ethnic differences in ectopic fat (visceral, intermuscular and pericardial fat; and hepatic attenuation), lean muscle mass and adipokines (adiponectin and resistin). Models were adjusted for age, sex, site, alcohol use, smoking, exercise, education, household income and body mass index. Ectopic fat models were additionally adjusted for hypertension, diabetes, high-density lipoprotein and triglycerides. Adipokine models were adjusted for subcutaneous, visceral, intermuscular and pericardial fat; and hepatic attenuation. Compared with all ethnic groups in MESA (Whites, Chinese Americans, African Americans and Latinos), SAs had greater intermuscular fat (pairwise comparisons with each MESA group, P<0.01), lower hepatic attenuation (P<0.001) and less lean mass (P<0.001). SAs had greater visceral fat compared with Chinese Americans, African Americans and Latinos (P<0.05) and greater pericardial fat compared with African Americans (P<0.001). SAs had lower adiponectin levels compared with other ethnic groups (P<0.01; except Chinese Americans) and higher resistin levels than all groups (P<0.001), even after adjusting for differences in body composition. There are significant ethnic differences in ectopic fat, lean mass and adipokines. A less favorable body composition and adipokine profile in SAs may partially explain the increased predisposition to cardiometabolic disease. The mechanisms that underlie these differences warrant further investigation.

Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure

PubMed Central

D’Apolito, Maria; Du, Xueliang; Zong, Haihong; Catucci, Alessandra; Maiuri, Luigi; Trivisano, Tiziana; Pettoello-Mantovani, Massimo; Campanozzi, Angelo; Raia, Valeria; Pessin, Jeffrey E.; Brownlee, Michael; Giardino, Ida

2009-01-01

Although supraphysiological concentrations of urea are known to increase oxidative stress in cultured cells, it is generally thought that the elevated levels of urea in chronic renal failure patients have negligible toxicity. We previously demonstrated that ROS increase intracellular protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc), and others showed that increased modification of insulin signaling molecules by O-GlcNAc reduces insulin signal transduction. Because both oxidative stress and insulin resistance have been observed in patients with end-stage renal disease, we sought to determine the role of urea in these phenotypes. Treatment of 3T3-L1 adipocytes with urea at disease-relevant concentrations induced ROS production, caused insulin resistance, increased expression of adipokines retinol binding protein 4 (RBP4) and resistin, and increased O-GlcNAc–modified insulin signaling molecules. Investigation of a mouse model of surgically induced renal failure (uremic mice) revealed increased ROS production, modification of insulin signaling molecules by O-GlcNAc, and increased expression of RBP4 and resistin in visceral adipose tissue. Uremic mice also displayed insulin resistance and glucose intolerance, and treatment with an antioxidant SOD/catalase mimetic normalized these defects. The SOD/catalase mimetic treatment also prevented the development of insulin resistance in normal mice after urea infusion. These data suggest that therapeutic targeting of urea-induced ROS may help reduce the high morbidity and mortality caused by end-stage renal disease. PMID:19955654

The levels of the adipokines adipsin and leptin are associated with knee osteoarthritis progression as assessed by MRI and incidence of total knee replacement in symptomatic osteoarthritis patients: a post hoc analysis.

PubMed

Martel-Pelletier, Johanne; Raynauld, Jean-Pierre; Dorais, Marc; Abram, François; Pelletier, Jean-Pierre

2016-04-01

Limited studies have explored the association between adipokines and knee OA structural progression using quantitative MRI (qMRI), and very few have included total knee replacement (TKR) as a disease outcome. The objective of this study was to compare serum levels of five adipokines to cartilage volume loss (CVL) and investigate their predictive value for TKR. The according-to-protocol population (n = 138) of a knee OA trial was used. Serum levels of adipsin (complement factor D), leptin, adiponectin, resistin and serpin E1, and cartilage volume were determined at baseline and 24 months with specific ELISAs and qMRI, respectively. Study knee TKR incidence up to 4 years post-trial was also assessed. Greater baseline values of adipsin and leptin correlated with increased CVL in the global knee and medial femur (P ⩽ 0.032) and of adipsin in the lateral compartment and femur (P ⩽ 0.028). Adiponectin showed an inverse correlation in the medial compartment and femur (P ⩽ 0.027). Resistin and serpin E1 were not associated with CVL. Multivariate analyses revealed that patients in the highest tertile at baseline of adipsin presented a greater odds ratio of CVL in the lateral compartment and femur (⩾2.87; P ⩽ 0.011), and those in the highest tertile of leptin in the medial compartment (2.78; P = 0.038). Most clinically relevant, patients in the highest tertile of adipsin or leptin at baseline had significantly greater incidence of TKR (P = 0.027). Data demonstrate that both adipsin and leptin predict greater CVL over time in the lateral and medial compartment, respectively. Importantly, this study also demonstrates that higher baseline levels of adipsin or leptin are associated with higher incidence of TKR. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Isomalto-oligosaccharides, a prebiotic, functionally augment green tea effects against high fat diet-induced metabolic alterations via preventing gut dysbacteriosis in mice.

PubMed

Singh, Dhirendra Pratap; Singh, Jagdeep; Boparai, Ravneet Kaur; Zhu, JianHua; Mantri, Shrikant; Khare, Pragyanshu; Khardori, Romesh; Kondepudi, Kanthi Kiran; Chopra, Kanwaljit; Bishnoi, Mahendra

2017-09-01

High fat diet (HFD)-induced alterations in gut microbiota and resultant 'leaky gut' phenomenon promotes metabolic endotoxemia, ectopic fat deposition, and low-grade systemic inflammation. Here we evaluated the effects of a combination of green tea extract (GTE) with isomalto-oligosaccharide (IMOs) on HFD-induced alterations in mice. Male Swiss albino mice were fed with HFD (58% fat kcal) for 12 weeks. Systemic adiposity, gut derangement parameters and V3-V4 region based 16S rRNA metagenomic sequencing, ectopic fat deposition, liver metabolome analysis, systemic and tissue inflammation, and energy homeostasis markers along with gene expression analysis in multiple tissues were done in mice supplemented with GTE, IMOs or their combination. The combination of GTE and IMOs effectively prevented HFD-induced adiposity and lipid accumulation in liver and muscle while normalizing fasting blood glucose, insulin, glucagon, and leptin levels. Co-administration of GTE with IMOs effectively modulated liver metabolome associated with lipid metabolism. It also prevented leaky gut phenotype and HFD-induced increase in circulating lipopolysaccharides and pro-inflammatory cytokines (e.g. resistin, TNF-α, and IL-1β) and reduction in anti-inflammatory cytokines (e.g. adiponectin and IL-6). Gene expression analysis across multiple tissues further supported these functional outcomes. Most importantly, this combination improved beneficial gut microbiota (Lactobacillus sp., Bifidobacteria, Akkermansia muciniphila, Roseburia spp.) abundances, restored Firmicutes/Bacteriodetes and improved Prevotella/Bacteroides proportions. In particular, a combination of these two agents has shown improved beneficial effects on multiple parameters studied. Data presented herein suggests that strategically chosen food components might be highly effective in the prevention of HFD-induced alterations and may further be developed as functional foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Two variants in the resistin gene and the response to long-term overfeeding.

PubMed

Ukkola, O; Kesäniemi, Y Antero; Tremblay, A; Bouchard, C

2004-04-01

To investigate the role of resistin gene variants on the adiposity and metabolic changes observed in response to a 100-day overfeeding protocol conducted with 12 pairs of monozygotic twins. Body-fat measurements included hydrodensitometry and abdominal fat from computed tomography. Plasma glucose and insulin during fasting and in response to an oral glucose tolerance test (OGTT) were assayed. A 4.2 MJ test meal was consumed, after which calorimetric measurements were performed for 240 min. Respiratory quotient (RQ) decreased (P=0.001) more in AA/AG than in GG subjects of the IVS2+181G>A polymorphism after the caloric surplus and the significance persisted when correction for multiple testing was performed. Total abdominal (P=0.027) and visceral (P=0.004) fat increased more in TC than in TT subjects of the IVS2+39C>T polymorphism. In response to overfeeding, glucose area under the curve during the OGTT showed a slight decrease (P=0.031) in the TC while it increased in TT subjects. OGTT insulin area tended to increase less (P=0.055) in TC than in TT subjects. After overfeeding, fasting insulin was lower in TC than in TT subjects (P=0.010). In addition, TC subjects experienced more decrease in RQ than TT subjects (P=0.034). The IVS2+181G>A variant was associated with the changes in RQ in response to overfeeding. The IVS2+39C>T polymorphism was associated with overfeeding-induced changes in abdominal visceral fat, OGTT glucose area and RQ. The results suggest that sequence variation in the resistin gene is involved in the adaptation to chronic positive energy balance.

Differential patterns of replacement and reactive fibrosis in pressure and volume overload are related to the propensity for ischaemia and involve resistin

PubMed Central

Chemaly, Elie R; Kang, Soojeong; Zhang, Shihong; McCollum, LaTronya; Chen, Jiqiu; Bénard, Ludovic; Purushothaman, K-Raman; Hajjar, Roger J; Lebeche, Djamel

2013-01-01

Pathological left ventricle (LV) hypertrophy (LVH) results in reactive and replacement fibrosis. Volume overload LVH (VOH) is less profibrotic than pressure overload LVH (POH). Studies attribute subendocardial fibrosis in POH to ischaemia, and reduced fibrosis in VOH to collagen degradation favouring dilatation. However, the mechanical origin of the relative lack of fibrosis in VOH is incompletely understood. We hypothesized that reduced ischaemia propensity in VOH compared to POH accounted for the reduced replacement fibrosis, along with reduced reactive fibrosis. Rats with POH (ascending aortic banding) evolved into either compensated-concentric POH (POH-CLVH) or dilated cardiomyopathy (POH-DCM); they were compared to VOH (aorta–caval fistula). We quantified LV fibrosis, structural and haemodynamic factors of ischaemia propensity, and the activation of profibrotic pathways. Fibrosis in POH-DCM was severe, subendocardial and subepicardial, in contrast with subendocardial fibrosis in POH-CLVH and nearly no fibrosis in VOH. The propensity for ischaemia was more important in POH versus VOH, explaining different patterns of replacement fibrosis. LV collagen synthesis and maturation, and matrix metalloproteinase-2 expression, were more important in POH. The angiotensin II-transforming growth-factor β axis was enhanced in POH, and connective tissue growth factor (CTGF) was overexpressed in all types of LVH. LV resistin expression was markedly elevated in POH, mildly elevated in VOH and independently reflected chronic ischaemic injury after myocardial infarction. In vitro, resistin is induced by angiotensin II and induces CTGF in cardiomyocytes. Based on these findings, we conclude that a reduced ischaemia propensity and attenuated upstream reactive fibrotic pathways account for the attenuated fibrosis in VOH versus POH. PMID:24018949

Correlations between serum adipocytokine concentrations, disease stage, radiological status and total body fat content in the patients with primary knee osteoarthritis.

PubMed

Richter, Magdalena; Trzeciak, Tomasz; Rybka, Jakub Dalibor; Suchorska, Wiktoria; Augustyniak, Ewelina; Lach, Michał; Kaczmarek, Małgorzata; Kaczmarczyk, Jacek

2017-05-01

The study was designed to investigate whether serum concentrations of leptin, resistin and adiponectin in obese and normal-weight patients with primary knee osteoarthritis (OA) correlate with clinical and radiological stages of the disease and percentage of total body fat. Seventy-three patients with knee OA, divided into obese and normal-weight groups, were clinically evaluated according to the Knee Society Score (KSS), and radiologically assessed using Kellgren and Lawrence scale. The percentage of total body fat and some anthropometric data were also given. Serum leptin, resistin and adiponectin concentrations were measured by Elisa and were correlated with the clinical, radiological and anthropometric parameters. Leptin concentrations were significantly higher (p = 0.001) in the obese patients and positively correlated (R = 0.63) with radiologically assessed OA grade, but only in the normal-weight group. Resistin and adiponectin concentrations were identical in obese and normal-weight patients and negatively correlated (R = -0.41) with the clinical status of obese patients. In both groups, percentage of total body fat positively correlated (R = 0.29 and R = 0.53 for obese and normal-weight respectively) with radiologically assessed OA grade. However, no correlations were found with clinical status of the patients. It was found that in the obese patients with knee OA, increased percentage of total body fat and elevated serum leptin concentration might favour the advancement of clinical but not radiologically assessed changes in the joint structures, while in normal-weight patients it correlates only with radiologically assessed changes but does not affect to an appreciable extent the clinical status of the patients.

Adipocytokines and insulin resistance across various degrees of glucose tolerance in pregnancy.

PubMed

Skvarca, A; Tomazic, M; Krhin, B; Blagus, R; Janez, A

2012-01-01

Gestational diabetes mellitus is characterized by progressive insulin resistance. Adipocytokines are thought to be associated with insulin resistance. This cross-sectional study evaluated the associations between serum concentrations of several adipocytokines and insulin resistance at different stages of glucose tolerance in pregnancy, using the homeostasis model assessment of insulin resistance (HOMA-IR) as a reference. According to oral glucose tolerance test results, 74 pregnant women were divided into three groups: normal glucose tolerance (n = 25); intermediate glucose tolerance (n = 19); gestational diabetes mellitus (n = 30). Adiponectin, leptin, resistin, visfatin and retinol-binding protein 4 (RBP4) concentrations were measured using enzyme-linked immuno sorbent assays. Groups were comparable regarding age, week of gestation and body mass index before gestation. There were statistically significant between-group differences in HOMA-IR, but no significant differences regarding serum adipocytokine concentrations. Adipo nectin, leptin, resistin, visfatin and RBP4 were not associated with the degree of glucose tolerance in pregnancy. Concentrations of these adipocytokines are not sufficiently sensitive to replace HOMA- IR in pregnancy.

[3'UTR +62G>A polymorphism of the RETN gene coding resistin and its association with metabolic syndrome components].

PubMed

Arráiz, Nailet; Escalona, Carolina; Prieto, Carem; Bermúdez, Valmore; Mújica, Endrina; Sánchez, María Patricia; Mújica, Andrea

2013-10-19

The polymorphism of the resistin gene (RETN/RSTN) has been associated with metabolic alterations. In this study the association between the 3'UTR +62G>A polymorphism and metabolic syndrome components was evaluated. The population (n=218) was distributed in 3 groups: the control group with no metabolic alterations (n=77), nSMA group with isolated metabolic alterations (n=94) and MS group with metabolic syndrome (n=47). The 3'UTR +62G>A polymorphism was analyzed by PCR-RFLP. Central obesity was the most frequent alteration in both nSMA (56.4%) and MS (91.5%) groups followed by low c-HDL levels in the nSMA group (42.6%) and arterial hypertension in the MS group (85%). The frequency of the +62G/A genotype was 20.2% in the population. The G/A genotype was more frequently found in the MS (38.3%) and nSMA (17%) groups than in the control group (13%). The allelic distribution between the control group (+62G=0.94, +62A=0.06) and MS group (+62G=0.81, +62A=0.19) was significantly different (P=.0001). Significant associations between the G/A genotype and high values of abdominal circumference (P=.047), basal glycemia (P=.02) and systolic arterial pressure (P=.003) were found. The findings suggest the association between the G/A genotype and high values of systolic arterial pressure, basal glycemia and abdominal circumference. This association was independent of the metabolic syndrome context. Copyright © 2012 Elsevier España, S.L. All rights reserved.

An acute intake of a walnut-enriched meal improves postprandial adiponectin response in healthy young adults.

PubMed

Lozano, Aquiles; Perez-Martinez, Pablo; Marin, Carmen; Tinahones, Francisco J; Delgado-Lista, Javier; Cruz-Teno, Cristina; Gomez-Luna, Purificacion; Rodriguez-Cantalejo, Fernando; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

2013-12-01

A deficit in adiponectin plays an important causal role in insulin resistance and metabolic syndrome. We hypothesized that as seen during the fasting state, the intake of a walnut-enriched meal increased postprandial adiponectin. Twenty-one healthy white men followed a 4-week baseline diet and then consumed 3 fat-loaded meals that included 1 g fat/kg body weight (65% fat) according to a randomized crossover design: olive oil-enriched meal (22% saturated fatty acids [SFA], 38% monounsaturated fatty acids [MUFA], 4% polyunsaturated fatty acids [PUFA]), butter-enriched meal (35% SFA, 22% MUFA, 4% PUFA), and walnut-enriched meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Leptin, resistin, adiponectin, and free fatty acids were determined at 0, 3, 6, and 8.5 hours after the fat load. After the walnut-enriched meal, plasma adiponectin concentrations were higher at 3 and 6 hours (P = .011, P = .046, respectively) compared with the butter-enriched meal and higher at 6 hours compared with the olive oil-enriched meal (P = .036). Free fatty acid levels decreased from baseline at 3 hours after the walnut-enriched meal (P = .001). No differences were observed between the 3 meals for leptin and resistin responses. Our data confirmed a beneficial profile in the postprandial response to walnuts, source of omega-3 PUFA with an increased postprandial adiponectin and lower postprandial free fatty acid responses. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with omega-3 PUFA dietary fat. © 2013 Elsevier Inc. All rights reserved.

Assessment of Abdominal Fat Using High-field Magnetic Resonance Imaging and Anthropometric and Biochemical Parameters.

PubMed

Al-Radaideh, Ali; Tayyem, Reema; Al-Fayomi, Kholoud; Nimer, Nisreen; Malkawi, Amer; Al-Zu Bi, Rana; Agraib, Lana; Athamneh, Imad; Hijjawi, Nawal

2016-12-01

To measure the abdominal subcutaneous fat (SF) and visceral fat (VF) volumes using high-field magnetic resonance imaging (MRI) and to investigate their association with selected anthropometric and biochemical parameters among obese and nonobese apparently healthy participants. A cross-sectional study was conducted by recruiting 167 healthy participants. Abdominal scans were acquired at 3T MRI, and the SF and VF were segmented and their volumes were calculated. Selected anthropometric and biochemical measurements were also determined. A significant difference (P < 0.05) was observed between normal body weight and overweight and obese participants for SF and VF, total abdominal fat volumes, leptin, resistin, adiponectin and waist circumference. Waist circumferences were measured by tape and MRI. Findings revealed that MRI-measured fat volumes were different between males and females and had a significant (P < 0.01) strong positive correlation with body mass index, leptin, resistin and WC and had a negative correlation with adiponectin level. MRI-measured fat volumes were found to correlate moderately with interleukin-6 and weakly with cholesterol, serum triglyceride and low-density lipoprotein. Except for cholesterol, all measured biochemical variables and abdominal fat volumes in the current study were significantly associated with body mass index. All anthropometric and biochemical parameters showed weak-to-strong associations with the MRI-measured fat volumes. Abdominal fat distribution was different between males and females and their correlations with some lipid profiles were found to be sex dependent. These findings revealed that MRI can be used as an alternative tool for obesity assessment. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Gene Expression in Human Meniscal Tears has Limited Association with Early Degenerative Changes in Knee Articular Cartilage

PubMed Central

Brophy, Robert H.; Sandell, Linda J.; Cheverud, James M.; Rai, Muhammad Farooq

2018-01-01

Purpose/Aim Meniscus tears are a common injury to the knee associated with the development of osteoarthritis. Gene expression in the injured meniscus may be associated with early degeneration in the articular cartilage. The purpose of this study was to test the hypothesis that gene expression in meniscus tears is associated with early degenerative changes in the articular cartilage at the time of partial meniscectomy. Materials and Methods Torn meniscus was removed at the time of partial meniscectomy in 63 patients without radiographic osteoarthritis. Meniscal mRNA expression was measured by quantitative PCR for multiple molecular markers of osteoarthritis and cartilage homeostasis. The presence of early degenerative changes in the knee was recorded by X-ray (N=63), magnetic resonance imaging (MRI, N=48) and arthroscopy (N=63). Gene expression was tested for correlation with the presence/absence of degenerative changes after adjusting for age, sex and body mass index. Results Overall gene expression varied significantly with degenerative changes based on X-ray (P=0.047) and MRI (P=0.018). The linear combination of gene variation was also significant. However, only adiponectin (ADIPOQ) (P=0.015) was expressed at a significantly lower level in patients with chondrosis on MRI while the expression of ADIPOQ (P=0.035) and resistin (RETN) (P=0.017) was higher in patients with early degenerative changes on X-ray. Conclusions There is an overall association of gene expression in meniscal tears to early degenerative changes in the knee, but only a limited number of specific genes demonstrate this relationship. The roles of adiponectin and resistin in knee injury and osteoarthritis deserve further study. PMID:27435997

Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection

USDA-ARS?s Scientific Manuscript database

IL-4 and IL-13 protect against parasitic helminths, but little is known about the mechanism of host protection. We show that IL-4/IL-13 confer immunity against worms by inducing intestinal epithelial cells (IEC) to differentiate into goblet cells that secrete resistin-like molecule beta (RELMB). R...

Adipokines in human reproduction.

PubMed

Dupont, Joëlle; Pollet-Villard, Xavier; Reverchon, Maxime; Mellouk, Namya; Levy, Rachel

2015-10-01

Adipose tissue communicates with other central and peripheral organs by the synthesis and release of substances called adipokines. The most studied adipokine is leptin but others have been recently identified including resistin, adiponectin, chemerin, omentin and visfatin. These adipokines have a critical role in the development of obesity-related complications and inflammatory conditions. However, they are also involved in other functions in the organism including reproductive functions. Indeed, many groups have demonstrated that adipokine receptors, such as adiponectin and chemerin, but also adipokines themselves (adiponectin, chemerin, resistin, visfatin and omentin) are expressed in human peripheral reproductive tissues and that these adipokines are likely to exert direct effects on these tissues. After a brief description of these new adipokines, an overview of their actions in different human reproductive organs (hypothalamus, pituitary, ovary, testis, uterus and placenta) will be presented. Finally, comments will be made on the eventual alterations of these adipokines in reproductive disorders, with special attention to polycystic ovary syndrome, a disease characterized by dysfunction of gonadal axis and systemic nerve endocrine metabolic network with a prevalence of up to 10% in women of reproductive age.

Associations between 25-hydroxyvitamin D and immunologic, metabolic, inflammatory markers in treatment-naive HIV-infected persons: the ANRS CO9 «COPANA» cohort study.

PubMed

Legeai, Camille; Vigouroux, Corinne; Souberbielle, Jean-Claude; Bouchaud, Olivier; Boufassa, Faroudy; Bastard, Jean-Philippe; Carlier, Robert; Capeau, Jacqueline; Goujard, Cécile; Meyer, Laurence; Viard, Jean-Paul

2013-01-01

Low 25(OH)D has been associated with dyslipidemia, insulin resistance and inflammation in both general and HIV-infected (mostly treated) populations. We investigated these associations in antiretroviral-naïve HIV-infected persons. We measured plasma 25(OH)D, metabolic, immunologic and inflammatory markers in 355 persons (204 Whites, 151 Blacks) at enrollment in the ANRS COPANA cohort. 25(OH)D levels were categorized <10 ng/mL (severe deficiency) and <20 ng/mL (deficiency). Statistical analyses were adjusted for sampling season, ethnicity and the interaction between season and ethnicity. 25(OH)D insufficiency (<30 ng/mL), deficiency (<20 ng/mL) and severe deficiency (<10 ng/mL) were highly prevalent (93%, 67% and 24% of patients, respectively). Blacks had significantly lower 25(OH)D than Whites (median: 13 vs. 17 ng/mL, P<0.001), with markedly less pronounced seasonal variation. Smoking and drinking alcohol were associated with having a 25 OHD level<10 ng/mL. In patients with 25(OH)D<10 ng/mL, the proportion of persons with a CD4 count<100/mm(3) was higher than in patients with 25(OH)D≥10 ng/mL (18.8% vs. 10.7%, P = 0.04). Persons with 25 OHD<10 ng/mL had higher levels of hsCRP (1.60 mg/L [IQR: 0.59-5.76] vs. 1.27 mg/L [0.58-3,39], P = 0.03) and resistin (16.81 ng/L [IQR: 13.82-25.74] vs. 11.56 ng/L [IQR: 8.87-20.46], P = 0.02), and, among Blacks only, sTNFR2 (2.92 ng/mL [2.31-4.13] vs. 2.67 ng/mL, [1.90-3.23], P = 0.04). The strength and significance of the association between CD4<100/mm(3) and 25 OHD<10 ng/mL were reduced after adjustment on sTNFR1, sTNFR2, and hsCRP levels. In multivariate analysis, a CD4 count <100/mm(3), resistin concentration and smoking were independently associated with 25(OH)D<10 ng/mL. Severe vitamin D deficiency was associated with low CD4 counts and increased markers of inflammation in ARV-naïve HIV-infected persons.

Metabolic cross-talk between skeletal muscle and adipose tissue in high-intensity interval training vs. moderate-intensity continuous training by regulation of PGC-1α.

PubMed

Shirvani, Hossein; Arabzadeh, Ehsan

2018-02-26

An imbalance in the production of adipokines and myokines impairs the energy expenditure, increases adipocyte and develops metabolic pathologies. Physical exercise is able to regulate the secretion of myokines and adipokines. The present study considers the metabolic cross talk between skeletal muscle and adipose tissue in high-intensity interval training vs. moderate-intensity continuous training by regulation of PGC-1α. A sample of 32 male Wistar rats (8 weeks old with mean weight 250 ± 55 g) were divided into four groups randomly: control of base (CO), control of 8 weeks (CO8w), moderate-intensity continuous training (MICT), and high-intensity interval training (HIIT). The rats were fed with standard chow diet. The CO group was killed at the start of the study and the CO8w group was kept alive for the same time as the experimental groups, but did not participate in any exercise. MICT and HIIT groups for 8 weeks were placed under the moderate-intensity continuous training (15-60 min, with speed of 15-30 m/min) and high-intensity interval training (8-4 intense period for 1 min, with speed of 28-55 m/min, with 3-7 slow-intensity period for 1 min, with a speed of 12-30 m/min) for 8 weeks, respectively. To measure the levels of serum irisin, nesfatin, and resistin the ELISA method was used and real-time PCR method was used to evaluate the relative expression of soleus PGC-1α gene mRNA. The levels of irisin and nesfatin significantly increased in the HIIT compared with control groups (p = 0.001). Resistin values in both training groups showed a significant decrease compared to the control groups (p = 0.005). The level of PGC-1α gene expression in both HIIT and MICT groups was significantly increased in comparison with the control groups (p = 0.001). The results showed that HIIT and MICT increase the transcription of the PGC-1α gene and possibly the increased expression of this gene after HIIT and MICT plays a central role in the secretion of skeletal muscle myokines and adipokines of adipose tissue. No Level of evidence: Animal study.

Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients.

PubMed

Jacobo-Cejudo, M Gorety; Valdés-Ramos, Roxana; Guadarrama-López, Ana L; Pardo-Morales, Rosa-Virgen; Martínez-Carrillo, Beatriz E; Harbige, Laurence S

2017-06-03

Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n- 3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n- 3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n- 3 PUFA intake was calculated in g/day. Waist circumference and blood glucose showed significant reductions in the FOG group ( p = 0.001 and p = 0.011, respectively). Hb1Ac ( p = 0.009 and p = 0.004), leptin ( p < 0.000 and p < 0.000), and leptin/adiponectin ratio ( p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols ( p = 0.002) and atherogenic index ( p = 0.031); in contrast, the PG group had increased total cholesterol ( p < 0.000), non-HDL cholesterol ( p < 0.000), and atherogenic index ( p = 0.017). We found a beneficial effect of n- 3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups.

Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients

PubMed Central

Jacobo-Cejudo, M. Gorety; Valdés-Ramos, Roxana; Guadarrama-López, Ana L.; Pardo-Morales, Rosa-Virgen; Martínez-Carrillo, Beatriz E.; Harbige, Laurence S.

2017-01-01

Background: Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n-3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n-3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. Methods: In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n-3 PUFA intake was calculated in g/day. Results: Waist circumference and blood glucose showed significant reductions in the FOG group (p = 0.001 and p = 0.011, respectively). Hb1Ac (p = 0.009 and p = 0.004), leptin (p < 0.000 and p < 0.000), and leptin/adiponectin ratio (p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols (p = 0.002) and atherogenic index (p = 0.031); in contrast, the PG group had increased total cholesterol (p < 0.000), non-HDL cholesterol (p < 0.000), and atherogenic index (p = 0.017). Conclusions: We found a beneficial effect of n-3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups. PMID:28587203

Identification of Biomarkers Associated with the Healing of Chronic Wounds

DTIC Science & Technology

2008-01-01

0.904793 1.01303 0.972086 0.872621 0.9002 Ras-related C3 botulinum toxin substrate 1 precursor (p21-Rac1) (Ras-like protein TC25) - Homo sapiens (Human...0.651342 1.003025 1.32526 Resistin precursor (Cysteine-rich secreted protein FIZZ3) (Adipose tissue-specific secretory factor) (ADSF) (C/EBP- epsilon

Postprandial response of ghrelin and PYY and indices of low-grade chronic inflammation in lean young women with polycystic ovary syndrome.

PubMed

Zwirska-Korczala, K; Sodowski, K; Konturek, S J; Kuka, D; Kukla, M; Brzozowski, T; Cnota, W; Woźniak-Grygiel, E; Jaworek, J; Bułdak, R; Rybus-Kalinowska, B; Fryczowski, M

2008-08-01

The aim of the study were to answer the question 1.) Whether circulating pro-inflammatory markers of endothelial dysfunction and due to chronic low-grade inflammation of obesity, are altered in untreated lean, young relatively healthy polycystic ovary syndrome (PCOS) patients in comparison with healthy controls; 2.) Whether postprandial plasma concentration pattern of ghrelin and PYY can be predictable as risk factors for atherosclerosis and depend of obesity. Forty young women with PCOS were divided in two groups: 19 lean and 21 obese. The control group included 20 lean, healthy volunteers. Plasma total and active ghrelin, total PYY and PYY(3-36), serum adiponectin and insulin were measured using RIA technique, serum sCD40L, visfatin, sP-, sE-selectins, resistin by EIA. Composition of test meal was: 527 kcal total and consisted of 24.1% fat, 54.4% carbohydrate and 21.5% protein. Total and active ghrelin and total PYY were significantly lower in obese PCOS women, whereas active ghrelin was also significantly lower in lean PCOS women compared to controls. Postprandial plasma total ghrelin levels decrease were blunted in lean and obese compared to controls (12.8 % and 18.2% vs 28.2 %). Postprandial plasma active ghrelin decreased in lean and obese PCOS groups (49.9 % and 44.1 %) and controls (63.8 %). PCOS subjects exhibited smaller rises in postprandial levels of total PYY. Postprandial plasma PYY(3-36) levels increased in obese PCOS women (30.9 %) and controls (41%), whereas lean PCOS women exhibited blunted increase (11.5%). sCD40L levels increased, whereas adiponectin decreased in PCOS groups independently, whereas rise in visfatin, sE- and sP-selectin and the fall in adiponectin was associated with obesity. sP- and sE -selectins correlated positively with obesity. In summary, our study provides the first evidence that lean untreated young PCOS women contribute to the so called "pancreatic islet adaptation to insulin resistance" because of ghrelin and PYY profiles. We confirmed existing of low-grade chronic inflammation in early stage of visceral obesity in lean PCOS patients. The lost endogenous "islet adaptation to insulin resistance" may lead to endothelial dysfunction and promote acceleration of atherosclerosis.

Extract of Irish potatoes (Solanum tuberosum L.) decreases body weight gain and adiposity and improves glucose control in the mouse model of diet-induced obesity.

PubMed

Kubow, Stan; Hobson, Luc; Iskandar, Michèle M; Sabally, Kebba; Donnelly, Danielle J; Agellon, Luis B

2014-11-01

Both sexes of mice were fed a high fat diet (HFD) for 10 weeks without and with polyphenolic-rich potato extracts (PRPE) of cultivars Onaway and Russet Burbank. PRPE attenuated weight gain in male and female mice by as much as 63.2%, which was associated mostly with a reduction in adiposity. Mice receiving PRPE showed enhanced capacity for blood glucose clearance. Sex differences regarding the impact of HFD and PRPE on plasma levels of insulin, ghrelin, leptin, gastric inhibitory peptide, and resistin were noted. PRPE may serve as part of a preventative dietary strategy against the development of obesity and type 2 diabetes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women.

PubMed

Lopez, Hector L; Ziegenfuss, Tim N; Hofheins, Jennifer E; Habowski, Scott M; Arent, Shawn M; Weir, Joseph P; Ferrando, Arny A

2013-04-19

Numerous natural products are marketed and sold claiming to decrease body weight and fat, but few undergo finished product-specific research demonstrating their safety and efficacy. To determine the safety and efficacy of a multi-ingredient supplement containing primarily raspberry ketone, caffeine, capsaicin, garlic, ginger and Citrus aurantium (Prograde Metabolism™ [METABO]) as an adjunct to an eight-week weight loss program. Using a randomized, placebo-controlled, double-blind design, 70 obese but otherwise healthy subjects were randomly assigned to METABO or a placebo and underwent 8 weeks of daily supplementation, a calorie restricted diet, and exercise training. Subjects were tested for changes in body composition, serum adipocytokines (adiponectin, resistin, leptin, TNF-α, IL-6) and markers of health including heart rate and blood pressure. Of the 45 subjects who completed the study, significant differences were observed in: body weight (METABO -2.0% vs. placebo -0.5%, P < 0.01), fat mass (METABO -7.8 vs. placebo -2.8%, P < 0.001), lean mass (METABO +3.4% vs. placebo +0.8%, P < 0.03), waist girth (METABO -2.0% vs. placebo -0.2%, P < 0.0007), hip girth (METABO -1.7% vs. placebo -0.4%, P < 0.003), and energy levels per anchored visual analogue scale (VAS) (METABO +29.3% vs. placebo +5.1%, P < 0.04). During the first 4 weeks, effects/trends for maintaining elevated serum leptin (P < 0.03) and decreased serum resistin (P < 0.08) in the METABO group vs. placebo were also observed. No changes in systemic hemodynamics, clinical blood chemistries, adverse events, or dietary intake were noted between groups. METABO administration is a safe and effective adjunct to an eight-week diet and exercise weight loss program by augmenting improvements in body composition, waist and hip girth. Adherence to the eight-week weight loss program also led to beneficial changes in body fat in placebo. Ongoing studies to confirm these results and clarify the mechanisms (i.e., biochemical and neuroendocrine mediators) by which METABO exerts the observed salutary effects are being conducted.

Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system.

PubMed

Budak, Erdal; Fernández Sánchez, Manuel; Bellver, José; Cerveró, Ana; Simón, Carlos; Pellicer, Antonio

2006-06-01

To summarize the effects of novel hormones (leptin, ghrelin, adiponectin, resistin, and PYY3-36) secreted from adipose tissue and the gastrointestinal tract that have been discovered to exert different effects on several reproductive functions, such as the hypothalamic-pituitary-gonadal axis, embryo development, implantation physiology, and clinically relevant conditions. A MEDLINE computer search was performed to identify relevant articles. Leptin and ghrelin exert important roles on body weight regulation, eating behavior, and reproduction, acting on the central nervous system and target reproductive organs. As a marker of adequate nutritional stores, these hormones may act on the central nervous system to initiate the complex process of puberty and maintain normal reproductive function. In addition, leptin and ghrelin and their receptors are involved in reproductive events such as gonadal function, embryo development, and embryo-endometrial interaction. Leptin and ghrelin and other adipose tissue-secreted hormones have significant effects on reproduction. Acting through the brain, these hormones may serve as links between adipose tissue and the reproductive system to supply and regulate energy needs for normal reproduction and pregnancy. Future studies are needed to further clarify the role of these hormones in reproductive events and other related gynecological conditions.

Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

PubMed

Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

2015-05-15

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM.

Vitamin D replacement ameliorates serum lipoprotein functions, adipokine profile and subclinical atherosclerosis in pre-menopausal women.

PubMed

Greco, D; Kocyigit, D; Adorni, M P; Marchi, C; Ronda, N; Bernini, F; Gurses, K M; Canpinar, H; Guc, D; Oguz, S H; Gurlek, A; Strazzella, A; Simonelli, S; Tokgozoglu, L; Zimetti, F

2018-05-12

Low vitamin D (vitD) has been linked to increased cardiovascular (CV) risk, but the effects of vitD supplementation are not clarified. We evaluated the impact of vitD normalization on HDL cholesterol efflux capacity (CEC), which inversely correlates with CV risk, the proatherogenic serum cholesterol loading capacity (CLC), adipokine profile and subclinical atherosclerosis. Healthy premenopausal women with vitD deficiency (n = 31) underwent supplementation. Subclinical atherosclerosis was evaluated by flow-mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AIx), measured with standard techniques. HDL CEC and serum CLC were measured by a radioisotopic and fluorimetric assay, respectively. Malondialdehyde (MDA) in HDL was quantified by the TBARS assay. Pre-β HDL was assessed by 2D-electrophoresis. Serum adipokines were measured by ELISA. VitD replacement restored normal levels of serum 25-hydroxyvitamin D (25OHD) and significantly improved FMD (+4%; p < 0.001), PWV (-4.1%: p < 0.001) and AIx (-16.1%; p < 0.001). Total CEC was significantly improved (+19.5%; p = 0.003), with a specific increase in the ABCA1-mediated CEC (+70.8%; p < 0.001). HDL-MDA slightly but significantly decreased (-9.6%; p = 0.027), while no difference was detected in pre-β HDL. No change was observed in aqueous diffusion nor in the ABCG1-mediated CEC. Serum CLC was significantly reduced (-13.3%; p = 0.026). Levels of adiponectin were increased (+50.6%; p < 0.0001) and resistin levels were decreased (-24.3%; p < 0.0001). After vitD replacement, an inverse relationship was found linking the ABCA1-mediated CEC with pre-β HDL (r 2  = 0.346; p < 0.001) and resistin (r 2  = 0.220; p = 0.009). Our data support vitD supplementation for CV risk prevention. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Association of circulating ANGPTL 3, 4, and 8 levels with medical status in a population undergoing routine medical checkups: A cross-sectional study.

PubMed

Morinaga, Jun; Zhao, Jiabin; Endo, Motoyoshi; Kadomatsu, Tsuyoshi; Miyata, Keishi; Sugizaki, Taichi; Okadome, Yusuke; Tian, Zhe; Horiguchi, Haruki; Miyashita, Kazuya; Maruyama, Nobuhiro; Mukoyama, Masashi; Oike, Yuichi

2018-01-01

Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 reportedly contribute to progression of metabolic disease, a risk factor for cardiovascular disease (CVD). The purpose of this study was to investigate whether circulating ANGPTL levels are associated with CVD risk after adjustment for potential confounding factors. We conducted a single center, cross-sectional study of 988 Japanese subjects undergoing routine health checks. Serum ANGPTL3, 4, and 8 levels were measured using an enzyme-linked immunosorbent assay. Using multiple regression analysis we evaluated potential association of circulating ANGPTL3, 4, and 8 levels with general medical status including age, sex, smoking, drinking, obesity, hypertension, impaired glycometabolism, dyslipidemia, hyperuricemia, hepatic impairment, chronic kidney disease, anemia, cardiac abnormality, and inflammation. Circulating ANGPTL3 levels were relatively high in health-related categories of hepatic impairment and inflammation. Circulating ANGPTL4 levels were also significantly high in impaired glycometabolism or hepatic impairment but decreased in inflammation. Finally, increased ANGPTL8 levels were observed in obesity, impaired glycometabolism and dyslipidemia. Particularly, increased levels of circulating ANGPTL8 were positively correlated with circulating triglycerides and LDL-cholesterol levels and inversely correlated with circulating HDL-cholesterol levels. Circulating ANGPTL3, 4, and 8 levels reflect some risk factors for CVD development.

Serum adiposity-induced biomarkers in obese and lean children with recently diagnosed autoimmune type 1 diabetes.

PubMed

Redondo, M J; Rodriguez, L M; Haymond, M W; Hampe, C S; Smith, E O; Balasubramanyam, A; Devaraj, S

2014-12-01

Obesity increases the risk of cardiovascular disease and diabetic complications in type 1 diabetes. Adipokines, which regulate obesity-induced inflammation, may contribute to this association. We compared serum adipokines and inflammatory cytokines in obese and lean children with new-onset autoimmune type 1 diabetes. We prospectively studied 32 lean and 18 obese children (age range: 2-18 yr) with new-onset autoimmune type 1 diabetes and followed them for up to 2 yr. Serum adipokines [leptin, total and high molecular weight (HMW) adiponectin, omentin, resistin, chemerin, visfatin], cytokines [interferon (IFN)-gamma, interleukin (IL)-10, IL-12, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha] and C-reactive protein (CRP) were measured at a median of 7 wk after diagnosis (range: 3-16 wk). Lean children were 71.9% non-Hispanic White, 21.9% Hispanic, and 6.3% African-American, compared with 27.8, 55.6, and 16.7%, respectively, for obese children (p = 0.01). Compared with lean children, obese children had significantly higher serum leptin, visfatin, chemerin, TNF-alpha and CRP, and lower total adiponectin and omentin after adjustment for race/ethnicity and Tanner stage. African-American race was independently associated with higher leptin among youth ≥10 yr (p = 0.007). Leptin levels at onset positively correlated with hemoglobin A1c after 1-2 yr (p = 0.0001) independently of body mass index, race/ethnicity, and diabetes duration. Higher TNF-alpha was associated with obesity and female gender, after adjustment for race/ethnicity (p = 0.0003). Obese children with new-onset autoimmune type 1 diabetes have a proinflammatory profile of circulating adipokines and cytokines that may contribute to the development of cardiovascular disease and diabetic complications. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

PubMed Central

Schleinitz, Dorit

2015-01-01

Adipose tissue secretes an abundance of proteins. Some of these proteins are known as adipokines and adipose-derived hormones which have been linked with metabolic disorders, including type 2 diabetes, and even with cancer. Variance in serum adipokine concentration is often closely associated with an increase (obesity) or decrease (lipodystrophy) in fat tissue mass, and it is affected by age, gender, and localization of the adipose tissue. However, there may be genetic variants which, in consequence, influence the serum concentration of a certain adipokine, and thereby promote metabolic disturbances or, with regard to the “protective” allele, exert beneficial effects. This review focuses on the genetic determination of serum levels of the following adipokines: adiponectin, chemerin, leptin, progranulin, resistin, retinol binding protein 4, vaspin, adipsin, apelin, and omentin. The article reports on the latest findings from genome-wide association studies (GWAS) and candidate gene studies, showing variants located in/nearby the adipokine genes and other (non-receptor) genes. An extra chapter highlights adipokine-receptor variants. Epigenetic studies on adipokines are also addressed. PMID:26859657

The ubiquitous interleukin-6: a time for reappraisal.

PubMed

Fisman, Enrique Z; Tenenbaum, Alexander

2010-10-11

Interleukin-6 (IL-6) is a multifunctional cytokine regulating humoral and cellular responses and playing a central role in inflammation and tissue injury. Its effects are mediated through interaction with its receptor complex, IL-6Rβ (also known as gp130). It plays an important role in the pathogenesis of coronary artery disease and large quantities of IL-6 are found in human atherosclerotic plaques. IL-6 levels positively correlate with higher all-cause mortality, unstable angina, left ventricular dysfunction, propensity to diabetes and its complications, hypertension, obesity and several types of cancer. IL-6 levels augmentation demonstrates a remarkable parallel with another biomarkers reflecting harmful processes, like tumor necrosis factor alpha, interleukins 8 and 18, YKL-40, C reactive protein and resistin. Due to these facts, IL-6 was classified as a noxious interleukin. Nonetheless, there are several facts that challenge this usually accepted point of view. Since IL-6 has also anti-inflammatory activity, it seems reasonable to assume that favorable aspects exist. These aspects are two: 1. protection against bacterial infections, inactivating proinflammatory mediators, mitigating the course of septic shock and inducing the production of cortisol; and 2. influence on insulin sensitivity during exercise; this aspect is even more important. During exercise IL-6 is synthesized and released by muscles, with enhanced insulin action immediately at early recovery. Skeletal muscle may be considered as an endocrine organ; contracting muscles produce IL-6 and release it into the blood exerting its effects on other organs. The increase in circulating levels of IL-6 after exercise is consistent and proportional to exercise duration, intensity, muscle mass involved and endurance capacity. Thus, the fascinating possibility that the plenteous beneficial health effects of exercise could be ultimately mediated by IL-6 merits further elucidation. Interleukins were termed "good" or "bad", probably due to a tendency to see things in black and white, with no gray area in between. Calling IL-6 "a molecule with both beneficial and destructive potentials" would be a more equitable approach. In the literary creatures of Dr. Jekyll and Mr. Hyde, a good and an evil personality are found in the same individual. IL-6 playing the role of Dr. Jekyll is emerging; the time for IL-6 reappraisal is coming.

Roles of G1359A polymorphism of the cannabinoid receptor gene (CNR1) on weight loss and adipocytokines after a hypocaloric diet.

PubMed

De Luis, D A; González Sagrado, M; Aller, R; Conde, R; Izaola, O; de la Fuente, B; Primo, D

2011-01-01

A intragenic biallelic polymorphism (1359 G/A) of the CB1 gene resulting in the substitution of the G to A at nucleotide position 1359 in codon 435 (Thr), was reported as a common polymorphism in Caucasian populations. Intervention studies with this polymorphism have not been realized. We decided to investigate the role of the polymorphism (G1359A) of CB1 receptor gene on adipocytokines response and weight loss secondary to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients. A population of 94 patients with obesity was analyzed. Before and after 3 months on a hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. The statistical analysis was performed for the combined G1359A and A1359A as a group and wild type G1359G as second group, with a dominant model. Forty seven patients (50%) had the genotype G1359G (wild type group) and 47 (50%) patients G1359A (41 patients, 43.6%) or A1359A (6 patients, 6.4%) (mutant type group) had the genotype. In wild and mutant type groups, weight, body mass index, fat mass, waist circumference and systolic blood pressure decreased. In mutant type group, resistin (4.15 ± 1.7 ng/ml vs. 3.90 ± 2.1 ng/ml: P < 0.05), leptin (78.4 ± 69 ng/ml vs 66.2 ± 32 ng/ml: P < 0.05) and IL-6 (1.40 ± 1.9 pg/ml vs 0.81 ± 1.5 pg/ml: P < 0.05) levels decreased after dietary treatment. The novel finding of this study is the association of the mutant allele (A1359) with a decrease of resistin, leptin and interleukin-6 secondary to weight loss.

High-intensity exercise and carbohydrate-reduced energy-restricted diet in obese individuals.

PubMed

Sartor, Francesco; de Morree, Helma M; Matschke, Verena; Marcora, Samuele M; Milousis, Athanasios; Thom, Jeanette M; Kubis, Hans-Peter

2010-11-01

Continuous high glycemic load and inactivity challenge glucose homeostasis and fat oxidation. Hyperglycemia and high intramuscular glucose levels mediate insulin resistance, a precursor state of type 2 diabetes. The aim was to investigate whether a carbohydrate (CHO)-reduced diet combined with high-intensity interval training (HIIT) enhances the beneficial effects of the diet alone on insulin sensitivity and fat oxidation in obese individuals. Nineteen obese subjects underwent 14 days of CHO-reduced and energy-restricted diet. Ten of them combined the diet with HIIT (4 min bouts at 90% VO(2peak) up to 10 times, 3 times a week). Oral glucose insulin sensitivity (OGIS) increased significantly in both groups; [diet-exercise (DE) group: pre 377 ± 70, post 396 ± 68 mL min(-1) m(-2); diet (D) group: pre 365 ± 91, post 404 ± 87 mL min(-1) m(-2); P < 0.001]. Fasting respiratory exchange ratio (RER) decreased significantly in both groups (DE group: pre 0.91 ± 0.06, post 0.88 ± 0.06; D group: pre 0.92 ± 0.07, post 0.86 ± 0.07; P = 0.002). VO(2peak) increased significantly in the DE group (pre 27 ± 5, post 32 ± 6 mL kg(-1) min(-1); P < 0.001), but not in the D group (pre 26 ± 9, post 26 ± 8 mL kg(-1) min(-1)). Lean mass and resistin were preserved only in the DE group (P < 0.05). Fourteen days of CHO-reduced diet improved OGIS and fat oxidation (RER) in obese subjects. The energy-balanced HIIT did not further enhance these parameters, but increased aerobic capacity (VO(2peak)) and preserved lean mass and resistin.

Pathophysiology of obesity on knee joint homeostasis: contributions of the infrapatellar fat pad.

PubMed

Santangelo, Kelly S; Radakovich, Lauren B; Fouts, Josie; Foster, Michelle T

2016-05-01

Osteoarthritis (OA) is a debilitating condition characterized by inflammation, breakdown, and consequent loss of cartilage of the joints. Epidemiological studies indicate obesity is an important risk factor involved in OA initiation and progression. Traditional views propose OA to be a biomechanical consequence of excess weight on weight-bearing joints; however, emerging data demonstrates that systemic and local factors released from white adipose depots play a role. Hence, current views characterize OA as a condition exacerbated by a metabolic link related to adipose tissue, and not solely related to redistributed/altered weight load. Factors demonstrated to influence cartilage and bone homeostasis include adipocyte-derived hormones ("adipokines") and adipose depot released cytokines. Epidemiological studies demonstrate a positive relation between systemic circulating cytokines, leptin, and resistin with OA types, while the association with adiponectin is controversial. Local factors in joints have also been shown to play a role in OA. In particular, this includes the knee, a weight-bearing joint that encloses a relatively large adipose depot, the infrapatellar fat pad (IFP), which serves as a source of local inflammatory factors. This review summarizes the relation of obesity and OA as it specifically relates to the IFP and other integral supporting structures. Overall, studies support the concept that metabolic effects associated with systemic obesity also extend to the IFP, which promotes inflammation, pain, and cartilage destruction within the local knee joint environment, thus contributing to development and progression of OA.

Resistin -420C>G promoter variant and colorectal cancer risk.

PubMed

Mahmoudi, Touraj; Karimi, Khatoon; Arkani, Maral; Farahani, Hamid; Vahedi, Mohsen; Dabiri, Reza; Nobakht, Hossein; Asadi, Asadollah; Mirakhorli, Mojgan; Arshi, Benafsheh; Derakhshan, Arash; Zali, Mohammad Reza

2014-09-30

Obesity is associated with an increased risk of colorectal cancer (CRC), and ghrelin (GHRL) and resistin (RETN) are thought to be related to obesity. Our aim was to investigate whether GHRL and RETN gene variants are associated with CRC risk. All 414 subjects, including 197 cases with CRC and 217 controls, were genotyped for the GHRL (rs26802) and RETN (rs1862513) or -420 C>G gene variants using the PCR-RFLP method. Our findings indicated that the RETN -420 C>G "CC" genotype, compared with the "GG" and "GC" genotypes, was a marker of decreased CRC susceptibility; the difference remained significant after adjustment for age, BMI, gender, smoking status, NSAID use, and family history of CRC (p=0.020; OR=0.52, 95% CI=0.30-0.90). Furthermore, after adjustment for confounding factors, the -420 C>G "CC" genotype, compared with the "GG" genotype, was associated with a decreased risk for CRC (p=0.044; OR=0.53, 95% CI=0.29-0.98). In addition, no significant difference was observed for the GHRL (rs26802) gene variant. To our knowledge, this is the first study suggesting that the RETN -420 C>G "CC" genotype is a marker of decreased CRC susceptibility. This observation is relevant from a scientific perspective and deserves further investigations.

Chronic features of allergic asthma are enhanced in the absence of resistin-like molecule-beta.

PubMed

LeMessurier, Kim S; Palipane, Maneesha; Tiwary, Meenakshi; Gavin, Brian; Samarasinghe, Amali E

2018-05-04

Asthma is characterized by inflammation and architectural changes in the lungs. A number of immune cells and mediators are recognized as initiators of asthma, although therapeutics based on these are not always effective. The multifaceted nature of this syndrome necessitate continued exploration of immunomodulators that may play a role in pathogenesis. We investigated the role of resistin-like molecule-beta (RELM-β), a gut antibacterial, in the development and pathogenesis of Aspergillus-induced allergic airways disease. Age and gender matched C57BL/6J and Retnlb -/- mice rendered allergic to Aspergillus fumigatus were used to measure canonical markers of allergic asthma at early and late time points. Inflammatory cells in airways were similar, although Retnlb -/- mice had reduced tissue inflammation. The absence of RELM-β elevated serum IgA and pro-inflammatory cytokines in the lungs at homeostasis. Markers of chronic disease including goblet cell numbers, Muc genes, airway wall remodelling, and hyperresponsiveness were greater in the absence RELM-β. Specific inflammatory mediators important in antimicrobial defence in allergic asthma were also increased in the absence of RELM-β. These data suggest that while characteristics of allergic asthma develop in the absence of RELM-β, that RELM-β may reduce the development of chronic markers of allergic airways disease.

Genetically elevated levels of circulating triglycerides and brachial-ankle pulse wave velocity in a Chinese population.

PubMed

Yao, W-M; Zhang, H-F; Zhu, Z-Y; Zhou, Y-L; Liang, N-X; Xu, D-J; Zhou, F; Sheng, Y-H; Yang, R; Gong, L; Yin, Z-J; Chen, F-K; Cao, K-J; Li, X-L

2013-04-01

Elevated levels of circulating triglycerides and increased arterial stiffness are associated with cardiovascular disease. Numerous studies have reported an association between levels of circulating triglycerides and arterial stiffness. We used Mendelian randomization to test whether this association is causal. We investigated the association between circulating triglyceride levels, the apolipoprotein A-V (ApoA5) -1131T>C single nucleotide polymorphism and brachial-ankle pulse wave velocity (baPWV) by examining data from 4421 subjects aged 18-74 years who were recruited from the Chinese population. baPWV was significantly associated with the levels of circulating triglycerides after adjusting for age, sex, body mass index (BMI), systolic blood pressure, heart rate, waist-to-hip ratio, antihypertensive treatment and diabetes mellitus status. The -1131C allele was associated with a 5% (95% confidence interval 3-8%) increase in circulating triglycerides (adjusted for age, sex, BMI, waist-to-hip ratio, diabetes mellitus and antihypertensive treatment). Instrumental variable analysis showed that genetically elevated levels of circulating triglycerides were not associated with increased baPWV. These results do not support the hypothesis that levels of circulating triglycerides have a causal role in the development of arterial stiffness.

Association between obesity-related biomarkers and cognitive and motor development in infants.

PubMed

Camargos, Ana Cristina R; Mendonça, Vanessa A; Oliveira, Katherine S C; de Andrade, Camila Alves; Leite, Hércules Ribeiro; da Fonseca, Sueli Ferreira; Vieira, Erica Leandro Marciano; Teixeira Júnior, Antônio Lúcio; Lacerda, Ana Cristina Rodrigues

2017-05-15

This study aimed to verify the association between obesity-related biomarkers and cognitive and motor development in infants between 6 and 24 months of age. A cross-sectional study was conducted with 50 infants and plasma levels of leptin, adiponectin, resistin, soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2), chemokines, brain-derived neurotrophic factor (BDNF), serum cortisol and redox status were measured. The Bayley-III test was utilized to evaluate cognitive and motor development, and multiple linear stepwise regression models were performed to verify the association between selected biomarkers and cognitive and motor development. A significant association was found among plasma leptin and sTNFR1 levels with cognitive composite scores, and these two independents variables together explained 37% of the variability of cognitive composite scores (p=0.001). Only plasma sTNFR1 levels were associated and explained 24% of the variability of motor composite scores (p=0.003). Plasma levels of sTNFR1 were associated with the increase in cognitive and motor development scores in infants between 6 and 24 months of age through a mechanism not directly related to excess body weight. Moreover, increase in plasma levels of leptin reduced the cognitive development in this age range. Copyright © 2017 Elsevier B.V. All rights reserved.

Early Whole Blood for Patients Requiring Massive Transfusion after Major Trauma. Addendum

DTIC Science & Technology

2013-10-01

process of determining which of the 45 patients had an abdominal CT. Measure serum (adipokines, leptin, adiponectin, and ghrelin ). We obtained serial...samples thru 24 hours on 60 patients and samples thru five days on 23 patients. We measured serum adiponectin, leptin, ghrelin , and resistin, and...adiponectin, leptin, and ghrelin were all lower in injured patients than in healthy volunteers at all timepoints. Adiponectin slowly decreased over time

High-intensity interval training acutely alters plasma adipokine levels in young overweight/obese women.

PubMed

Vardar, Selma Arzu; Karaca, Aziz; Güldiken, Sibel; Palabıyık, Orkide; Süt, Necdet; Demir, Ahmet Muzaffer

2018-05-01

The aim of this study was to investigate the plasma adipokine responses to high-intensity interval training (HIT) in overweight/obese women. Twelve women (age 21.7 ± 3.8 years) completed a 19 days of HIT comprising six session of 4-6 repeats of a Wingate test (0.065 kg load/kg). Plasma adipokine levels were measured before exercise, and at 5 and 90 min after exercise on the first and the last training days. Adiponectin was higher at 5 min than 90 min post-exercise (11.7 ± 7.3 and 10.5 ± 5.8 ng/ml; p = .01) in the first exercise day. Leptin decreased 5 min after exercise (23.6 ± 13.2 vs. baseline 27.8 ± 14.4 ng/ml; p < .01) and remained depressed following 90 min (p < .01). The changes in adiponectin and leptin concentrations were similar on the first and last exercise days. No consistent effect was found on resistin concentration. Future studies are required to disclose the functional consequences of these alterations in plasma adipokine levels.

Diabetic Foot Syndrome as a Possible Cardiovascular Marker in Diabetic Patients

PubMed Central

Tuttolomondo, Antonino; Maida, Carlo; Pinto, Antonio

2015-01-01

Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality; in fact, some authors showed a higher prevalence of major, previous and new-onset, cardiovascular, and cerebrovascular events in diabetic patients with foot ulcers than in those without these complications. This is consistent with the fact that in diabetes there is a complex interplay of several variables with inflammatory metabolic disorders and their effect on the cardiovascular system that could explain previous reports of high morbidity and mortality rates in diabetic patients with amputations. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects confirmed the pathogenetic issue of the “adipovascular” axis that may contribute to cardiovascular risk in patients with type 2 diabetes. In patients with diabetic foot, this “adipovascular axis” expression in lower plasma levels of adiponectin and higher plasma levels of IL-6 could be linked to foot ulcers pathogenesis by microvascular and inflammatory mechanisms. The purpose of this review is to focus on the immune inflammatory features of DFS and its possible role as a marker of cardiovascular risk in diabetes patients. PMID:25883983

Gut Hormones, Appetite Suppression and Cachexia in Patients with Pulmonary TB

PubMed Central

Chang, Suzanne W.; Pan, William S.; Lozano Beltran, Daniel; Oleyda Baldelomar, Lizet; Solano, Marco Antonio; Tuero, Iskra; Friedland, Jon S.; Torrico, Faustino; Gilman, Robert H.

2013-01-01

Background Cachexia is a hallmark of pulmonary tuberculosis and is associated with poor prognosis. A better understanding of the mechanisms behind such weight loss could reveal targets for therapeutic intervention. The role of appetite-regulatory hormones in tuberculosis is unknown. Methods and Findings 41 subjects with newly-diagnosed pulmonary TB (cases) were compared to 82 healthy controls. We measured appetite, body mass index (BMI), % body fat (BF), plasma peptide YY (PYY), leptin, ghrelin, and resistin for all subjects. Measurements were taken at baseline for controls and at treatment days 0, 30, and 60 for cases. Baseline appetite, BMI, and BF were lower in cases than in controls and improved during treatment. PYY, ghrelin, and resistin were significantly elevated in cases and fell during treatment. Leptin was lower in cases and rose with treatment. Appetite was inversely related to PYY in cases. High pre-treatment PYY predicted reduced gains in appetite and BF. PYY was the strongest independent predictor of appetite in cases across all time points. Conclusions Appetite-regulatory hormones are altered in TB patients. As hormones normalize during treatment, appetite is restored and nutritional status improves. High baseline PYY is an indicator of poor prognosis for improvement in appetite and nutrition during treatment. Wasting in TB patients may partly be mediated by upregulation of PYY with resulting appetite suppression. PMID:23358528

Combined Training Reduces Subclinical Inflammation in Obese Middle-Age Men.

PubMed

Brunelli, Diego T; Chacon-Mikahil, Mara Patrícia T; Gáspari, Arthur F; Lopes, Wendell Arthur; Bonganha, Valéria; Bonfante, Ivan Luiz P; Bellotto, Maria Luisa; Libardi, Cleiton Augusto; Cavaglieri, Cláudia Regina

2015-10-01

We investigated the effects of 24 wk of combined training on proinflammatory and anti-inflammatory markers associated with obesity in obese middle-age men. Thirty obese men (48.73 ± 1.04 yr; body mass index, 31.00 ± 0.29 kg·m) underwent 24 wk of combined training [CT (N = 17), aerobic (50%-85% of V˙O2peak) and resistance (6-10 maximum repetition [RM]) training)] three times per week, 60 min per session, or a control group (N = 13). Anthropometric measures, maximal strength for leg press and bench press, peak oxygen uptake (V˙O2peak) and serum concentrations of C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), IL-10, IL-15, resistin, leptin, and adiponectin were determined before (M1) and after 8 (M2), 16 (M3), and 24 (M4) wk of the experimental design. Significant increases were observed in the maximal strength for bench press and leg press, V˙O2peak, and serum concentrations of adiponectin and IL-15 for CT. Concomitantly, significant decreases were observed in percentage body fat and serum concentrations of CRP, resistin, and leptin for CT after the experimental period. Twenty-four weeks of moderate- to high-intensity CT reduced markers of subclinical inflammation associated with obesity and improved insulin resistance and functional capabilities of obese middle-age men, regardless of dietary intervention and weight loss.

Key Clinical Factors Predicting Adipokine and Oxidative Stress Marker Concentrations among Normal, Overweight and Obese Pregnant Women Using Artificial Neural Networks.

PubMed

Solis-Paredes, Mario; Estrada-Gutierrez, Guadalupe; Perichart-Perera, Otilia; Montoya-Estrada, Araceli; Guzmán-Huerta, Mario; Borboa-Olivares, Héctor; Bravo-Flores, Eyerahi; Cardona-Pérez, Arturo; Zaga-Clavellina, Veronica; Garcia-Latorre, Ethel; Gonzalez-Perez, Gabriela; Hernández-Pérez, José Alfredo; Irles, Claudine

2017-12-28

Maternal obesity has been related to adverse neonatal outcomes and fetal programming. Oxidative stress and adipokines are potential biomarkers in such pregnancies; thus, the measurement of these molecules has been considered critical. Therefore, we developed artificial neural network (ANN) models based on maternal weight status and clinical data to predict reliable maternal blood concentrations of these biomarkers at the end of pregnancy. Adipokines (adiponectin, leptin, and resistin), and DNA, lipid and protein oxidative markers (8-oxo-2'-deoxyguanosine, malondialdehyde and carbonylated proteins, respectively) were assessed in blood of normal weight, overweight and obese women in the third trimester of pregnancy. A Back-propagation algorithm was used to train ANN models with four input variables (age, pre-gestational body mass index (p-BMI), weight status and gestational age). ANN models were able to accurately predict all biomarkers with regression coefficients greater than R² = 0.945. P-BMI was the most significant variable for estimating adiponectin and carbonylated proteins concentrations (37%), while gestational age was the most relevant variable to predict resistin and malondialdehyde (34%). Age, gestational age and p-BMI had the same significance for leptin values. Finally, for 8-oxo-2'-deoxyguanosine prediction, the most significant variable was age (37%). These models become relevant to improve clinical and nutrition interventions in prenatal care.

Resistin-like molecule β regulates innate colonic function: Barrier integrity and inflammation susceptibility

PubMed Central

Hogan, Simon P.; Seidu, Luqman; Blanchard, Carine; Groschwitz, Katherine; Mishra, Anil; Karow, Margaret L.; Ahrens, Richard; Artis, David; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.; Rothenberg, Marc E.

2007-01-01

Background: Resistin-like molecule (RELM) β is a cysteine-rich cytokine expressed in the gastrointestinal tract and implicated in insulin resistance and gastrointestinal nematode immunity; however, its function primarily remains an enigma. Objective: We sought to elucidate the function of RELM-β in the gastrointestinal tract. Methods: We generated RELM-β gene-targeted mice and examined colonic epithelial barrier function, gene expression profiles, and susceptibility to acute colonic inflammation. Results: We show that RELM-β is constitutively expressed in the colon by goblet cells and enterocytes and has a role in homeostasis, as assessed by alterations in colon mRNA transcripts and epithelial barrier function in the absence of RELM-β. Using acute colonic inflammatory models, we demonstrate that RELM-β has a central role in the regulation of susceptibility to colonic inflammation. Mechanistic studies identify that RELM-β regulates expression of type III regenerating gene (REG) (REG3β and γ), molecules known to influence nuclear factor κB signaling. Conclusions: These data define a critical role for RELM-β in the maintenance of colonic barrier function and gastrointestinal innate immunity. Clinical implications: These findings identify RELM-β as an important molecule in homeostatic gastrointestinal function and colonic inflammation, and as such, these results have implications for a variety of human inflammatory gastrointestinal conditions, including allergic gastroenteropathies. PMID:16815164

Effects of regular exercise on obesity and type 2 diabete mellitus in Korean children: improvements glycemic control and serum adipokines level

PubMed Central

Lee, Sung Soo; Kang, Sunghwun

2015-01-01

[Purpose] The aim of the study was to clarify the effects of regular exercise on lipid profiles and serum adipokines in Korean children. [Subjects and Methods] Subjects were divided into controls (n=10), children who were obese (n=10), and children with type 2 diabetes mellitus (n=10). Maximal oxygen uptake (VO2max), body composition, lipid profiles, glucagon, insulin and adipokines (leptin, resistin, visfatin and retinol binding protein 4) were measured before to and after a 12-week exercise program. [Results] Body weight, body mass index, and percentage body fat were significantly higher in the obese and diabetes groups compared with the control group. Total cholesterol, triglycerides, low-density lipoprotein cholesterol and glycemic control levels were significantly decreased after the exercise program in the obese and diabetes groups, while high-density lipoprotein cholesterol levels were significantly increased. Adipokines were higher in the obese and diabetes groups compared with the control group prior to the exercise program, and were significantly lower following completion. [Conclusion] These results suggest that regular exercise has positive effects on obesity and type 2 diabetes mellitus in Korean children by improving glycemic control and reducing body weight, thereby lowering cardiovascular risk factors and adipokine levels. PMID:26180345

Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome

PubMed Central

Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

2016-01-01

The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

Biomarkers and insulin sensitivity in women with Polycystic Ovary Syndrome: Characteristics and predictive capacity.

PubMed

Cassar, Samantha; Teede, Helena J; Harrison, Cheryce L; Joham, Anju E; Moran, Lisa J; Stepto, Nigel K

2015-07-01

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic complications. Metabolic biomarkers with roles in obesity, glycaemic control and lipid metabolism are potentially relevant in PCOS. The aim was to investigate metabolic biomarkers in lean and overweight women with and without PCOS and to determine whether any biomarker was able to predict insulin resistance in PCOS. Cross-sectional study. Eighty-four women (22 overweight and 22 lean women with PCOS, 18 overweight and 22 lean women without PCOS) were recruited from the community and categorized based on PCOS and BMI status. Primary outcomes were metabolic biomarkers [ghrelin, resistin, visfatin, glucagon-like peptide-1 (GLP-1), leptin, plasminogen activator inhibitor -1 (PAI-1), glucose-dependent insulinotropic polypeptide (GIP) and C-Peptide] measured using the Bio-Plex Pro Diabetes assay and insulin sensitivity as assessed by glucose infusion rate on euglycaemic-hyperinsulinaemic clamp. The biomarkers C-peptide, leptin, ghrelin and visfatin were different between overweight and lean women, irrespective of PCOS status. The concentration of circulating biomarkers did not differ between women with PCOS diagnosed by the Rotterdam criteria or National Institute of Health criteria. PAI-1 was the only biomarker that significantly predicted insulin resistance in both control women (P = 0.04) and women with PCOS (P = 0.01). Biomarkers associated with metabolic diseases appear more strongly associated with obesity rather than PCOS status. PAI-1 may also be a novel independent biomarker and predictor of insulin resistance in women with and without PCOS. © 2014 John Wiley & Sons Ltd.

Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS.

PubMed

Nielsen, M J; Lehmann, J; Leeming, D J; Schierwagen, R; Klein, S; Jansen, C; Strassburg, C P; Bendtsen, F; Møller, S; Sauerbruch, T; Karsdal, M A; Krag, A; Trebicka, J

2015-11-01

Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhotic patients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS). We analyzed portal and hepatic venous samples of 110 cirrhotic patients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated. Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients. This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD.

Circulating DNA and its methylation level in inflammatory bowel disease and related colon cancer.

PubMed

Bai, Xuming; Zhu, Yaqun; Pu, Wangyang; Xiao, Li; Li, Kai; Xing, Chungen; Jin, Yong

2015-01-01

Both of chronic inflammation and abnormal immune in inflammatory bowel disease can induce colon cancer. Previous research showed that cell apoptosis and necrosis become the main source of circulating DNA in the peripheral blood during tumorigenesis that reduced along with methylation degree. However, its role in the process of colitis transforming to colon cancer is not clarified. Drinking 3% DSS was used to establish colitis model, while 3% dextran sodium sulfate (DSS) combined with azo oxidation methane (AOM) intraperitoneal injection was applied to establish colitis related colon cancer model. Circulating DNA and its methylation level in peripheral blood were tested. Morphology observation, HE staining, and p53 and β-catenin expression detection confirmed that drinking 3% DSS and 3% DSS combined with AOM intraperitoneal injection can successfully establish colitis and colitis associated colorectal cancer models. Circulating DNA level in colitis and colon cancer mice increased by gradient compared with control, while significant difference was observed between each other. Circulating DNA methylation level decreased obviously in colitis and colon cancer, and significant difference was observed between each other. Abnormal protein expression, circulating DNA and its methylation level in ulcerative colitis associated colorectal tissues change in gradient, suggesting that circulating DNA and its methylation level can be treated as new markers for colitis cancer transformation that has certain significance to explore the mechanism of human ulcerative colitis canceration.

Cardiovascular disease delay in centenarian offspring: role of heat shock proteins.

PubMed

Terry, Dellara F; McCormick, Maegan; Andersen, Stacy; Pennington, Jaemi; Schoenhofen, Emily; Palaima, Elizabeth; Bausero, Maria; Ogawa, Kishiko; Perls, Thomas T; Asea, Alexzander

2004-06-01

Cardiovascular disease is a major cause of morbidity and mortality of older Americans. We have demonstrated recently that centenarian offspring, when compared with age-matched controls, avoid and/or delay cardiovascular disease and cardiovascular risk factors. Given recent evidence suggesting that higher circulating levels of HSP70 predict the future development of cardiovascular disease in established hypertensives and a recent study demonstrating a decrease in HSP60 and HSP70 with advancing age, we hypothesized that HSP70 levels would be lower in centenarian offspring compared with controls. The circulating serum concentration of HSP70 in 20 centenarian offspring and 9 spousal controls was analyzed using a modified HSP70 ELISA method. Centenarian offspring showed approximately 10-fold lower levels of circulating serum HSP70 compared with spousal controls (P <.001). The exact biological significance of the extremely low levels of circulating serum HSP70 observed in centenarian offspring thus far is not clear. However, circulating HSP has been shown to correlate in diseases or disorders in which there is destruction or damage to target tissues or organs, including cardiovascular diseases and numerous autoimmune disorders. We hypothesize that low levels of circulating serum HSP70 may be an indicator of a healthy state and point to longevity of the host; therefore, our results suggest that levels of circulating serum HSP70 may be a marker for longevity.

Cardiovascular Disease Delay in Centenarian Offspring: Role of Heat Shock Proteins

PubMed Central

TERRY, DELLARA F.; McCORMICK, MAEGAN; ANDERSEN, STACY; PENNINGTON, JAEMI; SCHOENHOFEN, EMILY; PALAIMA, ELIZABETH; BAUSERO, MARIA; OGAWA, KISHIKO; PERLS, THOMAS T.; ASEA, ALEXZANDER

2006-01-01

Cardiovascular disease is a major cause of morbidity and mortality of older Americans. We have demonstrated recently that centenarian offspring, when compared with age-matched controls, avoid and/or delay cardiovascular disease and cardiovascular risk factors. Given recent evidence suggesting that higher circulating levels of HSP70 predict the future development of cardiovascular disease in established hypertensives and a recent study demonstrating a decrease in HSP60 and HSP70 with advancing age, we hypothesized that HSP70 levels would be lower in centenarian offspring compared with controls. The circulating serum concentration of HSP70 in 20 centenarian offspring and 9 spousal controls was analyzed using a modified HSP70 ELISA method. Centenarian offspring showed approximately 10-fold lower levels of circulating serum HSP70 compared with spousal controls (P < .001). The exact biological significance of the extremely low levels of circulating serum HSP70 observed in centenarian offspring thus far is not clear. However, circulating HSP has been shown to correlate in diseases or disorders in which there is destruction or damage to target tissues or organs, including cardiovascular diseases and numerous autoimmune disorders. We hypothesize that low levels of circulating serum HSP70 may be an indicator of a healthy state and point to longevity of the host; therefore, our results suggest that levels of circulating serum HSP70 may be a marker for longevity. PMID:15247074

Circulating testosterone and inhibin levels at different ages in the male beluga (Delphinapterus leucas).

PubMed

Katsumata, Etsuko; Ueda, Yoko; Arai, Kazutoshi; Katsumata, Hiroshi; Kishimoto, Miori; Watanabe, Gen; Taya, Kazuyoshi

2012-03-01

This study is the first report on circulating testosterone and inhibin levels in a species of whales, the beluga. Circulating testosterone and immunoreactive (ir-) inhibin levels in two captive male belugas ("Nack", originally from Canada and "Duke", from the Okhotsk Sea) were measured every month for 9 years between 1995 and 2003. Assuming that clearly increased testosterone levels in the circulation indicates that the belugas had reached sexual maturity, at the ages of 10 ("Nack") and 11 years old ("Duke"). Their testosterone levels before the significant increase (pre-pubertal) were 0.42 ± 0.07 ng/ml (n=18) and 0.35 ± 0.10 ng/ml (n=18) and, those of after the increase (maturity) were 1.65 ± 0.14 ng/m l (n=74) and 2.06 ± 0.14 ng/ml (n=74). Circulating ir-inhibin levels before sexual maturity were 0.78 ± 0.04 ng/ml (n=18) and 0.64 ± 0.04 ng/ml (n=15) and, after sexual maturity were 0.52 ± 0.02 ng/ml (n=56) and 0.43 ± 0.02 ng/ml (n=67). Seasonal changes were observed in the testosterone levels after sexual maturity and the levels increased during March and April in Canadian origin "Nack", and peaked in February in Okhotsk origin "Duke". Circulating ir-inhibin level gradually decreased as they aged. A negative correlation between the circulating testosterone and ir-inhibin was observed. No seasonal changes were observed in the ir-inhibin levels after sexual maturity. These data will surely correspond to clarification of endocrinology and the successful reproduction of the beluga.

Red raspberry (Rubus idaeus L.) intake decreases oxidative stress in obese diabetic (db/db) mice.

PubMed

Noratto, Giuliana D; Chew, Boon P; Atienza, Liezl M

2017-07-15

Red raspberry fruit intake was investigated on obese diabetic (db/db) mice for 8weeks. Animals fed isocaloric diets (5.3% freeze-dried raspberry, or control) were assessed for obesity-diabetes-disease risk biomarkers. Results showed that raspberry intake improved antioxidant status and lessened plasma interleukin (IL)-6 (0.3-fold of control, p<0.1); most likely through enhancing glutathione peroxidase (GPx) activity in liver (4.3-fold of control), and in blood (2.1-fold of control). Other disease-risk biomarkers were similar between groups (p>0.05). Plasma levels of total cholesterol (T-CHL), low density lipoprotein-cholesterol (LDL-CHL), and resistin were higher in the raspberry group. Overall, the enhanced detoxifying cell defenses exerted by raspberry intake might be due to its polyphenolics and fibre. This study demonstrates in vivo that raspberry intake, at a dose that can be achieved by human consumption, might protect against diabetes-induced oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters: associations with HPA-axis hyperactivity

PubMed Central

Lindqvist, D; Fernström, J; Grudet, C; Ljunggren, L; Träskman-Bendz, L; Ohlsson, L; Westrin, Å

2016-01-01

Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and would be associated with hypothalamic–pituitary–adrenal (HPA)-axis hyperactivity. Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared with healthy controls at different time points (pre- and post-DST; all P-values<2.98E−12, Cohen's d ranging from 2.55 to 4.01). Pre-DST plasma levels of mtDNA were positively correlated with post-DST cortisol levels (rho=0.49, P<0.003). Suicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with an increased cellular or mitochondrial damage. The specific cells and tissues contributing to plasma levels of free-circulating mtDNA are not known, as is the specificity of this finding for suicide attempters. Future studies are needed in order to better understand the relevance of increased free-circulating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression. PMID:27922635

Metabolites associated with circulating interleukin-6 in older adults

USDA-ARS?s Scientific Manuscript database

Background: Circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) levels are elevated in older adults, but mechanisms are unclear. In the current study, we used an untargeted metabolomic approach to develop an improved understanding about mechanisms related to circulating IL-6 in ...

The beneficial effects of combined grape pomace and omija fruit extracts on hyperglycemia, adiposity and hepatic steatosis in db/db mice: a comparison with major index compounds.

PubMed

Cho, Su-Jung; Park, Hae-Jin; Jung, Un Ju; Kim, Hye-Jin; Moon, Byoung Seok; Choi, Myung-Sook

2014-09-30

This study investigated the effects of combined grape pomace and omija fruit extracts (GO) on diabetes-related metabolic changes in type 2 diabetic db/db mice. The effects of GO were compared with those of a resveratrol and schizandrin mixture (RS), which is a mixture of major components of GO. Mice were fed a normal diet with RS (0.005% resveratrol and 0.02% schizandrin in diet, w/w) or GO (0.3% grape pomace ethanol extract and 0.05% omija fruit ethanol extract in diet, w/w) for seven weeks. RS and GO not only lowered the levels of blood and plasma glucose, HbA1c, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) with a simultaneous decrease in hepatic gluconeogenic enzymes activities and adiposity, but also improved preservation of the pancreatic β-cells. Plasma leptin and resistin levels were lower while the plasma adiponectin level was higher in the RS and GO groups than in the control group. Especially, GO increased hepatic glucokinase activity and gene expression and improved hepatic steatosis by elevating fatty acid oxidation compared to RS. These findings suggest that GO ameliorates hyperglycemia, adiposity and hepatic steatosis in type 2 diabetic mice.

Can hormones contained in mothers' milk account for the beneficial effect of breast-feeding on obesity in children?

PubMed

Savino, Francesco; Fissore, Maria F; Liguori, Stefania A; Oggero, Roberto

2009-12-01

Nutrition and growth during infancy are an emerging issue because of their potential link to metabolic health disorders in later life. Moreover, prolonged breast-feeding appears to be associated with a lower risk of obesity than formula feeding. Human milk is a source of various hormones and growth factors, namely adipokines (leptin and adiponectin), ghrelin, resistin and obestatin, which are involved in food intake regulation and energy balance. These compounds are either not found in commercial milk formulas or their presence is still controversial. Diet-related differences during infancy in serum levels of factors involved in energy metabolism might explain anthropometric differences and also differences in dietary habits between breast-fed (BF) and formula-fed (FF) infants later in life, and may thus have long-term health consequences. In this context, the recent finding of higher leptin levels and lower ghrelin levels in BF than in FF infants suggests that differences in hormonal values together with different protein intake could account for the differences in growth between BF and FF infants both during infancy and later in life. In this review, we examine the data related to hormones contained in mothers' milk and their potential protective effect on subsequent obesity and metabolic-related disorders.

Changes in biomarkers during a six-month oral immunotherapy intervention for cow's milk allergy.

PubMed

Salmivesi, Susanna; Paassilta, Marita; Huhtala, Heini; Nieminen, Riina; Moilanen, Eeva; Korppi, Matti

2016-11-01

Oral immunotherapy (OIT) is a promising but still experimental method to treat children with cow's milk (CM) allergy (CMA). We evaluated changes in allergic, immunological and inflammatory parameters, which happened during the six-month OIT for CMA. We treated 28 school-aged children with CMA using OIT with a double-blind placebo-controlled design. After the controlled study finished, the placebo group was treated with the same but open-label OIT protocol. Sixteen immune variables were tested before and after the six-month OIT. Before OIT, the median serum CM-specific immunoglobulin (Ig) E was 18.0kIU/L in the intervention group and 9.4kIU/L in the placebo group (p = 0.46). At six months, interleukin (IL)-6 and IL-10 were significantly higher in the intervention group. When the changes during the blinded and open OIT were analysed together for both groups, blood eosinophils and serum total IgE decreased and milk-specific IgG and IgG4, serum IL-4 and IL-6, and serum leptin and resistin increased significantly. Preliminary evidence was found that markers of allergy such as blood eosinophils and serum IgE decreased and milk-specific IgG and IgG4 increased during OIT. Adipokines, leptin and resistin, which functionally are cytokines linked to Th1-type response, increased during OIT. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Expression of adipokines in osteoarthritis osteophytes and their effect on osteoblasts.

PubMed

Junker, Susann; Frommer, Klaus W; Krumbholz, Grit; Tsiklauri, Lali; Gerstberger, Rüdiger; Rehart, Stefan; Steinmeyer, Jürgen; Rickert, Markus; Wenisch, Sabine; Schett, Georg; Müller-Ladner, Ulf; Neumann, Elena

2017-10-01

Osteophyte formation in osteoarthritis (OA) is mediated by increased osteoblast activity, which is -in turn- regulated by the Wnt signaling pathway. Obesity is regarded a risk factor in OA, yet little is known about the interaction between adipose tissue-derived factors, the adipokines, and bone formation, although adipokines are associated with the pathogenesis of OA. Therefore, the effect of adipokines on bone and cartilage forming cells and osteophyte development was analyzed. Human OA osteophytes were histologically characterized and adipokine expression was evaluated by immunohistochemistry. Osteoblasts and chondrocytes were isolated from OA tissue and stimulated with adiponectin, resistin, or visfatin. Cytokine and osteoblast/chondrocyte markers were quantified and activation of Wnt and p38 MAPK signaling was analyzed. Adiponectin, resistin, and visfatin were expressed in OA osteophytes by various articular cell types. Stimulation of OA osteoblasts with adiponectin and of OA chondrocytes with visfatin led to an increased release of proinflammatory mediators but not to osteoblast differentiation or activation. Additionally, visfatin increased matrix degrading factors in chondrocytes. Wnt signaling was not altered by adipokines, but adiponectin induced p38 MAPK signaling in osteoblasts. Adipokines are present in OA osteophytes, and adiponectin and visfatin increase the release of proinflammatory mediators by osteoblasts and chondrocytes. The effects of adiponectin were mediated by p38 MAPK but not Wnt signaling in osteoblasts. Therefore, the results support the idea that adipokines do not directly influence osteophyte development but the proinflammatory conditions in OA. Copyright © 2016 Elsevier B.V. All rights reserved.

Vildagliptin compared to glimepiride on post-prandial lipemia and on insulin resistance in type 2 diabetic patients.

PubMed

Derosa, Giuseppe; Bonaventura, Aldo; Bianchi, Lucio; Romano, Davide; Fogari, Elena; D'Angelo, Angela; Maffioli, Pamela

2014-07-01

To evaluate the effects of vildagliptin compared to glimepiride on glycemic control, insulin resistance and post-prandial lipemia. 167 type 2 diabetic patients, not adequately controlled by metformin, were randomized to vildagliptin 50 mg twice a day or glimepiride 2 mg three times a day for 6 months, in a double blind, randomized clinical trial. We evaluated: body mass index (BMI), glycemic control, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), fasting plasma proinsulin (FPPr), glucagon, lipid profile, resistin, retinol binding protein-4 (RBP-4), visfatin and vaspin. Furthermore, at the randomization and at the end of the study all patients underwent an euglycemic hyperinsulinemic clamp to evaluate M value and an oral fat load. Despite a similar decrease of glycated hemoglobin, there were an increase of body weight with glimepiride + metformin and a decrease with vildagliptin + metformin. Fasting plasma insulin increased with glimepiride + metformin, while it did not change with vildagliptin + metformin. Vildagliptin + metformin improved lipid profile. Regarding insulin sensitivity, vildagliptin + metformin increased M value. Resistin, RBP-4, vaspin and visfatin were decreased by vildagliptin + metformin, but in group to group comparison, only vaspin reduction resulted statistically significant. Vildagliptin + metformin reduced post-prandial lipemia and insulinemia compared to glimepiride + metformin. Vildagliptin, in addition to metformin, was more effective than glimepiride + metformin in reducing insulin resistance and post-prandial lipemia. Copyright © 2014 Elsevier Inc. All rights reserved.

Tuberculosis-diabetes co-morbidity is characterized by heightened systemic levels of circulating angiogenic factors

PubMed Central

Kumar, Nathella Pavan; Moideen, Kadar; Sivakumar, Shanmugam; Menon, Pradeep A; Viswanathan, Vijay; Kornfeld, Hardy; Babu, Subash

2016-01-01

Background Tuberculosis-diabetes co-morbidity (TB-DM) is characterized by increased inflammation with elevated circulating levels of inflammatory cytokines and other factors. Circulating angiogenic factors are intricately involved in the angiogenesis-inflammation nexus. Methods To study the association of angiogenic factors with TB-DM, we examined the systemic levels of VEGF-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2, VEGF-R3 in individuals with either TB-DM (n=44) or TB alone (n=44). Results Circulating levels of VEGF-A, C, D, R1, R2 and R3 were significantly higher in TB-DM compared to TB individuals. Moreover, the levels of VEGF-A, C, R2 and/or R3 were significantly higher in TB-DM with bilateral or cavitary disease or with hemoptysis, suggesing an association with both disease severity and adverse clinical presentation. The levels of these factors also exhibited a significant positive relationship with bacterial burdens and HbA1c levels. In addition, VEGF-A, C and R2 levels were signifantly higher (at 2 months of treatment) in culture positive compared to culture negative TB-DM individuals. Finally, the circulating levels of VEGF-A, C, D, R1, R2 and R3 were significantly reduced following successful chemotherapy at 6 months. Conclusion Our data demonstrate that TB-DM is associated with heightened levels of circulating angiogenic factors, possibly reflecting both dysregulated angiogenesis and exaggerated inflammation. PMID:27717783

Association of Circulating Orexin-A Level With Metabolic Risk Factors in North Indian Pre Menopausal Women.

PubMed

Gupta, Vani; Mishra, Sameeksha; Kumar, Sandeep; Mishra, Supriya

2015-01-01

The present study was designed to investigate the association between circulating Orexin-A level with metabolic risk factors in North Indian adult women. 342 women were enrolled for the case-control study, 172 women were with metabolic syndrome (mets) and 170 healthy control women were without metabolic syndrome, (womets) according to (NCEP ATP III criteria). Circulating Orexin-A level was determined by enzyme-linked immunosorbent assay. Observations indicated low levels of orexin-A (26.06 ± 6.09 ng/ml) in women with mets and other metabolic risk factors compared to women without metabolic syndrome (36.50 ± 10.42 ng/ml). Further, in women with metabolic syndrome, circulating Orexin A was significantly associated with waist circumference, triglyceride (negative correlation) and hyperdensity lipoprotein (positive correlation). Our study shows that circulating Orexin A was found to be significantly associated with hyperlipidemia, obesity and obesity-related disorders in North Indian premenopausal women.

Effect of long-term dietary sphingomyelin supplementation on atherosclerosis in mice

PubMed Central

Chung, Rosanna W. S.; Wang, Zeneng; Bursill, Christina A.; Wu, Ben J.; Barter, Philip J.

2017-01-01

Sphingomyelin (SM) levels in the circulation correlate positively with atherosclerosis burden. SM is a ubiquitous component of human diets, but it is unclear if dietary SM increases circulating SM levels. Dietary choline increases atherosclerosis by raising circulating trimethylamine N-oxide (TMAO) levels in mice and humans. As SM has a choline head group, we ask in this study if dietary SM accelerates atherosclerotic lesion development by increasing circulating SM and TMAO levels. Three studies were performed: (Study 1) C57BL/6 mice were maintained on a high fat diet with or without SM supplementation for 4 weeks prior to quantification of serum TMAO and SM levels; (Study 2) atherosclerosis was studied in apoE-/- mice after 16 weeks of a high fat diet without or with SM supplementation and (Study 3) apoE-/- mice were maintained on a chow diet for 19 weeks without or with SM supplementation and antibiotic treatment prior to quantification of atherosclerotic lesions and serum TMAO and SM levels. SM consumption did not increase circulating SM levels or atherosclerosis in high fat-fed apoE-/- mice. Serum TMAO levels in C57BL/6 mice were low and had no effect atherosclerosis lesion development. Dietary SM supplementation significantly reduced atherosclerotic lesion area in the aortic arch of chow-fed apoE-/- mice. This study establishes that dietary SM does not affect circulating SM levels or increase atherosclerosis in high fat-fed apoE-/- mice, but it is anti-atherogenic in chow-fed apoE-/- mice. PMID:29240800

Mendelian Randomization Studies Do Not Support a Role for Raised Circulating Triglyceride Levels Influencing Type 2 Diabetes, Glucose Levels, or Insulin Resistance

PubMed Central

De Silva, N. Maneka G.; Freathy, Rachel M.; Palmer, Tom M.; Donnelly, Louise A.; Luan, Jian'an; Gaunt, Tom; Langenberg, Claudia; Weedon, Michael N.; Shields, Beverley; Knight, Beatrice A.; Ward, Kirsten J.; Sandhu, Manjinder S.; Harbord, Roger M.; McCarthy, Mark I.; Smith, George Davey; Ebrahim, Shah; Hattersley, Andrew T.; Wareham, Nicholas; Lawlor, Debbie A.; Morris, Andrew D.; Palmer, Colin N.A.; Frayling, Timothy M.

2011-01-01

OBJECTIVE The causal nature of associations between circulating triglycerides, insulin resistance, and type 2 diabetes is unclear. We aimed to use Mendelian randomization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance. RESEARCH DESIGN AND METHODS We tested 10 common genetic variants robustly associated with circulating triglyceride levels against the type 2 diabetes status in 5,637 case and 6,860 control subjects and four continuous outcomes (reflecting glycemia and hepatic insulin resistance) in 8,271 nondiabetic individuals from four studies. RESULTS Individuals carrying greater numbers of triglyceride-raising alleles had increased circulating triglyceride levels (SD 0.59 [95% CI 0.52–0.65] difference between the 20% of individuals with the most alleles and the 20% with the fewest alleles). There was no evidence that the carriers of greater numbers of triglyceride-raising alleles were at increased risk of type 2 diabetes (per weighted allele odds ratio [OR] 0.99 [95% CI 0.97–1.01]; P = 0.26). In nondiabetic individuals, there was no evidence that carriers of greater numbers of triglyceride-raising alleles had increased fasting insulin levels (SD 0.00 per weighted allele [95% CI −0.01 to 0.02]; P = 0.72) or increased fasting glucose levels (0.00 [−0.01 to 0.01]; P = 0.88). Instrumental variable analyses confirmed that genetically raised circulating triglyceride levels were not associated with increased diabetes risk, fasting glucose, or fasting insulin and, for diabetes, showed a trend toward a protective association (OR per 1-SD increase in log10 triglycerides: 0.61 [95% CI 0.45–0.83]; P = 0.002). CONCLUSIONS Genetically raised circulating triglyceride levels do not increase the risk of type 2 diabetes or raise fasting glucose or fasting insulin levels in nondiabetic individuals. One explanation for our results is that raised circulating triglycerides are predominantly secondary to the diabetes disease process rather than causal. PMID:21282362

Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.

PubMed

De Silva, N Maneka G; Freathy, Rachel M; Palmer, Tom M; Donnelly, Louise A; Luan, Jian'an; Gaunt, Tom; Langenberg, Claudia; Weedon, Michael N; Shields, Beverley; Knight, Beatrice A; Ward, Kirsten J; Sandhu, Manjinder S; Harbord, Roger M; McCarthy, Mark I; Smith, George Davey; Ebrahim, Shah; Hattersley, Andrew T; Wareham, Nicholas; Lawlor, Debbie A; Morris, Andrew D; Palmer, Colin N A; Frayling, Timothy M

2011-03-01

The causal nature of associations between circulating triglycerides, insulin resistance, and type 2 diabetes is unclear. We aimed to use Mendelian randomization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance. We tested 10 common genetic variants robustly associated with circulating triglyceride levels against the type 2 diabetes status in 5,637 case and 6,860 control subjects and four continuous outcomes (reflecting glycemia and hepatic insulin resistance) in 8,271 nondiabetic individuals from four studies. Individuals carrying greater numbers of triglyceride-raising alleles had increased circulating triglyceride levels (SD 0.59 [95% CI 0.52-0.65] difference between the 20% of individuals with the most alleles and the 20% with the fewest alleles). There was no evidence that the carriers of greater numbers of triglyceride-raising alleles were at increased risk of type 2 diabetes (per weighted allele odds ratio [OR] 0.99 [95% CI 0.97-1.01]; P = 0.26). In nondiabetic individuals, there was no evidence that carriers of greater numbers of triglyceride-raising alleles had increased fasting insulin levels (SD 0.00 per weighted allele [95% CI -0.01 to 0.02]; P = 0.72) or increased fasting glucose levels (0.00 [-0.01 to 0.01]; P = 0.88). Instrumental variable analyses confirmed that genetically raised circulating triglyceride levels were not associated with increased diabetes risk, fasting glucose, or fasting insulin and, for diabetes, showed a trend toward a protective association (OR per 1-SD increase in log(10) triglycerides: 0.61 [95% CI 0.45-0.83]; P = 0.002). Genetically raised circulating triglyceride levels do not increase the risk of type 2 diabetes or raise fasting glucose or fasting insulin levels in nondiabetic individuals. One explanation for our results is that raised circulating triglycerides are predominantly secondary to the diabetes disease process rather than causal.

Lower Circulating Irisin Level in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis.

PubMed

Du, X-L; Jiang, W-X; Lv, Z-T

2016-09-01

Studies measuring circulating irisin levels in patients with insulin resistance conditions such as type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) have achieved controversial results. Our systematic review and meta-analysis aim to assess the circulating irisin levels in patients with diabetes mellitus. Pubmed, EMBASE, CENTRAL, ISI Web of Science, and CNKI were searched to identify observational studies of circulating irisin levels in patients with diabetes mellitus. Two reviewers independently searched the databases and screened studies according to the inclusion criteria. Data were extracted using a standardized collection form. Meta-analysis was performed. A total of 23 studies (17 cross-sectional and 6 case control) involving 1 745 diabetic patients and 1 337 non-diabetic controls were selected. Compared with non-diabetic controls, circulating irisin concentrations were significantly lower in patients with T2DM (SMD -1.72, 95%CI -2.49, -0.96; p<0.00001) and GDM (SMD -0.76, 95CI -1.31, -0.22; p=0.006), but 30 percent higher in patients with T1DM. Circulating irisin in Asian diabetic patients decreased more than European patients. The findings of our current review suggest that circulating irisin levels were decreased in patients with T2DM and GDM, but not in patients with T1DM. © Georg Thieme Verlag KG Stuttgart · New York.

The effect of circulating nitric oxide level on axial bone mineral density in postmenopausal Turkish women with rheumatoid arthritis: A preliminary report.

PubMed

Sahin, Gunsah; Guler, Hayal; Sezgin, Melek; Incel, Nurgul Arinci; Polat, Gurbuz

2006-07-01

The aim is to investigate the differences in the circulating nitric oxide (NO) levels of rheumatoid arthritis (RA) patients, healthy controls and osteoporotic (OP) patients. We also examined whether the circulating NO levels may be correlated with bone mineral density (BMD) in RA patients. Forty-five patients with RA, 30 healthy women and 30 osteoporotic patients were recruited from the outpatient clinic. All the subjects were female and postmenopausal. Serum NO levels were measured (Nitrite/Nitrate, calorimetric method 1746081, Roche diagnostics, Mannheim, Germany) and BMD was measured at the spine and hip using dual energy X-Ray absorbtiometry (DEXA, Norland XR-46). Height and weight were measured and body mass index was calculated. Circulating NO levels were significantly higher in RA patients than other groups. Moreover, the RA group showed significantly higher BMD at lumbar spine and femoral neck regions compared to osteoporotic patients. However, the RA group showed significantly lower BMD at all sites than the controls. There was no correlation between circulating NO levels and BMD in all groups. We suggest that, unlike postmenopausal osteoporosis, inflammation induced osteoporosis is associated with RA is characterised by relatively preserved bone mass at the axial bone regions, and circulating NO levels as a parameter or determinant of inflammation are not correlated with axial BMD in RA patients.

Circulating levels of dickkopf-1, osteoprotegerin and sclerostin are higher in old compared with young men and women and positively associated with whole-body bone mineral density in older adults.

PubMed

Coulson, J; Bagley, L; Barnouin, Y; Bradburn, S; Butler-Browne, G; Gapeyeva, H; Hogrel, J-Y; Maden-Wilkinson, T; Maier, A B; Meskers, C; Murgatroyd, C; Narici, M; Pääsuke, M; Sassano, L; Sipilä, S; Al-Shanti, N; Stenroth, L; Jones, D A; McPhee, J S

2017-09-01

Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during 'healthy' ageing. WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18-30 years; 53% female). WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r values ranging from 0.174 to 0.254, all p < 0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.

The effects of conventional extracorporeal circulation versus miniaturized extracorporeal circulation on microcirculation during cardiopulmonary bypass-assisted coronary artery bypass graft surgery.

PubMed

Yuruk, Koray; Bezemer, Rick; Euser, Mariska; Milstein, Dan M J; de Geus, Hilde H R; Scholten, Evert W; de Mol, Bas A J M; Ince, Can

2012-09-01

OBJECTIVES To reduce the complications associated with cardiopulmonary bypass (CPB) during cardiac surgery, many modifications have been made to conventional extracorporeal circulation systems. This trend has led to the development of miniaturized extracorporeal circulation systems. Cardiac surgery using conventional extracorporeal circulation systems has been associated with significantly reduced microcirculatory perfusion, but it remains unknown whether this could be prevented by an mECC system. Here, we aimed to test the hypothesis that microcirculatory perfusion decreases with the use of a conventional extracorporeal circulation system and would be preserved with the use of an miniaturized extracorporeal circulation system. METHODS Microcirculatory density and perfusion were assessed using sublingual side stream dark-field imaging in patients undergoing on-pump coronary artery bypass graft (CABG) surgery before, during and after the use of either a conventional extracorporeal circulation system (n = 10) or a miniaturized extracorporeal circulation system (n = 10). In addition, plasma neutrophil gelatinase-associated lipocalin and creatinine levels and creatinine clearance were assessed up to 5 days post-surgery to monitor renal function. RESULTS At the end of the CPB, one patient in the miniaturized extracorporeal circulation-treated group and five patients in the conventional extracorporeal circulation-treated group received one bag of packed red blood cells (300 ml). During the CPB, the haematocrit and haemoglobin levels were slightly higher in the miniaturized extracorporeal circulation-treated patients compared with the conventional extracorporeal circulation-treated patients (27.7 ± 3.3 vs 24.7 ± 2.0%; P = 0.03; and 6.42 ± 0.75 vs 5.41 ± 0.64 mmol/l; P < 0.01). The density of perfused vessels with a diameter <25 µm (i.e. perfused vessel density) decreased slightly in the conventional extracorporeal circulation-treated group from 16.4 ± 3.8 to 12.8 ± 3.3 mm/mm(2) (P < 0.01) and remained stable in the miniaturized extracorporeal circulation-treated group (16.3 ± 2.7 and 15.2 ± 2.9 mm/mm(2) before and during the pump, respectively). Plasma neutrophil gelatinase-associated lipocalin levels were increased following the use of extracorporeal circulation in both groups, and no differences were observed between the groups. Plasma creatinine levels and creatinine clearance were not affected by CABG surgery or CPB. CONCLUSIONS The results from this relatively small study suggest that the use of the miniaturized extracorporeal circulation system is associated with a statistically significant (but clinically insignificant) reduction in haemodilution and microcirculatory hypoperfusion compared with the use of the conventional extracorporeal circulation system.

Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

NASA Astrophysics Data System (ADS)

Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

2013-06-01

Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

High Levels of Peripheral Blood Circulating Plasma Cells as a Specific Risk Factor for Progression of Smoldering Multiple Myeloma

PubMed Central

Bianchi, Giada; Kyle, Robert A.; Larson, Dirk R.; Witzig, Thomas E.; Kumar, Shaji; Dispenzieri, Angela; Morice, William G.; Rajkumar, S. Vincent

2012-01-01

Smoldering multiple myeloma (SMM) carries a 50% risk of progression to multiple myeloma (MM) or related malignancy within the first 5 years following diagnosis. The goal of this study was to determine if high levels of circulating plasma cells (PCs) are predictive of SMM transformation within the first 2–3 years from diagnosis. Ninety-one patients diagnosed with SMM at Mayo Clinic from January 1994 through January 2007 who had testing for circulating PCs using an immunofluorescent assay and adequate follow up to ascertain disease progression, were studied. High level of circulating PCs was defined as absolute peripheral blood PCs >5000 ×106/L and/or > 5% cytoplasmic immunoglobulin (Ig) positive PCs per 100 peripheral blood mononuclear cells. Patients with high circulating PCs (14 of 91 patients, 15%) were significantly more likely to progress to active disease within 2 years compared with patients without high circulating PCs, 71% versus 25%, respectively, P=0.001. Corresponding rates for progression within 3 years were 86% versus 35%, respectively, P<0.001. Overall survival (OS) after both SMM diagnosis and MM diagnosis was also significantly different. High levels of circulating PCs identify SMM patients with an elevated risk of progression within the first 2 to 3 years following diagnosis. PMID:22902364

Association of 1-y changes in diet pattern with cardiovascular disease risk factors and adipokines: results from the 1-y randomized Oslo Diet and Exercise Study.

PubMed

Jacobs, David R; Sluik, Diewertje; Rokling-Andersen, Merethe H; Anderssen, Sigmund A; Drevon, Christian A

2009-02-01

We hypothesized that favorable changes in dietary patterns would lead to a reduction in body size and an improvement in metabolic status. The objective was to study changes in diet patterns relative to changes in body size, blood pressure, and circulating concentrations of lipids, glucose, insulin, adiponectin, and other cytokines in the context of a 1-y randomized intervention study. For 1 y, 187 men aged 45 +/- 2 y, approximately 50% of whom met the criteria of the metabolic syndrome, were randomly assigned to a diet protocol (n = 45), an exercise protocol (n = 48), a protocol of diet plus exercise (n = 58), or a control protocol (n = 36). A previously defined a priori diet score was created by summing tertile rankings of 35 food group variables; a higher score generally reflected recommended dietary changes in the trial (mean +/- SD at baseline: 31 +/- 6.5; range: 15-47). Over the study year, the diet score increased by approximately 2 +/- 5.5 in both diet groups, with a decrease of an equivalent amount in the exercise and control groups. The weight change was -3.5 +/- 0.6 kg/10-point change in diet score (P < 0.0001), similarly within each intervention group, independently of the change in energy intake or baseline age and smoking status. Weight change was attenuated but remained significant after adjustment for intervention group and percentage body fat. Subjects with an increased diet score had more favorable changes in other body size variables, systolic blood pressure, and blood lipid, glucose, insulin, and adiponectin concentrations. Change in diet score was unrelated to resistin and several cytokines. The change toward a more favorable diet pattern was associated with improved body size and metabolic profile.

Impact of Tumour Epithelial Subtype on Circulating microRNAs in Breast Cancer Patients

PubMed Central

Brougham, Cathy; Glynn, Claire L.; Wall, Deirdre; Hyland, Peter; Duignan, Maria; McLoughlin, Mark; Newell, John; Kerin, Michael J.

2014-01-01

While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and microRNA extracted. MicroRNA microArray analysis was performed comparing samples harvested at week 1 to those collected at week 6 from the same animals. Significantly altered miRNAs were validated across all murine samples by RQ-PCR (n = 45). Three miRNAs of interest were then quantified in the circulation(n = 166) and tissue (n = 100) of breast cancer patients and healthy control individuals. MicroArray-based analysis of murine blood samples revealed levels of 77 circulating microRNAs to be changed during disease progression, with 44 demonstrating changes >2-fold. Validation across all samples revealed miR-138 to be significantly elevated in the circulation of animals during disease development, with miR-191 and miR-106a levels significantly decreased. Analysis of patient tissue and blood samples revealed miR-138 to be significantly up-regulated in the circulation of patients with breast cancer, with no change observed in the tissue setting. While not significantly changed overall in breast cancer patients compared to controls, circulating miR-106a and miR-191 were significantly decreased in patients with basal breast cancer. In tissue, both miRNAs were significantly elevated in breast cancer compared to normal breast tissue. The data demonstrates an impact of tumour epithelial subtype on circulating levels of miRNAs, and highlights divergent miRNA profiles between tissue and blood samples from breast cancer patients. PMID:24626163

Circulating follistatin displays a day-night rhythm and is associated with muscle mass and circulating leptin levels in healthy, young humans

PubMed Central

Anastasilakis, Athanasios D.; Polyzos, Stergios A.; Skouvaklidou, Elpida C.; Kynigopoulos, Georgios; Saridakis, Zacharias G.; Apostolou, Aggeliki; Triantafyllou, Georgios A.; Karagiozoglou-Lampoudi, Thomai; Mantzoros, Christos S.

2016-01-01

Purpose Follistatin may affect lean and fat mass and be implicated in metabolic diseases. We aimed to elucidate physiological predictors of circulating follistatin variation in healthy young humans. Procedures This was an observational, cross-sectional study with two additional prospective observational arms (circadian, seasonal sub-studies) and one prospective interventional arm (mixed meal sub-study). Healthy, young individuals of both sexes (n=122) were subjected to anthropometric and body composition measurements and their eating and exercise behavior profiles were assessed by validated questionnaires. Sub-groups were subjected to standardized meal ingestion (n=36), day-night rhythm (n=20) and seasonal variation (n=20) studies. Main outcome of the study were circulating follistatin levels. Results At baseline follistatin levels were correlated with creatinine (r=0.24; p=0.01), creatine phosphokinase (rs=0.22; p=0.02), and with lean body mass (rs=0.19; p=0.04) and were higher in males than females (p=0.004) after adjustment for leptin, which was its major predictor. Follistatin levels showed a circadian (p<0.001), but not a seasonal, variation, and were also affected by the phase of menstrual cycle in females (p=0.004). Follistatin levels were not affected by dietary or exercise habits but levels increased after a standardized meal ingestion (250 kcal) (p=0.002). Conclusions In healthy young individuals circulating follistatin levels are correlated with muscle mass. Follistatin levels are associated with circulating leptin levels and display a day-night rhythm and a menstrual cycle, but not a seasonal, variation. PMID:27621181

Circulating follistatin displays a day-night rhythm and is associated with muscle mass and circulating leptin levels in healthy, young humans.

PubMed

Anastasilakis, Athanasios D; Polyzos, Stergios A; Skouvaklidou, Elpida C; Kynigopoulos, Georgios; Saridakis, Zacharias G; Apostolou, Aggeliki; Triantafyllou, Georgios A; Karagiozoglou-Lampoudi, Thomai; Mantzoros, Christos S

2016-10-01

Follistatin may affect lean and fat mass and be implicated in metabolic diseases. We aimed to elucidate physiological predictors of circulating follistatin variation in healthy young humans. This was an observational, cross-sectional study with two additional prospective observational arms (circadian, seasonal sub-studies) and one prospective interventional arm (mixed meal sub-study). Healthy, young individuals of both sexes (n=122) were subjected to anthropometric and body composition measurements and their eating and exercise behavior profiles were assessed by validated questionnaires. Sub-groups were subjected to standardized meal ingestion (n=36), day-night rhythm (n=20) and seasonal variation (n=20) studies. Main outcome of the study were circulating follistatin levels. At baseline follistatin levels were correlated with creatinine (r=0.24; p=0.01), creatine phosphokinase (rs=0.22; p=0.02), and with lean body mass (rs=0.19; p=0.04) and were higher in males than females (p=0.004) after adjustment for leptin, which was its major predictor. Follistatin levels showed a circadian (p<0.001), but not a seasonal, variation, and were also affected by the phase of menstrual cycle in females (p=0.034). Follistatin levels were not affected by dietary or exercise habits but levels increased after a standardized meal ingestion (250kcal) (p=0.002). In healthy young individuals circulating follistatin levels are correlated with muscle mass. Follistatin levels are associated with circulating leptin levels and display a day-night rhythm and a menstrual cycle, but not a seasonal, variation. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhanced risk profiling of implanted defibrillator shocks with circulating SCN5A mRNA splicing variants: a pilot trial

PubMed Central

Gao, Ge; Brahmanandam, Vikram; Raicu, Mihai; Gu, Lianzhi; Zhou, Li; Kasturirangan, Srinivasan; Shah, Anish; Negi, Smita I.; Wood, Melissa R.; Desai, Ankit A.; Tatooles, Antone; Schwartz, Alan; Dudley, Samuel C.

2014-01-01

Objectives The aim of this study was to determine the association of SCN5A cardiac sodium (Na+) channel mRNA splice variants in white blood cells (WBCs) with risk of arrhythmias in heart failure (HF). Background HF is associated with upregulation of two cardiac SCN5A mRNA splice variants. that encode prematurely truncated, nonfunctional Na+ channels. Since circulating WBCs demonstrate similar SCN5A splicing patterns, we hypothesized that these WBC-derived splice variants might further stratify HF patients at risk for arrhythmias. Methods Simultaneously obtained myocardial core samples and WBCs were compared for SCN5A variants C (VC) and D (VD). Circulating variant levels were compared between HF patients divided into three groups: HF without an implantable cardioverter-defibrillator (ICD), HF with an ICD without appropriate intervention, and HF with an ICD with appropriate intervention. Results Myocardial tissue-derived SCN5A variant expression levels strongly correlated with circulating WBC samples for both VC and VD variants (r = 0.78 and 0.75, respectively). After controlling for covariates, HF patients who had received an appropriate ICD intervention had higher expression levels of both WBC-derived SCN5A variants compared to HF patients with ICDs who had not (OR= 3.25 (95% CI 1.64–6.45; p=0.001)). Receiver operating characteristics analysis revealed that circulating SCN5A variants levels were highly associated with the risk for appropriate ICD intervention (area under the curve ≥ 0.97). Conclusions Circulating expression levels of SCN5A variants were strongly associated with myocardial tissue levels. Furthermore, circulating variant levels were correlative with arrhythmic risk as measured by ICD events in a HF population within one year. PMID:24703920

Genome-wide association meta-analysis of circulating odd-numbered chain saturated fatty acids: Results from the CHARGE Consortium

PubMed Central

King, Irena B.; Wu, Jason H. Y.; Manichaikul, Ani; Rich, Stephen S.; Tsai, Michael Y.; Chen, Y. D.; Fornage, Myriam; Weihua, Guan; Aslibekyan, Stella; Irvin, Marguerite R.; Kabagambe, Edmond K.; Arnett, Donna K.; Jensen, Majken K.; McKnight, Barbara; Psaty, Bruce M.; Steffen, Lyn M.; Smith, Caren E.; Risérus, Ulf; Lind, Lars; Hu, Frank B.; Rimm, Eric B.; Siscovick, David S.; Mozaffarian, Dariush

2018-01-01

Background Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established. Objective To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA. Design We performed a meta-analysis of genome-wide association studies (GWAS) of plasma phospholipid/erythrocyte levels of C15:0, C17:0, C19:0, and C23:0 among 11,494 individuals of European descent. We also investigated relationships between specific single nucleotide polymorphisms (SNPs) in the lactase (LCT) gene, associated with adult-onset lactase intolerance, with circulating levels of dairy-derived OCSFA, and evaluated associations of candidate sphingolipid genes with C23:0 levels. Results We found no genome-wide significant evidence that common genetic variation is associated with circulating levels of C15:0 or C23:0. In two cohorts with available data, we identified one intronic SNP (rs13361131) in myosin X gene (MYO10) associated with C17:0 level (P = 1.37×10−8), and two intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C19:0 level (P = 7.07×10−9). In contrast, when using a candidate-gene approach, we found evidence that three SNPs in LCT (rs11884924, rs16832067, and rs3816088) are associated with circulating C17:0 level (adjusted P = 4×10−2). In addition, nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C23:0 levels (adjusted P<5×10−2). Conclusions Our findings suggest that circulating levels of OCSFA may be predominantly influenced by non-genetic factors. SNPs associated with C17:0 level in the LCT gene may reflect genetic influence in dairy consumption or in metabolism of dairy foods. SNPs associated with C23:0 may reflect a role of genetic factors in the synthesis of sphingomyelin. PMID:29738550

Ovarian Cancer, Stem Cells, and Bioreactors

DTIC Science & Technology

2009-10-01

also indirectly assessed by measuring CEA and CA125 levels in the circulating medium. CEA and CA125, belonging to the CEA antigen family, are...with OVC#6 could not be detected. The low level of CA125 may be due to a dilution of the protein in the circulating medium as protein concentrations...lower than 8.7U/ml are below the assay sensitivity. Unfortunately, we have been unable to obtain the CA125 circulating level for either patient so

What Is the Role of Apelin regarding Cardiovascular Risk and Progression of Renal Disease in Type 2 Diabetic Patients with Diabetic Nephropathy?

PubMed Central

Fragoso, André; Silva, Claudia; Viegas, Carla; Tavares, Nelson; Guilherme, Patrícia; Santos, Nélio; Rato, Fátima; Camacho, Ana; Cavaco, Cidália; Pereira, Victor; Faísca, Marilia; Ataíde, João; Jesus, Ilídio; Neves, Pedro

2013-01-01

Aims. To evaluate the association of different apelin levels with cardiovascular mortality, hospitalization, renal function, and cardiovascular risk factors in type 2 diabetic patients with mild to moderate CKD. Methods. An observational, prospective study involving 150 patients divided into groups according to baseline apelin levels: 1 ≤ 98 pg/mL, 2 = 98–328 pg/mL, and 3 ≥ 329 pg/mL. Baseline characteristics were analyzed and compared. Multivariate Cox regression was used to find out predictors of cardiovascular mortality, and multivariate logistic regression was used to find out predictors of hospitalization and disease progression. Simple linear regressions and Pearson correlations were used to investigate correlations between apelin and renal disease and cardiovascular risk factors. Results. Patients' survival at 83 months in groups 1, 2, and 3 was 39%, 40%, and 71.2%, respectively (P = 0.046). Apelin, age, and eGFR were independent predictors of mortality, and apelin, creatinine, eGFR, resistin, and visfatin were independent predictors of hospitalization. Apelin levels were negatively correlated with cardiovascular risk factors and positively correlated with eGFR. Patients with lower apelin levels were more likely to start a depurative technique. Conclusions. Apelin levels might have a significant clinical use as a marker/predictor of cardiovascular mortality and hospitalization or even as a therapeutic agent for CKD patients with cardiovascular disease. PMID:24089668

Diversity in the representation of large-scale circulation associated with ENSO-Indian summer monsoon teleconnections in CMIP5 models

NASA Astrophysics Data System (ADS)

Ramu, Dandi A.; Chowdary, Jasti S.; Ramakrishna, S. S. V. S.; Kumar, O. S. R. U. B.

2018-04-01

Realistic simulation of large-scale circulation patterns associated with El Niño-Southern Oscillation (ENSO) is vital in coupled models in order to represent teleconnections to different regions of globe. The diversity in representing large-scale circulation patterns associated with ENSO-Indian summer monsoon (ISM) teleconnections in 23 Coupled Model Intercomparison Project Phase 5 (CMIP5) models is examined. CMIP5 models have been classified into three groups based on the correlation between Niño3.4 sea surface temperature (SST) index and ISM rainfall anomalies, models in group 1 (G1) overestimated El Niño-ISM teleconections and group 3 (G3) models underestimated it, whereas these teleconnections are better represented in group 2 (G2) models. Results show that in G1 models, El Niño-induced Tropical Indian Ocean (TIO) SST anomalies are not well represented. Anomalous low-level anticyclonic circulation anomalies over the southeastern TIO and western subtropical northwest Pacific (WSNP) cyclonic circulation are shifted too far west to 60° E and 120° E, respectively. This bias in circulation patterns implies dry wind advection from extratropics/midlatitudes to Indian subcontinent. In addition to this, large-scale upper level convergence together with lower level divergence over ISM region corresponding to El Niño are stronger in G1 models than in observations. Thus, unrealistic shift in low-level circulation centers corroborated by upper level circulation changes are responsible for overestimation of ENSO-ISM teleconnections in G1 models. Warm Pacific SST anomalies associated with El Niño are shifted too far west in many G3 models unlike in the observations. Further large-scale circulation anomalies over the Pacific and ISM region are misrepresented during El Niño years in G3 models. Too strong upper-level convergence away from Indian subcontinent and too weak WSNP cyclonic circulation are prominent in most of G3 models in which ENSO-ISM teleconnections are underestimated. On the other hand, many G2 models are able to represent most of large-scale circulation over Indo-Pacific region associated with El Niño and hence provide more realistic ENSO-ISM teleconnections. Therefore, this study advocates the importance of representation/simulation of large-scale circulation patterns during El Niño years in coupled models in order to capture El Niño-monsoon teleconnections well.

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

PubMed Central

Wirth, Eva K.; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-01-01

Background The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). Methods We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated. PMID:26601078

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase.

PubMed

Wirth, Eva K; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-09-01

The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.

Determination of Viremia and Concentration of Circulating Nonstructural Protein 1 in Patients Infected with Dengue Virus in Mexico

PubMed Central

de la Cruz-Hernández, Sergio I.; Flores-Aguilar, Hilario; González-Mateos, Silvia; López-Martinez, Irma; Alpuche-Aranda, Celia; Ludert, Juan E.; del Angel, Rosa M.

2013-01-01

Higher levels of viremia and circulating nonstructural protein 1 (NS1) have been associated with dengue disease severity. In this study, viremia and circulating NS1 levels were determined in 225 serum samples collected from patients in Mexico infected with dengue virus serotypes 1 and 2 (DENV-1 and DENV-2). Patients with dengue hemorrhagic fever (DHF) who were infected with DENV-1 showed higher levels of circulating NS1 than patients with dengue fever (DF) (P = 0.0175). Moreover, NS1 levels were higher in patients with primary infections with DENV-1 than in patient infected with DENV-2 (P < 0.0001) and in patients with primary infections with DENV-2 than in patients with secondary infections with DENV-2 (P = 0.0051). Unexpectedly, viremia levels were higher in patients with DF than in those with DHF infected with either DENV-1 or DENV-2 (P = 0.0019 and P = 0.001, respectively) and in patients with primary infections than those with secondary DENV-2 infections (P < 0.0001). Results indicate that levels of circulating NS1 vary according to the infecting serotype, immunologic status (primary or secondary infection), and dengue disease severity. PMID:23339203

Determination of viremia and concentration of circulating nonstructural protein 1 in patients infected with dengue virus in Mexico.

PubMed

de la Cruz-Hernández, Sergio I; Flores-Aguilar, Hilario; González-Mateos, Silvia; López-Martinez, Irma; Alpuche-Aranda, Celia; Ludert, Juan E; del Angel, Rosa M

2013-03-01

Higher levels of viremia and circulating nonstructural protein 1 (NS1) have been associated with dengue disease severity. In this study, viremia and circulating NS1 levels were determined in 225 serum samples collected from patients in Mexico infected with dengue virus serotypes 1 and 2 (DENV-1 and DENV-2). Patients with dengue hemorrhagic fever (DHF) who were infected with DENV-1 showed higher levels of circulating NS1 than patients with dengue fever (DF) (P = 0.0175). Moreover, NS1 levels were higher in patients with primary infections with DENV-1 than in patient infected with DENV-2 (P < 0.0001) and in patients with primary infections with DENV-2 than in patients with secondary infections with DENV-2 (P = 0.0051). Unexpectedly, viremia levels were higher in patients with DF than in those with DHF infected with either DENV-1 or DENV-2 (P = 0.0019 and P = 0.001, respectively) and in patients with primary infections than those with secondary DENV-2 infections (P < 0.0001). Results indicate that levels of circulating NS1 vary according to the infecting serotype, immunologic status (primary or secondary infection), and dengue disease severity.

Parity-induced decrease in systemic growth hormone alters mammary gland signaling: A potential role in pregnancy protection from breast cancer

PubMed Central

Dearth, Robert K.; Delgado, David A.; Hiney, Jill K; Pathiraja, Thushangi; Oesterreich, Steffi; Medina, Dan; Dees, W. Les; Lee, Adrian V.

2009-01-01

Early full-term pregnancy is an effective natural protection against breast cancer in both humans and experimental rodents. The protective effect of an early pregnancy is in part linked to changes in circulating hormones that are involved in both normal breast development and breast cancer. For example, a reduction in circulating growth hormone (GH) has been shown to protect rats from carcinogen-induced mammary tumors. We examined the ability of a full-term pregnancy to alter the endocrine GH/IGF-I axis and how this change affected normal mammary gland function in two commonly used rat models (Sprague-Dawley and Wistar-Furth). Circulating GH and IGF-I were measured in blood drawn every 30 minutes from parous and aged-matched virgin (AMV) female rats. Mean serum GH levels were significantly decreased (p<0.01) in parous compared to AMV in both rat strains. Changes in GH levels were independent of estrous cycle, indicated by a significant (p<0.05) reduction in circulating levels of GH during estrus and diestrus in both parous strains. Despite the decrease in circulating GH, pituitary GH mRNA levels were unaltered in parous rats. Circulating IGF-I and hepatic IGF-I mRNA were also unaltered by parity in either rat strain. Immunoblot analysis of mammary glands showed decreases in phosphorylation of Stat5A and Jak2, suggesting reduced action of GH in the mammary gland. Therefore, while the parity reduction in circulating GH doesn’t impact upon circulating IGF-I levels, it is possible that reduced GH action directly at the mammary gland and may play a role in pregnancy protection from breast cancer. PMID:20145191

The effects of conventional extracorporeal circulation versus miniaturized extracorporeal circulation on microcirculation during cardiopulmonary bypass-assisted coronary artery bypass graft surgery

PubMed Central

Yuruk, Koray; Bezemer, Rick; Euser, Mariska; Milstein, Dan M.J.; de Geus, Hilde H.R.; Scholten, Evert W.; de Mol, Bas A.J.M.; Ince, Can

2012-01-01

OBJECTIVES To reduce the complications associated with cardiopulmonary bypass (CPB) during cardiac surgery, many modifications have been made to conventional extracorporeal circulation systems. This trend has led to the development of miniaturized extracorporeal circulation systems. Cardiac surgery using conventional extracorporeal circulation systems has been associated with significantly reduced microcirculatory perfusion, but it remains unknown whether this could be prevented by an mECC system. Here, we aimed to test the hypothesis that microcirculatory perfusion decreases with the use of a conventional extracorporeal circulation system and would be preserved with the use of an miniaturized extracorporeal circulation system. METHODS Microcirculatory density and perfusion were assessed using sublingual side stream dark-field imaging in patients undergoing on-pump coronary artery bypass graft (CABG) surgery before, during and after the use of either a conventional extracorporeal circulation system (n = 10) or a miniaturized extracorporeal circulation system (n = 10). In addition, plasma neutrophil gelatinase-associated lipocalin and creatinine levels and creatinine clearance were assessed up to 5 days post-surgery to monitor renal function. RESULTS At the end of the CPB, one patient in the miniaturized extracorporeal circulation-treated group and five patients in the conventional extracorporeal circulation-treated group received one bag of packed red blood cells (300 ml). During the CPB, the haematocrit and haemoglobin levels were slightly higher in the miniaturized extracorporeal circulation-treated patients compared with the conventional extracorporeal circulation-treated patients (27.7 ± 3.3 vs 24.7 ± 2.0%; P = 0.03; and 6.42 ± 0.75 vs 5.41 ± 0.64 mmol/l; P < 0.01). The density of perfused vessels with a diameter <25 µm (i.e. perfused vessel density) decreased slightly in the conventional extracorporeal circulation-treated group from 16.4 ± 3.8 to 12.8 ± 3.3 mm/mm2 (P < 0.01) and remained stable in the miniaturized extracorporeal circulation-treated group (16.3 ± 2.7 and 15.2 ± 2.9 mm/mm2 before and during the pump, respectively). Plasma neutrophil gelatinase-associated lipocalin levels were increased following the use of extracorporeal circulation in both groups, and no differences were observed between the groups. Plasma creatinine levels and creatinine clearance were not affected by CABG surgery or CPB. CONCLUSIONS The results from this relatively small study suggest that the use of the miniaturized extracorporeal circulation system is associated with a statistically significant (but clinically insignificant) reduction in haemodilution and microcirculatory hypoperfusion compared with the use of the conventional extracorporeal circulation system. PMID:22700685

Combination of plasma HA and circulating M2-like monocytes may serve as a diagnostic marker for breast cancer.

PubMed

Zhang, Boke; Cao, Manlin; He, Yiqing; Liu, Yiwen; Zhang, Guoliang; Yang, Cuixia; Du, Yan; Xu, Jing; Hu, Jiajie; Gao, Feng

2017-01-01

Background: Breast cancer (BC)-derived hyaluronan (HA) can induce the formation of M2-like tumor-associated macrophages (TAMs) in tumor context. However, little is known about the correlation between circulating M2-like monocytes and plasma HA in BC patients. This study focused on evaluating the relationship between circulating M2-like monocytes and plasma HA, and further appraised the diagnostic value of them in BC. Methods: The expression of M2-like TAMs and HA was determined in pathological tissues by immunohistochemistry. Flow cytometry was used to detect the levels of circulating CD14 + CD204 + M2-like monocytes in 81 BC patients, 45 patients with breast benign diseases, and 46 healthy subjects. The levels of HA, CEA, and CA15-3 were measured in plasma samples using chemiluminescence method. Results: M2-like TAMs and HA expressions were elevated in BC tissues compared with benign tissues. In correspondence, the frequency of circulating CD14 + CD204 + M2-like monocytes and the plasma HA levels were significantly higher in patients with BC than those in control groups. Importantly, there was a positive correlation between circulating M2-like monocytes and the plasma HA (Spearman r = 0.404, p < 0.001). Area under receiver operating characteristic curve (ROC) for the combination of circulating M2-like monocytes and HA was 0.899 (95% CI: 0.853-0.946), which was higher than the panel of CEA and CA15-3. Conclusions: The frequency of circulating CD14 + CD204 + M2-like monocytes was positively correlated to plasma HA levels. The combination of circulating CD14 + CD204 + M2-like monocytes and plasma HA could provide considerable diagnostic value in BC.

Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials.

PubMed

Eichelmann, F; Schwingshackl, L; Fedirko, V; Aleksandrova, K

2016-11-01

Plant-based dietary interventions have been proposed to reduce obesity induced chronic low-grade inflammation and hence prevent chronic disease risk; however, human evidence remains unclear. This systematic review and meta-analysis of intervention trials aimed to assess the effect of plant-based diets on obesity-related inflammatory biomarker profiles. Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published until January 2016 and mean differences in biomarkers of inflammatory status were assessed for: C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-ɑ), soluble intercellular adhesion molecule 1 (sICAM), leptin, adiponectin and resistin. Of initially identified 2,583 publications, 29 met the meta-analysis inclusion criteria [a total of 2,689 participants]. Consumption of plant-based diets was associated with a reduction in the mean concentrations of the following biomarkers: CRP [effect size, -0.55 mg/l, 95% confidence intervals (CI): -0.78; -0.32, I 2  = 94.4%], IL-6 [effect size, -0.25 ng/l, 95% CI: -0.56; 0.06, I 2  = 74%], and, to some degree, sICAM (-25.07 ng/ml [95% CI: -52.32; 2.17, I 2  = 93.2%]). No substantial effects were revealed for TNF-ɑ, resistin, adiponectin and leptin. Plant-based diets are associated with an improvement in obesity-related inflammatory profiles and could provide means for therapy and prevention of chronic disease risk. © 2016 World Obesity.

Effects of one year treatment of sibutramine on insulin resistance parameters in type 2 diabetic patients.

PubMed

Derosa, Giuseppe; Maffioli, Pamela; Ferrari, Ilaria; Palumbo, Ilaria; Randazzo, Sabrina; D'Angelo, Angela; Cicero, Arrigo F G

2010-01-01

Comparison of the effects of one year treatment with sibutramine compared to placebo on insulin resistance parameters, body weight, glycemic control, and lipid profile, in type 2 diabetic patients. Two hundred and forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg or placebo for one year. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: homeostasis model assessment insulin resistance index (HOMA-IR), retinol binding protein-4 (RBP-4), resistin, visfatin, and high sensitivity-C reactive protein (Hs-CRP), body weight, body mass index (BMI), glycated hemoglobin (HbA(₁c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and triglycerides (T(g)). A faster decrease of HOMA-IR, resistin, and RBP-4 was recorded with sibutramine compared to the control group. We observed a significant decrease of Hs-CRP in both groups, and a faster improvement of HbA(₁c), FPG and PPG with sibutramine compared to the control group; furthermore we recorded a decrease of FPI, TC, LDL-C, body weight, and BMI in the sibutramine group, but not in the control group. Sibutramine gave a faster improvement of insulin resistance parameters and glycemic control compared to placebo; furthermore sibutramine gave also an improvement of lipid profile, and body weight.

Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer.

PubMed

Chang, Yoon Soo; Kim, Hyung Jung; Chang, Joon; Ahn, Chul Min; Kim, Sung Kyu; Kim, Se Kyu

2007-09-01

Osteopontin (OPN) plays important roles in tumor progression and metastasis through binding to OPN receptors such as alpha(v)beta(beta) integrin and CD44, and its overexpression in tumor is associated poor clinical outcome of NSCLC patients. Circulating OPN levels, measured by ELISA in 130 NSCLC cases that had not been treated for cancer at the time of sampling, were analyzed according to clinical, pathologic parameters and single nucleotide polymorphisms (SNPs) in the OPN gene promoter. Advanced disease states had higher circulating levels of OPN (T4 versus T1-3, N3 versus N0-2, and M1 versus M0, P=.029, .001, and .001, respectively, Kruskal-Wallis H-test), reflected by higher level of OPN in stage IV than stage I-III (P=.029, Kruskal-Wallis H-test). Among the clinical and pathological parameters including age, gender, smoking status, histologic subtypes and grade of differentiation, smoking status influences circulating OPN level showing higher level of OPN in ex-smokers than current and non-smokers (P=.038, Kruskal-Wallis H-test). Variation at nucleotide (nt) -443 of the OPN gene promoter had no influence on circulating OPN levels, however, patients with G/G at nt -156 showed higher concentrations of OPN than those with G/GG or GG/GG (P=.003, Kruskal-Wallis H-test). A patient with G/G at nt -156 was more frequently diagnosed with advanced stage (IIIB-IV) than with early stage (I-IIIA) NSCLC (P=.048, Mantel-Haenszel-test). In multivariate analysis, stage is the only independent factor influencing circulating level of OPN. Although circulating level of OPN in the patients with bone metastasis was higher than in those without bone metastasis (P=.028, Mann-Whitney U-test), there was no difference in the OPN levels between bone metastasis group and non-bone metastasis group. Given that the elevated levels of OPN is associated with advanced stages of NSCLC, elucidating OPN regulatory mechanisms may contribute to the development of a new therapeutic modality for NSCLC.

Multidecadal Weakening of Indian Summer Monsoon Circulation Induces an Increasing Northern Indian Ocean Sea Level

NASA Astrophysics Data System (ADS)

Swapna, P.; Jyoti, J.; Krishnan, R.; Sandeep, N.; Griffies, S. M.

2017-10-01

North Indian Ocean sea level has shown significant increase during last three to four decades. Analyses of long-term climate data sets and ocean model sensitivity experiments identify a mechanism for multidecadal sea level variability relative to global mean. Our results indicate that North Indian Ocean sea level rise is accompanied by a weakening summer monsoon circulation. Given that Indian Ocean meridional heat transport is primarily regulated by the annual cycle of monsoon winds, weakening of summer monsoon circulation has resulted in reduced upwelling off Arabia and Somalia and decreased southward heat transport, and corresponding increase of heat storage in the North Indian Ocean. These changes in turn lead to increased retention of heat and increased thermosteric sea level rise in the North Indian Ocean, especially in the Arabian Sea. These findings imply that rising North Indian Ocean sea level due to weakening of monsoon circulation demands adaptive strategies to enable a resilient South Asian population.

Circulating Influenza Virus and Adverse Pregnancy Outcomes: A Time-Series Study.

PubMed

Fell, Deshayne B; Buckeridge, David L; Platt, Robert W; Kaufman, Jay S; Basso, Olga; Wilson, Kumanan

2016-08-01

Individual-level epidemiologic studies of pregnancy outcomes after maternal influenza are limited in number and quality and have produced inconsistent results. We used a time-series design to investigate whether fluctuation in influenza virus circulation was associated with short-term variation in population-level rates of preterm birth, stillbirth, and perinatal death in Ontario between 2003 and 2012. Using Poisson regression, we assessed the association between weekly levels of circulating influenza virus and counts of outcomes offset by the number of at-risk gestations during 3 gestational exposure windows. The rate of preterm birth was not associated with circulating influenza level in the week preceding birth (adjusted rate ratio = 1.01, 95% confidence interval: 1.00, 1.02) or in any other exposure window. These findings were robust to alternate specifications of the model and adjustment for potential confounding. Stillbirth and perinatal death rates were similarly not associated with gestational exposure to influenza circulation during late pregnancy. We could not assess mortality outcomes relative to early gestational exposure because of missing dates of conception for many stillbirths. In this time-series study, population-level influenza circulation was not associated with short-term variation in rates of preterm birth, stillbirth, or perinatal death. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Circulating levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α and risk of colorectal adenomas: a meta-analysis.

PubMed

Zhang, Xiaoqian; Liu, Shanglong; Zhou, Yanbing

2016-09-27

Results from publications on inflammatory markers of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and risk of colorectal adenomas are not consistent. A meta-analysis was conducted to explore the above-mentioned associations. Relevant studies were identified by a search of Embase, Medline and PubMed through February 2016. A random effect model was adopted to combine study-specific odds ratio (OR) and 95% confidence interval (95% CI). Between-study heterogeneity and publications bias were assessed. Dose-response relationships were assessed by restricted cubic splines. Nineteen observational studies were included. For highest vs. lowest levels, results from this meta-analysis did not support an association between circulating levels of CRP [OR (95% CI): 1.15 (0.94-1.40)], IL-6 [1.17 (0.94-1.46)] and TNF-α [0.99 (0.75-1.31)] and risk of colorectal adenomas, respectively. The findings were supported by sensitivity analysis and subgroup analysis. In dose-response analysis, the risk of colorectal adenomas increased by 2% [1.02 (0.97-1.08)] for each 1 mg/L increment in circulation CRP levels, 9% [1.09 (0.91-1.31)] for each 1 ng/L increment in circulation IL-6 levels, and 6% [1.06 (0.93-1.21)] for each 1 pg/mL increment in circulation TNF-α levels. Moderate between-study heterogeneity was found. No evidence of publication bias was found. Circulation levels of CRP, IL-6 and TNF-α might be not useful biomarkers for identifying colorectal adenomas, respectively.

Sustained apnea induces endothelial activation.

PubMed

Eichhorn, Lars; Dolscheid-Pommerich, Ramona; Erdfelder, Felix; Ayub, Muhammad Ajmal; Schmitz, Theresa; Werner, Nikos; Jansen, Felix

2017-09-01

Apnea diving has gained worldwide popularity, even though the pathophysiological consequences of this challenging sport on the human body are poorly investigated and understood. This study aims to assess the influence of sustained apnea in healthy volunteers on circulating microparticles (MPs) and microRNAs (miRs), which are established biomarkers reflecting vascular function. Short intermittent hypoxia due to voluntary breath-holding affects circulating levels of endothelial cell-derived MPs (EMPs) and endothelial cell-derived miRs. Under dry laboratory conditions, 10 trained apneic divers performed maximal breath-hold. Venous blood samples were taken, once before and at 4 defined points in time after apnea. Samples were analyzed for circulating EMPs and endothelial miRs. Average apnea time was 329 seconds (±103), and SpO 2 at the end of apnea was 79% (±12). Apnea was associated with a time-dependent increase of circulating endothelial cell-derived EMPs and endothelial miRs. Levels of circulating EMPs in the bloodstream reached a peak 4 hours after the apnea period and returned to baseline levels after 24 hours. Circulating miR-126 levels were elevated at all time points after a single voluntary maximal apnea, whereas miR-26 levels were elevated significantly only after 30 minutes and 4 hours. Also miR-21 and miR-92 levels increased, but did not reach the level of significance. Even a single maximal breath-hold induces acute endothelial activation and should be performed with great caution by subjects with preexisting vascular diseases. Voluntary apnea might be used as a model to simulate changes in endothelial function caused by hypoxia in humans. © 2017 Wiley Periodicals, Inc.

Flavanol-rich lychee fruit extract alleviates diet-induced insulin resistance via suppressing mTOR/SREBP-1 mediated lipogenesis in liver and restoring insulin signaling in skeletal muscle.

PubMed

Liu, Hung-Wen; Wei, Chu-Chun; Chen, Yen-Ju; Chen, Yun-An; Chang, Sue-Joan

2016-10-01

An elevated intracellular lipid contents resulted from lipid oversupply links obesity to insulin resistance. Flavanol-rich lychee fruit extract, oligonol, exhibited anti-obesity property in vitro and in vivo; however, the effects of oligonol on peripheral lipid metabolism and insulin sensitivity have not been fully investigated. We hypothesized that oligonol alleviated insulin resistance via decreasing intracellular lipid contents in peripheral tissues. Dietary oligonol supplementation (20 or 200 mg/kg bw) reduced glucose and insulin levels, improved oral glucose tolerance, and suppressed inflammatory markers, MCP-1 and IL-6, in High-Fat diet (HFD) induced obese mice. Marked decreases in subcutaneous and visceral fat area, adipocyte size, and adipocyte released hormones including leptin and resistin by high-dose oligonol treatment were associated with downregulation of PPARγ gene expression. Significantly reduced intrahepatocellular lipid contents and hepatic triglyceride levels by oligonol (both doses) were associated with downregulation of mTOR/SREBP-1-mediated de novo lipogenesis. In skeletal muscle, oligonol enhanced Sirtuin1 protein expression and AMPKα activation, consequently resulted in reductions of intramuscular lipid contents and triglyceride levels and restoration of IRS-1 and AS160 phosphorylation. Oligonol reduced intracellular lipid contents in liver and skeletal muscle and suppressed inflammatory markers, thereby alleviating HFD-induced insulin resistance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural coloration signals condition, parental investment, and circulating hormone levels in Eastern bluebirds (Sialia sialis).

PubMed

Grindstaff, Jennifer L; Lovern, Matthew B; Burtka, Jennifer L; Hallmark-Sharber, Alesia

2012-08-01

Many of the brilliant plumage coloration displays of birds function as signals to conspecifics. One species in which the function of plumage ornaments has been assessed is the Eastern bluebird (Sialia sialis). Studies of a population breeding in Alabama (USA) have established that plumage ornaments signal quality, parental investment, and competitive ability in both sexes. Here we tested the additional hypotheses that (1) Eastern bluebird plumage ornamentation signals nest defense behavior in heterospecific competitive interactions and (2) individual variation in plumage ornamentation reflects underlying differences in circulating hormone levels. We also tested the potential for plumage ornaments to signal individual quality and parental investment in a population breeding in Oklahoma (USA). We found that Eastern bluebirds with more ornamented plumage are in better condition, initiate breeding earlier in the season, produce larger clutches, have higher circulating levels of the stress hormone corticosterone, and more ornamented males have lower circulating androgen levels. Plumage coloration was not related to nest defense behavior. Thus, plumage ornamentation may be used by both sexes to assess the physiological condition and parental investment of prospective mates. Experimental manipulations of circulating hormone levels during molt are needed to define the role of hormones in plumage ornamentation.

Exercise training with dietary restriction enhances circulating irisin level associated with increasing endothelial progenitor cell number in obese adults: an intervention study.

PubMed

Huang, Junhao; Wang, Shen; Xu, Fengpeng; Wang, Dan; Yin, Honggang; Lai, Qinhao; Liao, Jingwen; Hou, Xiaohui; Hu, Min

2017-01-01

Circulating endothelial progenitor cells (EPCs) correlate negatively with obesity. Previous studies have shown that exercise significantly restores circulating EPC levels in obese people; however, the underlying mechanisms have not been elucidated. Recently, irisin has been reported to have a critical role in the regulation of EPCs. This exercise-induced myokine has been demonstrated to play a therapeutic role in obesity. In this study, we hypothesized that the increase in circulating irisin may form a link with increasing EPC levels in obese people after exercise. Seventeen obese adults completed an 8-week program of combined exercise and dietary intervention. Clinical characteristics, blood biochemistry, and circulating irisin levels of subjects were measured before and after eight weeks of training. EPC levels were evaluated via flow cytometry, and EPC migratory and adhesive functions were also determined. Circulating irisin levels significantly increased following the 8-week training program ( P  < 0.05). We furthermore observed an improvement in EPC numbers ( P  < 0.05), and EPC migratory and adhesive functions ( P  < 0.001 and P  < 0.05, respectively) after the intervention. Additionally, we detected a positive correlation between changes in irisin and changes in EPC number ( r  = 0.52, P  < 0.05). For the first time, a positive correlation between increasing irisin levels and increasing EPC levels has been reported after an 8-week program, consisting of exercise and dietary intervention. This result suggests a novel effect of irisin on the regulation of EPC mobilization, which might contribute to improvement of endothelial function in obese people.

A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

PubMed Central

2011-01-01

Background Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. Methods We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. Results TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Conclusion Using the first transgenic animal model to elevate circulating levels of IGF-I to those comparable to women at increased risk of breast cancer, we showed that moderately high levels of systemic IGF-I have no effect on pubertal mammary gland development, initiating mammary tumorigenesis or promoting ErbB2 driven mammary carcinogenesis. Our work suggests that ErbB2-induced mammary tumorigenesis is independent of the normal variation in circulating levels of IGF-I. PMID:21867536

Circulating leptin levels are associated with increased craving to smoke in abstinent smokers

PubMed Central

al’Absi, Mustafa; Hooker, Stephanie; Fujiwara, Koji; Kiefer, Falk; von der Goltz, Christoph; Cragin, Tiffany; Wittmers, Lorentz E.

2018-01-01

The adipocyte hormone leptin regulates satiety and energy expenditure. Recent evidence suggests that leptin is associated with increased craving for alcohol and with shorter length of abstinence during alcohol treatment. This study examined leptin’s associations with craving for cigarettes and smoking relapse among smokers interested in cessation. Participants (32 smokers; 14 women) attended a laboratory session 24 h following their designated quit day where circulating leptin levels and craving for smoking were assessed. Other measures of withdrawal symptoms, affect, physical symptoms, as well as neuroendocrine and cardiovascular measures were collected before and after performing two stress tasks (public speaking and cognitive tasks). High circulating leptin levels were associated with increased craving, withdrawal symptoms, negative affect, physical symptoms, and reduced positive affect. Circulating leptin levels were not related to cardiovascular and neuroendocrine measures, responses to acute stressors, or to smoking relapse. These results indicate that circulating leptin is a promising biological marker of craving for smoking and warrant further investigation of the links between appetite regulation and nicotine dependence. PMID:20951159

The Pattern and Dynamics of the Meridional Overturning Circulation in the Upper Ocean

DTIC Science & Technology

2008-09-01

Atlantic . Figure 4a shows that the center of meridional overturning circulation occurs at a level of about one kilometer. Circulation is weak at...maintenance of the meridional overturning circulation in the Atlantic Ocean. 5. Global Simulation The most exciting experiment would be to fully model the...mechanisms responsible for the strength and maintenance of the meridional overturning circulation in the Atlantic Ocean are not

Clinical application of probiotics in type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled study.

PubMed

Tonucci, Livia Bordalo; Olbrich Dos Santos, Karina Maria; Licursi de Oliveira, Leandro; Rocha Ribeiro, Sonia Machado; Duarte Martino, Hercia Stampini

2017-02-01

Type 2 diabetes has been associated with dysbiosis and one of the possible routes to restore a healthy gut microbiota is by the regular ingestion of probiotics. We aimed to investigate the effects of probiotics on glycemic control, lipid profile, inflammation, oxidative stress and short chain fatty acids in T2D. In a double-blind, randomized, placebo-controlled trial, 50 volunteers consumed daily 120 g/d of fermented milk for 6 wk. Participants were assigned into two groups: probiotic group, consuming fermented milk containing Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp lactis BB-12 (10 9  colony-forming units/d, each) and control group, consuming conventional fermented milk. Anthropometric measurements, body composition, fasting blood and faecal samples were taken at baseline and after 6 wk. 45 subjects out of 50 (90%) completed follow-up. After 6 wk, there was a significant decrease in fructosamine levels (-9.91 mmol/L; p = 0.04) and hemoglobin A 1 c tended to be lower (-0.67%; p=0.06) in probiotic group. TNF-α and resistin were significantly reduced in probiotic and control groups (-1.5 and -1.3 pg/mL, -.1 and -2.8 ng/mL, respectively), while IL-10 was significantly reduced (- 0.65 pg/mL; p <0.001) only in the control group. Fecal acetic acid was increased in both groups (0.58 and 0.59% in probiotic and control groups, respectively; p <0.01). There was a significant difference between groups concerning mean changes of HbA 1c (+0.31 for control group vs -0.65 for probiotic group; p=0.02), total cholesterol (+0.55 for control group vs -0.15 for probiotic group; p=0.04) and LDL-cholesterol (+0.36 for control group vs -0.20 for probiotic group p=0.03). Probiotic consumption improved the glycemic control in T2D subjects, however, the intake of fermented milk seems to be involved with others metabolic changes, such as decrease in inflammatory cytokines (TNF-α and resistin) and increase in the acetic acid. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitahara, Kanako; Department of Immunology, Toho University School of Medicine, Tokyo; Kusunoki, Natsuko

The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.

Prognostic value of circulating VEGFR2+ bone marrow-derived progenitor cells in patients with advanced cancer.

PubMed

Massard, Christophe; Borget, Isabelle; Le Deley, Marie Cécile; Taylor, Melissa; Gomez-Roca, Carlos; Soria, Jean Charles; Farace, Françoise

2012-06-01

We hypothesised that host-related markers, possibly reflecting tumour aggressiveness, such as circulating endothelial cells (CEC) and circulating VEGFR2(+) bone marrow-derived (BMD) progenitor cells, could have prognostic value in patients with advanced cancer enrolled in early anticancer drug development trials. Baseline CECs (CD45(-)CD31(+)CD146(+)7AAD(-) cells) and circulating VEGFR2(+)-BMD progenitor cells (defined as CD45(dim)CD34(+)VEGFR2(+)7AAD(-) cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1 trials testing novel anti-vascular or anti-angiogenic agents. Correlations between levels of CECs, circulating VEGFR2(+)-BMD progenitor cells, clinical and biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and overall survival (OS) were studied. The median value of CECs was 12 CEC/ml (range 0-154/ml). The median level of VEGFR2(+)-BMD progenitor cells was 1.3% (range 0-32.5%) of circulating BMD-CD34(+) progenitors. While OS was not correlated with CEC levels, it was significantly worse in patients with high VEGFR2(+)-BMD progenitor levels (>1%) (median OS 9.0 versus 17.0 months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2 months). The prognostic value of VEGFR2(+)-BMD progenitor levels remained significant (hazard ratio (HR) = 2.3, 95% confidence interval (CI), 1.1-4.6, p = 0.02) after multivariate analysis. A composite VEGFR2(+)-BMD progenitor level/RHM score ≥ 2 was significantly associated with an increased risk of death compared to scores of 0 or 1 (median OS 9.0 versus 18.4 months, HR = 2.6 (95%CI, 1.2-5.8, p = 0.02)). High circulating VEGFR2(+)-BMD progenitor levels are associated with poor prognostics and when combined to classical clinical and biological parameters could provide a new tool for patient selection in early anticancer drug trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of diabatic heating on the ageostrophic circulation of an upper tropospheric jet streak

NASA Technical Reports Server (NTRS)

Keyser, D. A.; Johnson, D. R.

1982-01-01

Interaction between the mass circulation within a mesoscale convective complex (MCC) and a direct mass circulation in the entrance region of an upper tropospheric polar jet streak was examined within the isentropic structure to investigate mechanisms responsible for linking these two scales of motion. The results establish that latent heating in the MCC modifies the direct mass circulation in the jet streak entrance region through the diabatically induced components of ageostrophic motion analyzed within isentropic coordinates. Within the strong mesoscale mass circulation of each MCC, strong horizontal mass flux convergence into the MCC at low levels is balanced by strong horizontal mass flux divergence away from the convergence at upper levels. Locations of large diabatic heating rates correspond well to the MCC position for each case; diabatic heating forces the upward vertical branch for the mesoscale mass circulation.

Low levels of circulating platelet factor 4 (PF4, CXCL4) in subclinically hypothyroid autoimmune thyroiditis.

PubMed

Görar, S; Ademoğlu, E; Çarlıoğlu, A; Alioğlu, B; Bekdemir, H; Sağlam, B; Candan, Z; Üçler, R; Culha, C; Aral, Y

2016-02-01

Chemokines play an important role in the pathogenesis of autoimmune thyroid diseases. Platelet factor 4 (PF4, CXCL4) released from activated platelets is a chemokine. However, its clinical importance in autoimmune thyroiditis remains unknown. This study is intended to determine circulating levels of PF4 levels in patients with autoimmune thyroiditis (AIT). Circulating levels of PF4 were measured in 34 consecutive patients with newly diagnosed AIT and 18 euthyroid controls. Among AIT group, 16 patients were euthyroid and 18 had subclinic hypothyroidism. Controls and individuals with AIT were similar in terms of age. Serum levels of PF4 were comparable in patients with AIT and in controls. Among patients with AIT, PF4 was significantly lower in those with subclinical hypothyroidism than in euthyroid individuals (p = 0.001). In correlation analysis, PF4 was negatively correlated with TSH (r = -0.663, p = 0.000) and positively correlated with free T4 (r = 0.428, p = 0.012). There was not any significant correlation between PF4 and AbTPO, AbTg. The present study demonstrated for the first time that circulating PF4 levels are decreased in subclinically hypothyroid AIT. This result draws attention to the circulating PF4 levels in subclinically hypothyroid AIT and may shed light on further researches at this topic.

Impact of fibrates on circulating cystatin C levels: a systematic review and meta-analysis of clinical trials.

PubMed

Sahebkar, Amirhossein; Simental-Mendía, Luis E; Pirro, Matteo; Montecucco, Fabrizio; Carbone, Federico; Banach, Maciej; Barreto, George E; Butler, Alexandra E

2018-06-29

To assess the effect of fibrates on circulating cystatin C levels. Clinical studies evaluating the effect of a fibrate on circulating cystatin C levels were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases. A random-effect model and generic inverse variance method were used for quantitative data synthesis, sensitivity analysis conducted using the leave-one-out method, and weighted random-effects meta-regression performed to evaluate potential confounders on cystatin C levels. This meta-analysis of data from 9 published studies (16 treatment arms) involved a total of 2195 subjects. In a single-arm analysis of clinical trials (without control group; 8 studies comprising 14 treatment arms), fibrate therapy increased circulating cystatin C concentrations (WMD: 0.07 mg/dL, 95% CI: 0.04, 0.10, p <0.001; I 2 = 82.66%). When the analysis was restricted to randomized controlled trials (4 studies comprising 6 treatment arms), again elevation of circulating cystatin C levels was observed (WMD: 0.06 mg/L, 95% CI: 0.03, 0.09, p <0.001; I 2 = 42.98%). Elevated cystatin C levels were only seen with fenofibrate, not other fibrates. The results suggest that fenofibrate treatment adversely affects cystatin C levels and might partially explain the limited efficacy of fenofibrate in reducing cardiovascular events.

Measurement of Circulating Cytokines and Immune-Activation Markers by Multiplex Technology in the Clinical Setting: What Are We Really Measuring?

PubMed

Aziz, Najib

2015-01-01

Measurement of circulating cytokine levels can provide important information in the study of the pathogenesis of disease. John L. Fahey was a pioneer in the measurement of circulating cytokines and immune-activation markers and a leader in the quality assessment/control of assays for measurement of circulating cytokines. Insights into the measurement of circulating cytokines, including consideration of multiplex assays, are presented here.

The Variability of the Horizontal Circulation in the Troposphere and Stratosphere: A Comparison

NASA Technical Reports Server (NTRS)

Perlwitz, Judith; Graf, Hans-F.; Hansem, James E. (Technical Monitor)

2001-01-01

The variability of the horizontal circulation in the stratosphere and troposphere of the Northern Hemisphere (NH) is compared by using various approaches. Spatial degrees of freedom (dof) on different time scales were derived. Modes of variability were computed in geopotential height fields at the tropospheric and stratospheric pressure levels by applying multivariate statistical approaches. Features of the spatial and temporal variability of the winterly zonal wind were studied with the help of recurrence and persistence analyses. The geopotential height and zonally-averaged zonal wind at the 50-, 500- and 1000-hPa level are used to investigate the behavior of the horizontal circulation in the lower stratosphere, mid-troposphere and at the near surface level, respectively. It is illustrated that the features of the variability of the horizontal circulation are very similar in the mid-troposphere and at the near surface level. Due to the filtering of tropospheric disturbances by the stratospheric and upper tropospheric zonal mean flow, the variability of the stratospheric circulation exhibits less spatial complexity than the circulation at tropospheric pressure levels. There exist enormous differences in the number of degrees of freedom (or free variability modes) between both atmospheric layers. Results of the analyses clearly show that the concept of a zonally symmetric AO with a simple structure in the troposphere similar to the one in the stratosphere is not valid. It is concluded that the spatially filtered climate change signal can be detected earlier in the stratosphere than in the mid-troposphere or at the near surface level.

The investigation of circulating microRNAs associated with lipid metabolism in childhood obesity.

PubMed

Can, U; Buyukinan, M; Yerlikaya, F H

2016-06-01

Childhood obesity is an increasing health challenge related to increased risk of chronic diseases. microRNAs (miRNAs) are noncoding short RNA molecules regulating multiple biological processes linked to obesity. We aimed at evaluating the association between circulating miRNA levels and lipid metabolism in obese and non-obese children and adolescents. By constituting study group, 45 obese children and adolescents were recruited. To perform comparisons with study group, 41 lean controls were matched for age and sex. Using real-time quantitative PCR analysis, circulating miRNAs were evaluated in both groups. Circulating miR-335 (P < 0.001), miR-143 (P = 0.001) and miR-758 (P = 0.006) in obese children were significantly lower than those of controls. However, circulating miR-27 (P = 0.032), miR-378 (P < 0.001) and miR-370 (P = 0.045) in obese children were significantly higher, compared with those of controls. In addition, circulating miR-33 in obese children was higher than those of controls, but no significant difference was present (P = 0.687). Our findings showed that a significant association is present between circulating miR-370, miR-33, miR-378, miR-27, miR-335, miR-143 and miR-758 values, and childhood obesity. Low levels of miR-335, miR-143 and miR-758, and high levels of miR-27, miR-378, miR-33 and miR-370 may have been responsible for elevated triglycerides and low-density lipoprotein (LDL-C) levels, and low level of high-density lipoprotein (HDL-C) in obese subjects. Therefore, miRNAs may be a good novel biomarker for childhood obesity. © 2015 World Obesity.

Could circulating fetuin A be a biomarker of aortic valve stenosis?

PubMed

Di Minno, Alessandro; Zanobini, Marco; Myasoedova, Veronika A; Valerio, Vincenza; Songia, Paola; Saccocci, Matteo; Di Minno, Matteo Nicola Dario; Tremoli, Elena; Poggio, Paolo

2017-12-15

Aortic valve stenosis (AVS) is a multifactorial-progressive pathological process. In the past decades, many studies have focus their attention on circulating biomarkers able to identify AVS and/or to predict its progression. One of the many biomarkers studied is the fetuin A. The aim of the present meta-analysis was to evaluate the correlation between fetuin A levels and end-stage AVS. A systematic search was performed in three electronic databases (PubMed, Web of Science and Scopus), looking for studies that compared control subjects with AVS patients and that have measured fetuin A circulating levels in both groups. The main outcome was to evaluate the difference in circulating fetuin A concentration in the two groups. Seven studies, enrolling 2283 AVS patients and 1549 controls, were included. Differences between control subjects and AVS patients were expressed as standardized mean difference (SMD) with pertinent 95% confidence intervals (95%CI) and standard deviation (SD), analysing the data using a random effect model. We found significantly lower circulating levels of fetuin A in AVS patients compared to healthy subjects (SMD: -0.96μg/mL, 95% CI: -1.62, -0.30; p=0.004). In addition, meta-regression analyses showed that several cardiovascular risk factors were significantly associated with circulating levels of fetuin A between patients affected by AVS and healthy controls. In conclusion, our meta-analysis shows that AVS patients have significant lower circulating levels of fetuin A compared to control subjects. However, dedicated studies with large and matched cohorts are needed to validate these findings, evaluating if there is a real link or just a mere association. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels.

PubMed

Mahendran, Yuvaraj; Jonsson, Anna; Have, Christian T; Allin, Kristine H; Witte, Daniel R; Jørgensen, Marit E; Grarup, Niels; Pedersen, Oluf; Kilpeläinen, Tuomas O; Hansen, Torben

2017-05-01

Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with circulating BCAA levels and insulin resistance as instrumental variables. We measured circulating BCAA levels in blood plasma by NMR spectroscopy in 1,321 individuals from the ADDITION-PRO cohort. We complemented our analyses by using previously published genome-wide association study (GWAS) results from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 46,186) and from a GWAS of serum BCAA levels (n = 24,925). We used a genetic risk score (GRS), calculated using ten established fasting serum insulin associated variants, as an instrumental variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10 -7 ). However, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0.045] p = 0.7). By contrast, the insulin-resistance-increasing GRS was significantly associated with increased BCAA levels in ADDITION-PRO (β 0.027 [95% CI 0.005, 0.048] p = 0.01) and in GWAS results for serum BCAA levels (β 1.22 [95% CI 0.71, 1.73] p = 4 × 10 -6 , β 0.96 [95% CI 0.45, 1.47] p = 3 × 10 -4 , and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION-PRO indicated that HOMA-IR is causally related to higher circulating fasting BCAA levels (β 0.73 [95% CI 0.26, 1.19] p = 0.002). Our results suggest that higher BCAA levels do not have a causal effect on insulin resistance while increased insulin resistance drives higher circulating fasting BCAA levels.

Dietary intake of phytoestrogen is associated with increased circulating endothelial progenitor cells in patients with cardiovascular disease.

PubMed

Chan, Yap-Hang; Lam, Tai-Hing; Lau, Kui-Kai; Yiu, Kai-Hang; Siu, Chung-Wah; Li, Sheung-Wai; Chan, Hiu-Ting; Tam, Sidney; Lau, Chu-Pak; Tse, Hung-Fat

2011-06-01

Endogenous estrogen is known to positively influence the level and functionality of endothelial progenitor cells (EPC). However, the effect of phytoestrogen on EPC is unknown. Isoflavone is a major component of phytoestrogen. This study aims to investigate if the intake of isoflavone has any impact on the circulating level of EPC. We studied 102 consecutive patients (mean age: 66.5 ± 9.5 years, 78% male, all female post-menopausal) with cardiovascular disease (atherothrombotic stroke 62%, coronary artery disease 38%). Circulating levels of CD133(+) EPC were determined by flow cytometry. Non-invasive pulse wave velocity (PWV) was measured. Long-term intake of isoflavone was determined by a validated food frequency questionnaire. Isoflavone intake was positively associated with circulating CD133(+) EPC (r = 0.31, p = 0.001). Patients with circulating CD133(+) EPC <10th percentile had significantly lower isoflavone intake than patients with CD133(+)EPC ≥10th percentile (4.6 ± 3.7 mg/day versus 19.3 ± 30.2 mg/day, p < 0.001). A significant overall linear trend of circulating EPC across increasing tertiles of isoflavone intake was observed (p = 0.004). Adjusted for potential confounders, increased isoflavone intake from the 1st to the 3rd tertile independently predicted increased circulating CD133(+) EPC level by 221 cells/µl (95%CI: 71.4 to 369.8, relative increase 160%, p = 0.004). Gender was not a significant factor (p > 0.05). Furthermore, circulating CD133(+) EPC <10th percentile was independently predictive of increased PWV by 261.7 cm/s (95% CI: 37.1 to 486.2, p = 0.024). The study demonstrated that circulating EPC increased by more than one fold in patients with cardiovascular disease who had higher intake of isoflavone, suggesting that isoflavone may confer vascular protection through enhanced endothelial repair.

Levels of free fatty acids (FFA) are associated with insulin resistance but do not explain the relationship between adiposity and insulin resistance in Hispanic Americans: the IRAS Family Study.

PubMed

Miller, Melissa R; Pereira, Rocio I; Langefeld, Carl D; Lorenzo, Carlos; Rotter, Jerome I; Chen, Yii-Der Ida; Bergman, Richard N; Wagenknecht, Lynne E; Norris, Jill M; Fingerlin, Tasha E

2012-09-01

We investigated whether free fatty acids (FFA) mediate the association between adiposity and insulin resistance in the Hispanic-American families of the Insulin Resistance Atherosclerosis Family Study. In 815 Hispanic individuals in the Insulin Resistance Atherosclerosis Family Study, we tested for association between the following: 1) levels of adiposity [body mass index (BMI), visceral and sc adipose tissue area (VAT and SAT)] and circulating levels of FFA; 2) levels of circulating FFA and insulin sensitivity (S(I)); and 3) levels of adiposity and S(I), additionally testing to see whether levels of FFA mediated or modified the relationship between adiposity and S(I.) After adjusting for age, sex, clinic site, and admixture, increasing levels of BMI, VAT, and SAT were weakly associated with increasing levels of circulating FFA (BMI: P = 0.024; VAT: P = 2.33 × 10(-3); SAT: P = 0.018; percent variation explained: ∼1.00%). Increasing levels of circulating FFA were associated with decreasing S(I) (P = 8.10 × 10(-11)). Increasing BMI, VAT, and SAT were also associated with decreasing S(I) (BMI: P = 4.98 × 10(-71); VAT: P = 1.48 × 10(-64); SAT: P = 4.21 × 10(-62)), but this relationship was not significantly mediated by FFA. VAT, but not BMI or SAT, interacts with levels of FFA to influence S(I) (P = 0.021). Although levels of circulating FFA are associated both with increasing adiposity and decreasing S(I), they do not appear to mediate the association between levels of adiposity and S(I) in this large cohort of Hispanic-Americans. These results may indicate that FFA contribute to insulin resistance independent of adiposity.

Circulating magnesium levels and incidence of coronary heart diseases, hypertension, and type 2 diabetes mellitus: a meta-analysis of prospective cohort studies.

PubMed

Wu, Jiang; Xun, Pengcheng; Tang, Qingya; Cai, Wei; He, Ka

2017-09-19

Data on the associations between circulating magnesium (Mg) levels and incidence of coronary heart diseases (CHD), hypertension, and type 2 diabetes mellitus (T2DM) are inconsistent and inconclusive. The aim of this study was to examine circulating Mg levels in relation to incidence of CHD, hypertension, and T2DM. Prospective cohort studies published before May 2017 were searched through PubMed, EmBase, SCOPUS, and Google Scholar. A total of 11 studies that reported multivariable-adjusted associations of interest were identified. Information on the characteristics of study and participants, exposure, main outcomes, risk estimates, and cofounders was extracted and analyzed. Of the 11 included studies, 5 reported results on CHD (38,808 individuals [4437 cases] with an average 10.5-year follow-up), 3 on hypertension (14,876 participants [3149 cases] with a 6.7-year follow-up), and 4 on T2DM (31,284 participants [2680 cases] with an 8.8-year follow-up). Comparing the highest to the lowest category of circulating Mg concentration, the pooled relative risks [RRs] (95% confidence intervals [CIs]) were 0.86 (0.74, 0.996), 0.91 (0.80, 1.02), and 0.64 (0.50, 0.81) for incidence of CHD, hypertension, and T2DM, respectively. Every 0.1 mmol/L increment in circulating Mg levels was associated with 4% (RR, 0.96; 95% CI: 0.94, 0.99) reduction in hypertension incidence. No significant linear association was found between circulating Mg levels and incidence of CHD (RR, 0.89; 95% CI: 0.77, 1.03) and T2DM (RR, 0.90; 95% CI: 0.81, 1.002). The observed associations of interest were sensitive to exclusion of individual studies. Findings in this meta-analysis suggest that circulating Mg levels are inversely associated with incidence of CHD, hypertension, and T2DM. Additional studies are needed to provide more solid evidence and identify the optimal range of circulating Mg concentration with respect to primary prevention of CHD, hypertension, and T2DM.

Circulating metastasis associated in colon cancer 1 transcripts in gastric cancer patient plasma as diagnostic and prognostic biomarker

PubMed Central

Burock, Susen; Herrmann, Pia; Wendler, Ina; Niederstrasser, Markus; Wernecke, Klaus-Dieter; Stein, Ulrike

2015-01-01

AIM: To evaluate the diagnostic and prognostic value of circulating Metastasis Associated in Colon Cancer 1 (MACC1) transcripts in plasma of gastric cancer patients. METHODS: We provide for the first time a blood-based assay for transcript quantification of the metastasis inducer MACC1 in a prospective study of gastric cancer patient plasma. MACC1 is a strong prognostic biomarker for tumor progression and metastasis in a variety of solid cancers. We conducted a study to define the diagnostic and prognostic power of MACC1 transcripts using 76 plasma samples from gastric cancer patients, either newly diagnosed with gastric cancer, newly diagnosed with metachronous metastasis of gastric cancer, as well as follow-up patients. Findings were controlled by using plasma samples from 54 tumor-free volunteers. Plasma was separated, RNA was isolated, and levels of MACC1 as well as S100A4 transcripts were determined by quantitative RT-PCR. RESULTS: Based on the levels of circulating MACC1 transcripts in plasma we significantly discriminated tumor-free volunteers and gastric cancer patients (P < 0.001). Levels of circulating MACC1 transcripts were increased in gastric cancer patients of each disease stage, compared to tumor-free volunteers: patients with tumors without metastasis (P = 0.005), with synchronous metastasis (P = 0.002), with metachronous metastasis (P = 0.005), and patients during follow-up (P = 0.021). Sensitivity was 0.68 (95%CI: 0.45-0.85) and specificity was 0.89 (95%CI: 0.77-0.95), respectively. Importantly, gastric cancer patients with high circulating MACC1 transcript levels in plasma demonstrated significantly shorter survival when compared with patients demonstrating low MACC1 levels (P = 0.0015). Furthermore, gastric cancer patients with high circulating transcript levels of MACC1 as well as of S100A4 in plasma demonstrated significantly shorter survival when compared with patients demonstrating low levels of both biomarkers or with only one biomarker elevated (P = 0.001). CONCLUSION: Levels of circulating MACC1 transcripts in plasma of gastric cancer patients are of diagnostic value and are prognostic for patient survival in a prospective study. PMID:25574109

Effect of aerobic training and resistance training on circulating irisin level and their association with change of body composition in overweight/obese adults: a pilot study.

PubMed

Kim, H-J; Lee, H-J; So, B; Son, J S; Yoon, D; Song, W

2016-06-20

The novel myokine irisin has been reported as a therapeutic target for metabolic disease. The objective of this study is to reveal the effects of aerobic training (AT) and resistance training (RT) on circulating irisin levels and their associations with change of body composition in overweight/obese adults. Twenty eight overweight/obese adults (BMI>23 kg/m(2)) were included in this study and compared before and after 8 weeks of exercise program (60 min/day, 5 times in a week). The subjects, in both aerobic and resistance training, showed significant improvement in anthropometric parameters and exercise capacities including maximal oxygen uptake and muscle strength. Interestingly, the circulating irisin was significantly increased in resistance training group (p=0.002) but not in aerobic training (p=0.426) compared to control group. In addition, we found the positive correlation between change of the circulating irisin and muscle mass (r=0.432, p=0.022) and the negative correlation between change of the circulating irisin and fat mass (r=-0.407, p=0.031). In the present pilot study, we found that circulating irisin level was increased by 8 weeks of resistance training in overweight/obese adults, suggesting that resistance training could be the efficient exercise type in overweight/obese considering positive change of body composition concomitant with increase of irisin levels.

Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota.

PubMed

Serena, Carolina; Ceperuelo-Mallafré, Victoria; Keiran, Noelia; Queipo-Ortuño, Maria Isabel; Bernal, Rosa; Gomez-Huelgas, Ricardo; Urpi-Sarda, Mireia; Sabater, Mónica; Pérez-Brocal, Vicente; Andrés-Lacueva, Cristina; Moya, Andres; Tinahones, Francisco J; Fernández-Real, Jose Manuel; Vendrell, Joan; Fernández-Veledo, Sonia

2018-02-12

Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe-microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk.

Increased body fat mass explains the positive association between circulating estradiol and insulin resistance in postmenopausal women.

PubMed

Marchand, Geneviève B; Carreau, Anne-Marie; Weisnagel, S John; Bergeron, Jean; Labrie, Fernand; Lemieux, Simone; Tchernof, André

2018-05-01

The relationship between circulating estrogen levels and cardiometabolic risk factors such as insulin resistance is unclear in postmenopausal women. High estradiol (E 2 ) levels have been reported to predict increased risk of type 2 diabetes in this population. We aimed to examine associations among estrogen levels, adiposity measurements, and cardiometabolic risk variables including insulin resistance in postmenopausal women. One hundred-one healthy participants (mean ± SD: age 57 ± 4 yr, BMI 27.9 ± 4.8 kg/m 2 ) were included in the analysis. Fifteen plasma steroids or metabolites were measured by liquid chromatography-tandem mass spectrometry. Insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp. Body composition and fat distribution were determined with hydrostatic weighing and computed tomography, respectively. Blood lipids and circulating cytokines were also measured. Circulating E 2 was positively correlated with all adiposity indexes ( r = 0.62 to 0.42, P < 0.0001) except waist-to-hip ratio. E 2 was positively correlated with VLDL-cholesterol, plasma-, VLDL-, and HDL-triglyceride levels ( r = 0.31 to 0.24, P < 0.02) as well as with hs-CRP and IL-6 ( r = 0.52 and 0.29, P < 0.005) and negatively with HDL-cholesterol, adiponectin, and insulin sensitivity ( r = -0.36 to -0.20, P < 0.02). With adjustments for percent body fat, correlations between E 2 and metabolic risk variables were no longer significant. Similar results were observed for circulating estrone (E 1 ) and estrone-sulfate (E 1 -S) levels. In conclusion, circulating estrogen concentrations are proportional to adipose mass in postmenopausal women, although they remain in the low range. Insulin resistance as well as altered blood lipids and cytokines are observed when circulating estrogen levels are high within that range, but these differences are explained by concomitant variation in total adiposity.

Significant sE-Selectin levels reduction after 6 months of anti-TNF-α therapy in non-diabetic patients with moderate-to-severe psoriasis.

PubMed

Genre, Fernanda; Armesto, Susana; Corrales, Alfonso; López-Mejías, Raquel; Remuzgo-Martínez, Sara; Pina, Trinitario; Ubilla, Begoña; Mijares, Verónica; Martín-Varillas, José Luis; Rueda-Gotor, Javier; Portilla, Virginia; Dierssen-Sotos, Trinidad; González-López, Marcos Antonio; González-Vela, María Del Carmen; Blanco, Ricardo; Llorca, Javier; Hernández, José Luis; González-Gay, Miguel Ángel

2017-12-01

Psoriasis patients have high risk of atherosclerosis, characterized by endothelial dysfunction. We aimed to study the association of the endothelial activation biomarkers monocyte chemoattractant protein 1 (MCP-1), soluble (s) E-selectin and P-selectin with disease activity and severity in psoriasis patients treated with anti-TNF-α therapy. Also, to evaluate the relationship of metabolic syndrome features with these biomarkers and the effect of anti-TNF-α therapy on these molecules. Twenty-nine consecutive non-diabetic patients with moderate-to-severe psoriasis who underwent 6 months of anti-TNF-α-adalimumab therapy were studied. Metabolic and clinical evaluation was performed prior to anti-TNF-α treatment (time 0) and 6 months later. MCP-1, sE-selectin and sP-selectin serum levels were determined by ELISA. Dyslipidemic and obese patients showed higher MCP-1 levels at month 6 from the onset of anti-TNF-α therapy (p = .05 and .01, respectively). sE-selectin positively correlated with pro-inflammatory molecules such as asymmetric dimethylarginine, sP-selectin and resistin at baseline and month 6 (p < .05). sE-selectin levels significantly reduced after 6 months of therapy (p = .0006). Metabolic syndrome features are associated with endothelial activation in patients with moderate-to-severe psoriasis. Adalimumab therapy led to a reduction in sE-selectin levels, supporting the beneficial effect of anti-TNF-α therapy on mechanisms associated with the development of atherosclerosis in psoriasis.

Groundwater-saline lakes interaction - The contribution of saline groundwater circulation to solute budget of saline lakes: a lesson from the Dead Sea

NASA Astrophysics Data System (ADS)

Kiro, Yael; Weinstein, Yishai; Starinsky, Abraham; Yechieli, Yoseph

2013-04-01

Saline lakes act as base level for both surface water and groundwater. Thus, a change in lake levels is expected to result in changes in the hydrogeological system in its vicinity, exhibited in groundwater levels, location of the fresh-saline water interface, sub-lacustrine groundwater discharge (SGD) and saline water circulation. All these processes were observed in the declining Dead Sea system, whose water level dropped by ~35 meters in the last 50 years. This work focuses mainly on the effect of circulation of Dead Sea water in the aquifer, which continues even in this very rapid base level drop. In general, seawater circulation in coastal aquifers is now recognized as a major process affecting trace element mass balances in coastal areas. Estimates of submarine groundwater discharge (SGD) vary over several orders of magnitude (1-1000000 m3/yr per meter shoreline). These estimates are sensitive to fresh-saline SGD ratios and to the temporal and spatial scales of the circulation. The Dead Sea system is an excellent natural field lab for studying seawater-groundwater interaction and large-scale circulation due to the absence of tides and to the minor role played by waves. During Dead Sea water circulation in the aquifer several geochemical reactions occur, ranging from short-term adsorption-desorption reactions and up to long-term precipitation and dissolution reactions. These processes affect the trace element distribution in the saline groundwater. Barite and celestine, which are supersaturated in the lake water, precipitate during circulation in the aquifer, reducing barium (from 5 to 1.5 mg/L), strontium (from 350 to 300 mg/L) and the long-lived 226Ra (from 145 to 60 dpm/L) in the saline groundwater. Redox-controlled reactions cause a decrease in uranium from 2.4 to 0.1 μg/L, and an increase in iron from 1 to 13 mg/L. 228Ra (t1/2=5.75 yr) activity in the Dead Sea is ~1 dpm/L and increase gradually as the saline water flows further inland until reaching steady-state activities (~27 dpm/L) with the aquifer sediments. The decrease in 226Ra and increase in 228Ra in the circulation process provide a robust method for calculating the amount of Dead Sea water circulating in the aquifer. This process can affect trace element concentrations in the Dead Sea and emphasize the potential of long-term seawater circulation in mass balances of saline water bodies.

Circulating tocopherols and risk of coronary artery disease: A systematic review and meta-analysis.

PubMed

Li, Guangxiao; Li, Ying; Chen, Xin; Sun, Hao; Hou, Xiaowen; Shi, Jingpu

2016-05-01

Circulating level of tocopherols was supposed to be associated with risk of coronary artery disease. However, the results from previous studies remain controversial. Therefore, we conducted a meta-analysis based on observational studies to evaluate the association between circulating tocopherols and coronary artery disease risk for the first time. Meta-analysis. PubMed, Embase and Cochrane databases were searched to retrieve articles published during January 1995 and May 2015. Articles were included if they provided sufficient information to calculate the weighted mean difference and its corresponding 95% confidence interval. Circulating level of total tocopherols was significantly lower in coronary artery disease patients than that in controls (weighted mean difference -4.33 μmol/l, 95% confidence interval -6.74 to -1.91, P < 0.01). However, circulating α-tocopherol alone was not significantly associated with coronary artery disease risk. Results from subgroup analyses showed that a lower level of circulating total tocopherols was merely associated with higher coronary artery disease risk in studies with higher sex ratio in cases (<2, weighted mean difference -0.07 μmol/l, 95% confidence interval -1.15 to 1.00, P = 0.90; ≥ 2, weighted mean difference -6.00 μmol/l, 95% confidence interval -9.76 to -2.22, P < 0.01). Similarly, a lower level of circulating total tocopherols was associated with early onset coronary artery disease rather than late onset coronary artery disease (<60 years, weighted mean difference -5.40 μmol/l, 95% confidence interval -9.22 to -1.57, P < 0.01; ≥ 60 years, weighted mean difference -1.37 μmol/l, 95% confidence interval -3.48 to 0.74, P = 0.20). We also found some discrepancies in circulating total tocopherols when the studies were stratified by matching status and assay methods. Our findings suggest that a deficiency in circulating total tocopherols might be associated with higher coronary artery disease risk. Whereas circulating α-tocopherol alone could not protect us from developing coronary artery disease. Further prospective studies were warranted to confirm our findings. © The European Society of Cardiology 2015.

Oxidative stress and inflammatory response increase during coronary artery bypass grafting with extracorporeal circulation.

PubMed

Melek, Flora Eli; Baroncini, Liz Andréa Villela; Repka, João Carlos Domingus; Nascimento, Celso Soares; Précoma, Dalton Bertolim

2012-01-01

Thiobarbituric acid-reactive substance is a marker of oxidative stress and has cytotoxic and genotoxic actions. C- reactive protein is used to evaluate the acute phase of inflammatory response. To assess the thiobarbituric acid-reactive substance and C-reactive protein levels during extracorporeal circulation in patients submitted to cardiopulmonary bypass. Twenty-five consecutive surgical patients (16 men and nine women; mean age 61.2 ± 9.7 years) with severe coronary artery disease diagnosed by angiography scheduled for myocardial revascularization surgery with extracorporeal circulation were selected. Blood samples were collected immediately before initializing extracorporeal circulation, T0; in 10 minutes, T10; and in 30 minutes, T30. The thiobarbituric acid-reactive substance levels increased after extracorporeal circulation (P=0.001), with average values in T0=1.5 ± 0.07; in T10=5.54 ± 0.35; and in T30=3.36 ± 0.29 mmoles/mg of serum protein. The C-reactive protein levels in T0 were negative in all samples; in T10 average was 0.96 ± 0.7 mg/dl; and in T30 average was 0.99 ± 0.76 mg/dl. There were no significant differences between the dosages in T10 and T30 (P=0.83). C-reactive protein and thiobarbituric acid-reactive substance plasma levels progressively increased during extracorporeal circulation, with maximum values of thiobarbituric acid-reactive substance at 10 min and of C-reactive protein at 30 min. It suggests that there are an inflammatory response and oxidative stress during extracorporeal circulation.

Airway and serum adipokines after allergen and diesel exposure in a controlled human crossover study of atopic adults.

PubMed

Kramer, Marabeth M; Hirota, Jeremy A; Sood, Akshay; Teschke, Kay; Carlsten, Christopher

2017-04-01

Adipokines are mediators released from adipose tissue. These proteins are regarded as active elements of systemic and pulmonary inflammation, whose dysregulation can alter an individual's risk of developing allergic lung diseases. Despite this knowledge, adipokine responses to inhaled stimuli are poorly understood. We sought to measure serum and lung adiponectin, leptin, and resistin in an atopic adult study population following exposure to allergen and diesel exhaust (DE). Two types of lung samples including bronchoalveolar lavage (BAL) and bronchial wash (BW), and a time course of serum samples, were collected from the 18 subjects who participated in the randomized, double-blinded controlled human study. The two crossover exposure triads in this study were inhaled DE and filtered air each followed by instilled allergen or saline. Serum and lung adipokine responses to these exposures were quantified using enzyme-linked immunosorbent assay. Allergen significantly increased adiponectin and leptin in BAL, and adiponectin in the BW 48 hours after exposure. Serum leptin and resistin responses were not differentially affected by exposure, but varied over time. Coexposure with DE and allergen revealed significant correlations between the adiponectin/leptin ratio and FEV 1 changes and airway responsiveness measures. Changes in lung and serum adipokines in response to allergen exposure were identified in the context of a controlled exposure study. Coexposure identified a potentially protective role of adiponectin in the lung. This response was not observed in those with baseline airway hyper-responsiveness, or after allergen exposure alone. The clinical relevance of this potentially adaptive adipokine pattern warrants further study. Copyright © 2016 Elsevier Inc. All rights reserved.

Visfatin alters the cytokine and matrix-degrading enzyme profile during osteogenic and adipogenic MSC differentiation.

PubMed

Tsiklauri, Lali; Werner, Janina; Kampschulte, Marian; Frommer, Klaus W; Berninger, Lucija; Irrgang, Martina; Glenske, Kristina; Hose, Dirk; El Khassawna, Thaqif; Pons-Kühnemann, Jörn; Rehart, Stefan; Wenisch, Sabine; Müller-Ladner, Ulf; Neumann, Elena

2018-06-13

Age-related bone loss is associated with bone marrow adiposity. Adipokines (e.g. visfatin, resistin, leptin) are adipocyte-derived factors with immunomodulatory properties and might influence differentiation of bone marrow-derived mesenchymal stem cells (MSC) in osteoarthritis (OA) and osteoporosis. Thus, the presence of adipokines and MMPs in bone marrow and their effects on MSC differentiation were analyzed. MSC and RNA were isolated from femoral heads after hip replacement surgery of OA or osteoporotic femoral neck fracture (FF) patients. Bone structural parameters were evaluated by μCT. MSC were differentiated towards adipocytes or osteoblasts with/without adipokines. Gene expression (adipokines, bone marker genes, MMPs, TIMPs) and cytokine production was evaluated by realtime-PCR and ELISA. Matrix mineralization was quantified using Alizarin red S staining. μCT showed an osteoporotic phenotype of FF compared to OA bone (reduced trabecular thickness and increased ratio of bone surface vs. volume of solid bone). Visfatin and leptin were increased in FF vs OA. Visfatin induced the secretion of IL-6, IL-8, and MCP-1 during osteogenic and adipogenic differentiation. In contrast to resistin and leptin, visfatin increased MMP2 and MMP13 during Adipognesis. In osteogenically differentiated cells, MMPs and TIMPs were reduced by visfatin. Visfatin significantly increased matrix mineralization during osteogenesis, whereas collagen type I expression was reduced. Visfatin-mediated increase of matrix mineralization and reduced collagen type I expression could contribute to bone fragility. Visfatin is involved in impaired bone remodeling at the adipose tissue/bone interface through induction of proinflammatory factors and dysregulated MMP/TIMP balance during MSC differentiation. Copyright © 2018. Published by Elsevier Ltd.

Higher Leptin and Adiponectin Concentrations Predict Poorer Performance-based Physical Functioning in Midlife Women: the Michigan Study of Women’s Health Across the Nation

PubMed Central

Zheng, Huiyong; Mancuso, Peter; Harlow, Siobán D.

2016-01-01

Background. Excess fat mass is a greater contributor to functional limitations than is reduced lean mass or the presence of obesity-related conditions. The impact of fat mass on physical functioning may be due to adipokines, adipose-derived proteins that have pro- or anti-inflammatory properties. Methods. Serum samples from 1996 to 2003 that were assayed for leptin, adiponectin, and resistin were provided by 511 participants from the Michigan site of the Study of Women’s Health Across the Nation. Physical functioning performance was assessed annually during study visits from 1996 to 2003. Results. Among this population of Black and White women (mean baseline age = 45.6 years, SD = 2.7 years), all of whom were premenopausal at baseline, higher baseline leptin concentrations predicted longer stair climb, sit-to-rise, and 2-pound lift times and shorter forward reach distance (all p < .01). This relationship persisted after adjustment for age, BMI, percent skeletal muscle mass, race/ethnicity, economic strain, bodily pain, diabetes, knee osteoarthritis, and C-reactive protein. Baseline total adiponectin concentrations did not predict any mobility measures but did predict quadriceps strength; a 1 µg/mL higher adiponectin concentration was associated with 0.64 Nm lower quadriceps strength (p = .02). Resistin was not associated with any of the physical functioning performance measures. Change in the adipokines was not associated with physical functioning. Conclusion. In this population of middle-aged women, higher baseline leptin concentrations predicted poorer mobility-based functioning, whereas higher adiponectin concentrations predicted reduced quadriceps strength. These findings suggest that the relationship between the adipokines and physical functioning performance is independent of other known correlates of poor functioning. PMID:26302979

Association of ADIPOQ, leptin, LEPR, and resistin polymorphisms with obesity parameters in Hammam Sousse Sahloul Heart Study.

PubMed

Zayani, Nesrine; Omezzine, Asma; Boumaiza, Imen; Achour, Ons; Rebhi, Lamia; Rejeb, Jihen; Ben Rejeb, Nabila; Ben Abdelaziz, Ahmed; Bouslama, Ali

2017-11-01

Adipose tissue is an important endocrine organ that secretes a number of adipokines, such as adiponectin (ADIPOQ), leptin (LEP), leptin receptor (LEPR), and resistin (RETN) which may be implicated in obesity. Some adipokines' polymorphisms of genes might influence their concentrations and/or activities. Our aim was to study the relationship between seven SNPs in ADIPOQ (+45T

Effect of maternal body mass index on hormones in breast milk: a systematic review.

PubMed

Andreas, Nicholas J; Hyde, Matthew J; Gale, Chris; Parkinson, James R C; Jeffries, Suzan; Holmes, Elaine; Modi, Neena

2014-01-01

Maternal Body Mass Index (BMI) is positively associated with infant obesity risk. Breast milk contains a number of hormones that may influence infant metabolism during the neonatal period; these may have additional downstream effects on infant appetite regulatory pathways, thereby influencing propensity towards obesity in later life. To conduct a systematic review of studies examining the association between maternal BMI and the concentration of appetite-regulating hormones in breast milk. Pubmed was searched for studies reporting the association between maternal BMI and leptin, adiponectin, insulin, ghrelin, resistin, obestatin, Peptide YY and Glucagon-Like Peptide 1 in breast milk. Twenty six studies were identified and included in the systematic review. There was a high degree of variability between studies with regard to collection, preparation and analysis of breast milk samples. Eleven of fifteen studies reporting breast milk leptin found a positive association between maternal BMI and milk leptin concentration. Two of nine studies investigating adiponectin found an association between maternal BMI and breast milk adiponectin concentration; however significance was lost in one study following adjustment for time post-partum. No association was seen between maternal BMI and milk adiponectin in the other seven studies identified. Evidence for an association between other appetite regulating hormones and maternal BMI was either inconclusive, or lacking. A positive association between maternal BMI and breast milk leptin concentration is consistently found in most studies, despite variable methodology. Evidence for such an association with breast milk adiponectin concentration, however, is lacking with additional research needed for other hormones including insulin, ghrelin, resistin, obestatin, peptide YY and glucagon-like peptide-1. As most current studies have been conducted with small sample sizes, future studies should ensure adequate sample sizes and standardized methodology.

Resistin polymorphisms are associated with muscle, bone, and fat phenotypes in white men and women.

PubMed

Pistilli, Emidio E; Gordish-Dressman, Heather; Seip, Richard L; Devaney, Joseph M; Thompson, Paul D; Price, Thomas B; Angelopoulos, Theodore J; Clarkson, Priscilla M; Moyna, Niall M; Pescatello, Linda S; Visich, Paul S; Zoeller, Robert F; Hoffman, Eric P; Gordon, Paul M

2007-02-01

The biological function of resistin (RST) is unknown, although it may have roles in obesity, diabetes, and insulin resistance. The objective of this study was to examine the effects of single nucleotide polymorphisms (SNPs) in the human RST gene on muscle, bone, and adipose tissue phenotypes and in response to resistance training (RT). Subjects were white and consisted of strength (n = 482) and size (n = 409) cohorts who had not performed RT in the previous year. Subjects completed 12 weeks of structured, unilateral upper arm RT aimed at increasing the size and strength of the non-dominant arm, using their dominant arm as an untrained control. Strength measurements were taken pre- and post-12-week RT and consisted of elbow flexor isometric strength and one-repetition maximum during a biceps curl using free weights. Whole muscle, subcutaneous fat, and cortical bone volumes were measured by magnetic resonance imaging. Six RST SNPs were identified. Analysis of covariance was used to test for effects of the SNPs on pre- and post-muscle strength and whole muscle, fat, and bone volumes independent of gender, age, and body weight. Five RST SNPs (-537 A>C, -420 C>G, 398 C>T, 540 G>A, 980 C>G) were associated with measured phenotypes among subjects when stratified by BMI (<25, >/ or = 25 kg/m(2)). Several gender-specific associations were observed between RST SNPs and phenotypes among individuals with a BMI > or = 25. Conversely, only two associations were observed among individuals with a BMI < 25. These data support previous identified associations of RST with adipose tissue and demonstrate additional associations with bone and skeletal muscle that warrant further investigation.

Sibutramine and L-carnitine compared to sibutramine alone on insulin resistance in diabetic patients.

PubMed

Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Gravina, Alessia; Mereu, Roberto; D'Angelo, Angela; Palumbo, Ilaria; Randazzo, Sabrina; Cicero, Arrigo F G

2010-01-01

To evaluate the effects of one year of treatment with sibutramine plus L-carnitine compared to sibutramine on body weight, glycemic control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-four patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) >8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). There was a decrease in body weight, BMI, HbA(1c), FPI, HOMA-IR, and RBP-4 in both groups, even when the values obtained with sibutramine plus L-carnitine were lower than the values obtained in sibutramine group. There was a faster decrease of FPG, PPG, TC, LDL-C, resistin and Hs-CRP with sibutramine plus L-carnitine even when no differences between the two groups were obtained. Furthermore, only sibutramine plus L-carnitine improved Tg, and visfatin. Sibutramine plus L-carnitine gave a faster improvement of lipid profile, insulin resistance parameters, glycemic control, and body weight compared to sibutramine.

Biological signatures of asymptomatic extra- and intracranial atherosclerosis: the Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study.

PubMed

López-Cancio, Elena; Galán, Amparo; Dorado, Laura; Jiménez, Marta; Hernández, María; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Barallat, Jaume; Massuet, Anna; Alzamora, Maria Teresa; Dávalos, Antonio; Arenillas, Juan Francisco

2012-10-01

Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis. The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects >50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index. After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD-extracranial atherosclerotic disease. Our findings show distinct clinical and biological profiles in subclinical ICAD and extracranial atherosclerotic disease. Insulin resistance emerged as an important molecular pathway involved in the development of ICAD from its asymptomatic stage.

Circulation weather types and their influence on precipitation in Serbia

NASA Astrophysics Data System (ADS)

Putniković, Suzana; Tošić, Ivana; Đurđević, Vladimir

2016-10-01

An objective classification scheme of atmospheric circulation, in which daily circulation is determined by the strength, direction, and vorticity of geostrophic flow, has been applied to the atmosphere over Serbia for the time period 1961-2010. The results for the sea level and isobaric level of 500 hPa for winter and summer are presented. The 26 circulation types (eight pure direction, 16 hybrid, cyclonic, and anticyclonic types) are determined and described. Each of the circulation types has a distinct underlying synoptic pattern that produces the expected type and direction of flow over the study area. The relative frequencies of the circulation types, and the relationship between the precipitation and circulation types at three stations on a seasonal time scale are analyzed. The anticyclonic weather type dominates in winter (18.93 %) and summer (18.70 %), followed by the northeasterly type (16.65 %) in summer, and the cyclonic type (12.83 %) in winter. The cyclonic types (C and hybrid) have a higher than average probability of rain at all stations. Conversely, the anticyclonic types are associated with a lower than average probability and intensity of rainfall.

Sex differences and the impact of steroid hormones on the developing human brain.

PubMed

Neufang, Susanne; Specht, Karsten; Hausmann, Markus; Güntürkün, Onur; Herpertz-Dahlmann, Beate; Fink, Gereon R; Konrad, Kerstin

2009-02-01

Little is known about the hormonal effects of puberty on the anatomy of the developing human brain. In a voxel-based morphometry study, sex-related differences in gray matter (GM) volume were examined in 46 subjects aged 8-15 years. Males had larger GM volumes in the left amygdala, whereas females had larger right striatal and bilateral hippocampal GM volumes than males. Sexually dimorphic areas were related to Tanner stages (TS) of pubertal development and to circulating level of steroid hormones in a subsample of 30 subjects. Regardless of sex, amygdala and hippocampal volumes varied as a function of TS and were associated with circulating testosterone (TEST) levels. By contrast, striatal GM volumes were unrelated to pubertal development and circulating steroid hormones. Whole-brain regression analyses revealed positive associations between circulating estrogen levels and parahippocampal GM volumes as well as between TEST levels and diencephalic brain structures. In addition, a negative association was found between circulating TEST and left parietal GM volumes. These data suggest that GM development in certain brain regions is associated with sexual maturation and that pubertal hormones might have organizational effects on the developing human brain.

Genetic and Dietary Determinants of Insulin-Like Growth Factor (IGF)-1 and IGF Binding Protein (BP)-3 Levels among Chinese Women

PubMed Central

Li, Hui; McCullough, Lauren E.; Qi, Ya-na; Li, Jia-yuan; Zhang, Jing; Miller, Erline; Yang, Chun-xia; Smith, Jennifer S.

2014-01-01

Background Higher insulin-like growth factor (IGF)-1 and lower IGF binding protein (BP)-3 levels have been associated with higher commoncancer risk, including breast cancer. Dietary factors, genetic polymorphisms, and the combination of both may influence circulating IGF-1 and IGFBP-3 serum concentrations. Methods From September 2011 to July 2012, we collected demographic, reproductive and dietary data on 143 women (≥40 years). We genotyped IGF-1 rs1520220 and IGFBP-3 rs2854744 and measured circulating IGF-1 and IGFBP-3 levels in serum. Covariance analyses were used to estimate the associations of serum levels of IGF-1 and IGFBP-3, and the molar ratio of IGF-1to IGFBP-3 with IGF-1 rs1520220 and IGFBP-3 rs2854744 genotypes. We subsequently assessed the combined influence of genetics and diet (daily intake of protein, fat and soy isoflavones) on IGF-1 and IGFBP-3 levels. Results Among women aged less than 50 years, circulating IGF-1 serum levels were significantly lower for those with CC genotype for IGF-1 rs1520220 than levels for those with the GC or GG genotypes (in recessive model: P = 0.007).In gene-diet analyses among these women, we found carrying CC genotype for IGF-1 rs1520220 and high soy isoflavone intake tend to be associated with lower circulating IGF-1 levels synthetically (P = 0.002). Women with GG or GC genotypes for IGF-1 rs1520220 and with low intake of soy isoflavones had the highest levels of circulating IGF-1 (geometric mean [95% CI]: 195 [37, 1021] µg/L). Comparatively, women with both the CC genotype and high soy intake had the lowest levels of circulating IGF-1 (geometric mean [95% CI]: 120 [38,378] µg/L). Conclusions IGF-1 serum levels are significantly lower among women with the CC genotype for IGF-1-rs1520220. High soy isoflavone intake may interact with carrying CC genotype for IGF-1-rs1520220 to lower women's serum IGF-1 levels more. PMID:25285521

Circulating prolactin level in systemic lupus erythematosus and its correlation with disease activity: a meta-analysis.

PubMed

Song, G G; Lee, Y H

2017-10-01

Objective This study aimed to evaluate the relationship between circulating prolactin level and systemic lupus erythematosus (SLE), and to establish a correlation between plasma/serum prolactin levels and SLE activity. Methods We performed a meta-analysis comparing the plasma/serum prolactin levels in patients with SLE to controls, and examined correlation coefficients between circulating prolactin level and SLE disease activity. Results Twenty-five studies with a total of 1056 SLE patients and 426 controls were included. Prolactin levels were significantly higher overall in the SLE group than in the control group (standardized mean difference (SMD) = 0.987, 95% CI = 0.512-1.463, p = 4.7 × 10 -5 ). Stratification by ethnicity showed significantly elevated prolactin levels in the SLE group in Asian, Latin American, and mixed populations (SMD = 0.813, 95% CI = 0.137-1.490, p = 0.018; SMD = 0.981, 95% CI = 0.307-1.655, p = 0.004; SMD = 1.469, 95% CI = 0.443-2.495, p = 0.005, respectively), but not in the European population. Subgroup analysis by sample size showed significantly higher prolactin levels in the SLE group by small ( n < 30) and large sample numbers ( n > 30). Meta-analysis of correlation coefficients showed a significantly positive correlation between circulating prolactin level and SLE activity (correlation coefficient = 0.379, 95% CI = 0.026-0.487, p = 4.0 × 10 -9 ). Circulating prolactin levels were positively associated with SLE activity in European, Asian, and mixed populations (SMD = 0.532, 95% CI = 0.443-0.609  p < 1.0 × 10 -8 ; SMD = 0.427, 95% CI = 0.240-0.583, p = 2.4 × 10 -5 ; SMD = 0.433, 95% CI = 0.212-0.591, p = 2.7 × 10 -5 , respectively). Conclusions Our meta-analysis demonstrated that circulating prolactin levels are higher in patients with SLE, and that a significantly positive correlation exists between prolactin levels and SLE activity.

PATHOGENESIS OF FEVER: EFFECTS OF VARIOUS ENDOGENOUS PYROGENS UPON THE LEVEL OF CIRCULATING GRANULOCYTES IN NORMAL RABBITS

PubMed Central

King, M. K.

1960-01-01

The endogenous pyrogen in the serum or plasma of rabbits 2 hours after the intravenous injection of typhoid vaccine had a marked effect on the circulating leucocytes of normal rabbits. Immediately following intravenous injection there was a brief, but marked, granulocytopenia which was quickly followed by a granulocytosis. Under the same circumstances pooled heterologous serum or plasma from normal rabbits produced no fever or significant change in the level of circulating leucocytes. The cell-free fluid of sterile peritoneal exudates produced a marked leucocytosis without a preceding leucopenia when injected intravenously into normal rabbits. When comparably pyrogenic doses of typhoid vaccine were injected in the same manner no significant change in the level of circulating leucocytes occurred. The relevance of these findings to the pathogenesis of fever is discussed. PMID:13756095

Pathogenesis of fever: effects of various endogenous pyrogens upon the level of circulating granulocytes in normal rabbits.

PubMed

KING, M K

1960-11-01

The endogenous pyrogen in the serum or plasma of rabbits 2 hours after the intravenous injection of typhoid vaccine had a marked effect on the circulating leucocytes of normal rabbits. Immediately following intravenous injection there was a brief, but marked, granulocytopenia which was quickly followed by a granulocytosis. Under the same circumstances pooled heterologous serum or plasma from normal rabbits produced no fever or significant change in the level of circulating leucocytes. The cell-free fluid of sterile peritoneal exudates produced a marked leucocytosis without a preceding leucopenia when injected intravenously into normal rabbits. When comparably pyrogenic doses of typhoid vaccine were injected in the same manner no significant change in the level of circulating leucocytes occurred. The relevance of these findings to the pathogenesis of fever is discussed.

Association of serum uric acid with high-sensitivity C-reactive protein in postmenopausal women.

PubMed

Raeisi, A; Ostovar, A; Vahdat, K; Rezaei, P; Darabi, H; Moshtaghi, D; Nabipour, I

2017-02-01

To explore the independent correlation between serum uric acid and low-grade inflammation (measured by high-sensitivity C-reactive protein, hs-CRP) in postmenopausal women. A total of 378 healthy Iranian postmenopausal women were randomly selected in a population-based study. Circulating hs-CRP levels were measured by highly specific enzyme-linked immunosorbent assay method and an enzymatic calorimetric method was used to measure serum levels of uric acid. Pearson correlation coefficient, multiple linear regression and logistic regression models were used to analyze the association between uric acid and hs-CRP levels. A statistically significant correlation was seen between serum levels of uric acid and log-transformed circulating hs-CRP (r = 0.25, p < 0.001). After adjustment for age and cardiovascular risk factors (according to NCEP ATP III criteria), circulating hs-CRP levels were significantly associated with serum uric acid levels (β = 0.20, p < 0.001). After adjustment for age and cardiovascular risk factors, hs-CRP levels ≥3 mg/l were significantly associated with higher uric acid levels (odds ratio =1.52, 95% confidence interval 1.18-1.96). Higher serum uric acid levels were positively and independently associated with circulating hs-CRP in healthy postmenopausal women.

Effects of polychlorinated biphenyl (PCB) on regulation of thyroid-, growth-, and neurochemically related developmental processes in young rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juarez de Ku, L.M.

1992-01-01

Neonatal exposure to the toxic chemical polychlorinated biphenyl (PCB) induces hypothyroidism and retarded growth. Neonatal rats made hypothyroid by chemical or surgical means experience retarded growth and subnormal activity of choline acetyltransferase (ChAT) This study compared thyroid-, growth-, and neurochemically-related processes altered by hypothyroidism induced by other means, with PCB-induced hypothyroidism: (1) titers of thyroid stimulating hormone (TSH); (2) titers of hormones that regulate growth [growth hormone (GH), insulin-growth like factor-I (IGF-1), growth hormone releasing hormone (GHRH) and somatostatin (SS)]; or (3) brain ChAT activity. Whether PCB-induced growth retardation and other alterations are secondary to accompanying hypothyroidism rather than ormore » in addition to a direct effect of PCB was also examined. Pregnant rats were fed chow containing 0 (controls), 62.5, 125, or 250 ppm PCB (entering offspring through placenta and milk) throughout pregnancy and lactation. Neonates exposed to PCB displayed many alterations similar to those made hypothyroid by other means: depression of overall and skeletal growth, circulating by other means: depression of overall and skeletal growth, circulating T[sub 4] levels and ChAT activity, and no change in hypothalamic GHRH and SS concentrations. Differences included a paradoxical increase in circulating GH levels, and no significant alteration of circulation IGF-1 and TSH levels and pituitary GH and TSH levels (although trends were in the expected direction). Thus, PCB-induced hypothyroidism may partially cause altered skeletal growth, circulating GH and TSH concentrations, and ChAT activity. Both T[sub 4] and T[sub 3] injections returned circulating TSH and GH levels and pituitary TSH content toward control levels; T[sub 3] restored skeletal, but not overall growth; and T[sub 4] elevated ChAT activity.« less

Usefulness of Circulating Decoy Receptor 3 in Predicting Coronary Artery Disease Severity and Future Major Adverse Cardiovascular Events in Patients With Multivessel Coronary Artery Disease.

PubMed

Chang, Ting-Yung; Hsu, Chien-Yi; Huang, Po-Hsun; Chiang, Chia-Hung; Leu, Hsin-Bang; Huang, Chin-Chou; Chen, Jaw-Wen; Lin, Shing-Jong

2015-10-01

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an antiapoptotic soluble receptor considered to play an important role in immune modulation and has pro-inflammatory functions. This study was designed to test whether circulating DcR3 levels are associated with coronary artery disease (CAD) severity and predict future major adverse cardiovascular events (MACEs) in patients with CAD. Circulating DcR3 levels and the Syntax score (SXscore) were determined in patients with multivessel CAD. The primary end point was the MACE within 12 months. In total, 152 consecutive patients with angiographically confirmed multivessel CAD who had received percutaneous coronary intervention were enrolled and were divided into 3 groups according to CAD lesion severity. Group 1 was defined as low SXscore (≤13), group 2 as intermediate SXscore (>13 and ≤22), and group 3 as high SXscore (>22). DcR3 levels were significantly higher in the high SXscore group than the other 2 groups (13,602 ± 7,256 vs 8,025 ± 7,789 vs 4,637 ± 4,403 pg/ml, p <0.001). By multivariate analysis, circulating DcR3 levels were identified as an independent predictor for high SXscore (adjusted odds ratio 1.15, 95% confidence interval 1.09 to 1.21; p <0.001). The Kaplan-Meier analysis showed that increased circulating DcR3 levels are associated with enhanced 1-year MACE in patients with multivessel CAD (log-rank p <0.001). In conclusion, increased circulating DcR3 levels are associated with CAD severity and predict future MACE in patients with multivessel CAD. Copyright © 2015 Elsevier Inc. All rights reserved.

Large-scale circulation departures related to wet episodes in north-east Brazil

NASA Technical Reports Server (NTRS)

Sikdar, Dhirendra N.; Elsner, James B.

1987-01-01

Large scale circulation features are presented as related to wet spells over northeast Brazil (Nordeste) during the rainy season (March and April) of 1979. The rainy season is divided into dry and wet periods; the FGGE and geostationary satellite data was averaged; and mean and departure fields of basic variables and cloudiness were studied. Analysis of seasonal mean circulation features show: lowest sea level easterlies beneath upper level westerlies; weak meridional winds; high relative humidity over the Amazon basin and relatively dry conditions over the South Atlantic Ocean. A fluctuation was found in the large scale circulation features on time scales of a few weeks or so over Nordeste and the South Atlantic sector. Even the subtropical High SLPs have large departures during wet episodes, implying a short period oscillation in the Southern Hemisphere Hadley circulation.

Large-scale circulation departures related to wet episodes in northeast Brazil

NASA Technical Reports Server (NTRS)

Sikdar, D. N.; Elsner, J. B.

1985-01-01

Large scale circulation features are presented as related to wet spells over northeast Brazil (Nordeste) during the rainy season (March and April) of 1979. The rainy season season is devided into dry and wet periods, the FGGE and geostationary satellite data was averaged and mean and departure fields of basic variables and cloudiness were studied. Analysis of seasonal mean circulation features show: lowest sea level easterlies beneath upper level westerlies; weak meridional winds; high relative humidity over the Amazon basin and relatively dry conditions over the South Atlantic Ocean. A fluctuation was found in the large scale circulation features on time scales of a few weeks or so over Nordeste and the South Atlantic sector. Even the subtropical High SLP's have large departures during wet episodes, implying a short period oscillation in the Southern Hemisphere Hadley circulation.

Circulating leptin level in rheumatoid arthritis and its correlation with disease activity: a meta-analysis.

PubMed

Lee, Y H; Bae, S-C

2016-12-01

This study aimed to evaluate the relationship between the circulating serum leptin level and rheumatoid arthritis (RA) and to establish a correlation between serum leptin levels and RA activity. We searched the PUBMED, EMBASE, and Cochrane databases. A meta-analysis was performed, comparing the serum/plasma leptin levels in patients with RA and healthy controls. Correlation coefficients between serum leptin level and either disease activity score 28 (DAS28) or C‑reactive protein (CRP) in RA patients were also examined. Thirteen studies with a total of 648 RA patients and 426 controls were included in this meta-analysis. Circulating leptin level was significantly higher in the RA group than in the control group (SMD = 1.056, 95 % CI = 0.647-1.465, p = 4.2 × 10 -7 ). In addition, stratification by ethnicity showed a significantly elevated leptin level in the RA group in Caucasian, Turkish, and Arab populations (SMD = 0.813, 95 % CI = 0.137-1.490, p = 0.018, SMD = 0.981, 95 % CI = 0.307-1.655, p = 0.004, and SMD = 1.469, 95 % CI = 0.443-2.495, p = 0.005 respectively). A meta-analysis of correlation coefficients showed a small but significantly positive correlation between the circulating leptin level and either DAS28 (correlation coefficient = 0.275, 95 % CI = 0.076-0.452, p = 0.007) or CRP (correlation coefficient = 0.274, 95 % CI = 0.068-0.458, p = 0.010). Our meta-analysis demonstrated that the circulating leptin level is significantly higher in patients with RA and that a small but significantly positive correlation exists between leptin levels and RA activity.

CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells are positively correlated with levels of IL-21 in active and transitional cystic echinococcosis patients.

PubMed

Zhang, Fengbo; Pang, Nannan; Zhu, Yuejie; Zhou, Dexian; Zhao, Hui; Hu, Jinwei; Ma, Xiumin; Li, Jun; Wen, Hao; Samten, Buka; Fan, Haining; Ding, Jianbing

2015-10-26

In our study, we investigated whether circulating T follicular helper (Tfh) and the related cytokines are involved in human cystic echinococcosis (CE). A total of 64 patients with CE and 30 healthy controls were enrolled in this study. Percentages of CCR7(lo)PD-1(hi) cells within CXCR5(+) CD4(+) T cells (circulating Tfh cells) were detected by flow cytometry. Levels of IL-21 and IL-4 in peripheral blood were detected by cytometric bead array. The mRNA expression of IL-21, IL-4, Bcl-6, and Blimp-1 in peripheral blood mononuclear cells (PBMCs) were measured by real-time PCR. Levels of IgG1, IgG2, IgG3, and IgG4 in the patients' sera were measured using enzyme-linked immunosorbent assay. Percentages of circulating Tfh cells were significantly increased in the CE1, CE2, and CE3 groups (p < 0.05). The concentrations of IL-21 and IL-4 in the serum were significantly increased in CE1, CE2, and CE3 groups (p < 0.05). IL-21 was positively correlated with circulating Tfh cells in CE3 group (r = 0.779, p < 0.05). The mRNA levels of IL-21, IL-4, and Bcl-6 were increased in CE1, CE2, and CE3 groups. Levels of IgG1 and IgG4 in patients' sera were increased in CE1, CE2, and CE3 groups. Levels of IgG2 and IgG3 were increased in CE4-5 group. Additionally, after stimulation with hydatid fluid in vitro, the levels of circulating Tfh cells, IL-21 and IL-4 in PBMCs isolated from CE patients were significantly increased (p < 0.05). The levels of circulating Tfh and related cytokines were significantly increased in CE patients, suggesting that they are involved in human CE.

Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

PubMed

Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

2010-04-09

Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

Numerical simulations of a transverse indirect circulation and low-level jet in the exit region of an upper-level jet

NASA Technical Reports Server (NTRS)

Brill, K. F.; Uccellini, L. W.; Burkhart, R. P.; Warner, T. T.; Anthes, R. A.

1985-01-01

A numerical study was performed of a severe weather event (tornado) which occurred on May 10, 1973 in the Ohio region. The situation was modeled with a primitive equation mesoscale dynamic formulation. Account was taken of precipitation, the planetary boundary layer parameters as bulk quantities, the vertical pressure gradient, and lateral boundary conditions based on radiosonde data. Two 12-hr simulations, adiabatic and nondivergent, respectively, were analyzed for relationships between upper and lower level jets. In the adiabatic formulation, a transverse circulation with a low level jet formed at the exit region of the upper level jet. The nondivergent situation led to similar, but weaker, phenomena. Both forms suggest that indirect circulation in the exit zone of an upper level jet is strongly influenced by the initial structure of the jet.

Gynaecomastia complicating the treatment of myeloma.

PubMed Central

Large, D. M.; Jones, J. M.; Shalet, S. M.; Scarffe, J. H.; Gibbs, A. C.

1983-01-01

The hormonal mechanisms involved in the development of gynaecomastia accompanying the treatment of multiple myeloma in adult men have been investigated by studying levels of circulating testosterone (T), oestrone (EI), oestradiol (E2), sex-hormone binding globulin (SHBG), prolactin (PRL) and the gonadotrophins LH and FSH, before, during and after development of gynaecomastia in 4 men. These have been compared with 5 closely matched men who did not develop gynaecomastia during similar treatment for myeloma. Levels of circulating T fell, and levels of E1 and E2 rose during treatment periods in all subjects, and the changes were statistically significant in subjects developing gynaecomastia, which resolved as levels of sex steroid returned towards normal following cessation of treatment. We conclude that treatment of adult men for myeloma results in testicular dysfunction with a reduction in circulating T and a rise in circulating oestrogens. These changes are most marked in subjects developing gynaecomastia in whom the normal breast tissue is stimulated by a subtle, transient oestrogen:androgen imbalance in favour of oestrogens. PMID:6409138

Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

PubMed Central

van Leeuwen, Elisabeth M; Sabo, Aniko; Bis, Joshua C; Huffman, Jennifer E; Manichaikul, Ani; Smith, Albert V; Feitosa, Mary F; Demissie, Serkalem; Joshi, Peter K; Duan, Qing; Marten, Jonathan; van Klinken, Jan B; Surakka, Ida; Nolte, Ilja M; Zhang, Weihua; Mbarek, Hamdi; Li-Gao, Ruifang; Trompet, Stella; Verweij, Niek; Evangelou, Evangelos; Lyytikäinen, Leo-Pekka; Tayo, Bamidele O; Deelen, Joris; van der Most, Peter J; van der Laan, Sander W; Arking, Dan E; Morrison, Alanna; Dehghan, Abbas; Franco, Oscar H; Hofman, Albert; Rivadeneira, Fernando; Sijbrands, Eric J; Uitterlinden, Andre G; Mychaleckyj, Josyf C; Campbell, Archie; Hocking, Lynne J; Padmanabhan, Sandosh; Brody, Jennifer A; Rice, Kenneth M; White, Charles C; Harris, Tamara; Isaacs, Aaron; Campbell, Harry; Lange, Leslie A; Rudan, Igor; Kolcic, Ivana; Navarro, Pau; Zemunik, Tatijana; Salomaa, Veikko; Kooner, Angad S; Kooner, Jaspal S; Lehne, Benjamin; Scott, William R; Tan, Sian-Tsung; de Geus, Eco J; Milaneschi, Yuri; Penninx, Brenda W J H; Willemsen, Gonneke; de Mutsert, Renée; Ford, Ian; Gansevoort, Ron T; Segura-Lepe, Marcelo P; Raitakari, Olli T; Viikari, Jorma S; Nikus, Kjell; Forrester, Terrence; McKenzie, Colin A; de Craen, Anton J M; de Ruijter, Hester M; Pasterkamp, Gerard; Snieder, Harold; Oldehinkel, Albertine J; Slagboom, P Eline; Cooper, Richard S; Kähönen, Mika; Lehtimäki, Terho; Elliott, Paul; van der Harst, Pim; Jukema, J Wouter; Mook-Kanamori, Dennis O; Boomsma, Dorret I; Chambers, John C; Swertz, Morris; Ripatti, Samuli; Willems van Dijk, Ko; Vitart, Veronique; Polasek, Ozren; Hayward, Caroline; Wilson, James G; Wilson, James F; Gudnason, Vilmundur; Rich, Stephen S; Psaty, Bruce M; Borecki, Ingrid B; Boerwinkle, Eric; Rotter, Jerome I; Cupples, L Adrienne; van Duijn, Cornelia M

2016-01-01

Background So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage. Results Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene. Conclusions This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels. PMID:27036123

Circulating Irisin Levels Are Not Regulated by Nutritional Status, Obesity, or Leptin Levels in Rodents.

PubMed

Quiñones, Mar; Folgueira, Cintia; Sánchez-Rebordelo, Estrella; Al-Massadi, Omar

2015-01-01

Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5) that is mainly released by skeletal muscle and was proposed to mediate the beneficial effects of exercise on metabolism. In the present study we aim to investigate the regulation of the circulating levels of irisin in obese animal models (diet-induced obese (DIO) rats and leptin-deficient (ob/ob) mice), as well as the influence of nutritional status and leptin. Irisin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) and Radioimmunoassay (RIA). Serum irisin levels remained unaltered in DIO rats and ob/ob mice. Moreover, its circulating levels were also unaffected by fasting, leptin deficiency, and exogenous leptin administration in rodents. In spite of these negative results we find a negative correlation between irisin and insulin in DIO animals and a positive correlation between irisin and glucose under short-term changes in nutritional status. Our findings indicate that serum irisin levels are not modulated by different physiological settings associated to alterations in energy homeostasis. These results suggest that in rodents circulating levels of irisin are not involved in the pathophysiology of obesity and could be unrelated to metabolic status; however, further studies should clarify its precise role in states of glucose homeostasis imbalance.

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

PubMed

Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F

2016-02-01

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

Sickle Cell Vaso-occlusive Crisis Induces the Release of Circulating Serum Heat Shock Protein-70

PubMed Central

Adewoye, Adeboye H.; Klings, Elizabeth S.; Farber, Harrison W.; Palaima, Elizabeth; Bausero, Maria A.; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H.; Asea, Alexzander

2006-01-01

Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P < 0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P < 0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD. PMID:15726596

Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70.

PubMed

Adewoye, Adeboye H; Klings, Elizabeth S; Farber, Harrison W; Palaima, Elizabeth; Bausero, Maria A; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H; Asea, Alexzander

2005-03-01

Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P <0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P <0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD.

Powering Up Mitichondrial Functions to Treat Mitochondrial Disease

DTIC Science & Technology

2017-10-01

derived hormone whose serum level correlates positively with the severity of mitochondrial cardiomyopathy (recently published with DOD grant support...derived hormone that regulates body growth. Circulating GDF15 level correlates positively with the severity of mitochondrial cardiomyopathy and can...Pei lab recently discovered that GDF15 is a heart-derived hormone that regulates body growth. Circulating GDF15 level correlates positively with the

Exploring Secondary Students' Epistemological Features Depending on the Evaluation Levels of the Group Model on Blood Circulation

ERIC Educational Resources Information Center

Lee, Shinyoung; Kim, Heui-Baik

2014-01-01

The purpose of this study is to identify the epistemological features and model qualities depending on model evaluation levels and to explore the reasoning process behind high-level evaluation through small group interaction about blood circulation. Nine groups of three to four students in the eighth grade participated in the modeling practice.…

Evaluation of Two Commercial Enzyme-Linked Immunosorbent Assay Kits for the Detection of Human Circulating Metrnl.

PubMed

Zheng, Si-Li; Li, Zhi-Yong; Zhang, Zheng; Wang, Dong-Sheng; Xu, Jian; Miao, Chao-Yu

2018-04-01

Metrnl is a newly discovered secreted protein with neurotrophic activity and metabolic effect, while in earlier studies its circulating level in human was not explored. We evaluated two commercial enzyme-linked immunosorbent assay kits (DY7867-05, R&D Systems and SK00478-02, Aviscera Bioscience) for the detection of human circulating Metrnl. The DY7867-05 kit showed superiority over the SK00478-02 kit since it generated better curve fitting degree, smaller variation among tests, higher inter-assay reproducibility and better specificity, and could effectively detect human Metrnl in six types of blood samples. Subsequent analysis was performed using the DY7867-05 kit. Sample storage conditions were investigated. No gender difference in circulating Metrnl levels was found, while people with newly diagnosed type 2 diabetes mellitus (T2DM) had significantly lower Metrnl levels compared to the healthy controls.

Increased Circulating FGF23 Does Not Lead to Cardiac Hypertrophy in the Male Hyp Mouse Model of XLH.

PubMed

Liu, Eva S; Thoonen, Robrecht; Petit, Elizabeth; Yu, Binglan; Buys, Emmanuel S; Scherrer-Crosbie, Marielle; Demay, Marie B

2018-05-01

Serum levels of fibroblast growth factor 23 (FGF23) markedly increase with renal impairment, with FGF23 levels correlating with the presence of left ventricular hypertrophy (LVH) and mortality in patients with chronic kidney disease (CKD). FGF23 activates calcineurin/nuclear factor of activated T cell (NFAT) signaling and induces hypertrophy in murine cardiomyocytes. X-linked hypophosphatemia (XLH) is characterized by high circulating levels of FGF23 but, in contrast to CKD, is associated with hypophosphatemia. The cardiac effects of high circulating levels of FGF23 in XLH are not well defined. Thus, studies were undertaken to define the cardiac phenotype in the mouse model of XLH (Hyp mice). Echocardiographic and histological analyses demonstrated that Hyp left ventricles (LVs) are smaller than those of wild-type mice. Messenger RNA expression of cardiac hypertrophy markers was not altered in the LV or right ventricle of Hyp mice. However, the Hyp LVs had increased expression of the NFAT target genes NFATc1 and RCAN1. To determine whether phosphate alone can induce markers of hypertrophy, differentiated C2C12 myocytes were treated with phosphate. Phosphate treatment increased expression of cardiac hypertrophy markers, supporting a primary role for phosphate in inducing LVH. Although previous studies showed that increased circulating FGF23 and phosphate levels are associated with LVH, our results demonstrated that in XLH, high circulating levels of FGF23 in the setting of hypophosphatemia do not induce cardiac hypertrophy.

Adipokines and Hepatic Insulin Resistance

PubMed Central

Hassan, Waseem

2013-01-01

Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarification of the regulatory processes about hepatic insulin resistance by adipokines in rodents and human would seem essential in order to understand the mechanism of type 2 diabetes and for developing novel therapeutic strategies to treat it. PMID:23762871

High levels of circulating VEGFR2+ Bone marrow-derived progenitor cells correlate with metastatic disease in patients with pediatric solid malignancies.

PubMed

Taylor, Melissa; Rössler, Jochen; Geoerger, Birgit; Laplanche, Agnès; Hartmann, Olivier; Vassal, Gilles; Farace, Françoise

2009-07-15

Pediatric solid malignancies display important angiogenic potential, and blocking tumor angiogenesis represents a new therapeutic approach for these patients. Recent studies have evidenced rare circulating cells with endothelial features contributing to tumor neovascularization and have shown the pivotal role of bone marrow-derived (BMD) progenitor cells in metastatic disease progression. We measured these cells in patients with pediatric solid malignancies as a prerequisite to clinical trials with antiangiogenic therapy. Peripheral blood was drawn from 45 patients with localized (n = 23) or metastatic (n = 22) disease, and 20 healthy subjects. Subsets of circulating vascular endothelial growth factor receptor (VEGFR)2+-BMD progenitor cells, defined as CD45-CD34+VEGFR2(KDR)+7AAD- and CD45(dim)CD34+VEGFR2+7AAD- events, were measured in progenitor-enriched fractions by flow cytometry. Mature circulating endothelial cells (CEC) were measured in whole blood as CD31+CD146+CD45-7AAD- viable events. Data were correlated with VEGF and sVEGFR2 plasma levels. The CD45-CD34+VEGFR2(KDR)+7AAD- subset represented <0.003% of circulating BMD progenitor cells (< or =0.05 cells/mL). However, the median level (range) of the CD45(dim)CD34+VEGFR2+7AAD- subset was higher in patients compared with healthy subjects, 1.5% (0%-10.3%) versus 0.3% (0%-1.6%) of circulating BMD progenitors (P < 0.0001), and differed significantly between patients with localized and metastatic disease, 0.7% (0%-8.6%) versus 2.9% (0.6%-10.3%) of circulating BMD progenitors (P < 0.001). Median CEC value was 7 cells/mL (0-152 cells/mL) and similar in all groups. Unlike VEGFR2+-BMD progenitors, neither CECs, VEGF, or sVEGFR2 plasma levels correlated with disease status. High levels of circulating VEGFR2+-BMD progenitor cells correlated with metastatic disease. Our study provides novel insights for angiogenesis mechanisms in pediatric solid malignancies for which antiangiogenic targeting of VEGFR2+-BMD progenitors could be of interest.

High sugar and butter (HSB) diet induces obesity and metabolic syndrome with decrease in regulatory T cells in adipose tissue of mice.

PubMed

Maioli, Tatiani Uceli; Gonçalves, Juliana Lauar; Miranda, Mariana Camila Gonçalves; Martins, Vinícius Dantas; Horta, Laila Sampaio; Moreira, Thais Garcias; Godard, Ana Lucia Brunialti; Santiago, Andrezza Fernanda; Faria, Ana Maria Caetano

2016-02-01

The purpose of the study was to develop a novel diet based on standard AIN93G diet that would be able to induce experimental obesity and impair immune regulation with high concentrations of both carbohydrate and lipids. To compare the effects of this high sugar and butter (HSB) diet with other modified diets, male C57BL/6 mice were fed either mouse chow, or AIN93G diet, or high sugar (HS) diet, or high-fat (HF) diet, or high sugar and butter (HSB) diet for 11 weeks ad libitum. HSB diet induced higher weight gain. Therefore, control AIN93G and HSB groups were chosen for additional analysis. Regulatory T cells were studied by flow cytometry, and cytokine levels were measured by ELISA. Although HF and HSB diets were able to induce a higher weight gain compatible with obesity in treated mice, HSB-fed mice presented the higher levels of serum glucose after fasting and the lowest frequency of regulatory T cells in adipose tissue. In addition, mice that were fed HSB diet presented higher levels of cholesterol and triglycerides, hyperleptinemia, increased resistin and leptin levels as well as reduced adiponectin serum levels. Importantly, we found increased frequency of CD4(+)CD44(+) effector T cells, reduction of CD4(+)CD25(+)Foxp3(+) and Th3 regulatory T cells as well as decreased levels of IL-10 and TGF-β in adipose tissue of HSB-fed mice. Therefore, HSB represents a novel model of obesity-inducing diet that was efficient in triggering alterations compatible with metabolic syndrome as well as impairment in immune regulatory parameters.

IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3).

PubMed

Patel, Alpa V; Cheng, Iona; Canzian, Federico; Le Marchand, Loïc; Thun, Michael J; Berg, Christine D; Buring, Julie; Calle, Eugenia E; Chanock, Stephen; Clavel-Chapelon, Francoise; Cox, David G; Dorronsoro, Miren; Dossus, Laure; Haiman, Christopher A; Hankinson, Susan E; Henderson, Brian E; Hoover, Robert; Hunter, David J; Kaaks, Rudolf; Kolonel, Laurence N; Kraft, Peter; Linseisen, Jakob; Lund, Eiliv; Manjer, Jonas; McCarty, Catherine; Peeters, Petra H M; Pike, Malcolm C; Pollak, Michael; Riboli, Elio; Stram, Daniel O; Tjonneland, Anne; Travis, Ruth C; Trichopoulos, Dimitrios; Tumino, Rosario; Yeager, Meredith; Ziegler, Regina G; Feigelson, Heather Spencer

2008-07-02

IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP) were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-I levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women.

Customized Internal Reference Controls for Improved Assessment of Circulating MicroRNAs in Disease.

PubMed

Schlosser, Kenny; McIntyre, Lauralyn A; White, R James; Stewart, Duncan J

2015-01-01

Altered levels of circulating extracellular miRNA in plasma and serum have shown promise as non-invasive biomarkers of disease. However, unlike the assessment of cellular miRNA levels for which there are accepted housekeeping genes, analogous reference controls for normalization of circulating miRNA are lacking. Here, we provide an approach to identify and validate circulating miRNA reference controls on a de novo basis, and demonstrate the advantages of these customized internal controls in different disease settings. Importantly, these internal controls overcome key limitations of external spike-in controls. Using a global RT-qPCR screen of 1066 miRNAs in plasma from pulmonary hypertension patients (PAH) and healthy subjects as a case example, we identified a large pool of initial candidate miRNAs that were systematically ranked according to their plasma level stability using a predefined algorithm. The performance of the top candidates was validated against multiple comparators, and in a second independent cohort of PAH and control subjects. The broader utility of this approach was demonstrated in a completely different disease setting with 372 miRNAs screened in plasma from septic shock patients and healthy controls. Normalization of data with specific internal reference controls significantly reduced the overall variation in circulating miRNA levels between subjects (relative to raw data), provided a more balanced distribution of up- and down-regulated miRNAs, replicated the results obtained by the benchmark geometric averaging of all detected miRNAs, and outperformed the commonly used external spike-in strategy. We demonstrate the feasibility of identifying circulating reference controls that can reduce extraneous technical variations, and improve the assessment of disease-related changes in plasma miRNA levels. This study provides a novel conceptual framework that addresses a critical and previously unmet need if circulating miRNAs are to advance as reliable diagnostic tools in medicine.

Customized Internal Reference Controls for Improved Assessment of Circulating MicroRNAs in Disease

PubMed Central

Schlosser, Kenny; McIntyre, Lauralyn A.; White, R. James; Stewart, Duncan J.

2015-01-01

Background Altered levels of circulating extracellular miRNA in plasma and serum have shown promise as non-invasive biomarkers of disease. However, unlike the assessment of cellular miRNA levels for which there are accepted housekeeping genes, analogous reference controls for normalization of circulating miRNA are lacking. Here, we provide an approach to identify and validate circulating miRNA reference controls on a de novo basis, and demonstrate the advantages of these customized internal controls in different disease settings. Importantly, these internal controls overcome key limitations of external spike-in controls. Methods Using a global RT-qPCR screen of 1066 miRNAs in plasma from pulmonary hypertension patients (PAH) and healthy subjects as a case example, we identified a large pool of initial candidate miRNAs that were systematically ranked according to their plasma level stability using a predefined algorithm. The performance of the top candidates was validated against multiple comparators, and in a second independent cohort of PAH and control subjects. The broader utility of this approach was demonstrated in a completely different disease setting with 372 miRNAs screened in plasma from septic shock patients and healthy controls. Results Normalization of data with specific internal reference controls significantly reduced the overall variation in circulating miRNA levels between subjects (relative to raw data), provided a more balanced distribution of up- and down-regulated miRNAs, replicated the results obtained by the benchmark geometric averaging of all detected miRNAs, and outperformed the commonly used external spike-in strategy. Conclusions We demonstrate the feasibility of identifying circulating reference controls that can reduce extraneous technical variations, and improve the assessment of disease-related changes in plasma miRNA levels. This study provides a novel conceptual framework that addresses a critical and previously unmet need if circulating miRNAs are to advance as reliable diagnostic tools in medicine. PMID:26010841

Recent changes in the summer monsoon circulation and their impact on dynamics and thermodynamics of the Arabian Sea

NASA Astrophysics Data System (ADS)

Pratik, Kad; Parekh, Anant; Karmakar, Ananya; Chowdary, Jasti S.; Gnanaseelan, C.

2018-05-01

The present study examines changes in the low-level summer monsoon circulation over the Arabian Sea and their impact on the ocean dynamics using reanalysis data. The study confirms intensification and northward migration of low-level jet during 1979 to 2015. Further during the study period, an increase in the Arabian Sea upper ocean heat content is found in spite of a decreasing trend in the net surface heat flux, indicating the possible role of ocean dynamics in the upper ocean warming. Increase in the anti-cyclonic wind stress curl associated with the change in the monsoon circulation induces downwelling over the central Arabian Sea, favoring upper ocean warming. The decreasing trend of southward Ekman transport, a mechanism transporting heat from the land-locked north Indian Ocean to southern latitudes, also supports increasing trend of the upper ocean heat content. To reinstate and quantify the role of changing monsoon circulation in increasing the heat content over the Arabian Sea, sensitivity experiment is carried out using ocean general circulation model. In this experiment, the model is forced by inter-annual momentum forcing while rest of the forcing is climatological. Experiment reveals that the changing monsoon circulation increases the upper ocean heat content, effectively by enhancing downwelling processes and reducing southward heat transport, which strongly endorses our hypothesis that changing ocean dynamics associated with low-level monsoon circulation is causing the increasing trend in the heat content of the Arabian Sea.

Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression.

PubMed

Roth, Carina; Pantel, Klaus; Müller, Volkmar; Rack, Brigitte; Kasimir-Bauer, Sabine; Janni, Wolfgang; Schwarzenbach, Heidi

2011-01-06

As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases. The concentrations of cell-free DNA and nucleosomes as well as the protease and caspase activities were measured in serum of patients with benign breast disease (n = 20), primary breast cancer (M0, n = 31), metastatic breast cancer (M1, n = 32), and healthy individuals (n = 28) by PicoGreen, Cell Death Detection ELISA, Protease Fluorescent Detection Kit and Caspase-Glo®3/7 Assay, respectively. Patients with benign and malignant tumors had significantly higher levels of circulating nucleic acids in their blood than healthy individuals (p = 0.001, p = 0.0001), whereas these levels could not discriminate between benign and malignant lesions. Our analyses of all serum samples revealed significant correlations of circulating nucleosome with DNA concentrations (p = 0.001), nucleosome concentrations with caspase activities (p = 0.008), and caspase with protease activities (p = 0.0001). High serum levels of protease and caspase activities associated with advanced tumor stages (p = 0.009). Patients with lymph node-positive breast cancer had significantly higher nucleosome levels in their blood than node-negative patients (p = 0.004). The presence of distant metastases associated with a significant increase in serum nucleosome (p = 0.01) and DNA levels (p = 0.04), and protease activities (p = 0.008). Our findings demonstrate that high circulating nucleic acid concentrations in blood are no indicators of a malignant breast tumor. However, the observed changes in apoptosis-related deregulation of proteolytic activities along with the elevated serum levels of nucleosomes and DNA in blood are linked to breast cancer progression.

The adaptation of the cerebral circulation to pregnancy: mechanisms and consequences

PubMed Central

Cipolla, Marilyn J

2013-01-01

The adaptation of the cerebral circulation to pregnancy is unique from other vascular beds. Most notably, the growth and vasodilatory response to high levels of circulating growth factors and cytokines that promote substantial hemodynamic changes in other vascular beds is limited in the cerebral circulation. This is accomplished through several mechanisms, including downregulation of key receptors and transcription factors, and production of circulating factors that counteract the vasodilatory effects of vascular endothelial growth factor (VEGF) and placental growth factor. Pregnancy both prevents and reverses hypertensive inward remodeling of cerebral arteries, possibly through downregulation of the angiotensin type 1 receptor. The blood–brain barrier (BBB) importantly adapts to pregnancy by preventing the passage of seizure provoking serum into the brain and limiting the permeability effects of VEGF that is more highly expressed in cerebral vasculature during pregnancy. While the adaptation of the cerebral circulation to pregnancy provides for relatively normal cerebral blood flow and BBB properties in the face of substantial cardiovascular changes and high levels of circulating factors, under pathologic conditions, these adaptations appear to promote greater brain injury, including edema formation during acute hypertension, and greater sensitivity to bacterial endotoxin. PMID:23321787

Culture and Characterization of Circulating Endothelial Progenitor Cells in Patients with Renal Cell Carcinoma.

PubMed

Gu, Wenyu; Sun, Wei; Guo, Changcheng; Yan, Yang; Liu, Min; Yao, Xudong; Yang, Bin; Zheng, Junhua

2015-07-01

Although emerging evidence demonstrates increased circulating endothelial progenitor cells in patients with solid tumors, to our knowledge it is still unknown whether such cells can be cultured from patients with highly angiogenic renal cell carcinoma. We cultured and characterized circulating endothelial progenitor cells from patients with renal cell carcinoma. The circulating endothelial progenitor cell level (percent of CD45(-)CD34(+) VEGF-R2(+) cells in total peripheral blood mononuclear cells) was quantified in 47 patients with renal cell carcinoma and 40 healthy controls. Peripheral blood mononuclear cells were then isolated from 33 patients with renal cell carcinoma and 30 healthy controls to culture and characterize circulating endothelial progenitor cells. The circulating endothelial progenitor cell level was significantly higher in patients with renal cell carcinoma than in healthy controls (0.276% vs 0.086%, p <0.001). A colony of circulating endothelial progenitor cells first emerged significantly earlier in patient than in control preparations (6.72 vs 14.67 days, p <0.001). The culture success rate (87.8% vs 40.0% of participants) and the number of colonies (10.06 vs 1.83) were significantly greater for patients than for controls (each p <0.001). The circulating endothelial progenitor cell level correlated positively with the number of patient colonies (r = 0.762, p <0.001). Cells cultured from patients and controls showed a similar growth pattern, immunophenotype, ability to uptake Ac-LDL and bind lectin, and form capillary tubes in vitro. However, significantly more VEGF-R2(+) circulating endothelial progenitor cells were found in preparations from patients with renal cell carcinoma than from healthy controls (21.1% vs 13.4%, p <0.001). Earlier emergence of circulating endothelial progenitor cell colonies, a higher cell culture success rate and more colonies were found for patients with renal cell carcinoma than for healthy controls. Results indicate the important significance of VEGF-R2(+) circulating endothelial progenitors in patients with renal cell carcinoma. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways.

PubMed

Derous, Davina; Mitchell, Sharon E; Green, Cara L; Chen, Luonan; Han, Jing-Dong J; Wang, Yingchun; Promislow, Daniel E L; Lusseau, David; Speakman, John R; Douglas, Alex

2016-04-01

Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti-ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin-like growth factor 1 (IGF-1), insulin, and tumor necrosis factor alpha (TNF-α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF-α, leptin and IGF-1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.

The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways

PubMed Central

Green, Cara L.; Chen, Luonan; Han, Jing‐Dong J.; Wang, Yingchun; Promislow, Daniel E.L.; Lusseau, David; Speakman, John R.; Douglas, Alex

2016-01-01

Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti‐ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin‐like growth factor 1 (IGF‐1), insulin, and tumor necrosis factor alpha (TNF‐α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF‐α, leptin and IGF‐1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes. PMID:26945906

Model projections of rapid sea-level rise on the northeast coast of the United States

NASA Astrophysics Data System (ADS)

Yin, Jianjun; Schlesinger, Michael E.; Stouffer, Ronald J.

2009-04-01

Human-induced climate change could cause global sea-level rise. Through the dynamic adjustment of the sea surface in response to a possible slowdown of the Atlantic meridional overturning circulation, a warming climate could also affect regional sea levels, especially in the North Atlantic region, leading to high vulnerability for low-lying Florida and western Europe. Here we analyse climate projections from a set of state-of-the-art climate models for such regional changes, and find a rapid dynamical rise in sea level on the northeast coast of the United States during the twenty-first century. For New York City, the rise due to ocean circulation changes amounts to 15, 20 and 21cm for scenarios with low, medium and high rates of emissions respectively, at a similar magnitude to expected global thermal expansion. Analysing one of the climate models in detail, we find that a dynamic, regional rise in sea level is induced by a weakening meridional overturning circulation in the Atlantic Ocean, and superimposed on the global mean sea-level rise. We conclude that together, future changes in sea level and ocean circulation will have a greater effect on the heavily populated northeastern United States than estimated previously.

Model Projections of Rapid Sea-Level Rise on the Northeast Coast of the United States

NASA Astrophysics Data System (ADS)

Yin, J.; Schlesinger, M.; Stouffer, R. J.

2009-12-01

Human-induced climate change could cause global sea-level rise. Through the dynamic adjustment of the sea surface in response to a possible slowdown of the Atlantic meridional overturning circulation, a warming climate could also affect regional sea levels, especially in the North Atlantic region, leading to high vulnerability for low-lying Florida and western Europe. In the present study, we analyse climate projections from a set of state-of-the-art climate models for such regional changes, and find a rapid dynamical rise in sea level on the northeast coast of the United States during the twenty-first century. For New York City, the rise due to ocean circulation changes amounts to 15, 20 and 21 cm for scenarios with low, medium and high rates of emissions respectively, at a similar magnitude to expected global thermal expansion. Analysing one of the climate models in detail, we find that a dynamic, regional rise in sea level is induced by a weakening meridional overturning circulation in the Atlantic Ocean, and superimposed on the global mean sea level rise. We conclude that together, future changes in sea level and ocean circulation will have a greater effect on the heavily populated northeastern United States than estimated previously.

Association of calcium sensing receptor polymorphisms at rs1801725 with circulating calcium in breast cancer patients.

PubMed

Wang, Li; Widatalla, Sarrah E; Whalen, Diva S; Ochieng, Josiah; Sakwe, Amos M

2017-08-02

Breast cancer (BC) patients with late-stage and/or rapidly growing tumors are prone to develop high serum calcium levels which have been shown to be associated with larger and aggressive breast tumors in post and premenopausal women respectively. Given the pivotal role of the calcium sensing receptor (CaSR) in calcium homeostasis, we evaluated whether polymorphisms of the CASR gene at rs1801725 and rs1801726 SNPs in exon 7, are associated with circulating calcium levels in African American and Caucasian control subjects and BC cases. In this retrospective case-control study, we assessed the mean circulating calcium levels, the distribution of two inactivating CaSR SNPs at rs1801725 and rs1801726 in 199 cases and 384 age-matched controls, and used multivariable regression analysis to determine whether these SNPs are associated with circulating calcium in control subjects and BC cases. We found that the mean circulating calcium levels in African American subjects were higher than those in Caucasian subjects (p < 0.001). As expected, the mean calcium levels were higher in BC cases compared to control subjects (p < 0.001), but the calcium levels in BC patients were independent of race. We also show that in BC cases and control subjects, the major alleles at rs1801725 (G/T, A986S) and at rs1801726 (C/G, Q1011E) were common among Caucasians and African Americans respectively. Compared to the wild type alleles, polymorphisms at the rs1801725 SNP were associated with higher calcium levels (p = 0.006) while those at rs1801726 were not. Using multivariable linear mixed-effects models and adjusting for age and race, we show that circulating calcium levels in BC cases were associated with tumor grade (p = 0.009), clinical stage (p = 0.003) and more importantly, with inactivating mutations of the CASR at the rs1801725 SNP (p = 0.038). These data suggest that decreased sensitivity of the CaSR to calcium due to inactivating polymorphisms at rs1801725, may predispose up to 20% of BC cases to high circulating calcium-associated larger and/or aggressive breast tumors.

Circulating vascular cell adhesion molecule-1 in pre-eclampsia, gestational hypertension, and normal pregnancy: evidence of selective dysregulation of vascular cell adhesion molecule-1 homeostasis in pre-eclampsia.

PubMed

Higgins, J R; Papayianni, A; Brady, H R; Darling, M R; Walshe, J J

1998-08-01

Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P < .0001) and peripheral (P < .0001) circulations of pre-eclamptic women by comparison with normotensive women. In the pre-eclamptic group there was a tendency toward higher vascular cell adhesion molecule-1 levels in the peripheral circulation than in the uteroplacental circulation (P = .06). In contrast to vascular cell adhesion molecule-1, circulating levels of E-selectin and intercellular adhesion molecule-1, other major leukocyte adhesion molecules expressed by the endothelium, were not different in pre-eclamptic and normotensive pregnancies. Established pre-eclampsia is characterized by selective dysregulation of vascular cell adhesion molecule-1 homeostasis. This event is not an early preclinical feature of pre-eclampsia, does not persist post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.

Circulating Mesenchymal Stem Cells Microparticles in Patients with Cerebrovascular Disease

PubMed Central

Cho, Yeon Hee; Kang, Ho Young; Hyung, Na Kyum; Kim, Donghee; Lee, Ji Hyun; Nam, Ji Yoon; Bang, Oh Young

2012-01-01

Preclinical and clinical studies have shown that the application of CD105+ mesenchymal stem cells (MSCs) is feasible and may lead to recovery after stroke. In addition, circulating microparticles are reportedly functional in various disease conditions. We tested the levels of circulating CD105+ microparticles in patients with acute ischemic stroke. The expression of CD105 (a surface marker of MSCs) and CXCR4 (a CXC chemokine receptor for MSC homing) on circulating microparticles was evaluated by flow cytometry of samples from 111 patients and 50 healthy subjects. The percentage of apoptotic CD105 microparticles was determined based on annexin V (AV) expression. The relationship between serum levels of CD105+/AV− microparticles, stromal cells derived factor-1α (SDF-1α), and the extensiveness of cerebral infarcts was also evaluated. CD105+/AV− microparticles were higher in stroke patients than control subjects. Correlation analysis showed that the levels of CD105+/AV− microparticles increased as the baseline stroke severity increased. Multivariate testing showed that the initial severity of stroke was independently associated with circulating CD105+/AV− microparticles (OR, 1.103 for 1 point increase in the NIHSS score on admission; 95% CI, 1.032–1.178) after adjusting for other variables. The levels of CD105+/CXCR4+/AV− microparticles were also increased in patients with severe disability (r = 0.192, p = 0.046 for NIHSS score on admission), but were decreased with time after stroke onset (r = −0.204, p = 0.036). Risk factor profiles were not associated with the levels of circulating microparticles or SDF-1α. In conclusion, our data showed that stroke triggers the mobilization of MSC-derived microparticles, especially in patients with extensive ischemic stroke. PMID:22615882

Myocardial revascularization with miniaturized extracorporeal circulation versus off pump: Evaluation of systemic and myocardial inflammatory response in a prospective randomized study.

PubMed

Formica, Francesco; Broccolo, Francesco; Martino, Antonello; Sciucchetti, Jennifer; Giordano, Vincenzo; Avalli, Leonello; Radaelli, Gianluigi; Ferro, Orazio; Corti, Fabrizio; Cocuzza, Clementina; Paolini, Giovanni

2009-05-01

This prospective randomized study sought to verify the systemic inflammatory response, inflammatory myocardial damage, and early clinical outcome in coronary surgery with the miniaturized extracorporeal circulation system or on the beating heart. Sixty consecutive patients were randomized to miniaturized extracorporeal circulation (n = 30) or off-pump coronary revascularization (off-pump coronary artery bypass grafting, n = 30). Intraoperative and postoperative data were recorded. Plasma levels of interleukin-6 and tumor necrosis factor-alpha were measured from systemic blood intraoperatively, at the end of operation, and 24 and 48 hours thereafter. Levels of the same markers and blood lactate were measured from coronary sinus blood intraoperatively to evaluate myocardial inflammation. Markers of myocardial damage were also analyzed. One patient died in the off-pump coronary artery bypass grafting group. There was no statistical difference in early clinical outcome in both groups. Release of interleukin-6 was higher in the off-pump coronary artery bypass grafting group 24 hours after the operation (P = .03), whereas levels of tumor necrosis factor-alpha were not different in both groups. Cardiac release of interleukin-6, tumor necrosis factor-alpha, and blood lactate were not different in both groups. Release of troponin T was not significantly different in both groups. Levels of creatine kinase mass were statistically higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group, but only at the end of the operation (P < .0001). Hemoglobin levels were significantly higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group after 24 hours (P = .01). Miniaturized extracorporeal circulation can be considered similar to off-pump surgery in terms of systemic inflammatory response, myocardial inflammation and damage, and early outcome.

Hydroxylated polychlorinated biphenyls decrease circulating steroids in female polar bears (Ursus maritimus).

PubMed

Gustavson, Lisa; Ciesielski, Tomasz M; Bytingsvik, Jenny; Styrishave, Bjarne; Hansen, Martin; Lie, Elisabeth; Aars, Jon; Jenssen, Bjørn M

2015-04-01

As a top predator in the Arctic food chain, polar bears (Ursus maritimus) are exposed to high levels of persistent organic pollutants (POPs). Because several of these compounds have been reported to alter endocrine pathways, such as the steroidogenesis, potential disruption of the sex steroid synthesis by POPs may cause implications for reproduction by interfering with ovulation, implantation and fertility. Blood samples were collected from 15 female polar bears in Svalbard (Norway) in April 2008. The concentrations of nine circulating steroid hormones; dehydroepiandrosterone (DHEA), androstenedione (AN), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2), 17β-estradiol (βE2), pregnenolone (PRE) and progesterone (PRO) were determined. The aim of the study was to investigate associations among circulating levels of specific POP compounds and POP-metabolites (hydroxylated PCBs [OH-PCBs] and hydroxylated PBDEs [OH-PBDEs]), steroid hormones, biological and capture variables in female polar bears. Inverse correlations were found between circulating levels of PRE and AN, and circulating levels of OH-PCBs. There were no significant relationships between the steroid concentrations and other analyzed POPs or the variables capture date and capture location (latitude and longitude), lipid content, condition and body mass. Although statistical associations do not necessarily represent direct cause-effect relationships, the present study indicate that OH-PCBs may affect the circulating levels of AN and PRE in female polar bears and that OH-PCBs thus may interfere with the steroid homeostasis. Increase in PRO and a decrease in AN concentrations suggest that the enzyme CYP17 may be a potential target for OH-PCBs. In combination with natural stressors, ongoing climate change and contaminant exposure, it is possible that OH-PCBs may disturb the reproductive potential of polar bears. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of acute exposure to coarse particulate matter air pollution in a rural location on circulating endothelial progenitor cells: results from a randomized controlled study

PubMed Central

Brook, Robert D.; Bard, Robert L.; Kaplan, Mariana J.; Yalavarthi, Srilakshmi; Morishita, Masako; Dvonch, J. Timothy; Wang, Lu; Yang, Hui-yu; Spino, Catherine; Mukherjee, Bhramar; Oral, Elif A.; Sun, Qinghua; Brook, Jeffrey R.; Harkema, Jack; Rajagopalan, Sanjay

2015-01-01

Context Fine particulate matter (PM) air pollution has been associated with alterations in circulating endothelial progenitor cell (EPC) levels, which may be one mechanism whereby exposures promote cardiovascular diseases. However, the impact of coarse PM on EPCs is unknown. Objective We aimed to determine the effect of acute exposure to coarse concentrated ambient particles (CAP) on circulating EPC levels. Methods Thirty-two adults (25.9±6.6 years) were exposed to coarse CAP (76.2±51.5 μgm−3) in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Peripheral venous blood was collected 2 and 20 h post-exposures for circulating EPC (n=21), white blood cell (n=24) and vascular endothelial growth factor (VEGF) (n=16–19) levels. The changes between exposures were compared by matched Wilcoxon signed-rank tests. Results Circulating EPC levels were elevated 2 [108.29 (6.24–249.71) EPC mL−1; median (25th–75th percentiles), p=0.052] and 20 h [106.86 (52.91–278.35) EPC mL−1, p=0.008] post-CAP exposure compared to the same time points following FA [38.47 (0.00–84.83) and 50.16 (0.00–104.79) EPC mL−1]. VEGF and white blood cell (WBC) levels did not differ between exposures. Conclusions Brief inhalation of coarse PM from a rural location elicited an increase in EPCs that persisted for at least 20 h. The underlying mechanism responsible may reflect a systemic reaction to an acute “endothelial injury” and/or a circulating EPC response to sympathetic nervous system activation. PMID:23919441

Induction of NPY/AgRP orexigenic peptide expression in rat hypothalamus is an early event in fasting: relationship with circulating leptin, insulin and glucose.

PubMed

Palou, Mariona; Sánchez, Juana; Rodríguez, Ana M; Priego, Teresa; Picó, Catalina; Palou, Andreu

2009-01-01

Hypothalamus is crucial in the control of energy intake and expenditure in mammals, presenting two interconnected populations of neurons producing orexigenic NPY/AgRP (neuropeptide Y; agouti related peptide) and anorexigenic POMC/CART (pro-opiomelanocortin; cocaine and amphetamine regulated transcript) neuropeptides. We aimed to shed more light on the response and sensitivity in the production of these neuropeptides to face nutritional changes, particularly food deprivation, and on the signals that regulate them. Male Wistar rats were fasted for 0, 4, 8 and 24h and refed for 3h after 8h fasting. mRNA levels of gastric and adipose tissue (retroperitoneal, mesenteric and inguinal) leptin, and of hypothalamic NPY, AgRP, POMC, CART, leptin receptor, SOCS3 (suppressor of cytokine signaling 3) and insulin receptor were analyzed. Gastric and circulating leptin, and circulating insulin, glucose and ghrelin were also determined. The only neuropeptide mRNAs that responded (increasing) to the short-term periods of fasting used were those of NPY (transiently) and AgRP, and these changes were accompanied by an increase in leptin receptor mRNA levels and by a decrease in adipose and gastric leptin expression and in the circulating levels of leptin, insulin and glucose, but without changes in circulating ghrelin. The elevation in AgRP and leptin receptor mRNA levels and the drop in circulating leptin were not reverted with refeeding. It is suggested that the induction of expression of the orexigenic molecules in NPY/AgRP neurons is an early event upon fasting, related with changes in leptin, insulin and glucose levels, but with the role of leptin signaling in particular. 2009 S. Karger AG, Basel.

Powering Up Mitochondrial Functions to Treat Mitochondrial Disease

DTIC Science & Technology

2017-10-01

derived hormone whose serum level correlates positively with the severity of mitochondrial cardiomyopathy (recently published with DOD grant support...o Pei lab has recently discovered that GDF15 is a heart-derived hormone that regulates body growth. Circulating GDF15 level correlates positively...Circulating GDF15 level correlates positively with the severity of mitochondrial cardiomyopathy and can be used as a serum biomarker for our 5

Level of maternal winter supplement and feed restriction during postweaning development influence circulating concentrations of IGF-I in heifers during the peripartum and rebreeding period

USDA-ARS?s Scientific Manuscript database

Objective of this research was to evaluate effects of 2 levels of supplemental feed provided to cows during late gestation and 2 levels of feed provided to their daughters during postweaning development on circulating concentrations of IGF-I in the daughters before calving, after calving and before ...

Ocean impact on decadal Atlantic climate variability revealed by sea-level observations.

PubMed

McCarthy, Gerard D; Haigh, Ivan D; Hirschi, Joël J-M; Grist, Jeremy P; Smeed, David A

2015-05-28

Decadal variability is a notable feature of the Atlantic Ocean and the climate of the regions it influences. Prominently, this is manifested in the Atlantic Multidecadal Oscillation (AMO) in sea surface temperatures. Positive (negative) phases of the AMO coincide with warmer (colder) North Atlantic sea surface temperatures. The AMO is linked with decadal climate fluctuations, such as Indian and Sahel rainfall, European summer precipitation, Atlantic hurricanes and variations in global temperatures. It is widely believed that ocean circulation drives the phase changes of the AMO by controlling ocean heat content. However, there are no direct observations of ocean circulation of sufficient length to support this, leading to questions about whether the AMO is controlled from another source. Here we provide observational evidence of the widely hypothesized link between ocean circulation and the AMO. We take a new approach, using sea level along the east coast of the United States to estimate ocean circulation on decadal timescales. We show that ocean circulation responds to the first mode of Atlantic atmospheric forcing, the North Atlantic Oscillation, through circulation changes between the subtropical and subpolar gyres--the intergyre region. These circulation changes affect the decadal evolution of North Atlantic heat content and, consequently, the phases of the AMO. The Atlantic overturning circulation is declining and the AMO is moving to a negative phase. This may offer a brief respite from the persistent rise of global temperatures, but in the coupled system we describe, there are compensating effects. In this case, the negative AMO is associated with a continued acceleration of sea-level rise along the northeast coast of the United States.

Three-dimensional circulation structures leading to heavy summer rainfall over central North China

NASA Astrophysics Data System (ADS)

Sun, Wei; Yu, Rucong; Li, Jian; Yuan, Weihua

2016-04-01

Using daily and hourly rain gauge records and Japanese 25 year reanalysis data over 30 years, this work reveals two major circulation structures leading to heavy summer rainfall events in central North China (CNC), and further analyzes the effects of the circulations on these rainfall events. One circulation structure has an extensive upper tropospheric warm anomaly (UTWA) covering North China (NC). By strengthening the upper anticyclonic anomaly and lower southerly flows around NC, the UTWA plays a positive role in forming upper level divergence and lower level moisture convergence. As a result, the warm anomalous circulation has a solid relationship with large-scale, long-duration rainfall events with a diurnal peak around midnight to early morning. The other circulation structure has an upper tropospheric cold anomaly (UTCA) located in the upper stream of NC. Contributed to by the UTCA, a cold trough appears in the upper stream of NC and an unstable configuration with upper (lower) cold (warm) anomalies forms around CNC. Consequently, CNC is covered by strong instability and high convective energy, and the cold anomalous circulation is closely connected with local, short-duration rainfall events concentrated from late afternoon to early nighttime. The close connections between circulation structures and typical rainfall events are confirmed by two independent converse analysis processes: from circulations to rainfall characteristics, and from typical rainfall events to circulations. The results presented in this work indicate that the upper tropospheric temperature has significant influences on heavy rainfall, and thus more attention should be paid to the upper tropospheric temperature in future analyses.

Irisin in response to exercise in humans with and without metabolic syndrome.

PubMed

Huh, Joo Young; Siopi, Aikaterina; Mougios, Vassilis; Park, Kyung Hee; Mantzoros, Christos S

2015-03-01

Irisin is a recently identified exercise-induced myokine. However, the circulating levels of irisin in response to different types of exercise in subjects with metabolic syndrome are unknown. This study aimed to study the levels of irisin in healthy males and subjects with metabolic syndrome at baseline and in response to exercise. Each individual completed high-intensity interval exercise (HIIE), continuous moderate-intensity exercise (CME), and resistance exercise (RE) sessions in a random, crossover design. Percentage change in circulating irisin levels was examined. Two different irisin assays were used to compare the results of the RE study. Circulating irisin increased immediately after HIIE, CME, and RE and declined 1 hour later. The increase was greater in response to resistance compared with either high-intensity intermittent exercise or CME. Change in irisin in response to exercise did not differ between individuals with and without metabolic syndrome. Exercise is able to increase circulating irisin levels in individuals with the metabolic syndrome as well as healthy individuals. Whether this increase may contribute to the beneficial effects of exercise on patients with the metabolic syndrome remains to be studied further.

Circulating levels of FAS/APO-1 in patients with the systemic inflammatory response syndrome.

PubMed

Torre, Donato; Tambini, Roberto; Manfredi, Mariangela; Mangani, Valerio; Livi, Paola; Maldifassi, Viviana; Campi, Paolo; Speranza, Filippo

2003-04-01

Resolution of inflammation/infection involves removal of neutrophils and other inflammatory cells by the induction of apoptosis. Fas/Apo-1 is a widely occurring apoptotic signal receptor molecule expressed by almost any type of cell, which is also released in a soluble circulating form. In this study we investigated the role of circulating Fas/Apo-1 in patients with systemic inflammatory response syndrome (SIRS). We evaluated 57 critically ill patients, 34 with infectious SIRS (sepsis and septic shock), and 23 patients with noninfectious SIRS. Circulating Fas/Apo-1 was determined by a commercially available immunoassay. Our results clearly show that levels of Fas/Apo-1 were significantly elevated in patients with infectious and noninfectious SIRS (10.4 +/- 8.1 pg/mL, controls: 5.0 +/- 0.7 pg/mL; p < 0.0001). In addition, Fas/Apo-1 levels were not able in predicting in predicting poor outcome of patients with SIRS. In conclusion, these results show that increased levels of Fas/Apo-1 from patients with SIRS is a mechanism which contribute to inflammatory response through accumulation of neutrophils at sites of inflammation/infection.

Development of the probability of return of spontaneous circulation in intervals without chest compressions during out-of-hospital cardiac arrest: an observational study.

PubMed

Gundersen, Kenneth; Kvaløy, Jan Terje; Kramer-Johansen, Jo; Steen, Petter Andreas; Eftestøl, Trygve

2009-02-06

One of the factors that limits survival from out-of-hospital cardiac arrest is the interruption of chest compressions. During ventricular fibrillation and tachycardia the electrocardiogram reflects the probability of return of spontaneous circulation associated with defibrillation. We have used this in the current study to quantify in detail the effects of interrupting chest compressions. From an electrocardiogram database we identified all intervals without chest compressions that followed an interval with compressions, and where the patients had ventricular fibrillation or tachycardia. By calculating the mean-slope (a predictor of the return of spontaneous circulation) of the electrocardiogram for each 2-second window, and using a linear mixed-effects statistical model, we quantified the decline of mean-slope with time. Further, a mapping from mean-slope to probability of return of spontaneous circulation was obtained from a second dataset and using this we were able to estimate the expected development of the probability of return of spontaneous circulation for cases at different levels. From 911 intervals without chest compressions, 5138 analysis windows were identified. The results show that cases with the probability of return of spontaneous circulation values 0.35, 0.1 and 0.05, 3 seconds into an interval in the mean will have probability of return of spontaneous circulation values 0.26 (0.24-0.29), 0.077 (0.070-0.085) and 0.040(0.036-0.045), respectively, 27 seconds into the interval (95% confidence intervals in parenthesis). During pre-shock pauses in chest compressions mean probability of return of spontaneous circulation decreases in a steady manner for cases at all initial levels. Regardless of initial level there is a relative decrease in the probability of return of spontaneous circulation of about 23% from 3 to 27 seconds into such a pause.

Gender-related different effects of a combined therapy of Exenatide and Metformin on overweight or obesity patients with type 2 diabetes mellitus.

PubMed

Quan, Huibiao; Zhang, Huachuan; Wei, Weiping; Fang, Tuanyu

2016-01-01

Although men and women have similar diabetes prevalence, the same medicine will cause different therapeutic results in different genders. To understand the molecular mechanism, we explored the effects of a combined therapy of Exenatide and Metformin on obesity and overweight female and male patients with newly diagnosed type 2 diabetes mellitus (T2DM). One hundred and five overweight and obesity patients with newly diagnosed T2DM (n=54 female in a female group and n=51 males in a male group) received the therapy: 5 μg Exenatide+0.5 g MET twice daily for 4 weeks, then 10 μg Exenatide+0.5 g MET twice daily for 24 weeks. There was an average of 8.2 ± 2.4 kg and 4.6 ± 2.3 kg weight loss in female and male patients, respectively. The combined therapy showed better effects on female than male patients for improving insulin sensitivity and serum lipid profile, reducing insulin resistance, increasing adiponectin levels, and decreasing the levels of HbA1c, BMI, resistin, TNF-alpha and C-reactive protein (P<0.05). The combined therapy of Exenatide and MET shows better therapeutic results in female patients than in male patients. Therefore, the dual therapy is more suitable for female patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Secoisolariciresinol diglucoside inhibits adipogenesis through the AMPK pathway.

PubMed

Kang, JongWook; Park, Jinbong; Kim, Hye-Lin; Jung, Yunu; Youn, Dong-Hyun; Lim, Seona; Song, Gahee; Park, Hyewon; Jin, Jong Sik; Kwak, Hyun Jeong; Um, Jae-Young

2018-02-05

Flaxseeds are used to treat metabolic diseases such as type 2 diabetes, fatty liver, hyperlipidemia and obesity. Secoisolariciresinol diglucoside (SDG) is a main substance of lignan which belongs to the phytoestrogen family and exists abundantly in flaxseeds. In this study, SDG reduced the body weight and size of adipose tissue, and decreased protein expressions of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (C/EBPα) in the high fat diet-fed-induced obese mice model. In the vitro study, we examined the anti-adipogenic effect of SDG during differentiation of 3T3-L1 cells into adipocytes. 3T3-L1 preadipocytes were differentiated and treated with various concentrations of SDG. Oil Red O staining was done to measure the quantity of lipid contents. As a result, SDG reduced lipid accumulation and decreased the expressions of adipogenic-related genes such as adipocyte fatty-acid-binding protein 2, adiponectin, and resistin. SDG also decreased the mRNA and protein levels of PPARγ and C/EBPα. Furthermore, phosphorylation levels of AMP-activated protein kinase α (AMPK α) and its upstream activator, liver kinase B1, were significantly increased by SDG in 3T3-L1 cells. These results suggest that SDG inhibits adipogenesis by activating AMPKα, suggesting it could be an attractive therapeutic candidate for the treatment of obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Why is the simulated climatology of tropical cyclones so sensitive to the choice of cumulus parameterization scheme in the WRF model?

NASA Astrophysics Data System (ADS)

Zhang, Chunxi; Wang, Yuqing

2018-01-01

The sensitivity of simulated tropical cyclones (TCs) to the choice of cumulus parameterization (CP) scheme in the advanced Weather Research and Forecasting Model (WRF-ARW) version 3.5 is analyzed based on ten seasonal simulations with 20-km horizontal grid spacing over the western North Pacific. Results show that the simulated frequency and intensity of TCs are very sensitive to the choice of the CP scheme. The sensitivity can be explained well by the difference in the low-level circulation in a height and sorted moisture space. By transporting moist static energy from dry to moist region, the low-level circulation is important to convective self-aggregation which is believed to be related to genesis of TC-like vortices (TCLVs) and TCs in idealized settings. The radiative and evaporative cooling associated with low-level clouds and shallow convection in dry regions is found to play a crucial role in driving the moisture-sorted low-level circulation. With shallow convection turned off in a CP scheme, relatively strong precipitation occurs frequently in dry regions. In this case, the diabatic cooling can still drive the low-level circulation but its strength is reduced and thus TCLV/TC genesis is suppressed. The inclusion of the cumulus momentum transport (CMT) in a CP scheme can considerably suppress genesis of TCLVs/TCs, while changes in the moisture-sorted low-level circulation and horizontal distribution of precipitation are trivial, indicating that the CMT modulates the TCLVs/TCs activities in the model by mechanisms other than the horizontal transport of moist static energy.

Post-Effect of Air Quality Improvement on Biomarkers for Systemic Inflammation and Microparticles in Asthma Patients After the 2008 Beijing Olympic Games: a Pilot Study.

PubMed

Gao, Jinming; Xu, Xiaohua; Ying, Zhekang; Jiang, Lei; Zhong, Mianhua; Wang, Aixia; Chen, Lung-Chi; Lu, Bo; Sun, Qinghua

2017-08-01

This study's aim was to investigate the post-effect of an air quality improvement on systemic inflammation and circulating microparticles in asthmatic patients during, and 2 months after, the Beijing Olympics 2008. We measured the levels of circulating inflammatory cytokines and microparticles in the peripheral blood from asthma patients and healthy controls during (phase 1), and 2 months after (phase 2) the Beijing 2008 Olympic Games. The concentrations of circulating cytokines (including TNFα, IL-6, IL-8, and IL-10) were still seen reduced in phase 2 when compared with those in phase 1. The number of circulating endothelial cell-derived microparticles was significantly lower during the phase 2 than that during phase 1 in asthma patients. The level of plasma lipopolysaccharide-binding protein (LBP) was significantly decreased in asthmatics in phase 2. The level of norepinephrine was significantly higher in phase 2 than that in phase 1 in plasma from both asthma patients and healthy subjects. There were no significant differences in the gene profile for the toll-like receptor (TLR) signaling from peripheral blood mononuclear cells. In vitro, microvesicles from patients with asthma impaired the relaxation to bradykinin and contraction to acetylcholine, whereas microparticles from healthy subjects did not. These data suggested that reduction in systemic pro-inflammatory responses and circulating LBP and increased level of norepinephrine in asthma patients persisted even after 2 months of the air pollution intervention. These changes were independent of the TLR signaling pathway. Circulating microparticles might be associated with airway smooth muscle dysfunction.

The association between circulating irisin levels and different phenotypes of polycystic ovary syndrome.

PubMed

Zhang, L; Fang, X; Li, L; Liu, R; Zhang, C; Liu, H; Tan, M; Yang, G

2018-05-21

The diagnosis of polycystic ovary syndrome (PCOS) is based on a combination of various clinical phenotypes in each patient. However, insulin resistance (IR) and dysmetabolism are not included in the diagnostic criteria of PCOS. Therefore, the definition of PCOS is controversial. The objective of this study is to investigate whether some PCOS phenotypes can be predicted by a circulating biomarker related to IR and metabolic dysfunction in PCOS women. One hundred and seventeen women with PCOS and 95 healthy women were recruited for this study. All individuals were assessed by the phenotypic and metabolic characteristics related to PCOS. A euglycemic-hyperinsulinemic clamp was performed to assess insulin sensitivity. Circulating irisin concentrations were determined with ELISA. In our PCOS cohort, 65.8% of individuals were found to have hyperandrogenism. 83.8% had chronic oligoanovulation, and 80.3% of subjects showed polycystic ovaries. According to the diagnostic criteria of PCOS, 30.8% of PCOS subjects were diagnosed with the classic phenotype. In addition, 65.8% of PCOS women had insulin resistance. Serum irisin levels were significantly higher in PCOS women compared with healthy women. However, PCOS women with a normoandrogenic phenotype had similar circulating irisin levels as healthy women. PCOS women with the normoandrogenic phenotype had a low homeostasis model assessment of insulin resistance (HOMA-IR) and higher M-values than PCOS women with other phenotypes. Circulating irisin levels were associated with hyperandrogenism, but not with oligoanovulation or PCO morphology. Circulating irisin may allow physicians to establish which women merit screening by a biomarker for PCOS.

Increased Obesity-Associated Circulating Levels of the Extracellular Matrix Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon Cancer

PubMed Central

Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Izaguirre, Maitane; Hernández-Lizoain, José Luis; Baixauli, Jorge; Martí, Pablo; Valentí, Víctor; Moncada, Rafael; Silva, Camilo; Salvador, Javier; Frühbeck, Gema

2016-01-01

Background Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth. Methods Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC). Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN), chitinase-3-like protein 1 (YKL-40), tenascin C (TNC) and lipocalin-2 (LCN-2) were determined by ELISA. Results Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01) and colon cancer (P<0.05). LCN-2 levels were affected by obesity (P<0.05), but no differences were detected regarding the presence or not of CC. A positive association (P<0.05) with different inflammatory markers was also detected. Conclusions To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics. PMID:27612200

Stabilization and Augmentation of Circulating AIM in Mice by Synthesized IgM-Fc

PubMed Central

Kai, Toshihiro; Yamazaki, Tomoko; Arai, Satoko; Miyazaki, Toru

2014-01-01

Owing to rapid and drastic changes in lifestyle and eating habits in modern society, obesity and obesity-associated diseases are among the most important public health problems. Hence, the development of therapeutic approaches to regulate obesity is strongly desired. In view of previous work showing that apoptosis inhibitor of macrophage (AIM) blocks lipid storage in adipocytes, thereby preventing obesity caused by a high-fat diet, we here explored a strategy to augment circulating AIM levels. We synthesized the Fc portion of the soluble human immunoglobulin (Ig)M heavy chain and found that it formed a pentamer containing IgJ as natural IgM does, and effectively associated with AIM in vitro. When we injected the synthesized Fc intravenously into mice lacking circulating IgM, it associated with endogenous mouse AIM, protecting AIM from renal excretion and preserving the circulating AIM levels. As the synthesized Fc lacked the antigen-recognizing variable region, it provoked no undesired immune response. In addition, a challenge with the Fc-human AIM complex in wild-type mice, which exhibited normal levels of circulating IgM and AIM, successfully maintained the levels of the human AIM in mouse blood. We also observed that the human AIM was effectively incorporated into adipocytes in visceral fat tissue, suggesting its functionality against obesity. Thus, our findings reveal potent strategies to safely increase AIM levels, which could form the basis for developing novel therapies for obesity. PMID:24804991

Residential Proximity to Major Roadways Is Associated With Increased Levels of AC133+ Circulating Angiogenic Cells.

PubMed

DeJarnett, Natasha; Yeager, Ray; Conklin, Daniel J; Lee, Jongmin; O'Toole, Timothy E; McCracken, James; Abplanalp, Wes; Srivastava, Sanjay; Riggs, Daniel W; Hamzeh, Ihab; Wagner, Stephen; Chugh, Atul; DeFilippis, Andrew; Ciszewski, Tiffany; Wyatt, Brad; Becher, Carrie; Higdon, Deirdre; Ramos, Kenneth S; Tollerud, David J; Myers, John A; Rai, Shesh N; Shah, Jasmit; Zafar, Nagma; Krishnasamy, Sathya S; Prabhu, Sumanth D; Bhatnagar, Aruni

2015-11-01

Previous studies have shown that residential proximity to a roadway is associated with increased cardiovascular disease risk. Yet, the nature of this association remains unclear, and its effect on individual cardiovascular disease risk factors has not been assessed. The objective of this study was to determine whether residential proximity to roadways influences systemic inflammation and the levels of circulating angiogenic cells. In a cross-sectional study, cardiovascular disease risk factors, blood levels of C-reactive protein, and 15 antigenically defined circulating angiogenic cell populations were measured in participants (n=316) with moderate-to-high cardiovascular disease risk. Attributes of roadways surrounding residential locations were assessed using geographic information systems. Associations between road proximity and cardiovascular indices were analyzed using generalized linear models. Close proximity (<50 m) to a major roadway was associated with lower income and higher rates of smoking but not C-reactive protein levels. After adjustment for potential confounders, the levels of circulating angiogenic cells in peripheral blood were significantly elevated in people living in close proximity to a major roadway (CD31(+)/AC133(+), AC133(+), CD34(+)/AC133(+), and CD34(+)/45(dim)/AC133(+) cells) and positively associated with road segment distance (CD31(+)/AC133(+), AC133(+), and CD34(+)/AC133(+) cells), traffic intensity (CD31(+)/AC133(+) and AC133(+) cells), and distance-weighted traffic intensity (CD31(+)/34(+)/45(+)/AC133(+) cells). Living close to a major roadway is associated with elevated levels of circulating cells positive for the early stem marker AC133(+). This may reflect an increased need for vascular repair. Levels of these cells in peripheral blood may be a sensitive index of cardiovascular injury because of residential proximity to roadways. © 2015 American Heart Association, Inc.

Assessing water quality of the Chesapeake Bay by the impact of sea level rise and warming

NASA Astrophysics Data System (ADS)

Wang, P.; Linker, L.; Wang, H.; Bhatt, G.; Yactayo, G.; Hinson, K.; Tian, R.

2017-08-01

The influence of sea level rise and warming on circulation and water quality of the Chesapeake Bay under projected climate conditions in 2050 were estimated by computer simulation. Four estuarine circulation scenarios in the estuary were run using the same watershed load in 1991-2000 period. They are, 1) the Base Scenario, which represents the current climate condition, 2) a Sea Level Rise Scenario, 3) a Warming Scenario, and 4) a combined Sea Level Rise and Warming Scenario. With a 1.6-1.9°C increase in monthly air temperatures in the Warming Scenario, water temperature in the Bay is estimated to increase by 0.8-1°C. Summer average anoxic volume is estimated to increase 1.4 percent compared to the Base Scenario, because of an increase in algal blooms in the spring and summer, promotion of oxygen consumptive processes, and an increase of stratification. However, a 0.5-meter Sea Level Rise Scenario results in a 12 percent reduction of anoxic volume. This is mainly due to increased estuarine circulation that promotes oxygen-rich sea water intrusion in lower layers. The combined Sea Level Rise and Warming Scenario results in a 10.8 percent reduction of anoxic volume. Global warming increases precipitation and consequently increases nutrient loads from the watershed by approximately 5-7 percent. A scenario that used a 10 percent increase in watershed loads and current estuarine circulation patterns yielded a 19 percent increase in summer anoxic volume, while a scenario that used a 10 percent increase in watershed loads and modified estuarine circulation patterns by the aforementioned sea level rise and warming yielded a 6 percent increase in summer anoxic volume. Impacts on phytoplankton, sediments, and water clarity were also analysed.

Relationships between hormones and aggressive behavior in green anole lizards: an analysis using structural equation modeling.

PubMed

Yang, Eun-Jin; Wilczynski, Walter

2002-09-01

We investigated the relationship between aggressive behavior and circulating androgens in the context of agonistic social interaction and examined the effect of this interaction on the androgen-aggression relationship in response to a subsequent social challenge in male Anolis carolinensis lizards. Individuals comprising an aggressive encounter group were exposed to an aggressive conspecific male for 10 min per day during a 5-day encounter period, while controls were exposed to a neutral stimulus for the same period. On the sixth day, their responses to an intruder test were observed. At intervals, individuals were sacrificed to monitor plasma androgen levels. Structural equation modeling (SEM) was used to test three a priori interaction models of the relationship between social stimulus, aggressive behavior, and androgen. Model 1 posits that exposure to a social stimulus influences androgen and aggressive behavior independently. In Model 2, a social stimulus triggers aggressive behavior, which in turn increases circulating levels of androgen. In Model 3, exposure to a social stimulus influences circulating androgen levels, which in turn triggers aggressive behavior. During the 5 days of the encounter period, circulating testosterone (T) levels of the aggressive encounter group followed the same pattern as their aggressive behavioral responses, while the control group did not show significant changes in their aggressive behavior or T level. Our SEM results supported Model 2. A means analysis showed that during the intruder test, animals with 5 days of aggressive encounters showed more aggressive responses than did control animals, while their circulating androgen levels did not differ. This further supports Model 2, suggesting that an animal's own aggressive behavior may trigger increases in levels of plasma androgen. Copyright 2002 Elsevier Science (USA)

Importance of 5α-reductase gene polymorphisms on circulating and intraprostatic androgens in prostate cancer.

PubMed

Lévesque, Éric; Laverdière, Isabelle; Lacombe, Louis; Caron, Patrick; Rouleau, Mélanie; Turcotte, Véronique; Têtu, Bernard; Fradet, Yves; Guillemette, Chantal

2014-02-01

Polymorphisms in the genes SRD5A1 and SRD5A2 encoding androgen biosynthetic 5α-reductase enzymes have been associated with an altered risk of biochemical recurrence after radical prostatectomy in localized prostate cancer. To gain potential insights into SRD5A biologic effects, we examined the relationship between SRD5A prognostic markers and endogenous sex-steroid levels measured by mass spectrometry in plasma samples and corresponding prostatic tissues of patients with prostate cancer. We report that five of the seven SRD5A markers differentially affect sex-steroid profiles of dihydrotestosterone and its metabolites in both the circulation and prostatic tissues of patients with prostate cancer. Remarkably, a 32% increase in intraprostatic testosterone levels was observed in the presence of the high-risk SRD5A rs2208532 polymorphism. Moreover, SRD5A2 markers were associated predominantly with circulating levels of inactive glucuronides. Indeed, the rs12470143 SRD5A2 protective allele was associated with high circulating androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) levels as opposed to lower levels of both 3α-diol-17G and androsterone-glucuronide observed with the rs2208532 SRD5A2 risk allele. Moreover, SRD5A2 rs676033 and rs523349 (V89L) risk variants, in strong linkage disequilibrium, were associated with higher circulating levels of 3α-diol-3G. The SRD5A2 rs676033 variant further correlated with enhanced intraprostatic exposure to 5α-reduced steroids (dihydrotestosterone and its metabolite 3β-diol). Similarly, the SRD5A1 rs166050C risk variant was associated with greater prostatic exposure to androsterone, whereas no association was noted with circulating steroids. Our data support the association of 5α-reductase germline polymorphisms with the hormonal milieu in patients with prostate cancer. Further studies are needed to evaluate if these variants influence 5α-reductase inhibitor efficacy. ©2013 AACR.

Arctic Ocean Freshwater Content and Its Decadal Memory of Sea-Level Pressure

NASA Astrophysics Data System (ADS)

Johnson, Helen L.; Cornish, Sam B.; Kostov, Yavor; Beer, Emma; Lique, Camille

2018-05-01

Arctic freshwater content (FWC) has increased significantly over the last two decades, with potential future implications for the Atlantic meridional overturning circulation downstream. We investigate the relationship between Arctic FWC and atmospheric circulation in the control run of a coupled climate model. Multiple linear lagged regression is used to extract the response of total Arctic FWC to a hypothetical step increase in the principal components of sea-level pressure. The results demonstrate that the FWC adjusts on a decadal timescale, consistent with the idea that wind-driven ocean dynamics and eddies determine the response of Arctic Ocean circulation and properties to a change in surface forcing, as suggested by idealized models and theory. Convolving the response of FWC to a change in sea-level pressure with historical sea-level pressure variations reveals that the recent observed increase in Arctic FWC is related to natural variations in sea-level pressure.

Non-Esterified Fatty Acids Profiling in Rheumatoid Arthritis: Associations with Clinical Features and Th1 Response.

PubMed

Rodríguez-Carrio, Javier; Alperi-López, Mercedes; López, Patricia; Ballina-García, Francisco Javier; Suárez, Ana

2016-01-01

Since lipid compounds are known to modulate the function of CD4+ T-cells and macrophages, we hypothesize that altered levels of serum non-esterified fatty acids (NEFA) may underlie rheumatoid arthritis (RA) pathogenesis. Serum levels of NEFA (palmitic, stearic, palmitoleic, oleic, linoleic, γ-linoleic, arachidonic -AA-, linolenic, eicosapentaenoic -EPA- and docosahexaenoic -DHA-) were quantified by LC-MS/MS after methyl-tert-butylether (MTBE)-extraction in 124 RA patients and 56 healthy controls (HC). CD4+ phenotype was studied by flow cytometry. TNFα, IL-8, VEGF, GM-CSF, IFNγ, IL-17, CCL2, CXCL10, leptin and resistin serum levels were quantified by immunoassays. The effect of FA on IFNγ production by PBMC was evaluated in vitro. Lower levels of palmitic (p<0.0001), palmitoleic (p = 0.002), oleic (p = 0.010), arachidonic (p = 0.027), EPA (p<0.0001) and DHA (p<0.0001) were found in RA patients, some NEFA being altered at onset. Cluster analysis identified a NEFA profile (hallmarked by increased stearic and decreased EPA and DHA) overrepresented in RA patients compared to HC (p = 0.002), being associated with clinical features (RF, shared epitope and erosions), increased IFNγ expression in CD4+ T-cells (p = 0.002) and a Th1-enriched serum milieu (IFNγ, CCL2 and CXCL10, all p<0.005). In vitro assays demonstrated that imbalanced FA could underlie IFNγ production by CD4+ T-cells. Finally, changes on NEFA levels were associated with clinical response upon TNFα-blockade. An altered NEFA profile can be found in RA patients associated with clinical characteristics of aggressive disease and enhanced Th1 response. These results support the relevance of lipidomic studies in RA and provide a rationale for new therapeutic targets.

Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats.

PubMed

Samat, Suhana; Kanyan Enchang, Francis; Nor Hussein, Fuzina; Wan Ismail, Wan Iryani

2017-01-01

Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

PubMed Central

Kanyan Enchang, Francis; Nor Hussein, Fuzina

2017-01-01

Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat. PMID:28246535

Enrichment, Distribution of Vanadium-Containing Protein in Vanadium-Enriched Sea Cucumber Apostichopus japonicus and the Ameliorative Effect on Insulin Resistance.

PubMed

Liu, Yanjun; Zhou, Qingxin; Zhao, Yanlei; Wang, Yiming; Wang, Yuming; Wang, Jingfeng; Xu, Jie; Xue, Changhu

2016-05-01

Sea cucumbers are a potential source of natural organic vanadium that may improve insulin resistance. In this work, vanadium was accumulated rapidly in blood, body wall, and intestine by sea cucumber Apostichopus japonicus. Furthermore, water-soluble vanadium-containing proteins, the main form of the organic vanadium, were tentatively accumulated and isolated by a bioaccumulation experiment. It was also designed to evaluate the beneficial effect of vanadium-containing proteins (VCPs) from sea cucumber rich in vanadium on the development of hyperglycemia and insulin resistance in C57BL/6J mice fed with a high-fat high-sucrose diet (HFSD). HFSD mice treated with VCPs significantly decreased fasting blood glucose, serum insulin, and HOMA-IR values as compared to HFSD mice, respectively. Serum adiponectin, resistin, TNF-α, and leptin levels in insulin-resistant mice were dramatically reduced by a VCP supplement. These results show an ameliorative effect on insulin resistance by treatment with VCPs. Such compound seems to be a valuable therapy to achieve and/or maintain glycemic control and therapeutic agents in the treatment arsenal for insulin resistance and type 2 diabetes.

Exercise training attenuated chronic cigarette smoking-induced up-regulation of FIZZ1/RELMα in lung of rats.

PubMed

Ma, Wan-li; Cai, Peng-cheng; Xiong, Xian-zhi; Ye, Hong

2013-02-01

FIZZ/RELM is a new gene family named "found in inflammatory zone" (FIZZ) or "resistin-like molecule" (RELM). FIZZ1/RELMα is specifically expressed in lung tissue and associated with pulmonary inflammation. Chronic cigarette smoking up-regulates FIZZ1/RELMα expression in rat lung tissues, the mechanism of which is related to cigarette smoking-induced airway hyperresponsiveness. To investigate the effect of exercise training on chronic cigarette smoking-induced airway hyperresponsiveness and up-regulation of FIZZ1/RELMα, rat chronic cigarette smoking model was established. The rats were treated with regular exercise training and their airway responsiveness was measured. Hematoxylin and eosin (HE) staining, immunohistochemistry and in situ hybridization of lung tissues were performed to detect the expression of FIZZ1/RELMα. Results revealed that proper exercise training decreased airway hyperresponsiveness and pulmonary inflammation in rat chronic cigarette smoking model. Cigarette smoking increased the mRNA and protein levels of FIZZ1/RELMα, which were reversed by the proper exercise. It is concluded that proper exercise training prevents up-regulation of FIZZ1/RELMα induced by cigarette smoking, which may be involved in the mechanism of proper exercise training modulating airway hyperresponsiveness.

Fibrocyte measurement in peripheral blood correlates with number of cultured mature fibrocytes in vitro and is a potential biomarker for interstitial lung disease in Rheumatoid Arthritis.

PubMed

Just, Søren Andreas; Lindegaard, Hanne; Hejbøl, Eva Kildall; Davidsen, Jesper Rømhild; Bjerring, Niels; Hansen, Søren Werner Karlskov; Schrøder, Henrik Daa; Hansen, Inger Marie Jensen; Barington, Torben; Nielsen, Christian

2017-07-18

Interstitial lung disease (ILD) can be a severe extra-articular disease manifestation in Rheumatoid Arthritis (RA). A potential role of fibrocytes in RA associated ILD (RA-ILD) has not previously been described. We present a modified faster method for measuring circulating fibrocytes, without intracellular staining. The results are compared to the traditional culture method, where the number of monocytes that differentiate into mature fibrocytes in vitro are counted. The results are following compared to disease activity in patients with severe asthma, ILD, RA (without diagnosed ILD) and RA with verified ILD (RA-ILD). CD45 + CD34 + CD11b + (7-AAD - CD3 - CD19 - CD294 - ) cells were isolated by cell sorting and stained for pro-collagen type 1. Thirty-nine patients (10 RA, 9 ILD and 10 with severe asthma, 10 with RA-ILD) and 10 healthy controls (HC) were included. Current medication, disease activity, pulmonary function test and radiographic data were collected. Circulating fibrocytes were quantified by flow cytometry. Peripheral blood mononuclear cells were isolated and cultured for 5 days and the numbers of mature fibrocytes were counted. 90.2% (mean, SD = 1.5%) of the sorted cells were pro-collagen type 1 positive and thereby fulfilled the criteria for being circulating fibrocytes. The ILD and RA-ILD groups had increased levels of circulating fibrocytes compared to HC (p < 0.05). Levels of circulating fibrocytes correlated overall to number of monocytes that subsequently in vitro differentiated to mature fibrocytes (r = 0.81, p < 0.001). RA patients with pathologically reduced diffusion capacity for carbon monoxide adjusted for hemoglobin (DLCO c ) in both the RA and in the combined RA + RA-ILD group, had significantly higher levels of both circulating and number of cultured mature fibrocytes (both p < 0.05). In both groups, the level of circulating fibrocytes and number of mature fibrocytes in culture also correlated to a reduction in DLCO c (r = -0.61 an r = -0.58 both p < 0.05). We presented a fast and valid method for measuring circulating fibrocytes using flow cytometry on lysed peripheral blood. Further, we showed for the first time, that the level of circulating fibrocytes correlated with the number of peripheral blood mononuclear cells, that differentiated into mature fibrocytes in vitro. Reduced DLCO c was correlated with high levels of circulating and mature fibrocytes in RA, which have not been reported previously. In such, this study suggests that fibrocytes may exhibit an important role in the pathogenesis of RA-ILD, which requires further clarification in future studies. ClinicalTrials.gov : NCT02711657 , registered 13/3-2016, retrospectively registered.

Wind-induced circulation in a large tropical lagoon: Chetumal Bay

NASA Astrophysics Data System (ADS)

Palacios, E.; Carrillo, L.

2013-05-01

Chetumal Bay is a large tropical lagoon located at the Mesoamerican Reef System. Windinduced circulation in this basin was investigated by using direct measurements of current, sea level, and 2d barotropic numerical model. Acoustic Doppler Profiler (ADP) transects covering the north of Chetumal Bay during two campaigns September 2006 and March 2007 were used. The 2d barotropic numerical model was ROMs based and wind forced. Wind information was obtained from a meteorological station located at ECOSUR Chetumal. Sea level data was collected from a pressure sensor deployed in the lagoon. A seasonal pattern of circulation was observed. From observations, during September 2006, a northward flow was shown in most part of the bay and a southward flow in the eastern coast was observed with velocities ranged from 6 cm s-1 to 36 cm s-1. In March 2007, the current pattern was more complex; divergences and converges were identified. The dominant circulation was northward in eastern portion, and southward in the central and western zone. The average current speed was 6 cm s-1 with maximum values of 26 -34 cm s-1. During September 2006 predominant wind was easternsoutheastern and during March 2007, northerly wind events were recorded. Sea level amplitude responded quickly to changes in the magnitude and direction of the wind. Results of sea level and circulation from the 2d barotropic numerical model agreed with observations at first approximation.

Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease.

PubMed

Kohara, Marina; Masuda, Takahiro; Shiizaki, Kazuhiro; Akimoto, Tetsu; Watanabe, Yuko; Honma, Sumiko; Sekiguchi, Chuji; Miyazawa, Yasuharu; Kusano, Eiji; Kanda, Yoshinobu; Asano, Yasushi; Kuro-O, Makoto; Nagata, Daisuke

2017-01-01

Fibroblast growth factor 21 (FGF21) is an endocrine factor that regulates glucose and lipid metabolism. Circulating FGF21 predicts cardiovascular events and mortality in type 2 diabetes mellitus, including early-stage chronic kidney disease, but its impact on clinical outcomes in end-stage renal disease (ESRD) patients remains unclear. This study enrolled 90 ESRD patients receiving chronic hemodialysis who were categorized into low- and high-FGF21 groups by the median value. We investigated the association between circulating FGF21 levels and the cardiovascular event and mortality during a median follow-up period of 64 months. A Kaplan-Meier analysis showed that the mortality rate was significantly higher in the high-FGF21 group than in the low-FGF21 group (28.3% vs. 9.1%, log-rank, P = 0.034), while the rate of cardiovascular events did not significantly differ between the two groups (30.4% vs. 22.7%, log-rank, P = 0.312). In multivariable Cox models adjusted a high FGF21 level was an independent predictor of all-cause mortality (hazard ratio: 3.98; 95% confidence interval: 1.39-14.27, P = 0.009). Higher circulating FGF21 levels were associated with a high mortality rate, but not cardiovascular events in patient with ESRD, suggesting that circulating FGF21 levels serve as a predictive marker for mortality in these subjects.

Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study.

PubMed

Jadoon, Khalid A; Ratcliffe, Stuart H; Barrett, David A; Thomas, E Louise; Stott, Colin; Bell, Jimmy D; O'Sullivan, Saoirse E; Tan, Garry D

2016-10-01

Cannabidiol (CBD) and Δ(9)-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes. In this randomized, double-blind, placebo-controlled study, 62 subjects with noninsulin-treated type 2 diabetes were randomized to five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks. The primary end point was a change in HDL-cholesterol concentrations from baseline. Secondary/tertiary end points included changes in glycemic control, lipid profile, insulin sensitivity, body weight, liver triglyceride content, adipose tissue distribution, appetite, markers of inflammation, markers of vascular function, gut hormones, circulating endocannabinoids, and adipokine concentrations. Safety and tolerability end points were also evaluated. Compared with placebo, THCV significantly decreased fasting plasma glucose (estimated treatment difference [ETD] = -1.2 mmol/L; P < 0.05) and improved pancreatic β-cell function (HOMA2 β-cell function [ETD = -44.51 points; P < 0.01]), adiponectin (ETD = -5.9 × 10(6) pg/mL; P < 0.01), and apolipoprotein A (ETD = -6.02 μmol/L; P < 0.05), although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin (-898 pg/ml; P < 0.05) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml; P < 0.05). None of the combination treatments had a significant impact on end points. CBD and THCV were well tolerated. THCV could represent a new therapeutic agent in glycemic control in subjects with type 2 diabetes. © 2016 by the American Diabetes Association.

Effects of leptin treatment and Western diet on wheel running in selectively bred high runner mice.

PubMed

Meek, Thomas H; Dlugosz, Elizabeth M; Vu, Kim T; Garland, Theodore

2012-05-15

The role of leptin in regulating physical activity is varied. The behavioral effects of leptin signaling depend on the type of activity and the animal's physiological state. We used mice from lines selectively bred for high voluntary wheel running to further study how leptin regulates volitional exercise. Mice from four replicate high runner (HR) lines typically run ~3-fold more revolutions per day than those from four non-selected control (C) lines. HR mice have altered dopamine function and differences from C in brain regions known to be important in leptin-mediated behavior. Furthermore, male HR mice have been found to dramatically increase running when administered Western diet, an effect possibly mediated through leptin signaling. Male mice from generation 61 (representing three HR lines and one C line) were allowed wheel access at 24 days of age and given either Western diet (high in fat and with added sucrose) or standard chow. After four weeks, Western diet significantly increased circulating leptin, insulin, C-peptide, gastric inhibitory polypeptide, and inflammatory hormone resistin concentrations in HR mice (C mice not measured). Western diet increased running in HR mice, but did not significantly affect running in C mice. During the fifth week, all mice received two days of intra-peritoneal sham injections (physiological saline) followed by three days of murine recombinant leptin injections, and then another six days of sham injections. Leptin treatment significantly decreased caloric intake (adjusted for body mass) and body mass in all groups. Wheel running significantly increased with leptin injections in HR mice (fed Western or standard diet), but was unaffected in C mice. Whether Western diet and leptin treatment stimulate wheel running in HR mice through the same physiological pathways awaits future study. These results have implications for understanding the neural and endocrine systems that control locomotor activity, food consumption, and body weight, and how they may vary with genetic background. Copyright © 2012 Elsevier Inc. All rights reserved.

Relationship between circulating visfatin/NAMPT, nutritional status and insulin resistance in an elderly population - results from the PolSenior substudy.

PubMed

Olszanecka-Glinianowicz, Magdalena; Owczarek, Aleksander; Bożentowicz-Wikarek, Maria; Brzozowska, Aniceta; Mossakowska, Małgorzata; Zdrojewski, Tomasz; Grodzicki, Tomasz; Więcek, Andrzej; Chudek, Jerzy

2014-11-01

Circulating visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) levels according to some studies are related to nutritional status and insulin resistance. These associations have not been studied in large elderly populations. Therefore, the aim of our study was to assess the relationships between circulating visfatin/NAMPT levels, nutritional status, and insulin resistance in a large population of the elderly. Concentrations of glucose, albumin, creatinine, CRP, interleukin-6, insulin, and visfatin/NAMPT (by ELISA) were assessed, and HOMA-IR calculated in 3050 elderly participants of the PolSenior study. The highest plasma visfatin/NAMPT levels were observed in obese, as well as in non-diabetic insulin resistant subjects; however there were only significant differences found in women. The regression models showed that plasma visfatin/NAMPT levels decline with age and increased with waist circumference, BMI, and hs-CRP. Waist circumference was better correlated than BMI for visfatin/NAMPT levels in statistical models not adjusted by sex, and just the opposite in models which were. We demonstrated a 0.023ng/mL increase of Visfatin/NAMPT levels for 1mg/L increase of hs-CRP, and a 0.007ng/mL decline for each year of age. Our study revealed that in elderly subjects, circulating visfatin/NAMPT levels are related to age, nutritional status, especially visceral obesity, and inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

Vertical Helicity Flux as an Index of General Atmospheric Circulation

NASA Astrophysics Data System (ADS)

Kurgansky, M. V.; Maksimenkov, L. O.; Khapaev, A. A.; Chkhetiani, O. G.

2018-04-01

As an index of the general atmospheric circulation over the hemisphere, it is proposed to calculate the hemisphere-area-averaged (poleward of the latitude 20°) product of the Coriolis parameter by the wind velocity squared at the upper boundary of the planetary boundary layer. In practical calculations, data on the wind velocity at an isobaric level of 850 hPa were used. Control calculations for the 900 hPa level gave similar results. It is shown that the index introduced adequately characterizes the seasonal and interannual variability of the general atmospheric circulation over both hemispheres.

Circulating miR-1, miR-133a, and miR-206 levels are increased after a half-marathon run.

PubMed

Gomes, Clarissa P C; Oliveira, Getúlio P; Madrid, Bibiano; Almeida, Jeeser A; Franco, Octávio L; Pereira, Rinaldo W

2014-11-01

Circulating miRNAs are potential biomarkers that can be important molecules driving cell-to-cell communication. To investigate circulating muscle-specific miRNAs in recreational athletes. Three miRNAs from whole plasma before and after a half-marathon were analyzed by qPCR. MiR-1, -133a, and -206 significantly increased after the race. Increased levels of miRNAs after exercise point to potential biomarkers and to the possibility of being functional players following endurance training. These miRNAs are potential biomarkers of muscle damage or adaptation to exercise.

Circulating Plasma and Exosomal microRNAs as Indicators of Drug-Induced Organ Injury in Rodent Models

PubMed Central

Cho, Young-Eun; Kim, Sang-Hyun; Lee, Byung-Heon; Baek, Moon-Chang

2017-01-01

This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine. Circulating miR-146a and miR-206 were increased in cisplatin-induced nephrotoxicity and bupivacaine-induced myotoxicity, respectively. Taken together, these results indicate that circulating plasma and exosomal miRNAs can be used as potential biomarkers specific for drug-induced liver, kidney or muscle injury. PMID:28208010

Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired aplastic anemia and myelodysplastic syndromes.

PubMed

Giudice, Valentina; Wu, Zhijie; Kajigaya, Sachiko; Fernandez Ibanez, Maria Del Pilar; Rios, Olga; Cheung, Foo; Ito, Sawa; Young, Neal S

2018-06-26

The alarmin family members S100A8 and S100A9 are acute phase inflammation proteins, but they also have been proposed as biomarkers in many malignant and non-malignant diseases. In this study, circulating S100A8 and S100A9 homodimers and S100A8/A9 heterodimers in plasma were systematically investigated by ELISA in aplastic anemia (AA) and myelodysplastic syndromes (MDS). Plasma was obtained from 58 severe AA (SAA) and 30 MDS patients, and from 47 age- and sex-matched healthy donors. In 40 out of the 58 AA subjects, S100A protein levels were measured before and 6 months after immunosuppressive therapy (IST). No differences were observed in AA patients at diagnosis compared to healthy controls for circulating S100A homodimers and heterodimers. After therapy, SAA-responders showed significantly increased circulating S100A8. Non-responding patients had significantly higher levels of circulating S100A8/A9 compared to responders and healthy controls, but without variations of S100A8 and S100A9 homodimers. In MDS patients, circulating S100A8 was significantly elevated compared to those of AA and/or healthy controls. By Pearson correlation analysis of protein levels and blood counts, multiple correlations were found. However, as S100A8 and S100A9 are abundantly present in white blood cells and platelets, correlations with blood counts likely mirror the higher number of cells in the blood of some patients. In conclusion, our findings indicate that circulating S100A8 is increased in MDS but not in AA, and that may be useful to distinguish these diseases in the differential diagnosis of bone marrow failure syndromes. Clinicaltrials.gov identifiers: NCT00260689, NCT00604201, NCT01328587, NCT01623167, NCT00001620, NCT00001397. Published by Elsevier Ltd.

Optimizing 18F-FDG PET/CT Imaging of Vessel Wall Inflammation –The Impact of 18F-FDG Circulation Time, Injected Dose, Uptake Parameters, and Fasting Blood Glucose Levels

PubMed Central

Bucerius, Jan; Mani, Venkatesh; Moncrieff, Colin; Machac, Josef; Fuster, Valentin; Farkouh, Michael E.; Tawakol, Ahmed; Rudd, James H. F.; Fayad, Zahi A.

2014-01-01

Purpose 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly used for imaging of vessel wall inflammation. However, limited data is available regarding the impact of methodological variables, i. e. patient’s pre-scan fasting glucose, the FDG circulation time, the injected FDG dose, and of different FDG uptake parameters, in vascular FDG-PET imaging. Methods 195 patients underwent vascular FDG-PET/CT of the aorta and the carotids. Arterial standard uptake values (meanSUVmax) as well as target-to-background-ratios (meanTBRmax) and the FDG blood pool activity in the superior vein cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake classified according to tertiles of patient’s pre-scan fasting glucose levels, the FDG circulation time, and the injected FDG dose was compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood pool FDG uptake. Results Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l showing favorable relations between the arterial and blood pool FDG uptake. FDG circulation times showed negative associations with the aortic meanSUVmax values as well as SVC- and JV FDG blood pool activity but a positive correlation with the aortic- and carotid meanTBRmax values. Pre-scan glucose was negatively associated with aortic- and carotid meanTBRmax and carotid meanSUVmax values, but correlated positively with the SVC blood pool uptake. Injected FDG dose failed to show any significant association with the vascular FDG uptake. Conclusion FDG circulation times and pre-scan blood glucose levels significantly impact FDG uptake within the aortic and carotid wall and may bias the results of image interpretation in patients undergoing vascular FDG-PET/CT. FDG dose injected was less critical. Therefore, circulation times of about 2.5 h and pre-scan glucose levels less than 7.0 mmol/l should be preferred in this setting. PMID:24271038

Relationship between inflammation, insulin resistance and type 2 diabetes: 'cause or effect'?

PubMed

Greenfield, Jerry R; Campbell, Lesley V

2006-05-01

Inflammation has been implicated as an important aetiological factor in the development of both insulin resistance and type 2 diabetes mellitus. This conclusion is predominantly drawn from studies demonstrating associations between elevated (but 'normal range') levels of circulating acute phase inflammatory markers, typified by C-reactive protein (CRP), and indices of insulin resistance and the development of type 2 diabetes. There is debate as to whether these associations are independent of body fatness or, rather, an epiphenomenon of obesity, particularly central obesity, a strong predictor of insulin resistance and type 2 diabetes and an important source of inflammatory cytokines, such as interleukin-6. Some of this controversy and the inability to draw definitive conclusions from these studies relate to the fact that most studies measure body fat and its distribution indirectly using anthropometric estimates, such as Body Mass Index and waist circumference, rather than directly by dual-energy X-ray absorptiometry, computed tomography or magnetic resonance imaging. Furthermore, use of the term inflammation may be inappropriate when describing mild elevations of CRP in the 'normal range' in the absence of the other changes that characterise classical inflammatory diseases, such as a reduction in levels (or evidence of consumption) of complement proteins. Debate as to whether obesity mediates the association between circulating levels of inflammatory markers and insulin resistance can be resolved by well-designed studies using body fat measured by gold-standard methods. In this review, we present evidence to support the suggestion that body fat is the primary determinant of circulating inflammatory marker levels in the basal state and that marginally elevated levels of circulating interleukin-6 and CRP in obesity are a consequence rather than a cause of insulin resistance. The importance of genetic influences in determining both body fatness and circulating CRP levels will also be discussed. The review will conclude with a discussion of possible mechanisms linking body fat and insulin resistance to elevated circulating levels of inflammatory markers, including the possible role of the toll-like family of immune receptors.

Uncoupled iron homeostasis in type 2 diabetes mellitus.

PubMed

Altamura, Sandro; Kopf, Stefan; Schmidt, Julia; Müdder, Katja; da Silva, Ana Rita; Nawroth, Peter; Muckenthaler, Martina U

2017-12-01

Diabetes mellitus is frequently associated with iron overload conditions, such as primary and secondary hemochromatosis. Conversely, patients affected by type 2 diabetes mellitus (T2DM) show elevated ferritin levels, a biomarker for increased body iron stores. Despite these documented associations between dysregulated iron metabolism and T2DM, the underlying mechanisms are poorly understood. Here, we show that T2DM patients have reduced serum levels of hepcidin, the iron-regulated hormone that maintains systemic iron homeostasis. Consistent with this finding, we also observed an increase in circulating iron and ferritin levels. Our analysis of db/db mice demonstrates that this model recapitulates the systemic alterations observed in patients. Interestingly, db/db mice show an overall hepatic iron deficiency despite unaltered expression of ferritin and the iron importer TfR1. In addition, the liver correctly senses increased circulating iron levels by activating the BMP/SMAD signaling pathway even though hepcidin expression is decreased. We show that increased AKT phosphorylation may override active BMP/SMAD signaling and decrease hepcidin expression in 10-week old db/db mice. We conclude that the metabolic alterations occurring in T2DM impact on the regulation of iron homeostasis on multiple levels. As a result, metabolic perturbations induce an "iron resistance" phenotype, whereby signals that translate increased circulating iron levels into hepcidin production, are dysregulated. T2DM patients show increased circulating iron levels. T2DM is associated with inappropriately low hepcidin levels. Metabolic alterations in T2DM induce an "iron resistance" phenotype.

Interleukin-20 circulating levels in obese women: effect of weight loss.

PubMed

Maiorino, M I; Schisano, B; Di Palo, C; Vietri, M T; Cioffi, M; Giugliano, G; Giugliano, D; Esposito, K

2010-03-01

Obesity is associated with an increased risk of developing atherosclerosis. Interleukin-20 (IL-20) is a pleiotropic cytokine thought to be involved in the onset and progression of atherosclerosis. The aim of this study was to determine whether circulating levels of IL-20 are elevated in obese women and whether they could be affected by a substantial decrease in body weight. Fifty obese and 50 age-matched, normal weight, premenopausal women participated in the study. Obese women entered into a medically supervised weight loss program aimed at reducing body weight to 90% of baseline. We measured anthropometric, glucose and lipid parameters, and IL-20, C-Reactive Protein (CRP) and interleukin-10 (IL-10) circulating levels. Circulating IL-20 and CRP levels were significantly higher in obese than control women (P=0.01), while IL-10 levels were significantly lower; IL-20 levels were positively associated with body weight (r=0.35; P=0.02) and visceral fat (waist-hip ratio; r=0.32; P=0.025). Caloric restriction-induced weight loss (>10% of original weight) over 6 months reduced IL-20 levels from 152 (112/184) to 134 (125/153)pg/ml (median and 25%/75%; P=0.03), and it was positively associated with changes in body mass index and waist-hip ratio. In premenopausal obese women, IL-20 levels are higher than matched normal weight control women, are associated with body weight and waist-hip ratio, and are reduced by weight loss. (c) 2009 Elsevier B.V. All rights reserved.

Circulating insulin-like peptide 5 levels and its association with metabolic and hormonal parameters in women with polycystic ovary syndrome.

PubMed

Bicer, M; Alan, M; Alarslan, P; Guler, A; Kocabas, G U; Imamoglu, C; Aksit, M; Bozkaya, G; Isil, A M; Baloglu, A; Aslanipoiur, B; Calan, Mehmet

2018-06-28

Insulin-like peptide 5 (INSL5) is a gut peptide hormone that is a member of relaxin/insulin superfamily. Growing evidence implicates the crucial role of the peptide in some metabolisms including food intake, glucose homeostasis and reproductive system. Polycystic ovary syndrome (PCOS) is involved in both reproductive and metabolic issues. The aim of the study was determination of circulating levels of INSL5 alteration in women with PCOS and evaluation of the relationship between INSL5 and hormonal-metabolic parameters as well as carotid intima media thickness (cIMT). A total of 164 subjects were recruited in this cross-sectional study (82 women with PCOS and 82 age- and BMI-matched controls). Circulating INSL5 levels were assessed via ELISA method. High-resolution B-mode ultrasound was used to measure cIMT. The hormonal and metabolic parameters of the recruited subjects were determined. Circulating INSL5 levels were significantly elevated in women with PCOS compared to controls (27.63 ± 7.74 vs. 19.90 ± 5.85 ng/ml, P < 0.001). The mean values of INSL5 were significantly higher in overweight subjects compared to lean weight subjects in both groups. The women with PCOS having insulin resistance have increased INSL5 compared to those of PCOS subjects without insulin resistance. INSL5 is associated with insulin resistance, BMI, luteinizing hormone and free androgen index. Multivariate logistic regression analyses revealed that the odds ratio for having PCOS in the highest tertile of INSL5 was higher than in the lowest tertile. PCOS subjects exhibited an elevation in circulating INSL5 levels along with a link between INSL5 level induction and metabolic-hormonal parameters.

Circulating CTRP9 levels are increased in patients with newly diagnosed type 2 diabetes and correlated with insulin resistance.

PubMed

Jia, Yanjun; Luo, Xiaohe; Ji, Ying; Xie, Jingwen; Jiang, Han; Fu, Mao; Li, Xiaoqiang

2017-09-01

C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has been shown to promote lipid metabolism, enhance insulin sensitivity and protect against cardiovascular disease. However, previous studies in humans have produced controversial results regarding the association between CTRP9 and insulin resistance. The objective of this study was to evaluate the relationships between CTRP9 and insulin resistance in Chinese population. Subjects with normal glucose tolerance (NGT, n=108), impaired glucose tolerance (IGT, n=92), and newly diagnosed type 2 diabetes mellitus (nT2DM, n=106) were recruited to determining the circulating CTRP9 and adiponectin levels by enzyme linked immunosorbent assay. Anthropometric and biochemical measurements related to insulin resistance, adiposity and lipid profile were examined for all participants. Oral glucose tolerance test was performed in healthy subjects (17 male and 17 female). Circulating CTRP9 level was significantly higher in both IGT and nT2DM than in individuals with NGT. Overweight/obese subjects had much higher CTRP9 levels than lean individuals, and in all subjects, females also had higher CTRP9 levels than males. In addition, circulating CTRP9 level was positively correlated with markers of obesity and insulin resistance, including body mass index, fasting blood glucose, insulin, HbA1c, homeostasis model assessment of insulin resistance and low-density lipoprotein-cholesterol, while was inversely correlated with high-density lipoprotein-cholesterol and adiponectin. Moreover, hyperglycemia during an oral glucose challenge increased circulating CTRP9 concentrations. We conclude that CTRP9 was strongly associated with insulin resistance, suggesting that CTRP9 might be important in the development of type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels.

PubMed

Khetarpal, Sumeet A; Zeng, Xuemei; Millar, John S; Vitali, Cecilia; Somasundara, Amritha Varshini Hanasoge; Zanoni, Paolo; Landro, James A; Barucci, Nicole; Zavadoski, William J; Sun, Zhiyuan; de Haard, Hans; Toth, Ildikó V; Peloso, Gina M; Natarajan, Pradeep; Cuchel, Marina; Lund-Katz, Sissel; Phillips, Michael C; Tall, Alan R; Kathiresan, Sekar; DaSilva-Jardine, Paul; Yates, Nathan A; Rader, Daniel J

2017-09-01

Recent large-scale genetic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipoprotein (TRL) clearance pathway that are protective against coronary heart disease (CHD), independently of LDL cholesterol (LDL-C) levels. Insight into the mechanisms of protection of these variants may facilitate the development of new therapies for lowering TRL levels. The gene APOC3 encodes apoC-III, a critical inhibitor of triglyceride (TG) lipolysis and remnant TRL clearance. Here we report a detailed interrogation of the mechanism of TRL lowering by the APOC3 Ala43Thr (A43T) variant, the only missense (rather than protein-truncating) variant in APOC3 reported to be TG lowering and protective against CHD. We found that both human APOC3 A43T heterozygotes and mice expressing human APOC3 A43T display markedly reduced circulating apoC-III levels. In mice, this reduction is due to impaired binding of A43T apoC-III to lipoproteins and accelerated renal catabolism of free apoC-III. Moreover, the reduced content of apoC-III in TRLs resulted in accelerated clearance of circulating TRLs. On the basis of this protective mechanism, we developed a monoclonal antibody targeting lipoprotein-bound human apoC-III that promotes circulating apoC-III clearance in mice expressing human APOC3 and enhances TRL catabolism in vivo. These data reveal the molecular mechanism by which a missense variant in APOC3 causes reduced circulating TG levels and, hence, protects from CHD. This protective mechanism has the potential to be exploited as a new therapeutic approach to reduce apoC-III levels and circulating TRL burden.

A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels

PubMed Central

Khetarpal, Sumeet A; Zeng, Xuemei; Millar, John S; Vitali, Cecilia; Somasundara, Amritha Varshini Hanasoge; Zanoni, Paolo; Landro, James A; Barucci, Nicole; Zavadoski, William J; Sun, Zhiyuan; de Haard, Hans; Toth, Ildikó V; Peloso, Gina M; Natarajan, Pradeep; Cuchel, Marina; Lund-Katz, Sissel; Phillips, Michael C; Tall, Alan R; Kathiresan, Sekar; DaSilva-Jardine, Paul; Yates, Nathan A; Rader, Daniel J

2017-01-01

Recent large-scale genetic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipoprotein (TRL) clearance pathway that are protective against coronary heart disease (CHD), independently of LDL cholesterol (LDL-C) levels1. Insight into the mechanisms of protection of these variants may facilitate the development of new therapies for lowering TRL levels. The gene APOC3 encodes apoC-III, a critical inhibitor of triglyceride (TG) lipolysis and remnant TRL clearance2. Here we report a detailed interrogation of the mechanism of TRL lowering by the APOC3 Ala43Thr (A43T) variant, the only missense (rather than protein-truncating) variant in APOC3 reported to be TG lowering and protective against CHD3–5. We found that both human APOC3 A43T heterozygotes and mice expressing human APOC3 A43T display markedly reduced circulating apoC-III levels. In mice, this reduction is due to impaired binding of A43T apoC-III to lipoproteins and accelerated renal catabolism of free apoC-III. Moreover, the reduced content of apoC-III in TRLs resulted in accelerated clearance of circulating TRLs. On the basis of this protective mechanism, we developed a monoclonal antibody targeting lipoprotein-bound human apoC-III that promotes circulating apoC-III clearance in mice expressing human APOC3 and enhances TRL catabolism in vivo. These data reveal the molecular mechanism by which a missense variant in APOC3 causes reduced circulating TG levels and, hence, protects from CHD. This protective mechanism has the potential to be exploited as a new therapeutic approach to reduce apoC-III levels and circulating TRL burden. PMID:28825717

IGF2R Genetic Variants, Circulating IGF2 Concentrations and Colon Cancer Risk in African Americans and Whites

PubMed Central

Hoyo, Cathrine; Murphy, Susan K.; Schildkraut, Joellen M.; Vidal, Adriana C.; Skaar, David; Millikan, Robert C.; Galanko, Joseph; Sandler, Robert S.; Jirtle, Randy; Keku, Temitope

2012-01-01

The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9–5.4)], whereas carrying the IGF2R c.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2. PMID:22377707

IGF2R genetic variants, circulating IGF2 concentrations and colon cancer risk in African Americans and Whites.

PubMed

Hoyo, Cathrine; Murphy, Susan K; Schildkraut, Joellen M; Vidal, Adriana C; Skaar, David; Millikan, Robert C; Galanko, Joseph; Sandler, Robert S; Jirtle, Randy; Keku, Temitope

2012-01-01

The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9-5.4)], whereas carrying the IGF2R c.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2.

B Cell Depletion Therapy Normalizes Circulating Follicular Th Cells in Primary Sjögren Syndrome.

PubMed

Verstappen, Gwenny M; Kroese, Frans G M; Meiners, Petra M; Corneth, Odilia B; Huitema, Minke G; Haacke, Erlin A; van der Vegt, Bert; Arends, Suzanne; Vissink, Arjan; Bootsma, Hendrika; Abdulahad, Wayel H

2017-01-01

To assess the effect of B cell depletion therapy on effector CD4+ T cell homeostasis and its relation to objective measures of disease activity in patients with primary Sjögren syndrome (pSS). Twenty-four patients with pSS treated with rituximab (RTX) and 24 healthy controls (HC) were included. Frequencies of circulating effector CD4+ T cell subsets were examined by flow cytometry at baseline and 16, 24, 36, and 48 weeks after the first RTX infusion. Th1, Th2, follicular Th (TFH), and Th17 cells were discerned based on surface marker expression patterns. Additionally, intracellular cytokine staining was performed for interferon-γ, interleukin (IL)-4, IL-21, and IL-17 and serum levels of these cytokines were analyzed. In patients with pSS, frequencies of circulating TFH cells and Th17 cells were increased at baseline compared with HC, whereas frequencies of Th1 and Th2 cells were unchanged. B cell depletion therapy resulted in a pronounced decrease in circulating TFH cells, whereas Th17 cells were only slightly lowered. Frequencies of IL-21-producing and IL-17-producing CD4+ T cells and serum levels of IL-21 and IL-17 were also reduced. Importantly, the decrease in circulating TFH cells was associated with lower systemic disease activity over time, as measured by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index scores and serum IgG levels. B cell depletion therapy in patients with pSS results in normalization of the elevated levels of circulating TFH cells. This reduction is associated with improved objective clinical disease activity measures. Our observations illustrate the pivotal role of the crosstalk between B cells and TFH cells in the pathogenesis of pSS.

Anthropogenic Influence on the Changes of the Subtropical Gyre Circulation in the South Pacific in the 20th Century

NASA Astrophysics Data System (ADS)

Albrecht, F.; Pizarro, O.; Montecinos, A.

2016-12-01

The subtropical ocean gyre in the South Pacific is a large scale wind-driven ocean circulation, including the Peru-Chile Current, the westward South Equatorial Current, the East Australian Current, and the eastward South Pacific Current. Large scale ocean circulations play an essential role in the climate of the Earth over long and short term time scales.In the recent years a spin-up of this circulation has been recognized analyzing observations of sea level, temperature and salinity profiles, sea surface temperature and wind. Until now it is not clear whether this spin-up is decadal variability or whether it is a long-term trend introduced by anthropogenic forcing. This study aims to analyze whether and how anthropogenic forcing influences the position and the strength of the gyre in the 20th century. To determine that, yearly means of different variables of an ensemble of CMIP5 models are analyzed. The experiments 'historical' and 'historicalNat' are examined. The 'historical' experiment simulates the climate of the 20th century and the 'historicalNat' experiment covers the same time period, but only includes natural forcings. Comparing the outcomes of these two experiments is supposed to give information about the anthropogenic influence on the subtropical gyre of the South Pacific.The main variable we analyze is sea level change. This is directly related to the gyre circulation. The center of the gyre is characterized by a high pressure zone (high sea level) and the temporal and spatial variability of the sea level height field gives information about changes in the gyre circulation. The CMIP5 databank includes steric and dynamic sea level changes. Steric sea level, that is the contribution of temperature and salinity of the water, describes the major contribution to regional sea level change with respect to the global mean. Density changes contract or expand the water, which also changes the sea surface height. This does not only occur at the surface, but at all layers in the ocean. Sea level change thus integrates ocean variability throughout the depth of the ocean. Sea level simulations of the different experiments are compared using long-term trends, multi-year anomalies and EOF-Analysis. Changes in temperature and salinity in the deeper ocean are used to describe the development of the gyre below the surface.

Clarifying the Dynamics of the General Circulation: Phillips's 1956 Experiment.

NASA Astrophysics Data System (ADS)

Lewis, John M.

1998-01-01

In the mid-1950s, amid heated debate over the physical mechanisms that controlled the known features of the atmosphere's general circulation, Norman Phillips simulated hemispheric motion on the high-speed computer at the Institute for Advanced Study. A simple energetically consistent model was integrated for a simulated time of approximately 1 month. Analysis of the model results clarified the respective roles of the synoptic-scale eddies (cyclones-anticyclones) and mean meridional circulation in the maintenance of the upper-level westerlies and the surface wind regimes. Furthermore, the modeled cyclones clearly linked surface frontogenesis with the upper-level Charney-Eady wave. In addition to discussing the model results in light of the controversy and ferment that surrounded general circulation theory in the 1940s-1950s, an effort is made to follow Phillips's scientific path to the experiment.

Insights Into Circulating Cytokine Dynamics during Pregnancy in HIV-Infected Beninese Exposed to Plasmodium falciparum Malaria

PubMed Central

Ibitokou, Samad A.; Denoeud-Ndam, Lise; Ezinmegnon, Sèm; Ladékpo, Rodolphe; Zannou, Djimon-Marcel; Massougbodji, Achille; Girard, Pierre-Marie; Cot, Michel; Luty, Adrian J. F.; Ndam, Nicaise Tuikue

2015-01-01

We investigated the circulating plasma levels of Th1- (Interleukin-2 [IL-2], tumor necrosis factor-α [TNF-α], interferon-gamma [IFN-γ]) and Th2-type (IL-4, IL-5, IL-10) cytokines in human immunodeficiency virus (HIV)-infected pregnant women living in a malaria-endemic area. We analyzed samples from 200 pregnant women included in the prevention of pregnancy-associated malaria in HIV-infected women: cotrimoxazole prophylaxis versus mefloquine (PACOME) clinical trial who were followed until delivery. Cytokine concentrations were measured by flow cytometry-based multiplex bead array. Significantly elevated levels of IL-10 and lower levels of TNF-α were observed at delivery compared with inclusion (P = 0.005). At inclusion, the presence of circulating IFN-γ, a higher CD4+ T cell count and having initiated intermittent preventive treatment of malaria with sulfadoxine pyrimethamine (SP-IPTp) were all associated with a lower likelihood of Plasmodium falciparum infection. At delivery, the inverse relationship between the presence of infection and circulating IFN-γ persisted, although there was a positive association between the likelihood of infection and the presence of circulating TNF-α. Initiation of antiretroviral therapy was associated with elevated IL-5 production. Consistent with our own and others' observations in HIV seronegative subjects, this study shows circulating IL-10 to be a marker of infection with P. falciparum during pregnancy even in HIV-infected women, although plasma IFN-γ may be a marker of anti-malarial protection in such women. PMID:26101276

Association of circulating adipokines with metabolic dyslipidemia in obese versus non-obese individuals.

PubMed

Rahimlou, Mehran; Mirzaei, Khadijeh; Keshavarz, Seyed Ali; Hossein-Nezhad, Arash

2016-01-01

Previous studies have shown that circulating adipokines may play an important role in the pathogenesis of some obesity related chronic disease such as dyslipidemia and type2 diabetes mellitus. The aim of the present study was to investigate the association between vaspin, omentin-1 and retinol binding protein-4 levels with metabolic dyslipidemia (MD) criteria in obese and non-obese individuals. The study was conducted on 170 obese and 81 non-obese individuals. After collecting the blood samples, serum levels metabolic parameters as well as three circulating adipokines and body composition were measured. No significant difference was noted regarding the mean serum levels of omentin-1 and vaspin between the obese and non-obese groups, while, serum level of RBP4 was significantly higher in the non-obese group. We found the 0.22 increased risk of MD in obese individuals with higher RBP4 concentration. After the adjustment for confounding factors, this association was still significant. No significant association was noted between MD and its components relative risks with omentin-1 and vaspin levels. Our study demonstrated that circulating RBP4 was significantly higher in the obese individuals which may increase the risk of MD in them. Further researches are needed to address this association. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients.

PubMed

Cranenburg, Ellen C M; Brandenburg, Vincent M; Vermeer, Cees; Stenger, Melanie; Mühlenbruch, Georg; Mahnken, Andreas H; Gladziwa, Ulrich; Ketteler, Markus; Schurgers, Leon J

2009-02-01

Matrix gamma-carboxyglutamate (Gla) protein (MGP) is a potent local inhibitor of cardiovascular calcification and accumulates at areas of calcification in its uncarboxylated form (ucMGP). We previously found significantly lower circulating ucMGP levels in patients with a high vascular calcification burden. Here we report on the potential of circulating ucMGP to serve as a biomarker for vascular calcification in haemodialysis (HD) patients. Circulating ucMGP levels were measured with an ELISA-based assay in 40 HD patients who underwent multi-slice computed tomography (MSCT) scanning to quantify the extent of coronary artery calcification (CAC). The mean ucMGP level in HD patients (193 +/- 65 nM) was significantly lower as compared to apparently healthy subjects of the same age (441 +/- 97 nM; p < 0.001) and patients with rheumatoid arthritis (RA) without CAC (560 +/- 140 nM; p < 0.001). Additionally, ucMGP levels correlated inversely with CAC scores (r = -0.41; p = 0.009), and this correlation persisted after adjustment for age, dialysis vintage and high-sensitivity C-reactive protein (hs-CRP). Since circulating ucMGP levels are significantly and inversely correlated with the extent of CAC in HD patients, ucMGP may become a tool for identifying HD patients with a high probability of cardiovascular calcification.

Circulating Endothelial Microparticles and Correlation of Serum 1,25-Dihydroxyvitamin D with Adiponectin, Nonesterified Fatty Acids, and Glycerol from Middle-Aged Men in China.

PubMed

Wan, Zhongxiao; Yu, Lugang; Cheng, Jinbo; Zhang, Zengli; Xu, Baohui; Pang, Xing; Zhou, Hui; Lei, Ting

2016-01-01

The aim of the present study is (1) to determine the correlation between circulating 1,25-dihydroxyvitamin D [25(OH)D] and adiponectin, nonesterified fatty acids (NEFAs), and glycerol and (2) to determine the alterations in circulating endothelial microparticles (EMPs) in Chinese male subjects with increased body mass index (BMI). A total of 45 male adults were enrolled with varied BMI [i.e., lean, overweight (OW), and obese (OB), N = 15 per group]. Blood samples were collected under overnight fasting condition, and plasma was isolated for the measurement of endothelial microparticles (EMPs), total and high-molecular weight (HMW) adiponectin, 25(OH)D, nonesterified fatty acids (NEFAs), and glycerol. Circulating 25(OH)D levels were inversely associated with total adiponectin, NEFA, and glycerol levels. There is no difference for CD62E+ or CD31+/CD42b- EMPs among 3 groups. In Chinese male adults with varied BMI, an inverse correlation existed between 25(OH)D levels and total adiponectin, NEFA, and glycerol levels; and there is no significant difference for CD62E+ or CD31+/CD42b- EMPs among lean, overweight, and obese subjects.

Circulating Endothelial Microparticles and Correlation of Serum 1,25-Dihydroxyvitamin D with Adiponectin, Nonesterified Fatty Acids, and Glycerol from Middle-Aged Men in China

PubMed Central

Wan, Zhongxiao; Yu, Lugang; Cheng, Jinbo; Zhang, Zengli; Xu, Baohui; Pang, Xing; Zhou, Hui; Lei, Ting

2016-01-01

The aim of the present study is (1) to determine the correlation between circulating 1,25-dihydroxyvitamin D [25(OH)D] and adiponectin, nonesterified fatty acids (NEFAs), and glycerol and (2) to determine the alterations in circulating endothelial microparticles (EMPs) in Chinese male subjects with increased body mass index (BMI). A total of 45 male adults were enrolled with varied BMI [i.e., lean, overweight (OW), and obese (OB), N = 15 per group]. Blood samples were collected under overnight fasting condition, and plasma was isolated for the measurement of endothelial microparticles (EMPs), total and high-molecular weight (HMW) adiponectin, 25(OH)D, nonesterified fatty acids (NEFAs), and glycerol. Circulating 25(OH)D levels were inversely associated with total adiponectin, NEFA, and glycerol levels. There is no difference for CD62E+ or CD31+/CD42b− EMPs among 3 groups. In Chinese male adults with varied BMI, an inverse correlation existed between 25(OH)D levels and total adiponectin, NEFA, and glycerol levels; and there is no significant difference for CD62E+ or CD31+/CD42b− EMPs among lean, overweight, and obese subjects. PMID:27314039

The Clinical Development of Thalildomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer

DTIC Science & Technology

2005-10-01

regulation of cell adhesion molecules LFA-1 and ICAM-1 after in vitro treatment with the anti- TNF - alpha agent thalidomide . Settles B, Stevenson A...Plasma levels of circulating TNF -α and VEGF measured in 16 thalidomide treated patients seemed to increase after treatment (Table 2). Serum levels of...Logothetis, Christopher J. Page 6 Table 2. Levels of circulating VEGF, bFGF, TNF -α and IL-6 before and after thalidomide treatment. Comparison of

An exploratory study of inflammatory cytokines as prognostic biomarkers in patients with ductal pancreatic adenocarcinoma.

PubMed

Dima, Simona O; Tanase, Cristiana; Albulescu, Radu; Herlea, Vlad; Chivu-Economescu, Mihaela; Purnichescu-Purtan, Raluca; Dumitrascu, Traian; Duda, Dan G; Popescu, Irinel

2012-10-01

We measured the serum concentration of a panel of inflammatory cytokines and evaluated their association with circulating proangiogenic biomarkers and with outcome in patients with pancreatic ductal adenocarcinoma (PDAC). We collected serum samples from 36 patients with PDAC, 9 patients with chronic pancreatitis, and 22 healthy volunteers as a control. Inflammatory cytokines and proangiogenic biomarkers were measured using the multianalyte xMAP array and carcinoembryonic antigen (CEA) and carbohydrate 19-9 by immunoassay. Patients with PDAC had higher circulating levels of interleukin 6 (IL-6) than those of patients with pancreatitis or healthy individuals and higher levels of IL-10 and tumor necrosis factor α (TNF-α) compared with those of healthy individuals. In patients with PDAC, circulating IL-6, TNF-α, IL-1β, and IL-10 correlated with serum concentrations of vascular endothelial growth factor and basic fibroblast growth factor; circulating IL-6, IL-1β, and TNF-α correlated with carbohydrate 19-9; and IL-8, IL-10, and TNF-α correlated with CEA levels. Circulating IL-8, TNF-α, and CEA; tumor stage; and lymph node metastases were associated with a poor outcome. The results of this exploratory study indicate that inflammatory cytokines should be pursued as potential prognostic biomarkers as well as targets for therapy in larger studies in PDAC.

High levels of circulating extracellular vesicles with altered expression and function during pregnancy.

PubMed

Nardi, Fabiola da Silva; Michelon, Tatiana Ferreira; Neumann, Jorge; Manvailer, Luis Felipe Santos; Wagner, Bettina; Horn, Peter A; Bicalho, Maria da Graça; Rebmann, Vera

2016-07-01

Extracellular vesicles (EVs) are widely considered important modulators of cell-cell communication and may interact with target cells locally and on a systemic level. Several studies had shown that circulating EVs' levels are increased during pregnancy. However, EVs characteristics, composition and biological functions in pregnancy still need to be clarified. This study aims to determine if circulating EVs during pregnancy are modified regarding levels, markers and cytokine profile as well as their reactivity towards peripheral blood cells. 26 pregnant women (PW) being in the second gestational trimester and 59 non-pregnant women (NPW) were investigated. EVs enrichment was performed by ExoQuick™ or ultracentrifugation; nanoparticle tracking analysis, SDS-PAGE followed by Western Blotting and densitometry, and IFN-γ, IL-10 and TGF-β1 ELISA for EVs characterization; imaging flow cytometry to analyze EVs' uptake by peripheral blood cells and flow cytometry were performed to analyze EVs function regarding induction of caspase-3 activity. Circulating EVs' levels were increased during pregnancy [26.9×10(6)EVs/ml (range: 6.4-46.3); p=0.003] vs NPW [18.9×10(6)EVs/ml (range: 2.5-61.3)]. Importantly, the immunosuppressive TGF-β1 and IL-10 cytokine cargo were increased in EVs of PW even after normalization to 1 million EVs [TGF-β1: 0.25pg/10(6)EVs (range: 0.0-2.0); p<0.0001] and [IL-10: 0.21pg/10(6)EVs (range: 0.0-16.8); p=0.006] vs NPW. Although EVs derived from non-pregnant and pregnant women were taken up by NK cells, the latter exclusively enhanced the caspase-3 activity in CD56(dim) NK cells (8.2±0.9; p=0.02). The qualitative and quantitative pregnancy-related alterations of circulating EVs provide first hints for an immune modulating role of circulating EVs during pregnancy. Copyright © 2016 Elsevier GmbH. All rights reserved.

Responses of East Asian Summer Monsoon to Natural and Anthropogenic Forcings in the 17 Latest CMIP5 Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Fengfei; Zhou, Tianjun; Qian, Yun

2014-01-31

In this study, we examined the responses of East Asian Summer Monsoon (EASM) to natural (solar variability and volcanic aerosols) and anthropogenic (greenhouse gasses and aerosols) forcings simulated in the 17 latest Coupled Model Intercomparison Program phase 5 (CMIP5) models with 105 realizations. The observed weakening trend of low-level EASM circulation during 1958-2001 is partly reproduced under all-forcing runs. A comparison of separate forcing experiments reveals that the aerosol-forcing plays a primary role in driving the weakened low-level monsoon circulation. The preferential cooling over continental East Asia caused by aerosol affects the monsoon circulation through reducing the land-sea thermal contrastmore » and results in higher sea level pressure over northern China. In the upper-level, both natural-forcing and aerosol-forcing contribute to the observed southward shift of East Asian subtropical jet through changing the meridional temperature gradient.« less

Circulating levels of hydrogen sulfide and substance P in patients with sepsis.

PubMed

Gaddam, Ravinder Reddy; Chambers, Stephen; Murdoch, David; Shaw, Geoffrey; Bhatia, Madhav

2017-10-01

To determine alterations of circulating levels of hydrogen sulfide and substance P in patients with sepsis compared to non-sepsis patients with similar disease severity and organ dysfunction. This study included 23 septic and 14 non-septic patients during 2015-16 study period at the Christchurch Hospital Intensive Care Unit, Christchurch, New Zealand. Blood samples were collected from the time of admission to 96 h, with collection at different time points (0 h, 12 h, 24 h, 48 h, 72 h and 96 h) and subjected to measurement of hydrogen sulfide, substance P, procalcitonin, C-reactive protein, interleukin-6 and lactate levels. Patients with sepsis showed higher circulating hydrogen sulfide and substance P levels compared to patients without sepsis. Hydrogen sulfide levels were significantly higher at 12 h (1.45 vs 0.75 μM; p < 0.05) and 24 h (1.11 vs 0.72 μM; p < 0.01), whereas substance P levels were higher at 48 h (0.55 vs 0.31 ng/mL; p < 0.05). Increased hydrogen sulfide and substance P levels in septic patients were associated with increased levels of inflammatory mediators - procalcitonin, C-reactive protein and interleukin-6. These results provide evidence that higher circulating levels of hydrogen sulfide and substance P are associated with increased inflammatory response in patients with sepsis. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

The metabolic phenotype of Prader-Willi syndrome (PWS) in childhood: heightened insulin sensitivity relative to body mass index.

PubMed

Haqq, Andrea M; Muehlbauer, Michael J; Newgard, Christopher B; Grambow, Steven; Freemark, Michael

2011-01-01

Insulin sensitivity is higher in patients with Prader-Willi syndrome (PWS) than in body mass index-matched obese controls (OCs). Factors contributing to the heightened insulin sensitivity of PWS remain obscure. We compared the fasting levels of various hormones, cytokines, lipids, and liver function tests in 14 PWS patients and 14 OCs with those in 14 age- and gender-matched lean children (LC). We hypothesized that metabolic profiles of children with PWS are comparable with those of LC, but different from those of OCs. Leptin levels were comparable in PWS patients and OCs, suggesting comparable degrees of adiposity. Glucose levels were comparable among groups. However, fasting insulin concentrations and homeostasis model assessment insulin resistance index were lower in PWS patients than in OCs (P < 0.05) and similar to LC. Moreover, high-density lipoprotein levels were lower and triglycerides higher in OCs (P < 0.05) but not PWS patients. Total adiponectin, high-molecular-weight (HMW) adiponectin and the HMW to total adiponectin ratio were higher in PWS patients (P < 0.05) than in OCs and similar to LC. High-sensitivity C-reactive protein and IL-6 levels were higher in OCs than in PWS patients or LC (P < 0.05). Nevertheless, PAI-1 levels were elevated in both OC and PWS patients. There were no group differences in glucagon-like peptide-1, macrophage chemoattractant protein-1, TNFα, IL-2, IL-8, IL-10, IL-12p40, IL-18, resistin, total or low-density lipoprotein cholesterol, aspartate aminotransferase, or alanine aminotransferase. The heightened insulin sensitivity of PWS patients relative to OCs is associated with higher levels of adiponectin and lower levels of high-sensitivity C-reactive protein and IL-6. Future studies will determine whether PWS children are protected from obesity comorbidities such as type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver disease.

Planning for Downtown Circulation Systems. Volume 2. Analysis Techniques.

DOT National Transportation Integrated Search

1983-10-01

This volume contains the analysis and refinement stages of downtown circulator planning. Included are sections on methods for estimating patronage, costs, revenues, and impacts, and a section on methods for performing micro-level analyses.

PSA-alpha-2-macroglobulin complex is enzymatically active in the serum of patients with advanced prostate cancer and can degrade circulating peptide hormones.

PubMed

Kostova, Maya B; Brennen, William Nathaniel; Lopez, David; Anthony, Lizamma; Wang, Hao; Platz, Elizabeth; Denmeade, Samuel R

2018-08-01

Prostate cancer cells produce high levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the tumor microenvironment but is presumed to be enzymatically inactive in the blood due to complex formation with serum protease inhibitors α-1-antichymotrypsin and α-2-macroglobulin (A2M). PSA-A2M complexes cannot be measured by standard ELISA assays and are also rapidly cleared from the circulation. Thus the exact magnitude of PSA production by prostate cancer cells is not easily measured. The PSA complexed to A2M is unable to cleave proteins but maintains the ability to cleave small peptide substrates. Thus, in advanced prostate cancer, sufficient PSA-A2M may be in circulation to effect total A2M levels, levels of cytokines bound to A2M and hydrolyze small circulating peptide hormones. Total A2M levels in men with advanced prostate cancer and PSA levels above 1000 ng/mL were measured by ELISA and compared to controls. Additional ELISA assays were used to measure levels of IL-6 and TGF-beta which can bind to A2M. The ability of PSA-A2M complexes to hydrolyze protein and peptide substrates was analyzed ± PSA inhibitor. Enzymatic activity of PSA-A2M in serum of men with high PSA levels was also assayed. Serum A2M levels are inversely correlated with PSA levels in men with advanced prostate cancer. Il-6 Levels are significantly elevated in men with PSA >1000 ng/mL compared to controls with PSA <0.1 ng/mL. PSA-A2M complex in serum of men with PSA levels >1000 ng/mL can hydrolyze small fluorescently labeled peptide substrates but not large proteins that are PSA substrates. PSA can hydrolyze small peptide hormones like PTHrP and osteocalcin. PSA complexed to A2M retains the ability to degrade PTHrP. In advanced prostate cancer with PSA levels >1000 ng/mL, sufficient PSA-A2M is present in circulation to produce enzymatic activity against circulating small peptide hormones. Sufficient PSA is produced in advanced prostate cancer to alter total A2M levels, which can potentially alter levels of a variety of growth factors such as IL-6, TGF-beta, basic FGF, and PDGF. Alterations in levels of these cytokines and proteolytic degradation of small peptide hormones may have profound effect on host-cancer interaction. © 2018 Wiley Periodicals, Inc.

Prostate Cancer Detection by Molecular Urinalysis

DTIC Science & Technology

2008-04-01

proteins.13 We did not specifically assess whether the urinary endoglin we detected was a result of circulating and filtered endoglin or a result of...a marker of pan-endothelial damage and angiogenesis, it is unlikely that circulating endoglin levels would be significantly affected by localized... circulating endoglin is 33 15 increased in metastatic disease states.8,10, 11 Presumably, the angiogenic cascade necessary for metastasis is

Implication of circulating irisin levels with brown adipose tissue and sarcopenia in humans.

PubMed

Choi, Hae Yoon; Kim, Sungeun; Park, Ji Woo; Lee, Nam Seok; Hwang, Soon Young; Huh, Joo Young; Hong, Ho Cheol; Yoo, Hye Jin; Baik, Sei Hyun; Youn, Byung-Soo; Mantzoros, Christos S; Choi, Kyung Mook

2014-08-01

Irisin is an exercise-induced novel myokine that drives brown-fat-like conversion of white adipose tissue and has been suggested to be a promising target for the treatment of obesity-related metabolic disorders. To assess the association of circulating irisin concentrations with brown adipose tissue (BAT) and/or sarcopenia in humans. We examined irisin levels in 40 BAT-positive and 40 BAT-negative women detected by (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET). In a separate study, we also examined 401 subjects with or without sarcopenia defined by skeletal muscle mass index (SMMI) and appendicular skeletal muscle (ASM)/height(2) using dual-energy x-ray absorptiometry. Among 6877 consecutive (18)FDG-PET scans in 4736 subjects, 146 subjects (3.1%) had positive BAT scans. The BAT-detectable group and the matched BAT-undetectable group did not differ in circulating irisin levels measured using two different ELISA kits (P = .747 and P = .160, respectively). Serum irisin levels were not different between individuals with sarcopenia and those without sarcopenia using either kit (P = .305 and P = .569, respectively). Also, serum irisin levels were not different between groups defined by ASM/height(2) using either kit (P = .352 and P = .134, respectively). Although visceral fat area and skeletal muscle mass showed significant difference according to tertiles of SMMI levels, irisin concentrations did not differ. Circulating irisin levels were not different in individuals with detectable BAT or those with sarcopenia compared with control subjects and were not correlated with SMMI.

Mucosal-Associated Invariant T Cell Deficiency in Chronic Obstructive Pulmonary Disease.

PubMed

Kwon, Yong Soo; Jin, Hye-Mi; Cho, Young-Nan; Kim, Moon-Ju; Kang, Jeong-Hwa; Jung, Hyun-Ju; Park, Ki-Jeong; Kee, Hae Jin; Kee, Seung-Jung; Park, Yong-Wook

2016-01-01

Mucosal-associated invariant T (MAIT) cells have been reported to play an important role in mucosal immunity. However, little is known about the roles of MAIT cells in chronic obstructive pulmonary disease (COPD). The aims of this study were to examine the levels of circulating MAIT cells and their subsets in COPD patients and to investigate the potential relationship between clinical parameters and MAIT cell levels. Forty-five COPD patients and 57 healthy control subjects were enrolled in the study. Circulating MAIT cells and their subset levels in the peripheral blood were measured by flow cytometry. Disease grades were classified according to the GOLD criteria for the assessment of severity of COPD. Circulating MAIT cell levels were found to be significantly reduced in COPD patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets. Interestingly, elevated serum C-reactive protein level and reduced FEV1/FVC ratio were associated with MAIT cell deficiency in COPD patients. Furthermore, the circulating MAIT levels were found to be significantly lower in patients with moderate to severe COPD than in patients with mild COPD. Our data shows that MAIT cells are numerically deficient in the peripheral blood of patients with COPD. In addition, this MAIT cell deficiency was found to reflect inflammatory activity and disease severity. These findings provide important information for monitoring the changes in MAIT cell levels and for predicting the prognosis during the disease course.

Increased Circulating Levels of Vitamin D Binding Protein in MS Patients

PubMed Central

Rinaldi, Arturo Ottavio; Sanseverino, Isabella; Purificato, Cristina; Cortese, Antonio; Mechelli, Rosella; Francisci, Silvia; Salvetti, Marco; Millefiorini, Enrico; Gessani, Sandra; Gauzzi, Maria Cristina

2015-01-01

Vitamin D (vitD) low status is currently considered a main environmental factor in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP) and with lower affinity to albumin, while less than 1% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24 healthy controls. MS patients were found to have higher DBP levels than healthy subjects. Concomitant interferon beta therapy did not influence DBP concentration, and the difference with the control group was significant in both females and males. No significant correlation between DBP and albumin levels was observed either in healthy controls or in patients. These observations suggest the involvement of DBP in the patho-physiology of MS. PMID:25590278

Increased levels of circulating platelet-derived microparticles are associated with metastatic cutaneous melanoma.

PubMed

Moreau, Joséphine; Pelletier, Fabien; Biichle, Sabeha; Mourey, Guillaume; Puyraveau, Marc; Badet, Nicolas; Caubet, Matthieu; Laresche, Claire; Garnache-Ottou, Francine; Saas, Philippe; Seilles, Estelle; Aubin, François

2017-10-01

We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 μL -1 ) than in patients with stage III (2041 μL -1 ) melanoma (P=.0001). We calculated a highly specific (93.3%) and predictive (91.7%) cut-off value (5311 μL -1 ) allowing the distinction between high-risk stage III and metastatic stage IV melanoma. The thrombogenic activity of PMPs was significantly higher in patients with stage IV melanoma (clotting time: 40.7 second vs 65 second, P=.0001). There was no significant association between the radiological tumoral syndrome and the plasma level of PMPs. Our data suggest the role of PMPs in metastatic progression of melanoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Altered ghrelin secretion in mice in response to diet-induced obesity and Roux-en-Y gastric bypass

PubMed Central

Uchida, Aki; Zechner, Juliet F.; Mani, Bharath K.; Park, Won-mee; Aguirre, Vincent; Zigman, Jeffrey M.

2014-01-01

The current study examined potential mechanisms for altered circulating ghrelin levels observed in diet-induced obesity (DIO) and following weight loss resulting from Roux-en-Y gastric bypass (RYGB). We hypothesized that circulating ghrelin levels were altered in obesity and after weight loss through changes in ghrelin cell responsiveness to physiological cues. We confirmed lower ghrelin levels in DIO mice and demonstrated elevated ghrelin levels in mice 6 weeks post-RYGB. In both DIO and RYGB settings, these changes in ghrelin levels were associated with altered ghrelin cell responsiveness to two key physiological modulators of ghrelin secretion – glucose and norepinephrine. In DIO mice, increases in ghrelin cell density within both the stomach and duodenum and in somatostatin-immunoreactive D cell density in the duodenum were observed. Our findings provide new insights into the regulation of ghrelin secretion and its relation to circulating ghrelin within the contexts of obesity and weight loss. PMID:25353000

Leisure-time physical activity and circulating 25-hydroxyvitamin D levels in cancer survivors: a cross-sectional analysis using data from the US National Health and Nutrition Examination Survey.

PubMed

Yang, Lin; Toriola, Adetunji T

2017-07-10

Circulating 25-hydroxyvitamin D (25-OHD) is associated with improved cancer prognosis in some studies, yet it may be a surrogate marker for physical activity. We investigated the associations of leisure-time physical activity (LTPA) with circulating 25-OHD levels in cancer survivors, and determined whether associations differ by indoor and outdoor activity. Cross-sectional study. The US National Health and Nutrition Examination Survey (NHANES). Cancer survivors with available data on demographic information, measures of adiposity, smoking history, self-reported LTPA and circulating 25-OHD levels in five waves of NHANES (2001-2010). Circulating 25-OHD levels. Multivariable linear regression and logistic regression models were used to evaluate the associations of self-reported LTPA with 25-OHD, adjusting for potential confounders. Due to the differences in LTPA measure, the analyses were conducted separately for 2001-2006 and 2007-2010 data. We further estimated associations by indoor and outdoor activity in the 2001-2006 data. There were 1530 cancer survivors (mean age=60.5 years, mean body mass index=28.6 kg/m 2 ). The prevalent cancer sites were breast (19.3%), prostate (18.8%), cervix (10.4%) and colon (8.6%). Compared with inactive cancer survivors, being physically active was associated with higher circulating 25-OHD levels (8.07 nmol/L, 95% CI 4.63 to 11.52) for 2001-2006 data. In the mutually adjusted model, higher outdoor activity (5.83 nmol/L, 95% CI 1.64 to 10.01), but not indoor activity (2.93 nmol/L, 95% CI -1.80 to 7.66), was associated with statistically significantly higher 25-OHD levels. The interaction between indoor and outdoor activities was, however, not significant (p=0.29). The only statistically significant association seen in the 2007-2010 data was among obese cancer survivors. Physical activity, particularly outdoor activity, is associated with higher 25-OHD levels in cancer survivors. In view of the possible beneficial effects of vitamin D on cancer prognosis, engaging in outdoor physical activity could provide clinically meaningful increases in 25-OHD levels among cancer survivors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, Serum Metabolic Hormones, and Transcription Factor Expression

PubMed Central

Donepudi, Ajay C.; Cheng, Qiuqiong; Lu, Zhenqiang James; Cherrington, Nathan J.

2016-01-01

Metabolic syndrome is a multifactorial disease associated with obesity, insulin resistance, diabetes, and the alteration of multiple metabolic hormones. Obesity rates have been rising worldwide, which increases our need to understand how this population will respond to drugs and exposure to other chemicals. The purpose of this study was to determine in lean and obese mice the ontogeny of clinical biomarkers such as serum hormone and blood glucose levels as well as the physiologic markers that correlate with nuclear receptor– and transporter-related pathways. Livers from male and female wild-type (WT) (C57BL/6) and ob/ob mice littermates were collected before, during, and after the onset of obesity. Serum hormone and mRNA levels were analyzed. Physiologic changes and gene expression during maturation and progression to obesity were performed and correlation analysis was performed using canonical correlations. Significant ontogenic changes in both WT and ob/ob mice were observed and these ontogenic changes differ in ob/ob mice with the development of obesity. In males and females, the ontogenic pattern of the expression of genes such as Abcc3, 4, Abcg2, Cyp2b10, and 4a14 started to differ from week 3, and became significant at weeks 4 and 8 in ob/ob mice compared with WT mice. In obese males, serum resistin, glucagon, and glucose levels correlated with the expression of most hepatic ATP-binding cassette (Abc) transporters, whereas in obese females, serum glucagon-like peptide 1 levels were correlated with most hepatic uptake transporters and P450 enzymes. Overall, the correlation between physiologic changes and gene expression indicate that metabolism-related hormones may play a role in regulating the genes involved in drug metabolism and transport. PMID:26847773

Insulin sensitivity and its relation to hormones in adolescent boys and girls.

PubMed

Aldhoon-Hainerová, Irena; Zamrazilová, Hana; Hill, Martin; Hainer, Vojtěch

2017-02-01

A subset of obese individuals lacks cardiometabolic impairment. We aimed to analyze hormonal profiles of insulin-sensitive obese (ISO) and insulin-resistant obese (IRO) adolescents and determine hormonal predictors of homeostasis model of insulin resistance (HOMA-IR). A threshold of 3.16 of HOMA-IR was used to classify ISO (<3.16) IRO (≥3.16). In 702 individuals aged 13-18years (55.8% girls) anthropometric and laboratory [blood glucose, insulin, thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), sex hormone-binding globulin (SHBG), steroid hormones, luteinizing hormone, follicle stimulating hormone, prolactin, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like-peptide 1glucagon, leptin, resistin, visfatin, leptin, adiponectin and adipsin] assessments were performed. Orthogonal projections to latent structures and Mann-Whitney tests with Bonferroni correction were applied for statistical analysis. 52.6% girls and 42.9% boys were insulin sensitive. In the predictive model of HOMA-IR thyroid function tests, adiponectin, ghrelin and leptin concentrations played an important role in both genders. Prolactin, testosterone and glucagon contributed to the model only in boys, while progesterone and dehydroepiandrosterone sulfate levels only in girls. After Bonferroni correction levels of leptin, adiponectin, leptin/adiponectin ratio, SHBG and fT4/TSH ratio in both genders, testosterone and glucagon levels in boys and levels of TSH and fT3 in girls were related to insulin sensitivity. Metabolic health defined by HOMA-IR is partly predicted by various hormones. Some of them are gender specific. Free T4/TSH and leptin/adiponectin ratios are related to insulin sensitivity in both genders. Copyright © 2016 Elsevier Inc. All rights reserved.

Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, Serum Metabolic Hormones, and Transcription Factor Expression.

PubMed

Donepudi, Ajay C; Cheng, Qiuqiong; Lu, Zhenqiang James; Cherrington, Nathan J; Slitt, Angela L

2016-04-01

Metabolic syndrome is a multifactorial disease associated with obesity, insulin resistance, diabetes, and the alteration of multiple metabolic hormones. Obesity rates have been rising worldwide, which increases our need to understand how this population will respond to drugs and exposure to other chemicals. The purpose of this study was to determine in lean and obese mice the ontogeny of clinical biomarkers such as serum hormone and blood glucose levels as well as the physiologic markers that correlate with nuclear receptor- and transporter-related pathways. Livers from male and female wild-type (WT) (C57BL/6) and ob/ob mice littermates were collected before, during, and after the onset of obesity. Serum hormone and mRNA levels were analyzed. Physiologic changes and gene expression during maturation and progression to obesity were performed and correlation analysis was performed using canonical correlations. Significant ontogenic changes in both WT and ob/ob mice were observed and these ontogenic changes differ in ob/ob mice with the development of obesity. In males and females, the ontogenic pattern of the expression of genes such as Abcc3, 4, Abcg2, Cyp2b10, and 4a14 started to differ from week 3, and became significant at weeks 4 and 8 in ob/ob mice compared with WT mice. In obese males, serum resistin, glucagon, and glucose levels correlated with the expression of most hepatic ATP-binding cassette (Abc) transporters, whereas in obese females, serum glucagon-like peptide 1 levels were correlated with most hepatic uptake transporters and P450 enzymes. Overall, the correlation between physiologic changes and gene expression indicate that metabolism-related hormones may play a role in regulating the genes involved in drug metabolism and transport. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Regional climates in the GISS global circulation model - Synoptic-scale circulation

NASA Technical Reports Server (NTRS)

Hewitson, B.; Crane, R. G.

1992-01-01

A major weakness of current general circulation models (GCMs) is their perceived inability to predict reliably the regional consequences of a global-scale change, and it is these regional-scale predictions that are necessary for studies of human-environmental response. For large areas of the extratropics, the local climate is controlled by the synoptic-scale atmospheric circulation, and it is the purpose of this paper to evaluate the synoptic-scale circulation of the Goddard Institute for Space Studies (GISS) GCM. A methodology for validating the daily synoptic circulation using Principal Component Analysis is described, and the methodology is then applied to the GCM simulation of sea level pressure over the continental United States (excluding Alaska). The analysis demonstrates that the GISS 4 x 5 deg GCM Model II effectively simulates the synoptic-scale atmospheric circulation over the United States. The modes of variance describing the atmospheric circulation of the model are comparable to those found in the observed data, and these modes explain similar amounts of variance in their respective datasets. The temporal behavior of these circulation modes in the synoptic time frame are also comparable.

TNFα blockade for inflammatory rheumatic diseases is associated with a significant gain in android fat mass and has varying effects on adipokines: a 2-year prospective study.

PubMed

Toussirot, Éric; Mourot, Laurent; Dehecq, Barbara; Wendling, Daniel; Grandclément, Émilie; Dumoulin, Gilles

2014-04-01

To evaluate the long-term consequences of TNFα inhibitors on body composition and fat distribution, as well as changes in serum adipokines in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS). Eight patients with RA and twelve with AS requiring a TNFα inhibitor were prospectively followed for 2 years. Body composition was evaluated by dual X-ray absorptiometry and included measurements of total fat mass, lean mass, fat in the gynoid and android regions, and visceral fat. Serum leptin, total and high molecular weight (HMW) adiponectin, resistin, and ghrelin were also assessed. There was a significant gain in body mass index (p = 0.05) and a tendency for weight (p = 0.07), android fat (p = 0.07), and visceral fat (p = 0.059) increase in patients with RA, while in AS, total fat mass significantly increased (p = 0.02) with a parallel weight gain (p = 0.07). When examining the whole population of patients, we observed after 2 years a significant increase in body weight (+1.9%; p = 0.003), body mass index (+2.5%; p = 0.004), total fat mass (+11.1%; p = 0.007), and fat in the android region (+18.3%; p = 0.02). There was a substantial, albeit nonsignificant gain in visceral fat (+24.3%; p = 0.088). Lean mass and gynoid fat were not modified. No major changes were observed for serum leptin, total adiponectin, and ghrelin, while HMW adiponectin and the HMW/total adiponectin ratio tended to decrease (-15.2%, p = 0.057 and -9.3%, p = 0.067, respectively). Resistin decreased significantly (-22.4%, p = 0.01). Long-term TNFα inhibition in RA and AS is associated with a significant gain in fat mass, with a shift to the android (visceral) region. This fat redistribution raises questions about its influence on the cardiovascular profile of patients receiving these treatments.

Diagnosis of boundary-layer circulations.

PubMed

Beare, Robert J; Cullen, Michael J P

2013-05-28

Diagnoses of circulations in the vertical plane provide valuable insights into aspects of the dynamics of the climate system. Dynamical theories based on geostrophic balance have proved useful in deriving diagnostic equations for these circulations. For example, semi-geostrophic theory gives rise to the Sawyer-Eliassen equation (SEE) that predicts, among other things, circulations around mid-latitude fronts. A limitation of the SEE is the absence of a realistic boundary layer. However, the coupling provided by the boundary layer between the atmosphere and the surface is fundamental to the climate system. Here, we use a theory based on Ekman momentum balance to derive an SEE that includes a boundary layer (SEEBL). We consider a case study of a baroclinic low-level jet. The SEEBL solution shows significant benefits over Ekman pumping, including accommodating a boundary-layer depth that varies in space and structure, which accounts for buoyancy and momentum advection. The diagnosed low-level jet is stronger than that determined by Ekman balance. This is due to the inclusion of momentum advection. Momentum advection provides an additional mechanism for enhancement of the low-level jet that is distinct from inertial oscillations.

Effect of dietary fiber on circulating C-reactive protein in overweight and obese adults: a meta-analysis of randomized controlled trials.

PubMed

Jiao, Jun; Xu, Jia-Ying; Zhang, Weiguo; Han, Shufen; Qin, Li-Qiang

2015-02-01

Previous studies suggested that dietary fiber intake may have a lowing effect on circulating C-reactive protein (CRP) level, a sensitive marker of inflammation, in overweight/obese adults with inconsistent results. A literature search was performed in April 2014 for related randomized controlled trials (RCTs) and meta-analysis was conducted. Meta-analysis including 14 RCTs showed that intervention with dietary fiber or fiber-rich food, compared with control, produced a slight, but significant reduction of 0.37 mg/L (95% CI -0.74, 0) in circulating CRP level among this population. Subgroup analyses showed that such a significant reduction was only observed after combining studies where the total fiber intake was 8 g/d higher in the intervention group than in the control group. No obvious heterogeneity and publication bias were found in the meta-analysis. In conclusion, this meta-analysis provides evidence that dietary fiber or food naturally rich in fiber has beneficial effects on circulating CRP level in overweight/obese adults.

Detection of the secondary meridional circulation associated with the quasi-biennial oscillation

NASA Astrophysics Data System (ADS)

Ribera, P.; PeñA-Ortiz, C.; Garcia-Herrera, R.; Gallego, D.; Gimeno, L.; HernáNdez, E.

2004-09-01

The quasi-biennial oscillation (QBO) signal in stratospheric zonal and meridional wind, temperature, and geopotential height fields is analyzed based on the use of the National Centers for Environmental Prediction (NCEP) reanalysis (1958-2001). The multitaper method-singular value decomposition (MTM-SVD), a multivariate frequency domain analysis method, is used to detect significant and spatially coherent narrowband oscillations. The QBO is found as the most intense signal in the stratospheric zonal wind. Then, the MTM-SVD method is used to determine the patterns induced by the QBO at every stratospheric level and data field. The secondary meridional circulation associated with the QBO is identified in the obtained patterns. This circulation can be characterized by negative (positive) temperature anomalies associated with adiabatic rising (sinking) motions over zones of easterly (westerly) wind shear and over the subtropics and midlatitudes, while meridional convergence and divergence levels are found separated by a level of maximum zonal wind shear. These vertical and meridional motions form quasi-symmetric circulation cells over both hemispheres, though less intense in the Southern Hemisphere.

Impact of moisture variations on the circulation of the south-west monsoon

NASA Astrophysics Data System (ADS)

Kishtawal, C. M.; Pal, P. K.; Narayanan, M. S.; Manna, S. K.; Sharma, O. P.; Agarwal, Sangeeta; Upadhyaya, H. C.

1993-12-01

The impact of moisture anomalies on the circulation of the south-west Indian monsoon has been studied with a general circulation model. Newtonian relaxation is adopted to subject the model atmosphere under sustained moisture anomalies. The impact of negative anomalies of moisture was seen as a divergent circulation anomaly, while the positive anomaly was a stronger convergent anomaly. Although the humidity fields display a resilient behaviour, and relax back to normal patterns 1-2 days after the forcing terms in humidity are withdrawn, the circulation anomalies created by the moisture variation keeps growing. A feedback between positive moisture anomalies and low level convergence exists, which is terminated in the absence of external forcings.

Effect of Inflammatory and Noninflammatory Stress on Beta-Hydroxybutyrate and Free Fatty Acids in Rat Blood.

DTIC Science & Technology

fasting plus screen-restraint and fasting plus femoral fracture. Inflammatory stresses caused a marked inhibition of the normal fasting-induced ketosis ...and a reduction in the level of circulating free fatty acids. Noninflammatory stresses caused no inhibition of the normal fasting-induced ketosis but did cause a reduction in the level of circulating free fatty acids. (Author)

Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer

PubMed Central

Murtaza, Muhammed; Dawson, Sarah-Jane; Pogrebniak, Katherine; Rueda, Oscar M.; Provenzano, Elena; Grant, John; Chin, Suet-Feung; Tsui, Dana W. Y.; Marass, Francesco; Gale, Davina; Ali, H. Raza; Shah, Pankti; Contente-Cuomo, Tania; Farahani, Hossein; Shumansky, Karey; Kingsbury, Zoya; Humphray, Sean; Bentley, David; Shah, Sohrab P.; Wallis, Matthew; Rosenfeld, Nitzan; Caldas, Carlos

2015-01-01

Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution. PMID:26530965

Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer.

PubMed

Murtaza, Muhammed; Dawson, Sarah-Jane; Pogrebniak, Katherine; Rueda, Oscar M; Provenzano, Elena; Grant, John; Chin, Suet-Feung; Tsui, Dana W Y; Marass, Francesco; Gale, Davina; Ali, H Raza; Shah, Pankti; Contente-Cuomo, Tania; Farahani, Hossein; Shumansky, Karey; Kingsbury, Zoya; Humphray, Sean; Bentley, David; Shah, Sohrab P; Wallis, Matthew; Rosenfeld, Nitzan; Caldas, Carlos

2015-11-04

Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution.

The 14 month wind stressed residual circulation (pole tide) in the North Sea

NASA Technical Reports Server (NTRS)

Oconnor, W. P.

1986-01-01

From published research it is known that a quasi-periodic 14 month atmospheric pressure oscillation of a few tenths of a millibar exists in the region of the North and Baltic Seas. At some time in the cycle the associated wind stress has a westerly component that drives a circulation in the North Sea. The results of a dynamical model and comparisons with several North Sea residual circulation studies show that a large sea level gradient results along the Dutch coast. It is this feature that has been referred to as the enhanced pole tide. The dynamical similarity of this pole tide in the North and Baltic Seas to the annual and seasonal wind forced circulations is considered. It is inferred that the large deviations of the pole tide from equilibrium at coastal stations are the result of this sea level set up forces by the 14 month wind stress cycle.

The puzzling Venusian polar atmospheric structure reproduced by a general circulation model

PubMed Central

Ando, Hiroki; Sugimoto, Norihiko; Takagi, Masahiro; Kashimura, Hiroki; Imamura, Takeshi; Matsuda, Yoshihisa

2016-01-01

Unlike the polar vortices observed in the Earth, Mars and Titan atmospheres, the observed Venus polar vortex is warmer than the midlatitudes at cloud-top levels (∼65 km). This warm polar vortex is zonally surrounded by a cold latitude band located at ∼60° latitude, which is a unique feature called ‘cold collar' in the Venus atmosphere. Although these structures have been observed in numerous previous observations, the formation mechanism is still unknown. Here we perform numerical simulations of the Venus atmospheric circulation using a general circulation model, and succeed in reproducing these puzzling features in close agreement with the observations. The cold collar and warm polar region are attributed to the residual mean meridional circulation enhanced by the thermal tide. The present results strongly suggest that the thermal tide is crucial for the structure of the Venus upper polar atmosphere at and above cloud levels. PMID:26832195

Arctic Climate and Atmospheric Planetary Waves

NASA Technical Reports Server (NTRS)

Cavalieri, D. J.; Haekkinen, S.

2000-01-01

Analysis of a fifty-year record (1946-1995) of monthly-averaged sea level pressure data provides a link between the phases of planetary-scale sea level pressure waves and Arctic Ocean and ice variability. Results of this analysis show: (1) a breakdown of the dominant wave I pattern in the late 1960's, (2) shifts in the mean phase of waves 1 and 2 since this breakdown, (3) an eastward shift in the phases of both waves 1 and 2 during the years of simulated cyclonic Arctic Ocean circulation relative to their phases during the years of anticyclonic circulation, (4) a strong decadal variability of wave phase associated with simulated Arctic Ocean circulation changes. Finally, the Arctic atmospheric circulation patterns that emerge when waves 1 and 2 are in their extreme eastern and western positions suggest an alternative approach to determine significant forcing patterns of sea ice and high-latitude variability.

Normal growth and development in the absence of hepatic insulin-like growth factor I

PubMed Central

Yakar, Shoshana; Liu, Jun-Li; Stannard, Bethel; Butler, Andrew; Accili, Domenici; Sauer, Brian; LeRoith, Derek

1999-01-01

The somatomedin hypothesis proposed that insulin-like growth factor I (IGF-I) was a hepatically derived circulating mediator of growth hormone and is a crucial factor for postnatal growth and development. To reassess this hypothesis, we have used the Cre/loxP recombination system to delete the igf1 gene exclusively in the liver. igf1 gene deletion in the liver abrogated expression of igf1 mRNA and caused a dramatic reduction in circulating IGF-I levels. However, growth as determined by body weight, body length, and femoral length did not differ from wild-type littermates. Although our model proves that hepatic IGF-I is indeed the major contributor to circulating IGF-I levels in mice it challenges the concept that circulating IGF-I is crucial for normal postnatal growth. Rather, our model provides direct evidence for the importance of the autocrine/paracrine role of IGF-I. PMID:10377413

General circulation of the South Atlantic between 5 deg N and 35 deg S

NASA Technical Reports Server (NTRS)

Ollitrault, Michel; Mercier, H.; Blanc, F.; Letraon, L. Y.

1991-01-01

The TOPEX/POSEIDON altimeter will provide the temporal mean seal level. So, secondly, we propose to compute the difference between these two surfaces (mean sea level minus general circulation dynamic topography). The result will be an estimate of the marine geoid, which is time invariant for the 5-year period under consideration. If this geoid is precise enough, it will permit a description of seasonal variability of the large-scale surface circulation. If there happens to be enough float data, it may be possible to infer the first vertical modes of this variability. Thus the main goal of our investigation is to determine the 3-D general circulation of the South Atlantic and the large-scale seasonal fluctuations. This last objective, however, may be restricted to the western part of the South Atlantic because float deployments have been scheduled only in the Brasil basin.

Association between circulating leptin levels and multiple sclerosis: a systematic review and meta-analysis.

PubMed

Xie, Xue-Feng; Huang, Xiao-Hui; Shen, Ai-Zong; Li, Jun; Sun, Ye-Huan

2018-05-01

Leptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS. A comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI. Circulating leptin levels of patients with MS and healthy controls. Of 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type. Overall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial.

PubMed

Stevanovic, Ana; Coburn, Mark; Menon, Ares; Rossaint, Rolf; Heyland, Daren; Schälte, Gereon; Werker, Thilo; Wonisch, Willibald; Kiehntopf, Michael; Goetzenich, Andreas; Rex, Steffen; Stoppe, Christian

2014-01-01

Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress. In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points. At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL-6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r =  -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication. OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications. ClinicalTrials.gov NCT01409057.

A passive dual-circulator based transmit/receive switch for use with reflection resonators in pulse EPR

PubMed Central

Subramanian, V. S.; Epel, Boris; Mailer, Colin; Halpern, Howard J.

2009-01-01

In order to protect the low noise amplifier (LNA) in the receive arm of a pulsed 250 MHz EPR bridge, it is necessary to install as much isolation as possible between the power exciting the spin system and the LNA when high power is present in the receive arm of the bridge, while allowing the voltage induced by the magnetization in the spin sample to be passed undistorted and undiminished to the LNA once power is reduced below the level that can cause a LNA damage. We discuss a combination of techniques to accomplish this involving the power-routing circulator in the bridge, a second circulator acting as an isolator with passive shunt PIN diodes immediately following the second circulator. The low resistance of the forward biased PIN diode passively generates an impedance mismatch at the second circulator output port during the high power excitation pulse and resonator ring down. The mismatch reflects the high power to the remaining port of the second circulator, dumping it into a system impedance matched load. Only when the power diminishes below the diode conduction threshold will the resistance of the PIN diode rise to a value much higher than the system impedance. This brings the device into conduction mode. We find that the present design passively limits the output power to 14 dBm independent of the input power. For high input power levels the isolation may exceed 60 dB. This level of isolation is sufficient to fully protect the LNA of pulse EPR bridge. PMID:20052312

CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke.

PubMed

Roy-O'Reilly, Meaghan; Ritzel, Rodney M; Conway, Sarah E; Staff, Ilene; Fortunato, Gilbert; McCullough, Louise D

2017-12-01

Circulating levels of the pro-inflammatory cytokine C-C motif chemokine 11 (CCL11, also known as eotaxin-1) are increased in several animal models of neuroinflammation, including traumatic brain injury and Alzheimer's disease. Increased levels of CCL11 have also been linked to decreased neurogenesis in mice. We hypothesized that circulating CCL11 levels would increase following ischemic stroke in mice and humans, and that higher CCL11 levels would correlate with poor long-term recovery in patients. As predicted, circulating levels of CCL11 in both young and aged mice increased significantly 24 h after experimental stroke. However, ischemic stroke patients showed decreased CCL11 levels compared to controls 24 h after stroke. Interestingly, lower post-stroke CCL11 levels were predictive of increased stroke severity and independently predictive of poorer functional outcomes in patients 12 months after ischemic stroke. These results illustrate important differences in the peripheral inflammatory response to ischemic stroke between mice and human patients. In addition, it suggests CCL11 as a candidate biomarker for the prediction of acute and long-term functional outcomes in ischemic stroke patients.

Staff Training Aspects of Circulation System Implementation.

ERIC Educational Resources Information Center

Juergens, Bonnie

1979-01-01

Presents program guidelines for training library staff in the operation and use of automated library circulation systems. Advice is given on the qualificatons of the training coordinator, levels of training, training and training aids, vendor responsibilities and time frame. (RAA)

Rapid evolution of a jet streak circulation in a pre-convective environment

NASA Technical Reports Server (NTRS)

Kocin, P. J.; Uccellini, L. W.; Petersen, R. A.

1986-01-01

An analysis of the April 10, 1979 Red River Valley severe weather outbreak, using a three-hourly rawinsonde network, indicates that the preconvection environment is influenced by upper-level and lower-level tropospheric jet streaks (ULJs and LLJs) that act to destabilize the atmosphere, and contribute to low-level heat and moisture transports and convergence that act to initiate the storm system. Transformation of an indirect circulation noted within the exit region of the ULJ at 1200 and 1500 GMT is observed within a six-hour period. Dramatic changes are found in the jet streak circulations over a short period of time as the system deviates from that approximated by the geostrophic momentum approximation, and these deviations suggest that adjustments asssociated with ULJs in this case could not be resolved using a simplified two-dimensional approach.

Increase of endothelial progenitor cells in acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia.

PubMed

Medinger, Michael; Heim, Dominik; Gerull, Sabine; Halter, Jörg; Krenger, Werner; Buser, Andreas; Lengerke, Claudia; Bucher, Christoph; Passweg, Jakob

2016-08-01

Circulating endothelial progenitor cells (EPCs; CD31+ CD34(bright)CD133+ CD45(dim) cells) are novel markers of endothelial dysfunction and related to inflammatory processes such as acute graft-versus-host disease (aGvHD). 47 patients with acute myeloid leukaemia (AML) who were in complete remission as they underwent allogeneic hematopoietic stem cell transplantation with myeloablative conditioning with PBSC as stem cell source were enrolled in the study. Blood samples for the quantitative analysis of circulating EPC levels were drawn at different time points in patients with and without aGvHD. CD34+ VEGFR2/KDR+ CD133+ triple-positive cells identified among CD34+ cells by FACS. EPC were quantified and data are presented as cells/ml whole blood. Circulating EPC levels were not significantly different in patients with and without aGvHD prior to conditioning (baseline) and at the time of engraftment. However, at diagnosis of aGvHD≥grade 2, EPC levels increased whereas in patients without aGvHD the EPC levels remained significantly lower (3021±278 versus 2322±195 cells/ml; p<0.001). Patients with steroid-refractory aGvHD had high levels of EPC throughout. EPC levels fell in responding patients. Our results demonstrate that the number of circulating EPCs is increased in patients with aGvHD compared to patients without aGvHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Circulating Betatrophin Levels and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

PubMed

Kong, Fei-Juan; Ma, Lei-Lei; Li, Ge; Chen, Yi-Xin; Zhou, Jia-Qiang

2017-01-01

The association between circulating betatrophin levels and gestational diabetes mellitus (GDM) is controversial. The aim of our study was to systematically review available literature linking betatrophin to GDM for a comprehensive understanding of the relationship between circulating betatrophin levels and GDM in human. PubMed, The Cochrane Library, Medline and CNKI were searched for studies published up to August 2016. Manual searches of references of the relevant original studies were conducted. Pooled estimates were measured using the fixed or random effect model. Overall effect was reported in a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0. Of 25 references reviewed, 8 studies met our inclusion criteria and contributed to meta-analysis. All the studies were used to evaluate the relationship between betatrophin levels in blood and GDM. Betatrophin levels were significantly elevated in women with GDM compared with those without GDM (SMD = 1.05; 95% CI: 0.41-1.68, P = 0.001). This evidence was more consistent among women with betatrophin blood draw during the third trimester (SMD = 1.3, 95% CI: 1-1.61, P < 0.001) and for women BMI ≥ 28 kg/m2 (SMD = 1.53, 95% CI: 1.30-1.75, P < 0.001). The evidences from this meta-analysis indicated that the levels of circulating betatrophin were significantly elevated among women with GDM compared with women with normal glucose tolerance, especially with BMI ≥ 28 kg/m2 and in the third trimester.

Pleiotrophin levels are associated with improved coronary collateral circulation.

PubMed

Türker Duyuler, Pinar; Duyuler, Serkan; Gök, Murat; Kundi, Harun; Topçuoğlu, Canan; Güray, Ümit

2018-01-01

Elucidation of the underlying mechanisms of angiogenesis and arteriogenesis in coronary collateral formation is necessary for new therapies. Pleiotrophin is a secreted multifunctional cytokine and associated with the formation of functional cardiovascular neovascularization in a series of experimental animal models. We aimed to evaluate the serum levels of pleiotrophin in patients with chronic total coronary artery occlusion and poor or good collateral development. We included 88 consecutive patients (mean age of the entire population: 63.7±12.1 years, 68 male patients) with stable angina pectoris who underwent coronary angiography and had chronic total occlusion in at least one major coronary artery. Collateral grading was performed according to the Rentrop classification. After grading, patients were divided into poor collateral circulation (Rentrop grade 0 and 1) and good collateral circulation (Rentrop grades 2 and 3) groups. Serum pleiotrophin levels were measured using a commercial human ELISA kit. Fifty-eight patients had good and 30 patients had poor coronary collaterals. The good collateral group had higher serum pleiotrophin levels than the poor collateral group (690.1±187.9 vs. 415.3±165.9 ng/ml, P<0.001). Pleiotrophin levels were higher with higher Rentrop grade (P<0.001). In multivariate analysis, increased pleiotrophin was associated independently with good collateral development (odds ratio: 1.007; confidence interval: 1.003-1.012; P=0.002). This study showed that increased serum pleiotrophin levels are associated with better developed coronary collateral circulation. Further studies are needed to better understand the relationship.

Artificial blood circulation: stabilization, physiological control, and optimization.

PubMed

Lerner, A Y

1990-04-01

The requirements for creating an efficient Artificial Blood Circulation System (ABCS) have been determined. A hierarchical three-level adaptive control system is suggested for ABCS to solve the following problems: stabilization of the circulation conditions, left and right pump coordination, physiological control for maintaining a proper relation between the cardiac output and the level of gas exchange required for metabolism, and optimization of the system behavior. The adaptations to varying load and body parameters will be accomplished using the signals which characterize the real-time computer-processed values of correlations between the changes in hydraulic resistance of blood vessels, or the changes in aortic pressure, and the oxygen (or carbon dioxide) concentration.

A January angular momentum balance in the OSU two-level atmospheric general circulation model

NASA Technical Reports Server (NTRS)

Kim, J.-W.; Grady, W.

1982-01-01

The present investigation is concerned with an analysis of the atmospheric angular momentum balance, based on the simulation data of the Oregon State University two-level atmospheric general circulation model (AGCM). An attempt is also made to gain an understanding of the involved processes. Preliminary results on the angular momentum and mass balance in the AGCM are shown. The basic equations are examined, and questions of turbulent momentum transfer are investigated. The methods of analysis are discussed, taking into account time-averaged balance equations, time and longitude-averaged balance equations, mean meridional circulation, the mean meridional balance of relative angular momentum, and standing and transient components of motion.

Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36.

PubMed

Pfluger, P T; Kampe, J; Castaneda, T R; Vahl, T; D'Alessio, D A; Kruthaupt, T; Benoit, S C; Cuntz, U; Rochlitz, H J; Moehlig, M; Pfeiffer, A F H; Koebnick, C; Weickert, M O; Otto, B; Spranger, J; Tschöp, M H

2007-02-01

Recent findings suggest that low plasma peptide YY (PYY) levels may contribute to diet-induced human obesity and justify PYY replacement therapy. Although the pharmacological value of PYY is controversial, further study of the secretion of the precursor PYY(1-36) and the pharmacologically active PYY(3-36) is indicated to determine the potential role in energy balance regulation. Our objective was to determine the effects of acute and chronic changes in human body weight on circulating levels of the putative satiety hormone peptide YY. Total plasma PYY levels (PYY(1-36) + PYY(3-36)) were measured in 66 lean, 18 anorectic, 63 obese, and 16 morbidly obese humans. In addition, total PYY was measured in 17 of the obese patients after weight loss and in the 18 anorectic patients after weight gain. Fasting PYY(3-36) levels were measured in 17 lean and 15 obese individuals. Fasting total plasma PYY levels were highest in patients with anorexia nervosa (80.9 +/- 12.9 pg/ml, P < 0.05) compared with lean (52.4 +/- 4.6 pg/ml), obese (43.9 +/- 3.8 pg/ml), or morbidly obese (45.6 +/- 11.2 pg/ml) subjects. In obese patients, weight loss of 5.4% was associated with a 30% decrease in fasting total PYY plasma levels. In anorectic patients, weight gain had no effect on fasting PYY. PYY(3-36) levels did not differ between lean (96.2 +/- 8.6 pg/ml) and obese (91.5 +/- 6.9 pg/ml) subjects. Our findings do not support a role for abnormal circulating PYY in human obesity. We conclude that circulating PYY levels in humans are significantly elevated in anorexia nervosa and, given the controversially discussed anorectic effect of PYY, could theoretically contribute to that syndrome.

Correlation of Higher Levels of Soluble TNF-R1 with a Shorter Survival, Independent of Age, in Recurrent Glioblastoma

PubMed Central

Ahluwalia, Manmeet S.; Bou-Anak, Stephanie; Burgett, Monica E.; Sarmey, Nehaw; Khosla, Divya; Dahiya, Saurabh; Weil, Robert J.; Bae, Eunnyung; Huang, Ping; McGraw, Mary; Grove, Lisa M.; Olman, Mitchell A.; Prayson, Richard A.; Suh, John H.; Gillespie, G. Yancey; Barnholtz-Sloan, Jill; Nowacki, Amy S.; Barnett, Gene H.; Gladson, Candece L.

2016-01-01

The circulating levels of soluble tumor necrosis factor receptor-1 (sTNF-R1) and sTNF-R2 are altered in numerous diseases, including several types of cancer. Correlations with the risk of progression in some cancers, as well as systemic manifestations of the disease and therapeutic side-effects, have been described. However, there is very little information on the levels of these soluble receptors in glioblastoma (GBM). Here, we report on an exploratory retrospective study of the levels of sTNF-Rs in the vascular circulation of patients with GBM. Banked samples were obtained from 112 GBM patients (66 untreated, newly-diagnosed patients and 46 with recurrent disease) from two institutions. The levels of sTNF-R1 in the plasma were significantly lower in patients with newly-diagnosed or recurrent GBM than apparently healthy individuals and correlated with the intensity of expression of TNF-R1 on the tumor-associated endothelial cells (ECs) in the corresponding biopsies. Elevated levels of sTNF-R1 in patients with recurrent, but not newly-diagnosed GBM, were significantly associated with a shorter survival, independent of age (p=0.02) or steroid medication. In contrast, the levels of circulating sTNF-R2 were significantly higher in recurrent GBM than healthy individuals and there was no significant correlation with expression of TNF-R2 on the tumor-associated ECs or survival time. The results indicate that larger, prospective studies are warranted to determine the predictive value of the levels of sTNF-R1 in patients with recurrent GBM and the factors that regulate the levels of sTNF-Rs in the circulation in GBM patients. PMID:27858267

Omentin, an adipokine with insulin-sensitizing properties, is negatively associated with insulin resistance in normal gestation.

PubMed

Brandt, Benny; Mazaki-Tovi, Shali; Hemi, Rina; Yinon, Yoav; Schiff, Eyal; Mashiach, Roy; Kanety, Hannah; Sivan, Eyal

2015-05-01

Omentin, a newly identified adipokine, enhances insulin mediated glucose uptake in human adipocytes, thus, inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with insulin resistance indices and to assess which compartment, maternal, fetal, or placental, is the source of omentin in maternal circulation. Fasting serum glucose, insulin, and omentin were determined in 25 healthy pregnant women at the third trimester, before and 3 days after elective cesarean section. Cord blood omentin was measured in the 25 term neonates. Homeostasis model assessment (HOMA) was used to evaluate insulin sensitivity before and after delivery. Antepartum maternal omentin levels were negatively correlated with insulin levels (r=-0.41, P=0.04) and positively correlated with insulin sensitivity (HOMA%S; r=0.4, P=0.04). Postpartum omentin levels were negatively correlated with maternal body mass index (r=-0.44, P=0.02). Median maternal omentin levels was comparable before and after delivery (57.2, inter-quartile range: 38.2-76.2 ng/mL vs. 53.4, 39.8-69.4 ng/mL, respectively, P=0.25) and highly correlated (r=0.83, P<0.001). Antepartum maternal and neonatal omentin levels did not differ significantly (fetal: 62.2, 44.3-74.2 ng/mL, P=0.77) and did not correlate (P=0.6). Circulating maternal omentin levels are correlated with insulin resistance indices, suggesting that this adipokine may play a role in metabolic adaptations of normal gestation. The strong correlation between anteparum and postpartum maternal omentin levels, as well as the lack of association between maternal and neonatal omentin levels, suggest that placental or fetal compartments are unlikely as the main source of circulating maternal omentin.

Association between thyroid hormones and TRAIL.

PubMed

Bernardi, Stella; Bossi, Fleur; Toffoli, Barbara; Giudici, Fabiola; Bramante, Alessandra; Furlanis, Giulia; Stenner, Elisabetta; Secchiero, Paola; Zauli, Giorgio; Carretta, Renzo; Fabris, Bruno

2017-11-01

Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) might have a role in the regulation of body weight and metabolism. Interestingly, thyroid hormones seem to increase TRAIL tissue expression. This study aimed at evaluating whether overt thyroid disorders affected circulating TRAIL levels. TRAIL circulating levels were measured in euthyroid, hyperthyroid, and hypothyroid patients before and after thyroid function normalization. Univariate and multivariate analyses were performed to evaluate the correlation between thyroid hormones and TRAIL. Then, the stimulatory effect of both triiodothyronine (T3) and thyroxine (T4) on TRAIL was evaluated in vitro on peripheral blood mononuclear cells. Circulating levels of TRAIL significantly increased in hyperthyroid and decreased in hypothyroid patients as compared to controls. Once thyroid function was restored, TRAIL levels normalized. There was an independent association between TRAIL and both fT3 and fT4. Consistent with these findings, T3 and T4 stimulated TRAIL release in vitro. Here we show that thyroid hormones are associated with TRAIL expression in vivo and stimulate TRAIL expression in vitro. Given the overlap between the metabolic effects of thyroid hormones and TRAIL, this work sheds light on the possibility that TRAIL might be one of the molecules mediating thyroid hormones peripheral effects. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Circulating glucagon to ghrelin ratio as a determinant of insulin resistance in hyperthyroidism.

PubMed

Ağbaht, Kemal; Erdogan, Murat Faik; Emral, Rifat; Baskal, Nilgun; Güllü, Sevim

2014-02-01

Due to stimulated overall metabolism, a state of nutritional inadequacy often ensues, during thyrotoxicosis. We aimed to investigate circulating levels of some major components of the system that regulates energy stores, glucose, and fat metabolism, during thyrotoxicosis compared to euthyroidism. Fasting serum ghrelin, leptin, adiponectin, insulin, glucagon, glucose, as well as body fat composition were analyzed during thyrotoxicosis in 40 hyperthyroid patients (50.5 ± 15.2 years old, 22 females, 31 with Graves disease, and 9 with toxic nodular goiter). The same measurements were repeated an average 3 months later, when all patients achieved euthyroidism. Compared to euthyroidism, in thyrotoxicosis, patients had lower ghrelin and fat mass; had comparable insulin, HOMA-IR, glucagon, and leptin levels; higher levels of circulating adiponectin. Fasting serum glucose tended to be higher during thyrotoxicosis. The unique correlation of HOMA-IR was with the-glucagon to ghrelin ratio-(r = 0.801, p < 0.001) in hyperthyrodism, and with glucagon itself in euthyroidism (r = -0.844, p < 0.001). Circulating levels of ghrelin are decreased; leptin, insulin, glucagon are unchanged; adiponectin are increased during hyperthyroidism. The fasting HOMA-IR tends to be higher, despite the decreased adiposity in hyperthyroidism. The-glucagon to ghrelin ratio-strongly correlates with fasting HOMA-IR in hyperthyroidism.

[Establishment and evaluation of extracorporeal circulation model in rats].

PubMed

Xie, Xiao-Jun; Tao, Kai-Yu; Tang, Meng-Lin; Du, Lei; An, Qi; Lin, Ke; Gan, Chang-Ping; Chen, You-Wen; Luo, Shu-Hua

2012-09-01

To establish an extracorporeal circulation (ECC) rat model, and evaluate the inflammatory response and organ injury induced in the model. SD rats were anesthetized and cannulated from right common carotid artery to left femoral vein to establish the bypass of extracorporeal circulation. Then the rats were randomly divided into ECC group and sham group. The rats in ECC group were subjected to extracorporeal circulation for 2 hours and then rest for 2 hours, while the rats in sham group were only observed for 4 hours without extracorporeal circulation. After that, blood routine examination, blood gas analysis, the measurement of pro-inflammatory factors in bronchoalveolar lavage fluid and lung tissue were performed to evaluate the lung injury induced by ECC. Circulating endothelial cells were also calculated by flow cytometry to assess the vascular endothelial injury. At 2 hours after ECC, red blood cell counts in both groups kept normal, while leukocyte and neutrophil counts, plasmatic tumor necrosis factor-a level and neutrophil elastase level, circulating endothelial cells in the rats of ECC group were significantly higher than those in sham group. Tumor necrosis factor-alpha in bronchoalveolar lavage fluid and water content in lung of the ECC rats were also significantly higher, while the oxygenation index was significantly lower. Neutrophil infiltration was also observed in lung tissues with increased thickness of alveolar membrane in ECC group. The ECC model established from right common carotid artery to left femoral vein in our study can successfully induce systemic inflammatory response, and acute lung injury associated with inflammation.

Simulation and Interpretation of the Genesis of Tropical Storm Gert (2005) as Part of the NASA Tropical Cloud Systems and Processes Experiment

NASA Technical Reports Server (NTRS)

Braun, Scott A.; Montgomery, Michael T.; Mallen, Kevin

2009-01-01

Several hypotheses have been put forward for the how tropical cyclones (tropical storms and hurricanes in the Atlantic) first develop circulation at the surface, a key event that needs to occur before a storm can begin to draw energy from the warm ocean. One hypothesis suggests that the surface circulation forms from a "top-down" approach in which a storm s rotating circulation begins at middle levels of the atmosphere and builds down to the surface through processes related to light "stratiform" (horizontally extensive) precipitation. Another hypothesis suggests a bottom-up approach in which deep thunderstorm towers (convection) play the major role in spinning up the flow at the surface. These "hot towers" form in the area of the mid-level circulation and strongly concentrate this rotation at low levels within their updrafts. Merger of several of these hot towers then intensifies the surface circulation to the point in which a storm forms. This paper examines computer simulations of Tropical Storm Gert (2005), which formed in the Gulf of Mexico during the National Aeronautics and Space Administration s (NASA) Tropical Cloud Systems and Processes (TCSP) Experiment, to investigate the development of low-level circulation and, in particular, whether stratiform or hot tower processes were responsible for the storm s formation. Data from NASA satellites and from aircraft were used to show that the model did a good job of reproducing the formation and evolution of Gert. The simulation shows that a mix of both stratiform and convective rainfall occurred within Gert. While the stratiform rainfall clearly acted to increase rotation at middle levels, the diverging outflow beneath the stratiform rain worked against spinning up the low-level winds. The hot towers appeared to dominate the low-level flow, producing intense rotation within their cores and often being associated with significant pressure falls at the surface. Over time, many of these hot towers merged, with each merger adding to the rotation of the storm and the pressure falls at the surface. This process continued to increase the strength of the storm until the storm made landfall on the east coast of Mexico. These results support the bottom-up hypothesis for development.

A case of severe anorexia, excessive weight loss and high peptide YY levels after sleeve gastrectomy.

PubMed

Pucci, Andrea; Cheung, Wui Hang; Jones, Jenny; Manning, Sean; Kingett, Helen; Adamo, Marco; Elkalaawy, Mohamed; Jenkinson, Andrew; Finer, Nicholas; Doyle, Jacqueline; Hashemi, Majid; Batterham, Rachel L

2015-01-01

Sleeve gastrectomy (SG) is the second most commonly performed bariatric procedure worldwide. Altered circulating gut hormones have been suggested to contribute post-operatively to appetite suppression, decreased caloric intake and weight reduction. In the present study, we report a 22-year-old woman who underwent laparoscopic SG for obesity (BMI 46 kg/m(2)). Post-operatively, she reported marked appetite reduction, which resulted in excessive weight loss (1-year post-SG: BMI 22 kg/m(2), weight loss 52%, >99th centile of 1-year percentage of weight loss from 453 SG patients). Gastrointestinal (GI) imaging, GI physiology/motility studies and endoscopy revealed no anatomical cause for her symptoms, and psychological assessments excluded an eating disorder. Despite nutritional supplements and anti-emetics, her weight loss continued (BMI 19 kg/m(2)), and she required nasogastric feeding. A random gut hormone assessment revealed high plasma peptide YY (PYY) levels. She underwent a 3 h meal study following an overnight fast to assess her subjective appetite and circulating gut hormone levels. Her fasted nausea scores were high, with low hunger, and these worsened with nutrient ingestion. Compared to ten other post-SG female patients, her fasted circulating PYY and nutrient-stimulated PYY and active glucagon-like peptide 1 (GLP1) levels were markedly elevated. Octreotide treatment was associated with suppressed circulating PYY and GLP1 levels, increased appetite, increased caloric intake and weight gain (BMI 22 kg/m(2) after 6 months). The present case highlights the value of measuring gut hormones in patients following bariatric surgery who present with anorexia and excessive weight loss and suggests that octreotide treatment can produce symptomatic relief and weight regain in this setting. Roux-en-Y gastric bypass and SG produce marked sustained weight reduction. However, there is a marked individual variability in this reduction, and post-operative weight loss follows a normal distribution with extremes of 'good' and 'poor' response.Profound anorexia and excessive weight loss post-SG may be associated with markedly elevated circulating fasted PYY and post-meal PYY and GLP1 levels.Octreotide treatment can produce symptomatic relief and weight regain for post-SG patients that have an extreme anorectic and weight loss response.The present case highlights the value of measuring circulating gut hormone levels in patients with post-operative anorexia and extreme weight loss.

Effect of antipsychotics on peptides involved in energy balance in drug-naive psychotic patients after 1 year of treatment.

PubMed

Perez-Iglesias, Rocio; Vazquez-Barquero, Jose Luis; Amado, Jose Antonio; Berja, Ana; Garcia-Unzueta, Maria Teresa; Pelayo-Terán, Jose María; Carrasco-Marín, Eugenio; Mata, Ignacio; Crespo-Facorro, Benedicto

2008-06-01

Weight gain has become one of the most common and concerning side effects of antipsychotic treatment. The mechanisms whereby antipsychotics induce weight gain are not known. It has been suggested that peptides related to food intake and energy balance could play a role in weight gain secondary to antipsychotic therapy. To better understand the pathophysiology of antipsychotic-induced weight gain, we studied the effects of 3 antipsychotic drugs (haloperidol, olanzapine, and risperidone) on peptides involved in energy balance (insulin, ghrelin, leptin, adiponectin, visfatin, and resistin) in a population of drug-naive patients with first episode of psychosis.A significant increase in weight (10.16 kg [SD, 8.30 kg]; P < 0.001), body mass index (3.56 kg/m [SD, 2.89 kg/m]; P < 0.001), and fasting insulin (3.93 muU/mL [SD, 3.93 muU/mL]; P = 0.028), leptin (6.76 ng/mL [SD, 7.21 ng/mL]; P < 0.001), and ghrelin (15.47 fmol/mL [SD, 47.90 fmol/mL]; P = 0.009) plasma levels were observed. The increments in insulin and leptin concentrations were highly correlated with the increment in weight and body mass index and seem to be a consequence of the higher fat stores. The unexpected increase in ghrelin levels might be related with the causal mechanism of weight gain induced by antipsychotics. Finally, the 3 antipsychotics had similar effects in all parameters evaluated.

The role of pericardial adipose tissue in the heart of obese minipigs.

PubMed

Wang, Chia-Yu; Li, Sin-Jin; Wu, Twin-Way; Lin, Han-Jen; Chen, Jyun-Wei; Mersmann, Harry J; Ding, Shih-Torng; Chen, Ching-Yi

2018-04-23

Pericardial adipose tissue (PAT) volume is highly associated with the presence and severity of cardiometabolic diseases, but the underlying mechanism is unknown. We previously demonstrated that a high-fat diet (HFD) induced metabolic dysregulation, cardiac fibrosis and accumulation of more PAT in minipigs. This study used our obese minipig model to investigate the characteristics of PAT and omental visceral fat (VAT) induced by a HFD, and the potential link between PAT and HFD-related myocardial fibrosis. Five-month-old Lee-Sung minipigs were made obese by feeding a HFD for 6 months. The HFD induced dyslipidemia, cardiac fibrosis and more fat accumulation in the visceral and pericardial depots. The HFD changes the fatty acid composition in the adipose tissue by decreasing the portion of linoleic acid in the VAT and PAT. No arachidonic acid was detected in the VAT and PAT of control pigs, whereas it existed in the same tissues of obese pigs fed the HFD. Compared with the control pigs, elevated levels of malondialdehyde and TNFα were exhibited in the plasma and PAT of obese pigs. HFD induced greater size of adipocytes in VAT and PAT. Higher levels of GH, leptin, OPG, PDGF, resistin, SAA and TGFβ were observed in obese pig PAT compared to VAT. This study demonstrated the similarities and dissimilarities between PAT and VAT under HFD stimulus. In addition, this study suggested that alteration in PAT contributed to the myocardial damage. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Increased anxiety-like behavior is associated with the metabolic syndrome in non-stressed rats

PubMed Central

Díaz, Daniel; Rico-Rosillo, Guadalupe; Vega-Robledo, Gloria Bertha; Zambrano, Elena

2017-01-01

Metabolic syndrome (MS) is a cluster of signs that increases the risk to develop diabetes mellitus type 2 and cardiovascular disease. In the last years, a growing interest to study the relationship between MS and psychiatric disorders, such as depression and anxiety, has emerged obtaining conflicting results. Diet-induced MS rat models have only examined the effects of high-fat or mixed cafeteria diets to a limited extent. We explored whether an anxiety-like behavior was associated with MS in non-stressed rats chronically submitted to a high-sucrose diet (20% sucrose in drinking water) using three different anxiety paradigms: the shock-probe/burying test (SPBT), the elevated plus-maze (EPM) and the open-field test (OFT). Behaviorally, the high-sucrose diet group showed an increase in burying behavior in the SPBT. Also, these animals displayed both avoidance to explore the central part of the arena and a significant increase in freezing behavior in the OFT and lack of effects in the EPM. Also, high-sucrose diet group showed signs of an MS-like condition: significant increases in body weight and body mass index, abdominal obesity, hypertension, hyperglycemia, hyperinsulinemia, and dyslipidemia. Plasma leptin and resistin levels were also increased. No changes in plasma corticosterone levels were found. These results indicate that rats under a 24-weeks high-sucrose diet develop an MS associated with an anxiety-like behavior. Although the mechanisms underlying this behavioral outcome remain to be investigated, the role of leptin is emphasized. PMID:28463967

The Beneficial Effect of Anthocyanidin-Rich Vitis vinifera L. Grape Skin Extract on Metabolic Changes Induced by High-Fat Diet in Mice Involves Antiinflammatory and Antioxidant Actions.

PubMed

da Costa, Gisele França; Santos, Izabelle Barcellos; de Bem, Graziele Freitas; Cordeiro, Viviane Silva Cristino; da Costa, Cristiane Aguiar; de Carvalho, Lenize Costa Reis Marins; Ognibene, Dayane Teixeira; Resende, Angela Castro; de Moura, Roberto Soares

2017-10-01

We hypothesized that a polyphenol-rich extract from Vitis vinifera L. grape skin (GSE) may exert beneficial effects on obesity and related metabolic disorders induced by a high-fat diet (HFD). C57/BL6 mice were fed a standard diet (10% fat, control, and GSE groups) or an HFD (60% fat, high fat (HF), and HF + GSE) with or without GSE (200 mg/kg/day) for 12 weeks. GSE prevented weight gain; dyslipidemia; insulin resistance; the alterations in plasma levels of leptin, adiponectin, and resistin; and the deregulation of leptin and adiponectin expression in adipose tissue. These beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins (IR, pIRS, PI3K, pAKT), pAMPK/AMPK ratio, and GLUT4 expression in muscle and adipose tissue. In addition, GSE prevented the oxidative damage, evidenced by the restoration of antioxidant activity and decrease of malondialdehyde and carbonyl levels in muscle and adipose tissue. Finally, GSE showed an anti-inflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNF-α, IL-6). Our results suggest that GSE prevented the obesity and related metabolic disorders in HF-fed mice by regulating insulin sensitivity and GLUT4 expression as well as by preventing the oxidative stress and inflammation in skeletal muscle and adipose tissue. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Adipokines, adiposity, and bone marrow adipocytes: Dangerous accomplices in multiple myeloma.

PubMed

Morris, Emma V; Edwards, Claire M

2018-06-26

Obesity has become a global epidemic influencing the establishment and progression of a wide range of diseases, such as diabetes, cardiovascular disease, and cancer. In 2016, International Agency for Research on Cancer reported that obesity is now associated with 13 different cancers, one of which is multiple myeloma (MM), a destructive cancer of plasma cells that predominantly reside in the bone marrow. Obesity is the accumulation of excess body fat, which causes metabolic, endocrine, immunologic, and inflammatory-like changes. Obesity is usually associated with an increase in visceral and/or subcutaneous fat; however, an additional fat depot that also responds to diet-induced changes is bone marrow adipose tissue (BMAT). There have been several studies over the past few decades that have identified BMAT as a key driver in MM progression. Adipocytes secrete numerous adipokines, such as leptin, adiponectin, resistin, adipsin, and visfatin, which when secreted at normal controlled levels have protective properties. However, in obesity these levels of secretion change, coupled with an increase in adipocyte number and size causing a profound and lasting effect on the bone microenvironment, contributing to MM cell growth, survival, and migration as well as potentially fueling bone destruction. Obesity is a modifiable risk factor making it an attractive option for targeted therapy. This review discusses the link between obesity, monoclonal gammopathy of undetermined significance (a benign condition that precedes MM), and myeloma, and the contribution of key adipokines to disease establishment and progression. © 2018 Wiley Periodicals, Inc.

Endocan is a predictor of increased cardiovascular risk in women with polycystic ovary syndrome.

PubMed

Bicer, Merve; Guler, Aslı; Unal Kocabas, Gokcen; Imamoglu, Cetin; Baloglu, Ali; Bilgir, Oktay; Yuksel, Arif; Bozkaya, Giray; Calan, Mehmet

2017-05-01

Endocan is a proteoglycan secreted mainly from endothelial cells. It has been implicated that there is a link between endocan and endothelial dysfunction. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease associated with increased risk of cardiovascular events. The aims of this study were to ascertain whether circulating endocan levels are altered in women with PCOS, and whether there is an association between endocan and carotid intima media thickness (cIMT). This cross-sectional study included 80 women with PCOS and 80 age- and BMI-matched controls without PCOS. Circulating endocan levels were measured using ELISA. Metabolic, hormonal parameters and cIMT were determined. 2-h oral glucose tolerance test (2-h OGTT) was performed on all women. Circulating endocan levels were significantly elevated in women with PCOS compared with controls (5.99 ± 2.37 vs. 3.66 ± 1.79 ng/ml, P < 0.001). Endocan levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), free androgen index (FAI), high-sensitivity C-reactive protein (hs-CRP), and cIMT in both PCOS and control groups. Endocan levels did not correlate with fasting blood glucose, 2-h OGTT, A1 C and lipid parameters. Multiple linear regression analysis revealed that endocan is an independent predictor for cIMT (β = 0.128, 95% CI = 0.118-0.138, P = 0.011). Circulating endocan levels are significantly higher in women with PCOS and endocan is independently associated with cIMT. Elevated endocan levels can be a predictor of increased cardiovascular risk in PCOS subjects.

Circulating levels of environmental contaminants are associated with dietary patterns in older adults.

PubMed

Ax, Erika; Lampa, Erik; Lind, Lars; Salihovic, Samira; van Bavel, Bert; Cederholm, Tommy; Sjögren, Per; Lind, P Monica

2015-02-01

Food intake contributes substantially to our exposure to environmental contaminants. Still, little is known about our dietary habits' contribution to exposure variability. The aim of this study was to assess circulating levels of environmental contaminants in relation to predefined dietary patterns in an elderly Swedish population. Dietary data and serum concentrations of environmental contaminants were obtained from 844 70-year-old Swedish subjects (50% women) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Dietary data from 7-day food records was used to assess adherence to a Mediterranean-like diet, a low carbohydrate-high protein diet and the WHO dietary recommendations. Circulating levels of 6 polychlorinated biphenyl markers, 3 organochlorine pesticides, 1 dioxin and 1 polybrominated diphenyl ether, the metals cadmium, lead, mercury and aluminum and serum levels of bisphenol A and 4 phthalate metabolites were investigated in relation to dietary patterns in multivariate linear regression models. A Mediterranean-like diet was positively associated with levels of several polychlorinated biphenyls (118, 126, 153, and 209), trans-nonachlor and mercury. A low carbohydrate-high protein diet was positively associated with polychlorinated biphenyls 118 and 153, trans-nonachlor, hexachlorobenzene and p, p'-dichlorodiphenyldichloroethylene, mercury and lead. The WHO recommended diet was negatively related to levels of dioxin and lead, and borderline positively to polychlorinated biphenyl 118 and trans-nonachlor. Dietary patterns were associated in diverse manners with circulating levels of environmental contaminants in this elderly Swedish population. Following the WHO dietary recommendations seems to be associated with a lower burden of environmental contaminants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interannual-to-decadal variation of tropical-subtropical exchange in the Pacific Ocean: boundary versus interior pathways

NASA Technical Reports Server (NTRS)

Lee, T.; Fukumori, I.; Fu, L. L.

2002-01-01

In this study, we address issues using sea level measurements obtained by the TOPEX/Poseidon satellite altimter and circulation estimated by the Consortium for Estimating the Circulation and Climate of the Ocean (ECCO).

A STRATEGY FOR PROTECTING CIRCULATING SEAWATER SYSTEMS FROM OIL SPILLS

EPA Science Inventory

A strategy is described for establishing a simple, inexpensive monitoring program for determining approximate levels of petroleum hydrocarbons in ambient water collected near intake structures of circulating seawater systems. The ambient water is obtained from the depth of intake...

Weakening of tropical Pacific atmospheric circulation due to anthropogenic forcing

NASA Astrophysics Data System (ADS)

Vecchi, Gabriel A.; Soden, Brian J.; Wittenberg, Andrew T.; Held, Isaac M.; Leetmaa, Ants; Harrison, Matthew J.

2006-05-01

Since the mid-nineteenth century the Earth's surface has warmed, and models indicate that human activities have caused part of the warming by altering the radiative balance of the atmosphere. Simple theories suggest that global warming will reduce the strength of the mean tropical atmospheric circulation. An important aspect of this tropical circulation is a large-scale zonal (east-west) overturning of air across the equatorial Pacific Ocean-driven by convection to the west and subsidence to the east-known as the Walker circulation. Here we explore changes in tropical Pacific circulation since the mid-nineteenth century using observations and a suite of global climate model experiments. Observed Indo-Pacific sea level pressure reveals a weakening of the Walker circulation. The size of this trend is consistent with theoretical predictions, is accurately reproduced by climate model simulations and, within the climate models, is largely due to anthropogenic forcing. The climate model indicates that the weakened surface winds have altered the thermal structure and circulation of the tropical Pacific Ocean. These results support model projections of further weakening of tropical atmospheric circulation during the twenty-first century.

Irisin in response to acute and chronic whole-body vibration exercise in humans.

PubMed

Huh, Joo Young; Mougios, Vassilis; Skraparlis, Athanasios; Kabasakalis, Athanasios; Mantzoros, Christos S

2014-07-01

Irisin is a recently identified myokine, suggested to mediate the beneficial effects of exercise by inducing browning of white adipocytes and thus increasing energy expenditure. In humans, the regulation of irisin by exercise is not completely understood. We investigated the effect of acute and chronic whole-body vibration exercise, a moderate-intensity exercise that resembles shivering, on circulating irisin levels in young healthy subjects. Healthy untrained females participated in a 6-week program of whole-body vibration exercise training. Blood was drawn before and immediately after an acute bout of exercise at baseline (week 0) and after 6 weeks of training. The resting irisin levels were not different at baseline (week 0) and after 6 weeks of training. At both 0 and 6 weeks of training, an acute bout of vibration exercise significantly elevated circulating irisin levels by 9.5% and 18.1%, respectively (p=0.05 for the percent change of irisin levels). Acute bouts of whole-body vibration exercise are effective in increasing circulating irisin levels but chronic training does not change levels of baseline irisin levels in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Single-cell mRNA profiling reveals transcriptional heterogeneity among pancreatic circulating tumour cells.

PubMed

Lapin, Morten; Tjensvoll, Kjersti; Oltedal, Satu; Javle, Milind; Smaaland, Rune; Gilje, Bjørnar; Nordgård, Oddmund

2017-05-31

Single-cell mRNA profiling of circulating tumour cells may contribute to a better understanding of the biology of these cells and their role in the metastatic process. In addition, such analyses may reveal new knowledge about the mechanisms underlying chemotherapy resistance and tumour progression in patients with cancer. Single circulating tumour cells were isolated from patients with locally advanced or metastatic pancreatic cancer with immuno-magnetic depletion and immuno-fluorescence microscopy. mRNA expression was analysed with single-cell multiplex RT-qPCR. Hierarchical clustering and principal component analysis were performed to identify expression patterns. Circulating tumour cells were detected in 33 of 56 (59%) examined blood samples. Single-cell mRNA profiling of intact isolated circulating tumour cells revealed both epithelial-like and mesenchymal-like subpopulations, which were distinct from leucocytes. The profiled circulating tumour cells also expressed elevated levels of stem cell markers, and the extracellular matrix protein, SPARC. The expression of SPARC might correspond to an epithelial-mesenchymal transition in pancreatic circulating tumour cells. The analysis of single pancreatic circulating tumour cells identified distinct subpopulations and revealed elevated expression of transcripts relevant to the dissemination of circulating tumour cells to distant organ sites.

Circulatory shear flow alters the viability and proliferation of circulating colon cancer cells

NASA Astrophysics Data System (ADS)

Fan, Rong; Emery, Travis; Zhang, Yongguo; Xia, Yuxuan; Sun, Jun; Wan, Jiandi

2016-06-01

During cancer metastasis, circulating tumor cells constantly experience hemodynamic shear stress in the circulation. Cellular responses to shear stress including cell viability and proliferation thus play critical roles in cancer metastasis. Here, we developed a microfluidic approach to establish a circulatory microenvironment and studied circulating human colon cancer HCT116 cells in response to a variety of magnitude of shear stress and circulating time. Our results showed that cell viability decreased with the increase of circulating time, but increased with the magnitude of wall shear stress. Proliferation of cells survived from circulation could be maintained when physiologically relevant wall shear stresses were applied. High wall shear stress (60.5 dyne/cm2), however, led to decreased cell proliferation at long circulating time (1 h). We further showed that the expression levels of β-catenin and c-myc, proliferation regulators, were significantly enhanced by increasing wall shear stress. The presented study provides a new insight to the roles of circulatory shear stress in cellular responses of circulating tumor cells in a physiologically relevant model, and thus will be of interest for the study of cancer cell mechanosensing and cancer metastasis.

The role of atmospheric circulation patterns on short-term sea-level fluctuations along the eastern seaboard of the US

NASA Astrophysics Data System (ADS)

Sheridan, S. C.; Lee, C. C.; Pirhalla, D.; Ransi, V.

2017-12-01

Sea-level fluctuations over time are a product of short-term weather events, as well as long-term secular trends in sea-level rise. With sea-levl rise, these fluctuations increasingly have substantial impacts upon coastal ecosystems and impact society through coastal flooding events. In this research, we assess the impact of short-term events, combined with sea-level rise, through synoptic climatological analysis, exploring whether circulation pattern identification can be used to enhance probabilistic forecasts of flood likelihood. Self-organizing maps (SOMs) were created for two discrete atmospheric variables: 700-hPa geopotential height (700z) and sea-level pressure (SLP). For each variable, a SOM array of patterns was created based on data spanning 25°-50°N and 60°-90°W for the period 1979-2014. Sea-level values were derived from tidal gauges between Cape May, New Jersey and Charleston, South Carolina, along the mid-Atlantic coast of the US. Both anomalous sea-level values, as well as nuisance flood occurrence (defined using the local gauge threshold), were assessed. Results show the impacts of both the inverted barometer effect as well as surface wind forcing on sea levels. With SLP, higher sea levels are associated with either patterns that were indicative of on-shore flow or cyclones. At 700z, ridges situated along the east coast are associated with higher sea levels. As the SOM matrix arranges atmospheric patterns in a continuum, the nodes of each SOM show a clear spatial pattern in terms of anomalous sea level, including some significant sea-level anomalies associated with relatively ambiguous pressure patterns. Further, multi-day transitions are also analyzed, showing rapidly deepening cyclones, or persistent onshore flow, can be associated with the greatest likelihood of nuisance floods. Results are weaker with 700z than SLP; however, in some cases, it is clear that the mid-tropospheric circulation can modulate the connection between sea-level anomalies and surface circulation.

Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer.

PubMed

Lu, Ya-Ching; Chang, Joseph Tung-Chieh; Huang, Yu-Chen; Huang, Chi-Che; Chen, Wen-Ho; Lee, Li-Yu; Huang, Bing-Shen; Chen, Yin-Ju; Li, Hsiao-Fang; Cheng, Ann-Joy

2015-02-01

The aim of this study was to determine whether the oncogenic microRNA family members miR-196a and miR-196b can be circulating biomarkers for the early detection of oral cancer. To determine the stability of circulating miRNA, the blood sample was aliquot and stored at different temperature conditions for analysis. To assess the diagnostic efficacy, we determined the levels of miR-196s in plasma samples, including 53 from healthy individuals, 16 from pre-cancer patients, and 90 from oral cancer patients. In general, circulating miRNA was very stable when storing plasma samples at -20°C or below. In clinical study, both circulating miR-196a and miR-196b were substantially up-regulated in patients with oral pre-cancer lesions (5.9- and 14.8-fold, respectively; P < 0.01), as well as in oral cancer patients (9.3- and 17.0-fold, respectively; P < 0.01). These results show prominent discrimination between normal and pre-cancer patients (AUC = 0.764 or 0.840, miR-196a or miR-196b, respectively), and between normal and cancer patients (AUC = 0.864 or 0.960, miR-196a or miR-196b, respectively). The combined determination of miR-196a and miR-196b levels produces excellent sensitivity and specificity in the diagnosis of patients with oral pre-cancer (AUC = 0.845) or oral cancer (AUC = 0.963), as well as in the prediction of potential malignancy (AUC = 0.950, sensitivity = 91%, specificity = 85%). Combined determination of circulating miR-196a and miR-196b levels may serve as panel plasma biomarkers for the early detection of oral cancer. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Circulating monocyte chemoattractant protein‐1 (MCP‐1) is associated with cachexia in treatment‐naïve pancreatic cancer patients

PubMed Central

Talbert, Erin E.; Lewis, Heather L.; Farren, Matthew R.; Ramsey, Mitchell L.; Chakedis, Jeffery M.; Rajasekera, Priyani; Haverick, Ericka; Sarna, Angela; Bloomston, Mark; Pawlik, Timothy M.; Zimmers, Teresa A.; Lesinski, Gregory B.; Hart, Phil A.; Dillhoff, Mary E.; Schmidt, Carl R.

2018-01-01

Abstract Background Cancer‐associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer‐induced cachexia in patients with earlier stages of disease. Methods A custom multiplex array was used to measure circulating levels of 25 soluble factors from 70 pancreatic cancer patients undergoing attempted tumour resections. A high‐sensitivity multiplex was used for increased sensitivity for nine cytokines. Results Resectable pancreatic cancer patients with cachexia had low levels of canonical pro‐inflammatory cytokines including interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), interferon‐γ (IFN‐γ), and tumour necrosis factor (TNF). Even in our more sensitive analysis, these cytokines were not associated with cancer cachexia. Of the 25 circulating factors tested, only monocyte chemoattractant protein‐1 (MCP‐1) was increased in treatment‐naïve cachectic patients compared with weight stable patients and identified as a potential biomarker for cancer cachexia. Although circulating levels of leptin and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were found to be decreased in the same cohort of treatment‐naïve cachectic patients, these factors were closely associated with body mass index, limiting their utility as cancer cachexia biomarkers. Conclusions Unlike in advanced disease, it is possible that cachexia in patients with resectable pancreatic cancer is not associated with high levels of classical markers of systemic inflammation. However, cachectic, treatment‐naïve patients have higher levels of MCP‐1, suggesting that MCP‐1 may be useful as a biomarker of cancer cachexia. PMID:29316343

Circulating FABP4 and FABP5 Levels Are Differently Linked to OSA Severity and Treatment

PubMed Central

Català, Raquel; Cabré, Anna; Hernández-Flix, Salvador; Ferré, Raimón; Sangenís, Sandra; Plana, Núria; Texidó, Anna; Masana, Lluís

2013-01-01

Objective: To evaluate circulating adipocyte and epidermal fatty acid-binding protein (FABP4 and FABP5) concentrations in patients with obstructive sleep apnea (OSA), as well as the effects of continuous positive airway pressure (CPAP) treatment. Methods: Our cross-sectional study included 125 patients. After polysomnography, 58 participants met the criteria for CPAP treatment and were included in a closed cohort study of 8 weeks of CPAP treatment. General anthropometric and biochemical data and circulating FABP4 and FABP5 levels were determined in all patients at baseline and after CPAP treatment in those receiving this therapy. Results Circulating FABP4 but not FABP5 levels were higher in patients with OSA (P = 0.003). FABP4 but not FABP5 values were associated with parameters of OSA severity independently of age, gender, adiposity and insulin resistance (P < 0.05). FABP4 but not FABP5 concentrations were determinants of OSA presence (OR: 1.11, P = 0.010) and severity (OR: 1.06, P = 0.020). After CPAP treatment, FABP4 levels decreased in the more severe patients (P = 0.019), while FABP5 levels increased in all patients (P < 0.001). Conclusions FABP4 is directly associated with obstructive sleep apnea severity and did not change with continuous positive airway pressure treatment, while FABP5 was not associated with obstructive sleep apnea severity and increased with continuous positive airway pressure treatment. FABP4 and FABP5 have different associations with obstructive sleep apnea. FABP4 but not FABP5 could be considered a marker of metabolic alterations in obstructive sleep apnea patients. Citation: Català R; Cabré A; Hernández-Flix S; Ferré R; Sangenís S; Plana N; Texidó A; Masana L. Circulating FABP4 and FABP5 levels are differently linked to OSA severity and treatment. SLEEP 2013;36(12):1831-1837. PMID:24293757

Oxidative Burst of Circulating Neutrophils Following Traumatic Brain Injury in Human

PubMed Central

Liao, Yiliu; Liu, Peng; Guo, Fangyuan; Zhang, Zhi-Yuan; Zhang, Zhiren

2013-01-01

Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91phox) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage. PMID:23894384

Detection of circulating Bmi-1 mRNA in plasma and its potential diagnostic and prognostic value for uterine cervical cancer.

PubMed

Zhang, Xin; Wang, Chuanxin; Wang, Lili; Du, Lutao; Wang, Shun; Zheng, Guixi; Li, Wei; Zhuang, Xuewei; Zhang, Xuhua; Dong, Zhaogang

2012-07-01

Bmi-1 is overexpressed in uterine cervical cancer (UCC) and is found to be associated with adverse clinical characteristics and poor prognosis. However, little information is available on the status of circulating Bmi-1 mRNA in UCC. Because circulating cell-free nucleic acids have emerged as a novel class of markers for cancer detection, our research aims to address this question by detecting the circulating Bmi-1 mRNA and to assess its diagnostic and prognostic potential in UCC. Reverse transcription quantitative real-time PCR method was established to detect the circulating Bmi-1 mRNA in plasma of 109 patients with UCC, 138 patients with cervical intraepithelial neoplasia (CIN) and 80 healthy volunteers, and found that it was significantly increased in UCC compared with CINs and healthy controls (all at p < 0.001). Moreover, its high level was significantly correlated with advanced clinical stage (p < 0.001) and positive lymph nodes metastasis (p = 0.002). The area under the receiver operating characteristic curve (AUC) was 0.881, and the optimal cut-off value was 0.057, providing a sensitivity of 69.7% and a specificity of 95.9%. The AUC for circulating Bmi-1 mRNA showed higher diagnosis capability than that for SCC-Ag (p = 0.035) or CA125 (p < 0.001) currently utilized. Kaplan-Meier analysis demonstrated a correlation between increased circulating Bmi-1 mRNA level and reduced disease-free survival (DFS) (p = 0.001) and overall survival (OS) (p = 0.015). And, Cox analysis indicated that it was an independent prognostic factor for DFS and OS. We conclude that circulating Bmi-1 mRNA may be a potential noninvasive molecular marker for diagnosis and prognosis of UCC. Copyright © 2011 UICC.

Elevated levels of circulating IL-18BP and perturbed regulation of IL-18 in schizophrenia

PubMed Central

2012-01-01

Background The pleiotropic pro-inflammatory cytokine Interleukin (IL)-18 has been proposed to play a role in schizophrenia, since elevated circulating levels of its protein and altered frequencies of genetic variants in its molecular system are reported in schizophrenic patients. Methods We analyzed 77 patients with schizophrenia diagnosis (SCZ) and 77 healthy control subjects (HC) for serum concentration of both IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP). Results We confirmed that serum levels of total IL-18 are significantly increased in SCZ, as compared to HC. However, due to a highly significant increase in levels of circulating IL-18BP in SCZ, as compared to HC, the levels of free, bioactive IL-18 are not significantly different between the two groups. In addition, the relationships between the levels of IL-18 and its inhibitor, as well as between the two molecules and age appear dissimilar for SCZ and HC. In particular, the elevated levels of IL-18BP, likely a consequence of the body’s attempt to counteract the early prominent inflammation which characterizes schizophrenia, are maintained in earlier and later stages of the disease. However, the IL-18BP elevation appears ineffective to balance the IL-18 system in younger SCZ patients, while in older patients the levels of circulating bioactive IL-18 are comparable to those of HC, if not lower. Conclusions In conclusion, these findings indicate that the IL-18 system is perturbed in schizophrenia, supporting the idea that this pro-inflammatory cytokine might be part of a pathway of genetic and environmental components for vulnerability to the disease. PMID:22913567

Genetic drivers of von Willebrand Factor levels in an ischemic stroke population and association with risk for recurrent stroke

PubMed Central

Williams, Stephen R; Hsu, Fang-Chi; Keene, Keith L; Chen, Wei-Min; Dzhivhuho, Godfrey; Rowles, Joe L; Southerland, Andrew M; Furie, Karen L; Rich, Stephen S; Worrall, Bradford B; Sale, Michèle M

2017-01-01

Background and Purpose von Willebrand Factor (vWF) plays an important role in thrombus formation during cerebrovascular damage. We sought to investigate the potential role of circulating vWF in recurrent cerebrovascular events and identify genetic contributors to variation in vWF level in an ischemic stroke population. Methods We analyzed the effect of circulating vWF on risk of recurrent stroke using survival models in the Vitamin Intervention for Stroke Prevention (VISP) trial as well as the utility of vWF in reclassification over traditional factors. We conducted a genome-wide association study (GWAS) with imputation, based upon 1000 Genomes Project data, for circulating vWF levels and then interrogated loci previously associated with vWF levels. We performed expression quantitative trait locus (eQTL) analysis for vWF across different tissues. Results Elevated vWF levels were associated with increased risk for recurrent stroke in VISP. Adding vWF to traditional clinical parameters also improved recurrent stroke risk prediction. We identified SNPs significantly associated with circulating vWF at the ABO locus (p < 5×10-8) and replicated findings from previous genetic associations of vWF levels in humans. eQTL analyses demonstrate that most associated ABO SNPs were also associated with vWF gene expression. Conclusions Elevated vWF levels are associated with recurrent stroke in VISP. In the VISP population, genetic determinants of vWF levels that impact vWF gene expression were identified. These data add to our knowledge of the pathophysiologic and genetic basis for recurrent stroke risk, and may have implications for clinical care decision-making. PMID:28495826

Circulating Estrogen Levels and Self-Reported Health and Mobility Limitation in Community-Dwelling Men of the Framingham Heart Study.

PubMed

Jasuja, Guneet Kaur; Travison, Thomas G; Murabito, Joanne M; Davda, Maithili N; Rose, Adam J; Basaria, Shehzad; Coviello, Andrea; Vasan, Ramachandran S; D'Agostino, Ralph; Bhasin, Shalender

2017-08-01

Self-rated health is a commonly used global indicator of health status. Few studies have examined the association of self-rated health and mobility with estrone and estradiol in men. Accordingly, we determined the cross-sectional, incident, and mediating relations between circulating estrone and estradiol levels with self-rated health, mobility limitation, and physical performance in community-dwelling men. The cross-sectional sample included 1,148 men, who attended Framingham Offspring Study Examinations 7 and 8. Estrone and estradiol levels were measured using liquid chromatography tandem mass spectrometry at Examination 7. Self-reported mobility limitation and self-rated health were assessed at Examinations 7 and 8. Additionally, short physical performance battery, usual walking speed, and grip strength were assessed at Examination 7. In incident analysis, estradiol levels at Examination 7 were associated with increased odds of fair or poor self-rated health at Examination 8, after adjusting for age, body mass index, comorbidities, and testosterone levels; in an individual with 50% greater estradiol than other, the odds of reporting "fair or poor" self-rated health increased by 1.78 (95% confidence interval: 1.25-2.55; p = .001). Neither estrone nor estradiol levels were associated with any physical performance measure at baseline. Higher circulating levels of estradiol are associated with increased risk of incident fair/poor self-rated health in community-dwelling men. The mechanisms by which circulating levels of estradiol are related to self-rated health in men need further investigation. Published by Oxford University Press on behalf of The Gerontological Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

High levels of circulating TNFR1 increase the risk of all-cause mortality and progression of renal disease in type 2 diabetic nephropathy.

PubMed

Fernández-Juárez, Gema; Villacorta Perez, Javier; Luño Fernández, José Luis; Martinez-Martinez, Ernesto; Cachofeiro, Victoria; Barrio Lucia, Vicente; Tato Ribera, Ana M; Mendez Abreu, Angel; Cordon, Alfredo; Oliva Dominguez, Jesus Angel; Praga Terente, Manuel

2017-05-01

Several studies have demonstrated that levels of circulating inflammatory markers such as tumour necrosis factorα (TNFα), are associated with early progression of diabetic nephropathy (DN). The aim of this study was to investigate whether there is an association between circulating TNFα receptor and disease progression in patients with advanced type 2 DN and severe proteinuria. Between 2006 and 2011, we measured levels of circulating soluble TNFα receptor 1 (TNFR1) and soluble TNFα receptor 2 (TNFR2) at baseline and 4 and 12 months in 101 patients included in a multicenter randomized controlled trial to compare the effect of optimal doses of renin-angiotensin system blockers in monotherapy or in combination (dual blockade) to slow progression of established type 2 DN. The primary composite endpoint was a >50% increase in baseline serum creatinine, end-stage renal disease, or death. The median follow-up was 32 months (IQR, 18-48), during which time 28 patients (22.7%) achieved the primary endpoint. The TNFR1 level, but not the TNFR2 level, was correlated with other inflammatory markers. Cox regression analysis showed that the highest TNFR1 levels (HR, 2.60; 95%CI, 1.11-86.34) and baseline proteinuria (HR 1.32; 95%CI 1.15-1.52) were associated with the primary endpoint. The mixed model analysis revealed that TNFR1 and the TNFR2 levels did not change after starting treatment with renin-angiotensin system blockers. Our results show that the highest levels of TNFR1 are independently associated with progression of renal disease and death in type 2 DN. The renin angiotensin blockers have no effect on these inflammatory markers. © 2016 Asian Pacific Society of Nephrology.

FABP4 dynamics in obesity: discrepancies in adipose tissue and liver expression regarding circulating plasma levels.

PubMed

Queipo-Ortuño, María Isabel; Escoté, Xavier; Ceperuelo-Mallafré, Victoria; Garrido-Sanchez, Lourdes; Miranda, Merce; Clemente-Postigo, Mercedes; Pérez-Pérez, Rafael; Peral, Belen; Cardona, Fernando; Fernández-Real, Jose Manuel; Tinahones, Francisco J; Vendrell, Joan

2012-01-01

FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. In obesity FABP4 expression was down-regulated (at both mRNA and protein levels), with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity.

FABP4 Dynamics in Obesity: Discrepancies in Adipose Tissue and Liver Expression Regarding Circulating Plasma Levels

PubMed Central

Ceperuelo-Mallafré, Victoria; Garrido-Sanchez, Lourdes; Miranda, Merce; Clemente-Postigo, Mercedes; Pérez-Pérez, Rafael; Peral, Belen; Cardona, Fernando; Fernández-Real, Jose Manuel; Tinahones, Francisco J.; Vendrell, Joan

2012-01-01

Background FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. Objective In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. Methods The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. Results In obesity FABP4 expression was down-regulated (at both mRNA and protein levels), with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. Conclusion The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity. PMID:23139800

Elevated circulating irisin is associated with lower risk of insulin resistance: association and path analyses of obese Chinese adults.

PubMed

Shi, Xiulin; Lin, Mingzhu; Liu, Changqin; Xiao, Fangsen; Liu, Yongwen; Huang, Peiying; Zeng, Xin; Yan, Bing; Liu, Suhuan; Li, Xiaoying; Yang, Shuyu; Li, Xuejun; Li, Zhibin

2016-07-29

Evidence on the role of irisin in insulin resistance is limited and controversial, and pathways between them remain unknown. We aimed to examine the independent effects of circulating irisin and different adiposity measurements, as well as their potential interactions, on insulin resistance. We also aimed to explore possible pathways among circulating irisin, adiposity, glucose and insulin levels and insulin resistance. A cross-sectional study of 1,115 community- living obese Chinese adults, with data collection on clinical characteristics, glucose and lipid metabolic parameters and circulating irisin levels. Among the 1,115 subjects, 667 (59.8 %) were identified as insulin-resistance, and showed significantly decreased serum irisin than their controls (log-transformed irisin: 1.19 ± 2.34 v.s. 1.46 ± 2.05 ng/ml, p = 0.042). With adjustment for potential confounders, elevated circulating irisin was significantly associated with reduced risk of insulin resistance, with adjusted odds ratio per standard deviation increase of irisin of 0.871 (0.765-0.991, p = 0.036). As for different adiposity measurements, body fat percentage, but neither BMI nor waist, was significantly associated with increased risk of insulin resistance (OR: 1.152 (1.041-1.275), p = 0.006). No significant interaction effect between serum irisin and adiposity on insulin resistance was found. A one pathway model about the relationship between serum irisin and insulin resistance fits well (χ (2) = 44.09, p < 0.001; CFI-0.994; TLI =0.986; and RMSEA = 0.067), and shows that elevated circulating irisin might improve insulin resistance indirectly through lowering fasting insulin levels (standardized path coefficient = -0.046, p = 0.032). Elevated circulating irisin is associated with lower risk of insulin resistance indirectly through lowering fasting insulin.

Serum tissue inhibitor of matrix metalloproteinase-1 levels are associated with mortality in patients with malignant middle cerebral artery infarction.

PubMed

Lorente, Leonardo; Martín, María M; Ramos, Luis; Cáceres, Juan J; Solé-Violán, Jordi; Argueso, Mónica; Jiménez, Alejandro; Borreguero-León, Juan M; Orbe, Josune; Rodríguez, José A; Páramo, José A

2015-07-11

In the last years, circulating matrix metalloproteinases (MMP)-9 levels have been associated with functional outcome in ischemic stroke patients. However the prognostic value of circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 and MMP-10 in functional outcome of ischemic stroke patients has been scarcely studied. In addition, to our knowledge, serum MMP-9, MMP-10 and TIMP-1 levels in patients with malignant middle cerebral artery infarction (MMCAI) for mortality prediction have not been studied, and these were the objectives of this study. This was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. We included patients with severe MMCAI defined as Glasgow Coma Scale (GCS) lower than 9. We measured circulating levels of MMP-9, MMP-10, TIMP-1, in 50 patients with severe MMCAI at diagnosis and in 50 healthy subjects. Endpoint was 30-day mortality. Patients with severe MMCAI showed higher serum levels of MMP-9 (p = 0.001), MMP-10 (p < 0.001), and TIMP-1 (p = 0.02) than healthy subjects. Non-surviving MMCAI patients (n = 26) compared to survivor ones (n = 24) showed higher circulating levels of TIMP-1 (p < 0.001), MMP-10 (p = 0.02) and PAI-1(p = 0.02), and lower MMP-9 levels (p = 0.04). Multiple binomial logistic regression analysis showed that serum TIMP-1 levels > 239 ng/mL are associated with 30-day mortality (OR = 5.82; 95% CI = 1.37-24.73; P = 0.02) controlling for GCS and age. The area under the curve for TIMP-1 as predictor of 30-day mortality was 0.81 (95% CI = 0.67-0.91; P < 0.001). We found an association between circulating levels of TIMP-1 and MMP-10 (rho = 0.45; P = 0.001), plasminogen activator inhibitor (PAI)-1 (rho = 0.53; P < 0.001), and tumor necrosis factor (TNF)-alpha (rho = 0.70; P < 0.001). The most relevant and new findings of our study, were that serum TIMP-1 levels in MMCAI patients were associated with mortality, and could be used as a prognostic biomarker of mortality in MMCAI patients.

Circulating levels of insulin-like growth factor-I (IGF-I) correlate with disease status in leprosy

PubMed Central

2011-01-01

Background Caused by Mycobacterium leprae (ML), leprosy presents a strong immune-inflammatory component, whose status dictates both the clinical form of the disease and the occurrence of reactional episodes. Evidence has shown that, during the immune-inflammatory response to infection, the growth hormone/insulin-like growth factor-I (GH/IGF-I) plays a prominent regulatory role. However, in leprosy, little, if anything, is known about the interaction between the immune and neuroendocrine systems. Methods In the present retrospective study, we measured the serum levels of IGF-I and IGBP-3, its major binding protein. These measurements were taken at diagnosis in nonreactional borderline tuberculoid (NR BT), borderline lepromatous (NR BL), and lepromatous (NR LL) leprosy patients in addition to healthy controls (HC). LL and BL patients who developed reaction during the course of the disease were also included in the study. The serum levels of IGF-I, IGFBP-3 and tumor necrosis factor-alpha (TNF-α) were evaluated at diagnosis and during development of reversal (RR) or erythema nodosum leprosum (ENL) reaction by the solid phase, enzyme-labeled, chemiluminescent-immunometric method. Results The circulating IGF-I/IGFBP-3 levels showed significant differences according to disease status and occurrence of reactional episodes. At the time of leprosy diagnosis, significantly lower levels of circulating IGF-I/IGFBP-3 were found in NR BL and NR LL patients in contrast to NR BT patients and HCs. However, after treatment, serum IGF-I levels in BL/LL patients returned to normal. Notably, the levels of circulating IGF-I at diagnosis were low in 75% of patients who did not undergo ENL during treatment (NR LL patients) in opposition to the normal levels observed in those who suffered ENL during treatment (R LL patients). Nonetheless, during ENL episodes, the levels observed in RLL sera tended to decrease, attaining similar levels to those found in NR LL patients. Interestingly, IGF-I behaved contrary to what was observed during RR episodes in R BL patients. Conclusions Our data revealed important alterations in the IGF system in relation to the status of the host immune-inflammatory response to ML while at the same time pointing to the circulating IGF-I/IGFBP-3 levels as possible predictive biomarkers for ENL in LL patients at diagnosis. PMID:22166091

The 148 M allele of the PNPLA3 is associated with plasma irisin levels in a population sample of Caucasian children: The PANIC Study.

PubMed

Viitasalo, Anna; Atalay, Mustafa; Pihlajamäki, Jussi; Jääskeläinen, Jarmo; Korkmaz, Ayhan; Kaminska, Dorota; Lindi, Virpi; Lakka, Timo A

2015-07-01

There are no previous data on the association of PNPLA3 I148M polymorphism (rs738409) with circulating adipokines and myokines in children. Subjects were a population sample of 481 Caucasian children aged 6-8 years. We assessed circulating levels of irisin together with IL-6, TNF-α, leptin, high molecular weight (HMW)-adiponectin, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) while the subjects were stratified according to PNPLA3 I148M variants. The PNPLA3 rs738409 polymorphism had a linear relationship with plasma levels of irisin after adjustment for age, sex and body height (p=0.007) but it was not associated with circulating levels of interleukin- 6 (IL-6), tumor-necrosis factor α (TNF-α), leptin or HMW-adiponectin. PNPLA3 148M allele carriers had higher plasma levels of irisin than the non-carriers. This might be due to compensatory mechanism to limit early steatotic and inflammatory changes in the liver. Copyright © 2015 Elsevier Inc. All rights reserved.

The hypothalamic satiety peptide CART is expressed in anorectic and non-anorectic pancreatic islet tumors and in the normal islet of Langerhans.

PubMed

Jensen, P B; Kristensen, P; Clausen, J T; Judge, M E; Hastrup, S; Thim, L; Wulff, B S; Foged, C; Jensen, J; Holst, J J; Madsen, O D

1999-03-26

The hypothalamic satiety peptide CART (cocaine and amphetamine regulated transcript) is expressed at high levels in anorectic rat glucagonomas but not in hypoglycemic insulinomas. However, a non-anorectic metastasis derived from the glucagonoma retained high CART expression levels and produced circulating CART levels comparable to that of the anorectic tumors. Moreover, distinct glucagonoma lines derived by stable HES-1 transfection of the insulinoma caused severe anorexia but retained low circulating levels of CART comparable to that of insulinoma bearing or control rats. Islet tumor associated anorexia and circulating CART levels are thus not correlated, and in line with this peripheral administration of CART (5-50 mg/kg) produced no effect on feeding behavior. In the rat two alternatively spliced forms of CART mRNA exist and quantitative PCR revealed expression of both forms in the hypothalamus, in the different islet tumors, and in the islets of Langerhans. Immunocytochemistry as well as in situ hybridization localized CART expression to the somatostatin producing islet D cell. A potential endocrine/paracrine role of islet CART remains to be clarified.

Circulating Endothelial Cells and Endothelial Progenitor Cells in Pediatric Sepsis.

PubMed

Zahran, Asmaa Mohamad; Elsayh, Khalid Ibrahim; Mohamad, Ismail Lotfy; Hassan, Gamal Mohamad; Abdou, Madleen Adel A

2016-03-01

The aim of the study was to measure the number of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs) in pediatric patients with sepsis and correlating it with the severity of the disease and its outcome. The study included 19 children with sepsis, 26 with complicated sepsis, and 30 healthy controls. The patients were investigated within 48 hours of pediatric intensive care unit admission together with flow cytometric detection of CECs and CEPs. The levels of both CECs and CEPs were significantly higher in patient with sepsis and complicated sepsis than the controls. The levels of CECs were higher in patients with complicated sepsis, whereas the levels of CEPs were lower in patients with complicated sepsis. Comparing the survival and nonsurvival septic patients, the levels of CEPs were significantly higher in the survival than in nonsurvival patients, whereas the levels of CECs were significantly lower in the survival than in nonsurvival patients. Serum albumin was higher in survival than in nonsurvival patients. Estimation of CECs and CEPs and their correlation with other parameters such as serum albumen could add important information regarding prognosis in septic pediatric patients.

Circulating micrornas as potential biomarkers of muscle atrophy

NASA Astrophysics Data System (ADS)

Wang, Fei

2016-07-01

Noninvasive biomarkers with diagnostic value and prognostic applications have long been desired to replace muscle biopsy for muscle atrophy patients. Growing evidence indicates that circulating microRNAs are biomarkers to assess pathophysiological status. Here, we show that the medium levels of six muscle-specific miRNAs (miR-1/23a/206/133/499/208b, also known as myomiRs) were all elevated in the medium of starved C2C12 cell (P < 0.01). And, the level of miR-1 and miR-23a were all elevated in the serum of hindlimb unloaded mice (P < 0.01). miR-23a levels were negatively correlated with both muscle mass and muscle fiber cross section area in muscle atrophy patients, indicating that they might represent the degree of muscle atrophy. Collectively, our data indicated that circulating myomiRs could serve as promising biomarkers for muscle atrophy.

Positive association between leptin serum levels and disease activity on endoscopy in inflammatory bowel disease: A case-control study

PubMed Central

Trejo-Vazquez, Fabiola; Garza-Veloz, Idalia; Villela-Ramirez, Gabriela Alejandra; Ortiz-Castro, Yolanda; Mauricio-Saucedo, Panfilo; Cardenas-Vargas, Edith; Diaz-Baez, Mariana; Cid-Baez, Miguel A.; Castañeda-Miranda, Rodrigo; Ortiz-Rodriguez, Jose Manuel; Solis-Sanchez, Luis Octavio; Martinez-Fierro, Margarita L.

2018-01-01

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non-invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10-protein profile (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio-Plex Pro Human Diabetes 10-Plex Panel (Bio-Rad Laboratories, Inc.). Compared with those in the controls, leptin levels were significantly lower in patients with IBD (P=4.9×10−4). In addition, serum leptin displayed differences between groups with and without disease activity on endoscopy (P<0.001). Among the study population, serum leptin levels of <5,494 pg/ml significantly increased the odds of IBD by 12.8-fold [odds ratio (OR)=12.8, 95% confidence interval (CI)=3.04–53.9, P=0.001]. In addition, patients with serum leptin levels of <2,498 pg/ml displayed 5.8-fold greater odds of disease activity on endoscopy among the study population (OR=5.8, 95% CI=1.52–22.4, P=0.013). No differences in the serum levels of the remaining proteins were identified between the groups. Among the study population, serum leptin was associated with an increased risk of IBD and with disease activity on endoscopy. Additional studies will be necessary to validate the use of leptin as a non-invasive biomarker of IBD severity. PMID:29545852

Dynamic microvesicle release and clearance within the cardiovascular system: triggers and mechanisms.

PubMed

Ayers, Lisa; Nieuwland, Rienk; Kohler, Malcolm; Kraenkel, Nicolle; Ferry, Berne; Leeson, Paul

2015-12-01

Interest in cell-derived microvesicles (or microparticles) within cardiovascular diagnostics and therapeutics is rapidly growing. Microvesicles are often measured in the circulation at a single time point. However, it is becoming clear that microvesicle levels both increase and decrease rapidly in response to certain stimuli such as hypoxia, acute cardiac stress, shear stress, hypertriglyceridaemia and inflammation. Consequently, the levels of circulating microvesicles will reflect the balance between dynamic mechanisms for release and clearance. The present review describes the range of triggers currently known to lead to microvesicle release from different cellular origins into the circulation. Specifically, the published data are used to summarize the dynamic impact of these triggers on the degree and rate of microvesicle release. Secondly, a summary of the current understanding of microvesicle clearance via different cellular systems, including the endothelial cell and macrophage, is presented, based on reported studies of clearance in experimental models and clinical scenarios, such as transfusion or cardiac stress. Together, this information can be used to provide insights into potential underlying biological mechanisms that might explain the increases or decreases in circulating microvesicle levels that have been reported and help to design future clinical studies. © 2015 Authors; published by Portland Press Limited.

Free androgen index and Irisin in polycystic ovary syndrome.

PubMed

Li, H; Xu, X; Wang, X; Liao, X; Li, L; Yang, G; Gao, L

2016-05-01

PCOS is associated with hyperandrogenism and insulin resistance (IR). Recent studies have shown that circulating Irisin levels increase in PCOS women. However, no report has demonstrated a relationship between Irisin and hyperandrogenism in PCOS women. The purpose of the study was to compare interrelationship between Irisin or androgen excess with IR in PCOS and normal subjects. 166 PCOS and 103 control women were prospectively studied. Euglycemic- hyperinsulinemic clamps were preformed to assess their insulin sensitivity, which was expressed as M value. Circulating Irisin was determined by ELISA kit. Circulating androgens were measured using ultrasensitive assays. PCOS women with high FAI had significantly higher BMI, FAT%, TC, DHEA-S and HOMA-IR, and significantly lower levels of M values and SHBG than PCOS women with low FAI or the controls. Pearson correlations showed that in the entire population, FAI correlated positively with BMI, WHR, FAT%, blood pressure, TG, DHEA-S, LH/FSH, AUCinsulin, HOMA-IR and Irisin, and negatively with M values. In multiple stepwise regression analysis, only FAT%, DHEA-S and LH/FSH were independent related factors with FAI. The elevated Irisin levels in PCOS women were associated with androgen excess. Circulating Irisin is a primary predictor of hyperandrogenism, MetS and IR in PCOS women.

Cell–specific Variation in E-selectin Ligand Expression Among Human Peripheral Blood Mononuclear Cells: Implications for Immunosurveillance and Pathobiology

PubMed Central

Silva, Mariana; Fung, Ronald Kam Fai; Donnelly, Conor Brian; Videira, Paula Alexandra; Sackstein, Robert

2017-01-01

Both host defense and immunopathology are shaped by the ordered recruitment of circulating leukocytes to affected sites, a process initiated by binding of blood-borne cells to E-selectin displayed at target endothelial beds. Accordingly, knowledge of the expression and function of leukocyte E-selectin ligands is key to understanding the tempo and specificity of immunoreactivity. Here, we performed E-selectin adherence assays under hemodynamic flow conditions coupled with flow cytometry and western blot analysis to elucidate the function and structural biology of glycoprotein E-selectin ligands expressed on human peripheral blood mononuclear cells (PBMCs). Circulating monocytes uniformly express high levels of the canonical E-selectin binding determinant sLeX and display markedly greater adhesive interactions with E-selectin than do circulating lymphocytes, which exhibit variable E-selectin binding among CD4+ and CD8+ T-cells but no binding by B-cells. Monocytes prominently present sLeX decorations on an array of protein scaffolds including PSGL-1, CD43, and CD44 (rendering the E-selectin ligands CLA, CD43E, and HCELL, respectively), and B-cells altogether lack E-selectin ligands. Quantitative PCR gene expression studies of glycosyltransferases that regulate display of sLeX reveal high transcript levels among circulating monocytes and low levels among circulating B-cells, and, commensurately, cell surface α(1,3)-fucosylation reveals that acceptor sialyllactosaminyl glycans convertible into sLeX are abundantly expressed on human monocytes yet are relatively deficient on B-cells. Collectively, these findings unveil distinct cell-specific patterns of E-selectin ligand expression among human PBMCs, indicating that circulating monocytes are specialized to engage E-selectin and providing key insights into the molecular effectors mediating recruitment of these cells at inflammatory sites. PMID:28330896

Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery.

PubMed

Wu, Q; Li, J V; Seyfried, F; le Roux, C W; Ashrafian, H; Athanasiou, T; Fenske, W; Darzi, A; Nicholson, J K; Holmes, E; Gooderham, N J

2015-07-01

Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signaling pathways including G protein signaling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. The close association between energy metabolism, neuronal signaling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting.

Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery

PubMed Central

Wu, Q; Li, J V; Seyfried, F; le Roux, C W; Ashrafian, H; Athanasiou, T; Fenske, W; Darzi, A; Nicholson, J K; Holmes, E; Gooderham, N J

2015-01-01

Background/Objectives: Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. Subjects/Methods: We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. Results: The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signaling pathways including G protein signaling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. Conclusions: The close association between energy metabolism, neuronal signaling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting. PMID:25783038

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry.

PubMed

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group.

Circulating FABP4 is a marker of metabolic and cardiovascular risk in SLE patients.

PubMed

Parra, S; Cabré, A; Marimon, F; Ferré, R; Ribalta, J; Gonzàlez, M; Heras, M; Castro, A; Masana, L

2014-03-01

The aim of this study is to determine if circulating fatty acid-binding protein 4 (FABP4) plasma levels are a possible marker of metabolic risk in SLE patients. Circulating levels of adipose FABP4 are associated with adiposity, insulin resistance (IR), metabolic syndrome, diabetes and cardiovascular diseases. Patients affected by systemic lupus erythematosus (SLE) show an accelerated atherosclerosis that cannot be entirely explained by traditional cardiovascular risk factors. Sixty consecutive patients with SLE and 34 non-SLE age-matched controls were recruited for the study. Total plasma lipids and circulating FABP4 were determined. Subclinical atherosclerosis was evaluated by measuring carotid intimae-media thickness (c-IMT) by sonography, and the distribution of lipoprotein subclasses was analysed by nuclear magnetic resonance (NMR) spectroscopy. In the SLE group, FABP4 was associated with IR, atherogenic dyslipidaemia, as measured by NMR, and the presence of subclinical atherosclerosis. In multivariate analyses FABP4 was associated with increased c-IMT independent of the inflammatory state of the patient. In sum, circulating FABP4 is involved in the metabolic disturbances of SLE affecting lipid metabolism and IR, and it could be a biomarker of atherosclerosis in this population.

Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice.

PubMed

Kim, Myung Sunny; Hur, Haeng Jeon; Kwon, Dae Young; Hwang, Jin-Taek

2012-07-06

Although the flavonoid tangeretin (5, 6, 7, 8, 4'-pentamethoxyflavone) is known to possess beneficial health effects, the anti-diabetic effects and the mechanism of action have not been elucidated. Treatment with 100 μM tangeretin significantly increased the uptake of 2-NBDG in C2C12 myotubes. We also found that AMPK and AS160 were markedly phosphorylated by tangeretin treatment. In addition, pretreatment with an AMPK inhibitor significantly abrogated tangeretin-stimulated AS160 phosphorylation, glucose uptake, and Glut4 translocation from the cytosol to the plasma membrane. Furthermore, disruption of AMPK using siRNA transfection prevented the glucose uptake stimulated by tangeretin. We also examined the anti-diabetic properties of tangeretin in mice on HFD. Administration of HFD plus 200 mg/kg of tangeretin significantly altered weight gain, glucose tolerance, total cholesterol levels, and the secretion of adipocytokines, such as adiponectin, leptin, resistin, IL-6, and MCP-1. Moreover, AMPK was activated by 200 mg/kg of tangeretin in mouse muscle tissue, as expected from the cell system. These results suggest that tangeretin exerts anti-diabetic effects in both cell culture and mouse models, and these effects are necessary for activating AMPK. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory effects of omega 3 and omega 6 polyunsaturated fatty acids in cardiovascular disease and metabolic syndrome.

PubMed

Tortosa-Caparrós, Esther; Navas-Carrillo, Diana; Marín, Francisco; Orenes-Piñero, Esteban

2017-11-02

A lipid excess produces a systemic inflammation process due to tumor necrosis factor-α, interleukin-6 and C-reactive protein synthesis. Simultaneously, this fat excess promotes the appearance of insulin resistance. All this contributes to the development of atherosclerosis and increases the risk of cardiovascular diseases (CVDs). On the other hand, polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid and docosahexaenoic acid (omega 3), and arachidonic acid (omega 6) have shown anti-inflammatory properties. Lately, an inverse relationship between omega-3 fatty acids, inflammation, obesity and CVDs has been demonstrated. To check fatty acids effect, the levels of some inflammation biomarkers have been analyzed. Leptin, adiponectin and resistin represent a group of hormones associated with the development of CVDs, obesity, type 2 diabetes mellitus and insulin resistance and are modified in obese/overweight people comparing to normal weight people. Omega-3 PUFAs have been shown to decrease the production of inflammatory mediators, having a positive effect in obesity and diabetes mellitus type-2. Moreover, they significantly decrease the appearance of CVD risk factors. Regarding omega-6 PUFA, there is controversy whether their effects are pro- or anti-inflammatory. The aim of this manuscript is to provide a comprehensive overview about the role of omega-3 and omega-6 PUFAs in CVDs and metabolic syndrome.

Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer

PubMed Central

Chellappa, Karthikeyani; Deol, Poonamjot; Evans, Jane R; Vuong, Linh M; Chen, Gang; Briançon, Nadege; Bolotin, Eugene; Lytle, Christian; Nair, Meera G; Sladek, Frances M

2016-01-01

HNF4α has been implicated in colitis and colon cancer in humans but the role of the different HNF4α isoforms expressed from the two different promoters (P1 and P2) active in the colon is not clear. Here, we show that P1-HNF4α is expressed primarily in the differentiated compartment of the mouse colonic crypt and P2-HNF4α in the proliferative compartment. Exon swap mice that express only P1- or only P2-HNF4α have different colonic gene expression profiles, interacting proteins, cellular migration, ion transport and epithelial barrier function. The mice also exhibit altered susceptibilities to experimental colitis (DSS) and colitis-associated colon cancer (AOM+DSS). When P2-HNF4α-only mice (which have elevated levels of the cytokine resistin-like β, RELMβ, and are extremely sensitive to DSS) are crossed with Retnlb-/- mice, they are rescued from mortality. Furthermore, P2-HNF4α binds and preferentially activates the RELMβ promoter. In summary, HNF4α isoforms perform non-redundant functions in the colon under conditions of stress, underscoring the importance of tracking them both in colitis and colon cancer. DOI: http://dx.doi.org/10.7554/eLife.10903.001 PMID:27166517

Saliva as a non-invasive diagnostic tool for inflammation and insulin-resistance

PubMed Central

Desai, Gauri S; Mathews, Suresh T

2014-01-01

Saliva has been progressively studied as a non-invasive and relatively stress-free diagnostic alternative to blood. Currently, saliva testing is used for clinical assessment of hormonal perturbations, detection of HIV antibodies, DNA analysis, alcohol screening, and drug testing. Recently, there has been increasing interest in evaluating the diagnostic potential of saliva in obesity, inflammation, and insulin-resistance. Current literature has demonstrated elevated levels of inflammatory biomarkers including C-reactive protein, tumor necrosis factor-α, interleukin-6, and interferon-γ in saliva of obese/overweight children and adults. Salivary antioxidant status has also been studied as a measure of oxidative stress in individuals with type 2 diabetes. Further, several studies have demonstrated correlations of salivary markers of stress and insulin resistance including cortisol, insulin, adiponectin, and resistin with serum concentrations. These findings suggest the potential diagnostic value of saliva in health screening and risk stratification studies, particularly in the pediatric population, with implications for inflammatory, metabolic and cardiovascular conditions. However, additional studies are required to standardize saliva collection and storage procedures, validate analytical techniques for biomarker detection, and establish reference ranges for routine clinical use. The purpose of this review is to summarize and evaluate recent advancements in using saliva as a diagnostic tool for inflammation and insulin-resistance. PMID:25512775

Indomethacin Inhibits Circulating PGE2 and Reverses Postexercise Suppression of Natural Killer Cell Activity

DTIC Science & Technology

1999-01-01

after the oral administration of a placebo, the PG inhibitor indomethacin (75 mg/day for 5 days), or naltrexone (reported elsewhere). Circulating...which blocks PGE2 biosynthe- sis via inhibition of cyclooxygenase activity (57). Maxi- mal suppression of PG production occurs with doses between 50...and 150 mg (1). In addition to the indepen- dent effects of PGE2 on NKCA, low circulating levels of PGE2 can synergize with endogenous glucocorticoids

A genetic contribution to circulating cytokines and obesity in children

USDA-ARS?s Scientific Manuscript database

Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children...

Climate model biases in jet streams, blocking and storm tracks resulting from missing orographic drag

NASA Astrophysics Data System (ADS)

Pithan, Felix; Shepherd, Theodore G.; Zappa, Giuseppe; Sandu, Irina

2016-07-01

State-of-the art climate models generally struggle to represent important features of the large-scale circulation. Common model deficiencies include an equatorward bias in the location of the midlatitude westerlies and an overly zonal orientation of the North Atlantic storm track. Orography is known to strongly affect the atmospheric circulation and is notoriously difficult to represent in coarse-resolution climate models. Yet how the representation of orography affects circulation biases in current climate models is not understood. Here we show that the effects of switching off the parameterization of drag from low-level orographic blocking in one climate model resemble the biases of the Coupled Model Intercomparison Project Phase 5 ensemble: An overly zonal wintertime North Atlantic storm track and less European blocking events, and an equatorward shift in the Southern Hemispheric jet and increase in the Southern Annular Mode time scale. This suggests that typical circulation biases in coarse-resolution climate models may be alleviated by improved parameterizations of low-level drag.

Circulating irisin in healthy, young individuals: day-night rhythm, effects of food intake and exercise, and associations with gender, physical activity, diet, and body composition.

PubMed

Anastasilakis, Athanasios D; Polyzos, Stergios A; Saridakis, Zacharias G; Kynigopoulos, Georgios; Skouvaklidou, Elpida C; Molyvas, Dimitrios; Vasiloglou, Maria F; Apostolou, Aggeliki; Karagiozoglou-Lampoudi, Thomai; Siopi, Aikaterina; Mougios, Vassilis; Chatzistavridis, Panagiotis; Panagiotou, Grigorios; Filippaios, Andreas; Delaroudis, Sideris; Mantzoros, Christos S

2014-09-01

The myokine irisin may increase energy expenditure and affect metabolism. The objective of the study was to elucidate predictors of irisin and study whether circulating irisin may have day-night rhythm in humans. This was an observational, cross-sectional study with an additional 24-hour prospective observational arm (day-night rhythm substudy) and two prospective interventional arms (mixed meal substudy and exercise substudy). The study was conducted at the Hellenic Military School of Medicine (Thessaloniki, Greece). One hundred twenty-two healthy, young individuals were subjected to anthropometric and body composition measurements, and their eating and exercise behavior profiles were assessed with validated questionnaires. Subgroups were subjected to day-night rhythm, standardized meal ingestion, and 30-minute aerobic exercise studies. Circulating irisin levels were measured. Ιrisin levels were lower in males than females (P = .02) after adjustment for lean body mass, which was its major determinant. Irisin levels followed a day-night rhythm (P < .001) with peak at 9:00 pm. Irisin levels were increased at the end of exercise (84.1 ± 10.0 vs 105.8 ± 14.3 ng/mL; P < .001). Irisin levels were not affected by intake of a standardized meal and were not associated with caloric intake or diet quality. In healthy, young individuals, circulating irisin displays a day-night rhythm, is correlated with lean body mass, and increases acutely after exercise.

Circulating retinol binding protein 4 levels in nonalcoholic fatty liver disease: a systematic review and meta-analysis.

PubMed

Zhou, Zhongwei; Chen, Hongmei; Ju, Huixiang; Sun, Mingzhong

2017-09-20

Retinol binding protein 4 (RBP4) is implicated in obesity, insulin resistance and type 2 diabetes mellitus that are closely associated with nonalcoholic fatty liver disease (NAFLD). However, recent investigations regarding circulating RBP4 levels in NAFLD are conflicting. This meta-analysis is to determine whether NAFLD, non-alcoholic steatohepatitis (NASH) and simple steatosis (SS) patients have altered RBP4 levels. We performed a systematic search in PubMed, EMBASE and The Cochrane Library up until 18 March 2017, and 12 studies comprising a total of 4247 participants (2271 NAFLD patients and 1976 controls) were included in the meta-analysis. There were no significant differences of circulating RBP4 levels in the following comparisons: (1) NAFLD patients vs controls (standardized mean differences [SMD]: 0.08; 95% CI: -0.21, 0.38); (2) NASH patients vs controls (SMD: -0.49; 95% CI: -1.09, 0.12); (3) SS patients vs controls (SMD: -0.72; 95% CI: -1.64, 0.20) and (4) NASH vs SS patients (SMD: -0.04; 95% CI: -0.32, 0.24). The results remained essentially unchanged in the comparisons between NAFLD patients and controls after excluding single individual study or bariatric studies (n = 2). No significant publication bias was detected. However, there was significant heterogeneity among studies and the subgroup and meta-regression analyses did not find the potential sources. Circulating RBP4 levels may not be associated with NAFLD. Further prospective cohort studies are required to confirm these findings.

The Arcuate Nucleus: A Site of Fast Negative Feedback for Corticosterone Secretion in Male Rats

PubMed Central

Kawata, Mitsuhiro; Escobar, Carolina

2017-01-01

Abstract Variations in circulating corticosterone (Cort) are driven by the paraventricular nucleus of the hypothalamus (PVN), mainly via the sympathetic autonomic nervous system (ANS) directly stimulating Cort release from the adrenal gland and via corticotropin-releasing hormone targeting the adenohypophysis to release adrenocorticotropic hormone (ACTH). Cort feeds back through glucocorticoid receptors (GRs). Here we show in male Wistar rats that PVN neurons projecting to the adrenal gland do not express GRs, leaving the question of how the ANS in the PVN gets information about circulating Cort levels to control the adrenal. Since the arcuate nucleus (ARC) shows a less restrictive blood–brain barrier, expresses GRs, and projects to the PVN, we investigated whether the ARC can detect and produce fast adjustments of circulating Cort. In low Cort conditions (morning), local microdialysis in the ARC with type I GR antagonist produced a fast and sustained increase of Cort. This was not observed with a type II antagonist. At the circadian peak levels of Cort (afternoon), a type II GR antagonist, but not a type I antagonist, increased Cort levels but not ACTH levels. Antagonist infusions in the PVN did not modify circulating Cort levels, demonstrating the specificity of the ARC to give Cort negative feedback. Furthermore, type I and II GR agonists in the ARC prevented the increase of Cort after stress, demonstrating the role of the ARC as sensor to modulate Cort release. Our findings show that the ARC may be essential to sense blood levels of Cort and adapt Cort secretion depending on such conditions as stress or time of day. PMID:28275717

Increased level and interferon-γ production of circulating natural killer cells in patients with scrub typhus.

PubMed

Kang, Seung-Ji; Jin, Hye-Mi; Cho, Young-Nan; Kim, Seong Eun; Kim, Uh Jin; Park, Kyung-Hwa; Jang, Hee-Chang; Jung, Sook-In; Kee, Seung-Jung; Park, Yong-Wook

2017-07-01

Natural killer (NK) cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK cells in patients with scrub typhus. This study enrolled fifty-six scrub typhus patients and 56 health controls (HCs). The patients were divided into subgroups according to their disease severity. A flow cytometry measured NK cell level and function in peripheral blood. Circulating NK cell levels and CD69 expressions were significantly increased in scrub typhus patients. Increased NK cell levels reflected disease severity. In scrub typhus patients, tests showed their NK cells produced higher amounts of interferon (IFN)-γ after stimulation with interleukin (IL)-12 and IL-18 relative to those of HCs. Meanwhile, between scrub typhus patients and HCs, the cytotoxicity and degranulation of NK cells against K562 were comparable. CD69 expressions were recovered to the normal levels in the remission phase. This study shows that circulating NK cells are activated and numerically increased, and they produced more IFN-γ in scrub typhus patients.

Increased level and interferon-γ production of circulating natural killer cells in patients with scrub typhus

PubMed Central

Cho, Young-Nan; Kim, Seong Eun; Kim, Uh Jin; Park, Kyung-Hwa; Jang, Hee-Chang; Jung, Sook-In; Kee, Seung-Jung

2017-01-01

Background Natural killer (NK) cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK cells in patients with scrub typhus. Methodology/Principal findings This study enrolled fifty-six scrub typhus patients and 56 health controls (HCs). The patients were divided into subgroups according to their disease severity. A flow cytometry measured NK cell level and function in peripheral blood. Circulating NK cell levels and CD69 expressions were significantly increased in scrub typhus patients. Increased NK cell levels reflected disease severity. In scrub typhus patients, tests showed their NK cells produced higher amounts of interferon (IFN)-γ after stimulation with interleukin (IL)-12 and IL-18 relative to those of HCs. Meanwhile, between scrub typhus patients and HCs, the cytotoxicity and degranulation of NK cells against K562 were comparable. CD69 expressions were recovered to the normal levels in the remission phase. Conclusions This study shows that circulating NK cells are activated and numerically increased, and they produced more IFN-γ in scrub typhus patients. PMID:28750012

Association between circulating specific leukocyte types and incident chronic kidney disease: the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Tian, Niu; Penman, Alan D; Manning, R Davis; Flessner, Michael F; Mawson, Anthony R

2012-01-01

Progressive renal fibrosis is a characteristic of all the diseases that cause renal failure and is invariably accompanied by a prominent leukocyte infiltration in the kidney. The goal of this study was to determine the association between the circulating specific leukocyte types and incident chronic kidney disease (CKD). In a cohort of 10,056 middle-aged white and African American adults, levels of circulating neutrophils, lymphocytes, and monocytes were measured at baseline; blood pressure (BP) and serum creatinine were measured and estimated glomerular filtration rate (eGFR) was calculated at baseline and 3 and 9 years later; and surveillance for first hospitalization or death with CKD was carried out over a mean follow-up of 7.4 years (maximum, 11.9 years). Increased neutrophil levels and decreased lymphocyte levels were significantly associated with greater CKD incidence after adjustment for covariates. African Americans tended to have similar but stronger patterns of association between circulating leukocytes and CKD incidence than whites, although the differences between race groups were not statistically significant. We also found that eGFR and BP were higher at each visit in African Americans than whites between ages 45 and 65. These findings support a potential role for circulating specific leukocytes in the pathogenesis of kidney dysfunction, especially in African Americans, indicating the leukocyte-related renal mechanism of essential hypertension (HT). Copyright © 2012 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.