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1

Serum concentrations of high–molecular weight adiponectin and their association with sex steroids in premenopausal women  

Microsoft Academic Search

At present, the association between adiponectin and sex hormones in women is controversial. Recent studies suggest that it is high–molecular weight (HMW) adiponectin and the HMW to total adiponectin ratio rather than total adiponectin that are associated with antiatherogenic activities, insulin sensitivity, metabolic syndrome, and prediction of cardiovascular events. The present study aimed to investigate whether measuring HMW adiponectin and

Gabriele S. Merki-Feld; Bruno Imthurn; Marinella Rosselli; Katharina Spanaus

2011-01-01

2

Paradoxically Low Levels of Total and HMW Adiponectin in Relation to Metabolic Parameters in a Tongan Population  

PubMed Central

Aim. Adiponectin has demonstrated anti-inflammatory and insulin sensitising properties, and low circulating levels may be an important risk factor for diabetes. We examined levels of adiponectin and its insulin-sensitising HMW isoform and their relationship with metabolic parameters in Tongans, a population prone to type II diabetes. Methods. Adiponectin and its HMW isoform were quantitated by Elisa in specimens from a randomly recruited, multistage cluster population survey of Tongans and from a group of Caucasians. Anthropometric, clinical, and biochemical data were collected on each subject. Results. Both male and female Tongans had lower levels of total and HMW adiponectin than their Caucasian counterparts. Levels of total and HMW adiponectin were higher in females than males in each group. Adiponectin levels were inversely related to BMI, weight, and HOMA in Tongan males and females, as well as to dyslipidemia in both sexes. Conclusion. Tongans had lower levels of both total and HMW adiponectin than Caucasians population, even after matching Tongans to their Caucasian counterparts based on BMI, age, and sex. These findings may reflect differences in body composition between the populations not adequately assessed by BMI, lifestyle factors, or a genetic variant likely in a genetically homogenous population.

Peake, Philip; Colagiuri, Stephen; Campbell, Lesley V.; Shen, Yvonne

2013-01-01

3

Paradoxically Low Levels of Total and HMW Adiponectin in Relation to Metabolic Parameters in a Tongan Population.  

PubMed

Aim. Adiponectin has demonstrated anti-inflammatory and insulin sensitising properties, and low circulating levels may be an important risk factor for diabetes. We examined levels of adiponectin and its insulin-sensitising HMW isoform and their relationship with metabolic parameters in Tongans, a population prone to type II diabetes. Methods. Adiponectin and its HMW isoform were quantitated by Elisa in specimens from a randomly recruited, multistage cluster population survey of Tongans and from a group of Caucasians. Anthropometric, clinical, and biochemical data were collected on each subject. Results. Both male and female Tongans had lower levels of total and HMW adiponectin than their Caucasian counterparts. Levels of total and HMW adiponectin were higher in females than males in each group. Adiponectin levels were inversely related to BMI, weight, and HOMA in Tongan males and females, as well as to dyslipidemia in both sexes. Conclusion. Tongans had lower levels of both total and HMW adiponectin than Caucasians population, even after matching Tongans to their Caucasian counterparts based on BMI, age, and sex. These findings may reflect differences in body composition between the populations not adequately assessed by BMI, lifestyle factors, or a genetic variant likely in a genetically homogenous population. PMID:23936666

Peake, Philip; Colagiuri, Stephen; Campbell, Lesley V; Shen, Yvonne

2013-07-09

4

Lower ratio of high-molecular-weight adiponectin level to total may be associated with coronary high-risk plaque  

PubMed Central

Background Although high-molecular-weight (HMW) adiponectin is believed to protect against atherosclerosis, the association between HMW adiponectin and the composition of coronary plaques is unknown. We evaluated whether the HMW to total adiponectin ratio was associated with the presence of coronary plaque and its composition using multi-slice computed tomography coronary angiography (MSCTCA). Methods Serum total and HMW adiponectin levels were measured in 53 consecutive patients (age, 71) with >50% coronary artery stenosis detected by MSCTCA. A low-attenuation coronary plaque was defined as a plaque with a mean CT density <50 Hounsfield units. Multivariate logistic regression analyses were performed to evaluate the predictors of the presence of low-attenuation coronary plaques, which is thought to be high risk, on CT. Results Decreased serum levels of total as well as HMW adiponectin were significantly associated with the presence of at least one calcified or non-calcified coronary artery plaque (total adiponectin level: odds ratio 0.76, 95% CI 0.58–0.99, P?=?0.048; HMW adiponectin level: odds ratio 0.65, 95% CI 0.42–0.99, P?=?0.047). A low ratio of HMW to total adiponectin was significantly associated with the presence of low-attenuation coronary plaques (4.55, 1.94–21.90, P?=?0.049). However, neither the total adiponectin nor the HMW adiponectin level was associated with the presence of low-attenuation coronary plaques. Conclusion Lower total or HMW adiponectin levels are associated with the presence of calcified and non-calcified coronary plaques, whereas a lower ratio of HMW to total adiponectin associated with the presence of low-attenuation coronary plaques (thought to be high risk). Measurement of total and HMW adiponectin levels and the HMW to total adiponectin ratio may be useful for risk stratification of coronary artery plaques.

2013-01-01

5

Similar associations of total adiponectin and high molecular weight adiponectin with cardio-metabolic risk factors in a population of overweight and obese postmenopausal women: a MONET study.  

PubMed

The aim of the study was to examine the association between total adiponectin and high molecular weight (HMW) adiponectin levels with cardio-metabolic risk factors in a population of sedentary, overweight, and obese postmenopausal women. Cross-sectional study was carried out on 55 nondiabetic sedentary overweight and obese postmenopausal women aged between 50 and 70 years. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp technique. Body composition and visceral fat were measured using dual X-ray absorptiometry and computed tomography, respectively. Other cardio-metabolic risk factors included: plasma lipids, hsC-reactive protein, energy expenditure (doubly labeled water), peak oxygen consumption, muscle strength (using weight training equipment) as well as total and HMW adiponectin. Correlations of total and HMW adiponectin with various cardio-metabolic risk factors were comparable. In addition, regression analysis results showed similar independent predictors of total and HMW adiponectin. Finally, the receiver operator characteristic (ROC) curves for total and HMW adiponectin to predict insulin sensitivity showed no difference between the areas under curve (AUC) (AUC total adiponectin=0.80 [95% CI: 0.66-0.95] versus AUC HMW adiponectin=0.76 [95% CI: 0.60-0.91], p=0.36). The present study indicates that HMW adiponectin does not seem to provide additional information than total adiponectin in relation to cardio-metabolic risk factors in overweight/obese postmenopausal women. PMID:20486084

Elisha, B; Ziai, S; Karelis, A D; Rakel, A; Coderre, L; Imbeault, P; Rabasa-Lhoret, R

2010-05-18

6

Association of High-Molecular-Weight to Total Adiponectin Ratio with Pulse Wave Velocity in Hemodialysis Patients  

Microsoft Academic Search

High-molecular-weight adiponectin (HMW ADPN) plays an important role in the regulation of insulin action and atherogenic processes, but the role of HMW ADPN remains to be determined in hemodialysis (HD) patients. In this study, we measured serum total and HMW ADPN in 67 HD patients (age: 67 ± 14 years, time on HD: 75 ± 68 months, male\\/female = 39\\/28),

Akihiko Kato; Mari Odamaki; Junko Ishida; Akira Hishida

2008-01-01

7

Circulating concentrations of high-molecular-weight adiponectin are increased following Roux-en-Y gastric bypass surgery  

Microsoft Academic Search

Aims\\/hypothesis  In addition to weight loss, bariatric surgery for severe obesity dramatically alleviates insulin resistance. In this study, we investigated whether circulating concentrations of the high-molecular-weight (HMW) form of adiponectin are increased following gastric bypass surgery. The HMW form is implicated as the multimer responsible for adiponectin’s hepatic insulin-sensitising actions.Subjects and methods  We studied 19 women who were undergoing Roux-en-Y gastric bypass

M. M. Swarbrick; I. T. Austrheim-Smith; K. L. Stanhope; M. D. Van Loan; M. R. Ali; B. M. Wolfe; P. J. Havel

2006-01-01

8

Resistin is associated with biomarkers of inflammation while total and HMW adiponectin are associated with biomarkers of inflammation, insulin resistance, and endothelial function  

PubMed Central

Objective Adiponectin and resistin have been linked to inflammation, endothelial dysfunction, and/or insulin secretion or resistance. It remains to be elucidated which of these adipokines is associated primarily with biomarkers of all or only some of these categories i.e. biomarkers of inflammation, endothelial dysfunction, and/or insulin secretion or insulinemia. Design and Methods We studied 1065 healthy women, Nurses’ Health Study participants, who provided blood samples in 1989–1990. A cross-sectional analysis was conducted to assess the relationships between total and high molecular weight (HMW) adiponectin and resistin with inflammatory markers and biomarkers of endothelial dysfunction, insulin secretion and insulinemia. Results Resistin was positively associated with the inflammatory markers sTNF-?RII and IL-6 but not with any biomarkers of endothelial function, glycemia, insulinemia or markers of insulin secretion after multivariate adjustment for age and BMI. In both crude and multivariate analyses, total adiponectin was inversely associated with insulin, proinsulin, C-peptide, HbA1c, sE-selectin, and CRP levels. HMW adiponectin was inversely associated with circulating insulin, proinsulin, C-peptide, HbA1c, sE-selectin and CRP concentrations, even after adjustment for age, BMI, lifestyle factors, exercise, the use of medications as well as the other biomarkers of interest. Total and HMW adiponectin demonstrated negative associations with sICAM-1 which became nonsignificant after adjustment for confounders, whereas positive associations between sVCAM-1 and total adiponectin became significant only after multivariate adjustment. Conclusions Total and HMW adiponectin are inversely associated with markers of insulin secretion/insulinemia, endothelial function, and inflammation. Resistin is positively associated only with markers of inflammation

Fargnoli, Jessica L.; Sun, Qi; Olenczuk, Deanna; Qi, Lu; Zhu, Ying; Hu, Frank B.; Mantzoros, Christos S.

2010-01-01

9

High Molecular Weight Adiponectin and Incident Ischemic Stroke in Postmenopausal Women: A Women's Health Initiative Study  

PubMed Central

Background and Purpose While low levels of adiponectin are associated with coronary heart disease and cardiovascular disease (CVD) risk factors, it is unclear whether adiponectin levels are related to the risk of developing ischemic stroke. Methods We examined the relationship between baseline high molecular weight (HMW) adiponectin levels and incident ischemic stroke in postmenopausal women, using data and specimens from the Hormones and Biomarkers Predicting Stroke Study, a case-control study nested within the Women’s Health Initiative Observational Study. Included were 855 incident ischemic stroke cases and 855 controls, matched for age, race-ethnicity, date of entry into the cohort, and follow-up time. Odds ratios of incident ischemic stroke associated with baseline HMW adiponectin levels were calculated using conditional logistic regression modeling, adjusting for body mass index (BMI), type 2 diabetes, hypertension, smoking, LDL-C, HDL-C, physical activity, C-reactive protein, and aspirin use. Results Lower levels of HMW adiponectin were significantly associated with type 2 diabetes, hypertension, higher BMI, waist, glucose, and insulin levels, and lower HDL-C levels. The distribution of incident stroke cases by HMW adiponectin quartiles was 49.9%, 50.5%, 50.7%, and 48.9%, respectively (p =0.96). Multivariable-adjusted odds ratios of stroke associated with the top three quartiles of HMW adiponectin versus the first quartile were 0.99 (95%CI 0.71 to 1.37), 1.37 (0.99 to 1.91), and 1.25 (0.88 to 1.79), respectively (p-trend =0.14). Conclusion Despite moderate associations between HMW adiponectin and CVD risk factors, we found no evidence of an association between HMW adiponectin levels and incident ischemic stroke in these postmenopausal women.

Ogorodnikova, Alexandra D.; Wassertheil-Smoller, Sylvia; Mancuso, Peter; Sowers, MaryFran R.; Rajpathak, Swapnil N.; Allison, Matthew A.; Baird, Alison E.; Rodriguez, Beatriz; Wildman, Rachel P.

2010-01-01

10

Higher Adiponectin Levels Predict Greater Weight Gain in Healthy Women in the Nurses' Health Study  

Microsoft Academic Search

Adiponectin and resistin's possible roles in weight regulation have received little attention. We tested the hypothesis that adipokine levels predict future weight gain in women in the Nurses' Health Study. Among women who provided blood samples in 1990, we studied 1,063 women who did not develop diabetes (“healthy”) and 984 women who subsequently developed diabetes. Total and high-molecular-weight (HMW) adiponectin

Marie-France Hivert; Qi Sun; Peter Shrader; Christol S. Mantzoros; James B. Meigs; Frank B. Hu

2011-01-01

11

Total and high-molecular weight adiponectin and risk of colorectal cancer: the European Prospective Investigation into Cancer and Nutrition Study  

PubMed Central

Adiponectin—an adipose tissue-derived protein—may provide?a molecular link between obesity and colorectal cancer (CRC), but evidence from large prospective studies is limited. In particular, no epidemiological study explored high-molecular weight (HMW) and non-HMW adiponectin fractions in relation to CRC risk, despite them being hypothesized to have differential biological activities, i.e. regulating insulin sensitivity (HMW adiponectin) versus inflammatory response (non-HMW adiponectin). In a prospective, nested case–control study, we investigated whether prediagnostic serum concentrations of total, HMW and non-HMW adiponectin are associated with risk of CRC, independent of obesity and other known CRC risk factors. A total of 1206 incident cases (755 colon and 451 rectal) were matched to 1206 controls using incidence-density sampling. In conditional logistic regression, adjusted for dietary and lifestyle factors, total adiponectin and non-HMW adiponectin concentrations were inversely associated with risk of CRC [relative risk (RR) comparing highest versus lowest quintile = 0.71, 95% confidence interval (CI) = 0.53–0.95, P trend = 0.03 for total adiponectin and RR = 0.45, 95% CI = 0.34–0.61, P trend < 0.0001 for non-HMW adiponectin]. HMW adiponectin concentrations were not associated with CRC risk (RR = 0.91, 95% CI = 0.68–1.22, P trend = 0.55). Non-HMW adiponectin was associated with CRC risk even after adjustment for body mass index and waist circumference (RR = 0.39, 95% CI = 0.26–0.60, P trend < 0.0001), whereas the association with total adiponectin was no longer significant (RR = 0.81, 95% CI = 0.60–1.09, P trend = 0.23). When stratified by cancer site, non-HMW adiponectin was inversely associated with both colon and rectal cancer. These findings suggest an important role of the relative proportion of non-HMW adiponectin in CRC pathogenesis. Future studies are warranted to confirm these results and to elucidate the underlying mechanisms.

Aleksandrova, Krasimira; Boeing, Heiner; Jenab, Mazda; Bueno-de-Mesquita, H.Bas; Jansen, Eugene; van Duijnhoven, Franzel J.B.; Fedirko, Veronika; Rinaldi, Sabina; Romieu, Isabelle; Riboli, Elio; Romaguera, Dora; Westphal, Sabine; Overvad, Kim; Tj?nneland, Anne; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Francoise; Kaaks, Rudolf; Lukanova, Annekatrin; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Agnoli, Claudia; Mattiello, Amalia; Saieva, Calogero; Vineis, Paolo; Tumino, Rosario; Peeters, Petra H.; Arguelles, Marcial; Bonet, Catalina; Sanchez, Maria-Jose; Dorronsoro, Miren; Huerta, Jose-Maria; Barricarte, Aurelio; Palmqvist, Richard; Hallmans, Goran; Khaw, Kay-Tee; Wareham, Nick; Allen, Naomi E.; Crowe, Francesca L.; Pischon, Tobias

2012-01-01

12

Association of plasma total and high-molecular-weight adiponectin with risk of colorectal cancer: an observational study in Chinese male.  

PubMed

The research is to investigate the association between plasma concentrations of total and high-molecular-weight (HMW) adiponectin and risk of early and advanced colorectal cancer. One hundred and sixty-five male colorectal cancer patients and one hundred and two controls were enrolled; based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive carcinoma were defined as early cancer, and invasion into the muscularis propria or deeper was defined as advanced cancer. The plasma levels of glucose, fasting insulin, total cholesterol, triglyceride, and total and HMW adiponectin levels were measured. Each factor level was designated as low or high, and the risk of cancer was estimated by univariate and multivariate logistic regression analyses. In the patients with early cancer, high waist/hip ratio (WHR), high fasting insulin, high HOMA model insulin resistance index (HOMA-IR), low total adiponectin and HMW adiponectin were all associated with a significant increase in the odds ratio (OR) by univariate analysis. In multivariate analysis, WHR, HOMA-IR, total adiponectin and HMW adiponectin were all related to increased cancer risk. However, in the patients with advanced cancer, only low HMW adiponectin was associated with a significant increase in the OR by univariate analysis. In multivariate analysis, a low HMW adiponectin level was still related to increased cancer risk, with an adjusted OR of 3.971 (P = 0.036). In conclusion, a decreased level of adiponectin was a strong risk factor not only for early colorectal cancer but also for advanced colorectal in Chinese male patients. HMW adiponectin might be more closely associated with colorectal cancer risk than total adiponectin. PMID:22752603

Chen, Ming-Wei; Ye, Shuai; Zhao, Li-Li; Wang, Shen-Yi; Li, Yong-Xiang; Yu, Chang-Jun; Xie, Hui-Juan; Wang, You-Min

2012-07-03

13

High molecular weight adiponectin reduces apolipoprotein B and E release in human hepatocytes  

SciTech Connect

Low circulating levels of high molecular weight adiponectin (HMW-Apm) have been linked to dyslipidaemia and systemic HMW-Apm negatively correlates with very low density lipoprotein (VLDL), apolipoprotein B (ApoB), and ApoE and is positively associated with ApoA-I. Therefore, it was investigated whether HMW-Apm alters the hepatic synthesis of ApoB, ApoE, and ApoA-I or the activity of the hepatic ATP-binding cassette transporter A1 (ABCA1), as the main determinant of plasma HDL. HMW-Apm reduces hepatic ApoB and ApoE release whereas ABCA1 protein, activity and ApoA-I were not altered. Global gene expression analysis revealed that hepatic nuclear factor 4-{alpha} (HNF4-{alpha}) and HNF4-{alpha} regulated genes like ApoB are downregulated by HMW-Apm and this was confirmed at the mRNA and protein level. Therefore it is concluded that HMW-adiponectin may ameliorate dyslipidaemia by reducing the hepatic release of ApoB and ApoE, whereas ABCA1 function and ApoA-I secretion are not influenced.

Neumeier, Markus [Department of Internal Medicine I, Regensburg University Medical Center, D-93042 Regensburg (Germany); Sigruener, Alexander [Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, D-93042 Regensburg (Germany); Eggenhofer, Elke [Department of Internal Medicine I, Regensburg University Medical Center, D-93042 Regensburg (Germany); Weigert, Johanna [Department of Internal Medicine I, Regensburg University Medical Center, D-93042 Regensburg (Germany); Weiss, Thomas S. [Center for Liver Cell Research, University of Regensburg, D-93042 Regensburg (Germany); Department of Surgery, University of Regensburg, D-93042 Regensburg (Germany); Schaeffler, Andreas [Department of Internal Medicine I, Regensburg University Medical Center, D-93042 Regensburg (Germany); Schlitt, Hans J. [Department of Surgery, University of Regensburg, D-93042 Regensburg (Germany); Aslanidis, Charalampos [Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, D-93042 Regensburg (Germany); Piso, Pompiliu [Department of Surgery, University of Regensburg, D-93042 Regensburg (Germany); Langmann, Thomas [Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, D-93042 Regensburg (Germany); Schmitz, Gerd [Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, D-93042 Regensburg (Germany); Schoelmerich, Juergen [Department of Internal Medicine I, Regensburg University Medical Center, D-93042 Regensburg (Germany); Buechler, Christa [Department of Internal Medicine I, Regensburg University Medical Center, D-93042 Regensburg (Germany)]. E-mail: christa.buechler@klinik.uni-regensburg.de

2007-01-12

14

Weight loss is more important than the diet type in improving adiponectin levels among overweight/obese adults.  

PubMed

Objective: The study objective was to compare the effect of a standard calorie- and fat-restricted diet (STD-D) and a calorie- and fat-restricted lacto-ovo-vegetarian diet (LOV-D) on total and high-molecular-weight (HMW) adiponectin levels after 6 months of behavioral intervention. Design: This study is an ancillary study to a randomized clinical trial. Subjects: Subjects included 143 overweight/obese adults (STD-D = 79; LOV-D = 64). Intervention: Both groups received the same standard behavioral intervention; the only difference was that LOV-D participants were instructed to eliminate meat, poultry, and fish from their diet. Measures: Weight, dietary intake with the 3-day food diary, and total and HMW adiponectin levels were measured. Results: Both groups significantly increased total (STD-D +7.2 ± 17.8%; LOV-D +9.4 ± 21.8%) and HMW adiponectin levels (STD-D +18.5 ± 32.9%; LOV-D +15.8 ± 34.5%; ps < 0.05) with no significant differences between the groups. We found significant associations between weight loss and increases in total (? (SE) = -.071(.27); p = 0.003) and HMW adiponectin (? (SE) = -1.37(.47); p = 0.001) levels independent of the diet type. Weight loss at the higher quartile was associated with improvements of adiponectin levels (p < 0.05). Conclusion: Weight loss was associated with increased total and HMW adiponectin levels regardless of the diet type. Enhancing weight loss may be a means to improve adiponectin levels. PMID:24024771

Acharya, Sushama D; Brooks, Maria M; Evans, Rhobert W; Linkov, Faina; Burke, Lora E

2013-08-01

15

Adiponectin Multimers in Normal Pregnancy  

PubMed Central

Objective Adiponectin is an anti-diabetic, anti-atherogenic, anti-inflammatory and angiogenic adipokine that circulates in oligomeric complexes including: low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms. The aim of this study was to determine whether there are changes in adiponectin multimers in pregnancy and as a function of maternal weight. Study design In this cross-sectional study, serum concentrations of total, HMW, MMW and LMW adiponectin were determined in women included in three groups: 1) normal pregnant women of normal body mass index (BMI) (n=466); 2) overweight/obese pregnant women (BMI ?25; n=257); and 3) non-pregnant women of normal weight (n=40). Blood samples were collected once from each pregnant woman between 11 and 42 weeks of gestation. Serum adiponectin multimers concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results 1) The median HMW adiponectin concentration and the median HMW/Total adiponectin ratio were significantly higher and the median LMW adiponectin concentration was significantly lower in pregnant than in non-pregnant women; 2) among pregnant women, the median serum concentration of total, HMW and MMW adiponectin was significantly higher in normal weight women than in overweight/obese patients; 3) HMW adiponectin was the most prevalent multimer in maternal serum regardless of gestational age or BMI status; 4) there were no significant differences in the median concentration of total, MMW, LMW adiponectin, and their relative distribution with advancing gestation. Conclusion Human pregnancy is characterized by quantitative and qualitative changes in adiponectin multimers, especially of the most active isoform, HMW adiponectin.

MAZAKI-TOVI, S.; ROMERO, R.; KUSANOVIC, J.P.; EREZ, O.; VAISBUCH, E.; GOTSCH, F.; MITTAL, P.; THAN, N. G.; NHAN-CHANG, C.L.; CHAIWORAPONGSA, T.; EDWIN, S.; CAMACHO, N.; GOMEZ, R.; NIEN, J.K.; HASSAN, S.S.

2009-01-01

16

High Molecular Weight (HMW) Dissolved Organic Matter (DOM) in Seawater: Chemical Structure, Sources and Cycling.  

National Technical Information Service (NTIS)

The goal of this thesis was to use high resolution analytical techniques coupled with molecular level analyses to chemically characterize high molecular weight (> 1 k Da (HMW)) dissolved organic matter (DOM) isolated from seawater in an attempt to provide...

L. I. Aluwihare

1999-01-01

17

Body Composition and Circulating High-Molecular-Weight Adiponectin and IGF-I in Infants Born Small for Gestational Age  

PubMed Central

Prenatal growth restraint, if followed by postnatal overweight, confers risk for adult disease including diabetes. The mechanisms whereby neonatal nutrition may modulate such risk are poorly understood. We studied the effects of nutrition (breast-feeding [BRF] vs. formula-feeding [FOF]) on weight partitioning and endocrine state (as judged by high-molecular-weight [HMW] adiponectin and IGF-I) of infants born small for gestational age (SGA). Body composition (by absorptiometry), HMW adiponectin, and IGF-I were assessed at birth and 4 months in BRF infants born appropriate for gestational age (AGA; n = 72) and SGA infants receiving BRF (n = 46) or FOF (n = 56), the latter being randomized to receive a standard (FOF1) or protein-rich formula (FOF2). Compared with AGA-BRF infants, the catchup growth of SGA infants was confined to lean mass, independently of nutrition. Compared with AGA-BRF infants, SGA-BRF infants had normal HMW adiponectin and IGF-I levels at 4 months, whereas SGA-FOF infants had elevated levels of HMW adiponectin (particularly SGA-FOF1) and IGF-I (particularly SGA-FOF2). In conclusion, neonatal nutrition seems to influence endocrinology more readily than body composition of SGA infants. Follow-up will disclose whether the endocrine abnormalities in SGA-FOF infants can serve as early markers of an unfavorable metabolic course and whether they may contribute to design early interventions that prevent subsequent disease, including diabetes.

de Zegher, Francis; Sebastiani, Giorgia; Diaz, Marta; Sanchez-Infantes, David; Lopez-Bermejo, Abel; Ibanez, Lourdes

2012-01-01

18

Distribution of Adiponectin Multimeric Forms In Chinese Women With Polycystic Ovary Syndrome and Their Relation To Insulin Resistance  

PubMed Central

Objective Adiponectin, an abundant adipokine with insulin sensitizing properties, exists different multimeric forms, including low molecular weight (LMW), medium molecular weight (MMW), and high molecular weight (HMW) species. Alterations in the distribution of adiponectin multimers and the relationship between adiponectin multimers and insulin resistance (IR) in women with the polycystic ovary syndrome (PCOS) remain unclear. To compare adiponectin multimerization status and estimate of insulin sensitivity in Chinese women with PCOS compared with age and body mass index (BMI)-matched controls. Methods Cross-sectional study involving 64 Chinese women with PCOS and 59 normal women. Circulating total adiponectin and its multimeric forms were determined by ELISA and insulin resistance was estimated using the homeostasis assessment insulin resistance index (HOMA-IR). Results After controlling for BMI status, levels of both total and HMW adiponectin were significantly lower in women with PCOS compared with normal women (P<0.05). Furthermore, HMW adiponectin provided a stronger contribution to models predicting insulin resistance than total adiponectin. Lastly, decreased HMW adiponectin was associated with increased HOMA-IR in both normal and PCOS women, and this association was independent of both overall adiposity and visceral adiposity. Conclusion Levels of both total and HMW adiponectin are decreased in Chinese women with PCOS compared with normal control women and the differences in HMW adiponectin persists after controlling for BMI. Furthermore, HMW adiponectin is a stronger predictor of insulin resistance in both women with PCOS and normal women than total adiponectin.

Tao, Tao; Wickham, Edmond P.; Fan, WuQiang; Yang, Jiejin; Liu, Wei

2013-01-01

19

Adiponectin Multimers and Metabolic Syndrome Traits: Relative Adiponectin Resistance in African Americans  

PubMed Central

African Americans (AAs) tend to have lower total adiponectin levels compared to European Americans (EA); however, it is not known whether race affects adiponectin multimer distribution and their relationships to metabolic traits. We measured total adiponectin, high molecular weight (HMW), low molecular weight (LMW) (i.e., hexamer), and trimer adiponectin in 132 normoglycemic premenopausal women (75 AAs, 57 EAs), together with measures of total and abdominal fat, plasma lipids, insulin sensitivity (Si), and genetic admixture estimates. We found that lower total adiponectin in AAs was explained by reduced LMW, and trimer forms because levels of HMW did not differ between races. In EAs, HMW was highly correlated with multiple metabolic syndrome traits. In contrast, the LMW and trimer forms were most highly correlated with metabolic traits in AAs, including abdominal adiposity, lipids, and Si. At similar levels of visceral adiposity, AAs exhibited significantly lower LMW adiponectin than EAs. Similarly, at comparable levels of HMW and LMW adiponectin, AAs were more insulin resistant than their EA counterparts. In conclusion, (i) serum adiponectin is lower in AAs predominantly as a result of reduced concentrations of LMW and trimers multimeric forms; (ii) LMW and trimer, not HMW, are most broadly correlated with metabolic traits in AAs. Thus, HMW adiponectin may exert less bioactivity in explaining the metabolic syndrome trait cluster in populations of predominant African genetic background.

Lara-Castro, Cristina; Doud, Erin C.; Tapia, Patrick C.; Munoz, Andres J.; Fernandez, Jose R.; Hunter, Gary R.; Gower, Barbara A.; Garvey, W. Timothy

2009-01-01

20

C-Reactive Protein, High-Molecular-Weight Adiponectin and Development of Metabolic Syndrome in the Japanese General Population: A Longitudinal Cohort Study  

PubMed Central

Aims To clarify predictive values of C-reactive protein (CRP) and high-molecular-weight (HMW) adiponectin for development of metabolic syndrome. Research Design and Methods We conducted a prospective cohort study of Japanese workers who had participated in an annual health checkup in 2007 and 2011. A total of 750 subjects (558 men and 192 women, age 46±8 years) who had not met the criteria of metabolic syndrome and whose CRP and HMW-adiponectin levels had been measured in 2007 were enrolled in this study. Associations between CRP, HMW-adiponectin and development of metabolic syndrome after 4 years were assessed by logistic regression analysis and their predictive values were compared by receiver operating characteristic analysis. Results Among 750 subjects, 61 (8.1%) developed metabolic syndrome defined by modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria and 53 (7.1%) developed metabolic syndrome defined by Japan Society for the Study of Obesity (JASSO) in 2011. Although CRP and HMW-adiponectin were both significantly correlated with development of metabolic syndrome, multivariate logistic regression analysis revealed that HMW-adiponectin but not CRP was associated with metabolic syndrome independently of BMI or waist circumference. Adding these biomarkers to BMI or waist circumference did not improve the predictive value for metabolic syndrome. Conclusion Our findings indicate that the traditional markers of adiposity such as BMI or waist circumference remain superior markers for predicting metabolic syndrome compared to CRP, HMW-adiponectin, or the combination of both among the Japanese population.

Saisho, Yoshifumi; Hirose, Hiroshi; Roberts, Rachel; Abe, Takayuki; Kawabe, Hiroshi; Itoh, Hiroshi

2013-01-01

21

Body composition and circulating high-molecular-weight adiponectin and IGF-I in infants born small for gestational age: breast- versus formula-feeding.  

PubMed

Prenatal growth restraint, if followed by postnatal overweight, confers risk for adult disease including diabetes. The mechanisms whereby neonatal nutrition may modulate such risk are poorly understood. We studied the effects of nutrition (breast-feeding [BRF] vs. formula-feeding [FOF]) on weight partitioning and endocrine state (as judged by high-molecular-weight [HMW] adiponectin and IGF-I) of infants born small for gestational age (SGA). Body composition (by absorptiometry), HMW adiponectin, and IGF-I were assessed at birth and 4 months in BRF infants born appropriate for gestational age (AGA; n = 72) and SGA infants receiving BRF (n = 46) or FOF (n = 56), the latter being randomized to receive a standard (FOF1) or protein-rich formula (FOF2). Compared with AGA-BRF infants, the catchup growth of SGA infants was confined to lean mass, independently of nutrition. Compared with AGA-BRF infants, SGA-BRF infants had normal HMW adiponectin and IGF-I levels at 4 months, whereas SGA-FOF infants had elevated levels of HMW adiponectin (particularly SGA-FOF1) and IGF-I (particularly SGA-FOF2). In conclusion, neonatal nutrition seems to influence endocrinology more readily than body composition of SGA infants. Follow-up will disclose whether the endocrine abnormalities in SGA-FOF infants can serve as early markers of an unfavorable metabolic course and whether they may contribute to design early interventions that prevent subsequent disease, including diabetes. PMID:22648385

de Zegher, Francis; Sebastiani, Giorgia; Diaz, Marta; Sánchez-Infantes, David; Lopez-Bermejo, Abel; Ibáñez, Lourdes

2012-05-29

22

Adiponectin multimers, body weight and markers of cardiovascular risk in adolescence: Northern Ireland Young Hearts Project.  

PubMed

Background:Research examining the relationship between adiponectin (AN) isoforms, body weight and cardiovascular (CV) risk factors is limited, particularly in younger populations.Objectives:To investigate the inter-relationships between AN isoforms and CV risk factors, and their dependence on body weight status, in adolescents.Design:Blood samples from 92 obese, 92 overweight and 92 normal weight age- and sex-matched adolescents were analysed for traditional cardiovascular disease (CVD) risk biomarkers and also total, high molecular weight (HMW), medium and low molecular weight (LMW) AN.Results:A significant inverse association was observed between total and HMW AN and waist-hip ratio (P=0.015, P=0.006, respectively), triglycerides (P=0.003, P=0.003, respectively) and systolic blood pressure (P=0.012, P=0.024, respectively) and a significant positive association with high-density lipoprotein (P<0.001, P<0.001, respectively) in multi-adjusted analyses. There was no evidence of a relationship between multimeric AN and high-sensitivity C-reactive protein. There was also little evidence of a relationship between LMW AN and CVD risk factors. There was a strong, body mass index (BMI)-independent, association between AN, CVD biomarkers and the hypertriglyceridemic waist phenotype.Conclusion:Prominent, BMI-independent associations between total and HMW AN, but not LMW AN, and CVD risk factors were already evident in this young population. This research in adolescents supports the contention that AN subfractions may have different biological actions. These associations in apparently healthy adolescents suggest an important role for AN and its subfractions in the pathogenesis of metabolic syndrome traits and indicate that the potential for total or HMW AN to act as early universal biomarkers of CV risk warrants further study. PMID:23318722

McCourt, H J; Hunter, S J; Cardwell, C R; Young, I S; Murray, L J; Boreham, C A; McEneny, J; Woodside, J V; McKinley, M C

2013-01-15

23

Regulation of high molecular weight-melanoma associated antigen (HMW-MAA) gene expression by promoter DNA methylation in human melanoma cells.  

PubMed

The human high molecular weight-melanoma associated antigen (HMW-MAA) is a membrane-bound chondroitin sulfate proteoglycan that is variably expressed in a high percentage of melanoma cell lines and tumors. Since the mechanism(s) regulating HMW-MAA expression has(ve) not been defined, in this study, we have examined whether promoter DNA methylation regulates the level of HMW-MAA expression. In melanoma cell lines, the level of HMW-MAA mRNA and protein expression is coordinately regulated, implicating a transcriptional control mechanism. Consistent with a role for regulation by DNA methylation, we have found that a dense CpG island flanks the human HMW-MAA gene transcriptional start site. Methylation-specific PCR and sodium bisulfite DNA sequencing analyses indicate that the HMW-MAA promoter is heavily methylated in melanoma cell lines, melanoma lesions and normal lymphocytes that do not express HMW-MAA; in contrast, the HMW-MAA promoter is not methylated in melanoma cell lines and tumors that express this antigen. In addition, HMW-MAA expression is markedly induced in HMW-MAA-negative melanoma cell lines by incubation with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. In summary, our results establish DNA methylation as a key regulator of HMW-MAA expression by human melanoma cells. This information represents a useful background to optimize immunotherapeutic strategies targeting HMW-MAA. PMID:16407841

Luo, W; Wang, X; Kageshita, T; Wakasugi, S; Karpf, A R; Ferrone, S

2006-05-11

24

Adherence to healthy eating patterns is associated with higher circulating total and high-molecular-weight adiponectin and lower resistin concentrations in women from the Nurses' Health Study1-3  

Microsoft Academic Search

Background: Adherence to a healthy dietary pattern, such as the Alternate Healthy Eating Index (AHEI), is associated with a lower risk of diabetes and atherosclerosis. Objective: We aimed to determine whether adherence to the AHEI is associated with higher plasma total and high-molecular-weight (HMW) adiponectin concentrations and lower concentrations of re- sistin, as well as biomarkers of inflammation, endothelial dysfunc-

Jessica L Fargnoli; Teresa T Fung; Deanna M Olenczuk; John P Chamberland; Frank B Hu; Christos S Mantzoros

25

Relationships of Total Adiponectin and Molecular Weight Fractions of Adiponectin with Free Testosterone in African Men and Premenopausal Women  

PubMed Central

Adiponectin, a protein secreted by adipose tissue, has anti-inflammatory, anti-thrombogenic and anti-diabetogenic properties. Lower plasma adiponectin levels are present in diabetes, obesity, and metabolic syndrome. Adiponectin levels are higher in women compared to men. The purpose of this study was to determine if there are relationships between total adiponectin, or the molecular weight fractions of adiponectin, with testosterone levels in African American men and pre-menopausal women. A sample (N=48) of men and premenopausal women were selected, based on high and low serum free testosterone level. All cases had data on blood pressure, metabolic risk factors, and sex hormone levels. Stored plasma samples were assayed for total adiponectin (ELISA). Molecular weight fractions of adiponectin were separated by gel-electrophoresis and quantified by western blot. Data analysis compared adiponectin (total and fractions) levels with androgen status in both genders. Among men with high testosterone, all fractions of adiponectin were significantly lower than men with low testosterone (P<0.05). In women with high testosterone, total adiponectin (P=0.02) and all fractions of molecular weight adiponectin (P<0.05) were lower compared to women with low testosterone. Plasma adiponectin levels are lower in both men and pre-menopausal women with relatively higher testosterone levels.

Cui, Jie; Wu, XiangDong; Andrel, Jocelyn; Falkner, Bonita

2010-01-01

26

Induction of chemokine expression by adiponectin in vitro is isoform dependent.  

PubMed

Adiponectin is reported to have both proinflammatory and anti-inflammatory effects. Because adiponectin circulates in isoforms of various sizes and some responses to adiponectin are isoform dependent, it was postulated that the proinflammatory effects of adiponectin may be isoform specific. To test this theory, peripheral blood mononuclear cells (PBMCs), microvascular endothelial cells (MVECs), and human glomerular mesangial cells (HMCs) were treated with high-molecular-weight (HMW) or low-molecular-weight (LMW) recombinant human adiponectin, and chemokine production was measured. The PBMCs were isolated from healthy volunteers by density gradient centrifugation of ethylenediaminetetraacetic acid (EDTA) anticoagulated whole blood through endotoxin-free Ficoll (General Electric Healthcare Bio-Sciences, Uppsala, Sweden). The MVECs were of dermal origin, and the HMCs were isolated from kidneys not suitable for transplantation. Overnight (16 h) incubation with HMW adiponectin (0.01-1 microg/mL for PBMCs; 5-20 microg/mL for MVECs and HMCs) induced a dose-dependent increase in production of monocyte chemoattractant protein-1 and interleukin-8 by PBMCs and MVECs, but it had no effect on HMC chemokine production (n=3-5). LMW adiponectin at the same concentrations did not induce chemokine production in any of the cell types tested, and it did not block cytokine-induced chemokine production by PBMCs or MVECs (n=3-5). These in vitro data suggested that the HMW adiponectin isoform is proinflammatory. To examine the possibility of a relationship between HMW adiponectin and inflammation in vivo, the urine of patients with systemic lupus erythematosus (SLE) and kidney involvement, which was shown previously to contain immunoreactive adiponectin, was examined for the presence of specific adiponectin isoforms by nondenaturing gel electrophoresis. HMW adiponectin was found in the urine of patients with active lupus nephritis. Therefore, HMW adiponectin may contribute to the renal inflammation of SLE. PMID:19524870

Song, Huijuan; Chan, James; Rovin, Brad H

2009-05-09

27

Plasma Adiponectin Complexes Have Distinct Biochemical Characteristics  

PubMed Central

Adipocytes release the secretory protein adiponectin in a number of different higher-order complexes. Once synthesized and assembled in the secretory pathway of the adipocyte, these complexes circulate as biochemically distinct and stable entities with little evidence of interchange between the different forms that include a high-molecular-weight (HMW) species, a hexamer (low-molecular-weight form), and a trimeric form of the complexes. Here, we validate a high-resolution gel filtration method that reproducibly separates the three complexes in recombinant adiponectin and adiponectin from human and murine samples. We demonstrate that the HMW form is prominently reduced in male vs. female subjects and in obese, insulin-resistant vs. lean, insulin-sensitive individuals. A direct comparison of human and mouse adiponectin demonstrates that the trimer is generally more abundant in human serum. Furthermore, when the production of adiponectin is reduced, either by obesity or in mice carrying only a single functional allele of the adiponectin locus, then the amount of the HMW form is selectively reduced in circulation. The complex distribution of adiponectin can be regulated in several ways. Both mouse and human HMW adiponectin are very stable under basic conditions but are exquisitely labile under acidic conditions below pH 7. Murine and human adiponectin HMW forms also display differential susceptibility to the presence of calcium in the buffer. A mutant form of adiponectin unable to bind calcium is less susceptible to changes in calcium concentrations. However, the lack of calcium binding results in a destabilization of the structure. Disulfide bond formation (at position C39) is also important for complex formation. A mutant form of adiponectin lacking C39 prominently forms HMW and trimer but not the low-molecular-weight form. Injection of adiponectin with a fluorescent label reveals that over time, the various complexes do not interconvert in vivo. The stability of adiponectin complexes highlights that the production and secretion of these forms from fat cells has a major influence on the circulating levels of each complex.

Schraw, Todd; Wang, Zhao V.; Halberg, Nils; Hawkins, Meredith; Scherer, Philipp E.

2008-01-01

28

Adipose tissue depot and cell size dependency of adiponectin synthesis and secretion in human obesity  

PubMed Central

Adiponectin is an insulin sensitizing fat cell (FC) hormone whose levels are related to adipose tissue (AT) mass and depot distribution. We hypothesized that the nature of AT expansion (hypertrophy vs. hyperplasia) contributes to obesity-related reductions in serum adiponectin and that this effect is influenced by the regional distribution of AT to subcutaneous (S) and visceral (V) depots. Thirteen obese subjects provided paired AT biopsies. Serum total and high molecular weight (HMW) adiponectin levels were determined by ELISA. Secretion was quantified following 24-h explant culture. FC size, number, % large, and % small FC were determined by microscopic analysis. Secretion of total adiponectin was highest by SAT (P = 0.008) and correlated more strongly with serum adiponectin (total: P = 0.015, r = 0.77; HMW: P = 0.005, r = 0.83) than did secretion by VAT (P = 0.05, r = 0.66 for both). FC size was greatest in SAT and correlated negatively with both serum (total: P = 0.01, r = ?0.74; HMW: P = 0.03, r = ?0.69) and secreted (total: P = 0.05, r = ?0.72; HMW: P = 0.02, r = ?0.87) adiponectin. The % small FC in SAT correlated positively with both serum (total: P = 0.006, r = 0.87; HMW: P = 0.009, r = 0.79) and secreted (total: P = 0.03, r = 0.75; HMW: P = 0.01, r = 0.92) adiponectin. VAT FC size correlated negatively with serum HMW adiponectin (P = 0.01, r = ?0.76) but not with any measure of secretion. VAT had the greatest % small FC, which related positively to serum HMW (P = 0.004, r = 0.81) and to secreted total adiponectin (P = 0.02, r = 0.78). These studies indicate that differences in fat cell size and depot distribution of AT expansion are important influences on adiponectin in obesity.

Meyer, Lauren K; Ciaraldi, Theodore P; Henry, Robert R; Wittgrove, Alan C; Phillips, Susan A

2013-01-01

29

Adiponectin in mice with altered growth hormone action: links to insulin sensitivity and longevity?  

PubMed Central

Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high molecular weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered growth hormone (GH) signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH versus IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying the effects of GH on adiponectin are depot-specific. Interestingly rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity.

Lubbers, Ellen R.; List, Edward O.; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D.; Kineman, Rhonda D.; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J.; Berryman, Darlene E.

2013-01-01

30

Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?  

PubMed

Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high-molecular-weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered GH signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH vs IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying that the effects of GH on adiponectin are depot specific. Interestingly, rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity. PMID:23261955

Lubbers, Ellen R; List, Edward O; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D; Kineman, Rhonda D; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J; Berryman, Darlene E

2013-02-25

31

Association of Low Plasma Adiponectin With Early Diastolic Dysfunction  

PubMed Central

Diastolic dysfunction (DD) with preserved left ventricular (LV) ejection fraction (EF) has been linked to obesity. Adiponectin is a cytokine related to obesity and obesity-linked cardiovascular complications. The authors aimed to determine the independent association of DD with adiponectin. Fifty patients with impaired relaxation DD and a normal EF and age-matched normal controls were recruited. Plasma levels of total and high molecular weight (HMW) adiponectin were measured. Mid and low molecular weight (MMW+LMW) fractions of adiponectin were calculated by subtracting HMW fraction from total adiponectin. The DD group had significantly lower total (median, 4.4 vs 12.7 ?g/mL; P=.001), HMW fraction (median, 1.3 vs 3.4 ?g/mL; P=.02), and MMW+LMW fraction of adiponectin (median, 3.8 vs 7.2 ?g/mL; P=.01). Body mass index (BMI) negatively correlated with total (r:?0.46, P=.003), HMW (r:?0.32, P=.038), and MMW+LMW (r:?0.40, P=.006) fractions of adiponectin. DD had an independent association with both BMI (P<.05) and total adiponectin (P<.001) in linear regression model using sex, BMI, blood pressure, and total adiponectin as covariates. DD was associated with BMI (P=.02), HMW fraction (P=.03), and MMW+LMW fraction (P=.004) in similar linear regression analyses. Adiponectin deficiency may be one explanation for the adiposity-related cardiac oxidation known to be involved in the pathogenesis of DD.

Negi, Smita I.; Jeong, Euy-Myoung; Shukrullah, Irfan; Raicu, Mihai; Dudley, Samuel C.

2013-01-01

32

Maternal Serum Adiponectin Multimers In Gestational Diabetes  

PubMed Central

Objective Adiponectin, an adipokine with profound insulin-sensitizing effect, consists of heterogeneous species of multimers. These oligomeric complexes circulate as low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms and can exert differential biological effects. The aims of this study were to determine whether there is a change in circulating adiponectin multimers in the presence of gestational diabetes mellitus (GDM), overweight/obesity or with a treatment with sulfonylurea or insulin in patients with GDM. Study design This cross-sectional study included women with: 1) normal pregnancy (n=149); and 2) patients with GDM (n=72). Thirty three patients with GDM were managed with diet alone. Among the others 39 diabetic patients, 17 were treated with Glyburide and 22 with insulin. The study population was further stratified by first trimester BMI (normal weight <25 kg/m2 vs. overweight/obese ?25 kg/m2). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Results 1) The median maternal serum of total, HMW, MMW and LMW were lower in patients with GDM than in those with normal pregnancies (p<0.001 for all comparisons); 2) patients with GDM had a lower HMW/Total adiponectin ratio and a higher MMW/Total and LMW/Total adiponectin ratio than those with a normal pregnancy (p<0.001 for all comparisons); and 3) among GDM patients, there were no differences in the concentrations and relative distribution of adiponectin multimers between those who were managed with diet, and those who were treated with pharmacological agents. Conclusion 1) GDM is characterized by a distinctive pattern of concentrations and relative distribution of adiponectin multimers akin to Type-2 diabetes mellitus; 2) dysregulation of adiponectin multimeres can provide a mechanistic basis for the association between adiposity and GDM.

Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Gotsch, Francesca; Dong, Zhong; Yoon, Bo Hyun; Hassan, Sonia S.; Kusanovic, Juan Pedro

2013-01-01

33

DNA restriction-fragment variation in the gene family encoding high molecular weight (HMW) glutenin subunits of wheat  

Microsoft Academic Search

Restriction enzyme digests of DNA from nullisomic-tetrasomic and intervarietal chromosome substitution lines of wheat were probed with a high molecular weight (HMW) glutenin cDNA. Three restriction endonucleases were used to investigate restriction-fragment differences among five wheat varieties. The results suggest that the hybridizing fragments contain single gene copies and permit the identification of the subunit encoded by each gene. Restriction-fragment

N. P. Harberd; D. Bartels; R. D. Thompson

1986-01-01

34

Adiponectin Is Inversely Associated With Intramyocellular and Intrahepatic Lipids in Obese Premenopausal Women  

Microsoft Academic Search

Adiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. Adiponectin is found in several isoforms and the high-molecular weight (HMW) form has been linked most strongly to the insulin-sensitizing effects. Fat content in skeletal muscle (intramyocellular

Miriam A. Bredella; Martin Torriani; Reza H. Ghomi; Bijoy J. Thomas; Danielle J. Brick; Anu V. Gerweck; Lindsey M. Harrington; Karen K. Miller

2011-01-01

35

Human high molecular weight-melanoma-associated antigen (HMW-MAA): a melanoma cell surface chondroitin sulfate proteoglycan (MSCP) with biological and clinical significance.  

PubMed

The lack of effective conventional therapies for the treatment of advanced stage melanoma has stimulated interest in the application of novel strategies for the treatment of patients with malignant melanoma. Because of its expression in a large percentage of melanoma lesions and its restricted distribution in normal tissues, the high molecular weight-melanoma-associated antigen (HMW-MAA), also known as the melanoma chondroitin sulfate proteoglycan (MCSP), has been used to implement immunotherapy of melanoma. The potential clinical relevance of HMW-MAA/MCSP has stimulated investigations to characterize its structural properties and biological function in melanoma cells. Over the last 10 years, the field of HMW-MAA/MCSP research has seen tremendous growth. Specifically, a significant amount of information has been accumulated regarding (1) the structural characteristics of the HMW-MAA/MCSP, (2) its role in the biology of melanoma cells, and (3) the potential molecular mechanisms underlying the association between HMW-MAA/MCSP-specific immunity and survival prolongation in melanoma patients immunized with HMW-MAA/MCSP mimics. In this review, we summarize the characteristics of the HMW-MAA/MCSP in terms of its structure, antigenic profile, tissue distribution, and similarities with its counterparts in other animal species. Additionally, we discuss the role the HMW-MAA/MCSP plays in melanoma cell biology with emphasis on the recently identified signal transduction pathways triggered by the HMW-MAA/MCSP. Finally, we discuss the potential molecular mechanisms underlying the beneficial effect of anti-HMW-MAA/MCSP antibodies on the clinical course of the disease in patients with melanoma. PMID:15588226

Campoli, Michael R; Chang, Chien-Chung; Kageshita, Toshiro; Wang, Xinhui; McCarthy, James B; Ferrone, Soldano

2004-01-01

36

Adiponectin acts in the brain to decrease body weight  

Microsoft Academic Search

Adiponectin (ADP) is an adipocyte hormone involved in glucose and lipid metabolism. We detected a rise in ADP in cerebrospinal fluid after intravenous (i.v.) injection, consistent with brain transport. In contrast to leptin, intracerebroventricular (i.c.v.) administration of ADP decreased body weight mainly by stimulating energy expenditure. Full-length ADP, mutant ADP with Cys39 replaced with serine, and globular ADP were effective,

Yong Qi; Nobuhiko Takahashi; Stanley M Hileman; Hiralben R Patel; Anders H Berg; Utpal B Pajvani; Philipp E Scherer; Rexford S Ahima

2004-01-01

37

Atrial Natriuretic Peptide and Adiponectin Interactions in Man  

PubMed Central

Reduced circulating natriuretic peptide concentrations are independently associated with insulin resistance and type 2 diabetes, while increased natriuretic peptide levels appear to be protective. Observations in vitro and in heart failure patients suggest that atrial natriuretic peptide (ANP) promotes adiponectin release, an adipokine with insulin sensitizing properties. We tested the hypothesis that ANP acutely raises adiponectin levels in 12 healthy men. We infused ANP intravenously over 135 minutes while collecting venous blood and adipose tissue microdialysates at baseline and at the end of ANP-infusion. We obtained blood samples at identical time-points without ANP infusion in 7 age and BMI matched men. With infusion, venous ANP concentrations increased ?10 fold. Systemic and adipose tissue glycerol concentrations increased 70% and 80%, respectively (P<0.01). ANP infusion increased total adiponectin 14±5% and high molecular-weight (HMW)-adiponectin 13±5% (P<0.05). Adiponectin did not change in the control group (P<0.05 vs. infusion). ANP-induced changes in HMW adiponectin and adipose tissue lipolysis were directly correlated with each other, possibly suggesting a common mechanism. Our data show that ANP acutely increases systemic total and HMW-adiponectin concentrations in healthy subjects. Our study could have implications for the physiological regulation of adiponectin and for disease states associated with altered natriuretic peptide availability.

Birkenfeld, Andreas L.; Boschmann, Michael; Engeli, Stefan; Moro, Cedric; Arafat, Ayman M.; Luft, Friedrich C.; Jordan, Jens

2012-01-01

38

Adiponectin Is Inversely Associated With Intramyocellular and Intrahepatic Lipids in Obese Premenopausal Women  

PubMed Central

Adiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. Adiponectin is found in several isoforms and the high-molecular weight (HMW) form has been linked most strongly to the insulin-sensitizing effects. Fat content in skeletal muscle (intramyocellular lipids, IMCL) and liver (intrahepatic lipids, IHL) can be quantified noninvasively using proton magnetic resonance spectroscopy (1H-MRS). The purpose of our study was to assess the relationship between HMW adiponectin and measures of glucose homeostasis, IMCL and IHL, and to determine predictors of adiponectin levels. We studied 66 premenopausal women (mean BMI 31.0 ± 6.6 kg/m2) who underwent 1H-MRS of calf muscles and liver for IMCL and IHL, computed tomography (CT) of the abdomen for abdominal fat depots, dual-energy X-ray absorptiometry (DXA) for fat and lean mass assessments, HMW and total adiponectin, fasting lipid profile and an oral glucose tolerance test (homeostasis model assessment of insulin resistance (HOMAIR), glucose and insulin area under the curve). There were strong inverse associations between HMW adiponectin and measures of insulin resistance, IMCL and IHL, independent of visceral adipose tissue (VAT) and total body fat. IHL was the strongest predictor of adiponectin and adiponectin was a predictor of HOMAIR. Our study showed that in premenopausal obese women HMW adiponectin is inversely associated with IMCL and IHL content. This suggests that adiponectin exerts positive effects on insulin sensitivity in obesity by decreasing intracellular triglyceride content in skeletal muscle and liver; it is also possible that our results reflect effects of insulin on adiponectin.

Bredella, Miriam A.; Torriani, Martin; Ghomi, Reza H.; Thomas, Bijoy J.; Brick, Danielle J.; Gerweck, Anu V.; Harrington, Lindsey M.; Miller, Karen K.

2013-01-01

39

Adiponectin is inversely associated with intramyocellular and intrahepatic lipids in obese premenopausal women.  

PubMed

Adiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. Adiponectin is found in several isoforms and the high-molecular weight (HMW) form has been linked most strongly to the insulin-sensitizing effects. Fat content in skeletal muscle (intramyocellular lipids, IMCL) and liver (intrahepatic lipids, IHL) can be quantified noninvasively using proton magnetic resonance spectroscopy ((1)H-MRS). The purpose of our study was to assess the relationship between HMW adiponectin and measures of glucose homeostasis, IMCL and IHL, and to determine predictors of adiponectin levels. We studied 66 premenopausal women (mean BMI 31.0 ± 6.6 kg/m(2)) who underwent (1)H-MRS of calf muscles and liver for IMCL and IHL, computed tomography (CT) of the abdomen for abdominal fat depots, dual-energy X-ray absorptiometry (DXA) for fat and lean mass assessments, HMW and total adiponectin, fasting lipid profile and an oral glucose tolerance test (homeostasis model assessment of insulin resistance (HOMA(IR)), glucose and insulin area under the curve). There were strong inverse associations between HMW adiponectin and measures of insulin resistance, IMCL and IHL, independent of visceral adipose tissue (VAT) and total body fat. IHL was the strongest predictor of adiponectin and adiponectin was a predictor of HOMA(IR). Our study showed that in premenopausal obese women HMW adiponectin is inversely associated with IMCL and IHL content. This suggests that adiponectin exerts positive effects on insulin sensitivity in obesity by decreasing intracellular triglyceride content in skeletal muscle and liver; it is also possible that our results reflect effects of insulin on adiponectin. PMID:21151017

Bredella, Miriam A; Torriani, Martin; Ghomi, Reza H; Thomas, Bijoy J; Brick, Danielle J; Gerweck, Anu V; Harrington, Lindsey M; Miller, Karen K

2010-12-09

40

Specificity of Mimotope-Induced Anti-High Molecular Weight-Melanoma Associated Antigen (HMW-MAA) Antibodies Does Not Ensure Biological Activity  

PubMed Central

Vaccines based on peptide mimics (mimotopes) of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA) that elicited HMW-MAA-specific antibodies (Abs) with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polymimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs) VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH), both HMW-MAA mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate mimotopes of the corresponding epitopes.

Hofstetter, Gerlinde; Balazs, Nina; Smole, Ursula; Ferrone, Soldano; Scheiner, Otto; Breiteneder, Heimo; Pehamberger, Hubert; Wagner, Stefan

2011-01-01

41

Specificity of mimotope-induced anti-high molecular weight-melanoma associated antigen (HMW-MAA) antibodies does not ensure biological activity.  

PubMed

Vaccines based on peptide mimics (mimotopes) of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA) that elicited HMW-MAA-specific antibodies (Abs) with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polymimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs) VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH), both HMW-MAA mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate mimotopes of the corresponding epitopes. PMID:21573118

Latzka, Julia; Gaier, Sonja; Hofstetter, Gerlinde; Balazs, Nina; Smole, Ursula; Ferrone, Soldano; Scheiner, Otto; Breiteneder, Heimo; Pehamberger, Hubert; Wagner, Stefan

2011-05-06

42

CRP and Adiponectin and Its Oligomers in the Metabolic Syndrome  

PubMed Central

The metabolic syndrome (MetS) confers an increased risk for diabetes and cardiovascular disease. Although high-sensitive C-reactive protein (hsCRP) concentrations are higher and adiponectin concentrations lower in MetS, there is no reliable biochemical measure that can capture its various features. We evaluated whether hsCRP, adiponectin, or the ratio of adiponectin or its oligomers, especially the high-molecular-weight (HMW) oligomer, to hsCRP predict MetS in 123 subjects with MetS compared with that in 91 healthy control subjects. MetS subjects had significantly higher hsCRP levels and lower total adiponectin and oligomer levels relative to control subjects (P < .0001). The HMW/total adiponectin and adiponectin/CRP ratios were significantly lower in MetS subjects than control subjects (P < .005). The odds ratio (OR) of MetS using the 75th percentile cutoff for CRP was 3.8 (95% confidence interval [CI], 2.1–6.8) and equivalent to low total adiponectin (OR, 2.5; 95% CI, 1.3–4.5), its oligomers, or the adiponectin/hsCRP ratio (OR, 2.6; 95% CI, 1.5, 4.8). Thus, measurements of CRP, adiponectin, or its oligomers provide robust biomarkers for predicting MetS.

Devaraj, Sridevi; Swarbrick, Michael M.; Singh, Uma; Adams-Huet, Beverley; Havel, Peter J.; Jialal, Ishwarlal

2009-01-01

43

Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women  

Microsoft Academic Search

Background: Adiponectin, a novel adipocyte-derived collagen-like protein, is the gene product of the adipose most-abundant gene transcript 1 (apM1), which has been considered to have anti-inflamma- tory and anti-atherogenic effects. Objective: To characterize the relationship between adiponectin and leptin, the ob gene product, in normal-weight and obese women. Design and methods: In this cross-sectional study, we measured fasting plasma adiponectin

Miyao Matsubara; Shoji Maruoka; Shinji Katayose

2002-01-01

44

T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30\\/adiponectin  

Microsoft Academic Search

Acrp30\\/adiponectin is reduced in the serum of obese and diabetic individuals, and the genetic locus of adiponectin is linked to the metabolic syndrome. Recombinant adiponectin, administered to diet-induced obese mice, induced weight loss and improved insulin sensitivity. In muscle and liver, adiponectin stimulates AMP-activated protein kinase activation and fatty acid oxidation. To expression-clone molecules capable of binding adiponectin, we transduced

Christopher Hug; Jin Wang; Naina Shehzeen Ahmad; Jonathan S. Bogan; Tsu-Shuen Tsao; Harvey F. Lodish

2004-01-01

45

Cilnidipine regulates glucose metabolism and levels of high-molecular adiponectin in diet-induced obese mice.  

PubMed

The aim of the present study is to examine the effects of the antihypertensive drug cilnidipine on glucose metabolism and adipocytokines, including adiponectin, in diet-induced obese (DIO) mice. The effects of cilnidipine on insulin sensitivity and the levels of adiponectin in DIO mice were examined after the mice had been treated with cilnidipine dissolved in water at a dose of 0.2?g?l(-1) for 14 days. As expected, treatment with cilnidipine decreased the systolic and diastolic blood pressures in DIO mice, compared with control mice (P<0.05 for each parameter). Cilnidipine treatment improved glucose and insulin sensitivity in DIO mice. In addition, cilnidipine treatment dramatically increased the level of adiponectin in white adipose tissue (P<0.05) and the circulating levels of total and high-molecular weight (HMW) adiponectin in DIO mice (P<0.01 for each parameter). Furthermore, the secretion of HMW adiponectin and the ratio of HMW adiponectin/total adiponectin were both increased after cilnidipine treatment. Finally, the secretion of adiponectin from adipocytes was increased after cilnidipine treatment. Taken together, these results indicate that cilnidipine improves insulin tolerance and adiponectin levels, especially high-molecular type adiponectin, in DIO mice. PMID:23051658

Ueno, Daisuke; Masaki, Takayuki; Gotoh, Koto; Chiba, Seiichi; Kakuma, Tetsuya; Yoshimatsu, Hironobu

2012-10-11

46

Association of plasma adiponectin levels with cellular hydration state measured using bioelectrical impedance analysis in patients with COPD  

PubMed Central

Background It is widely recognized that chronic obstructive pulmonary disease (COPD) includes a variety of extra pulmonary complications and comorbidities. Recently, adiponectin was shown to regulate cellular metabolism in humans. Cellular hydration state is affected by a variety of hormonal factors and regulates cellular metabolic state. Therefore, this study was designed to determine whether adiponectin is a possible factor involved in cellular hydration state in COPD. Methods Thirty patients with COPD and 41 age-matched controls participated in the study. Plasma levels of total and high molecular weight (HMW) adiponectin were measured and anthropometry and pulmonary function tests were conducted. Intracellular water (ICW), extracellular water (ECW), and ECW/ICW ratio, which are parameters of cellular hydration state, were measured using bioelectrical impedance analysis. Results Higher levels of total and HMW adiponectin in plasma were found in patients with COPD compared with levels in controls. A significant inverse correlation was observed between body mass index and plasma levels of total and HMW adiponectin in the control group. However, this significant correlation was not observed in patients with COPD. The plasma levels of total and HMW adiponectin were also not significantly correlated with any pulmonary function parameters in patients with COPD. Regarding the state of cellular hydration, the plasma levels of total adiponectin were inversely correlated with the ECW/ICW ratio and positively with ICW values in patients with COPD. Moreover, closer correlations were found between these parameters and plasma HMW adiponectin levels. Conclusion The results of the present study suggest a novel association of the plasma adiponectin with cellular hydration state in patients with COPD. Accordingly, lower adiponectin levels may result in cellular shrinkage, leading to metabolic malfunction at a cellular level. Thus, our findings provide new insights regarding the preventive roles of adiponectin in the progression of comorbidities in COPD.

Yoshikawa, Takahiro; Kanazawa, Hiroshi

2012-01-01

47

Cross-reactivity of mimotopes with a monoclonal antibody against the high molecular weight melanoma-associated antigen (HMW-MAA) does not predict cross-reactive immunogenicity.  

PubMed

The high molecular weight melanoma-associated antigen (HMW-MAA) is highly expressed in advanced primary and metastatic melanoma. An epitope of the core protein of HMW-MAA is recognized by the murine monoclonal antibody (mAb) 225.28S. In this study, we aimed to characterize peptides that antigenically mimicked this epitope and to determine their efficacy as components of an HMW-MAA-based anti-melanoma vaccine. Therefore, we screened a constrained 10 mer phage display peptide library against mAb 225.28S. Selected phage-displayed peptides were then tested for their specificity for the antibody's antigen-binding site. DNA sequences coding for specific peptide ligands were determined. Binding of mAb 225.28S to HMW-MAA was inhibited in a dose-dependent manner by phage-displayed peptides from 51 to 83% and by synthetic peptides from 38 to 87%. Subsequently, the immunogenicity of the five mimotopes with the highest inhibition capacity was examined in rabbits. Immunizations with synthetic mimotopes conjugated to tetanus toxoid resulted in peptide-specific antibodies, but none of the highly antigenic mimotopes induced HMW-MAA cross-reactive antibodies. This report describes an example of disparity between antigenicity and cross-reactive immunogenicity, complicating the selection of potential vaccine candidates. PMID:15846144

Hafner, Christine; Wagner, Stefan; Allwardt, Dorothee; Riemer, Angelika B; Scheiner, Otto; Pehamberger, Hubert; Breiteneder, Heimo

2005-04-01

48

Disulfide-Dependent Self-Assembly of Adiponectin Octadecamers from Trimers and Presence of Stable Octadecameric Adiponectin Lacking Disulfide Bonds In Vitro†  

PubMed Central

Adiponectin is a circulating insulin-sensitizing hormone that homo-oligomerizes into trimers, hexamers, and higher molecular weight (HMW) species. Low levels of circulating HMW adiponectin appear to increase the risk for insulin resistance. Currently, assembly of adiponectin oligomers, and consequently mechanisms responsible for decreased HMW adiponectin in insulin resistance, are not well understood. In the work reported here, we analyzed the re-assembly of the most abundant HMW adiponectin species, the octadecamer, following its collapse to smaller oligomers in vitro. Purified bovine serum adiponectin octadecamer was treated with reducing agents at pH 5 to obtain trimers. These reduced trimers partially and spontaneously reassembled into octadecamers upon oxidative formation of disulfide bonds. Disulfide bonds appear to occupy a greater role in the process of oligomerization than in the structural stabilization of mature octadecamer. Stable octadecamers lacking virtually all disulfide bonds could be observed in abundance using native gel electrophoresis, dynamic light scattering, and collision-induced dissociation nano-electrospray ionization mass spectrometry. These findings indicate that while disulfide bonds help to maintain the mature octadecameric adiponectin structure, their more important function is to stabilize intermediates during the assembly of octadecamer. Adiponectin oligomerization must proceed through intermediates that are at least partially reduced. Accordingly, fully oxidized adiponectin hexamers failed to reassemble into octadecamers at a rate comparable to that of reduced trimers. As the findings from the present study are based on in vitro experiments, their in vivo relevance remains unclear. Nevertheless, they describe a redox environment-dependent model of adiponectin oligomerization that can be tested using cell-based approaches.

Briggs, David B.; Jones, Christopher M.; Mashalidis, Ellene H.; Nunez, Martha; Hausrath, Andrew C.; Wysocki, Vicki H.; Tsao, Tsu-Shuen

2009-01-01

49

Ratiometric Measurements of Adiponectin by Mass Spectrometry in Bottlenose Dolphins (Tursiops truncatus) with Iron Overload Reveal an Association with Insulin Resistance and Glucagon.  

PubMed

High molecular weight (HMW) adiponectin levels are reduced in humans with type 2 diabetes and insulin resistance. Similar to humans with insulin resistance, managed bottlenose dolphins (Tursiops truncatus) diagnosed with hemochromatosis (iron overload) have higher levels of 2?h post-prandial plasma insulin than healthy controls. A parallel reaction monitoring assay for dolphin serum adiponectin was developed based on tryptic peptides identified by mass spectrometry. Using identified post-translational modifications, a differential measurement was constructed. Total and unmodified adiponectin levels were measured in sera from dolphins with (n?=?4) and without (n?=?5) iron overload. This measurement yielded total adiponectin levels as well as site specific percent unmodified adiponectin that may inversely correlate with HMW adiponectin. Differences in insulin levels between iron overload cases and controls were observed 2?h post-prandial, but not during the fasting state. Thus, post-prandial as well as fasting serum adiponectin levels were measured to determine whether adiponectin and insulin would follow similar patterns. There was no difference in total adiponectin or percent unmodified adiponectin from case or control fasting animals. There was no difference in post-prandial total adiponectin levels between case and control dolphins (mean?±?SD) at 763?±?298 and 727?±?291?pmol/ml, respectively (p?=?0.91); however, percent unmodified adiponectin was significantly higher in post-prandial cases compared to controls (30.0?±?6.3 versus 17.0?±?6.6%, respectively; p?=?0.016). Interestingly, both total and percent unmodified adiponectin were correlated with glucagon levels in controls (r?=?0.999, p? adiponectin levels were not significantly different, the elevated percent unmodified adiponectin follows a trend similar to HMW adiponectin reported for humans with metabolic disorders. PMID:24065958

Neely, Benjamin A; Carlin, Kevin P; Arthur, John M; McFee, Wayne E; Janech, Michael G

2013-09-20

50

Ratiometric Measurements of Adiponectin by Mass Spectrometry in Bottlenose Dolphins (Tursiops truncatus) with Iron Overload Reveal an Association with Insulin Resistance and Glucagon  

PubMed Central

High molecular weight (HMW) adiponectin levels are reduced in humans with type 2 diabetes and insulin resistance. Similar to humans with insulin resistance, managed bottlenose dolphins (Tursiops truncatus) diagnosed with hemochromatosis (iron overload) have higher levels of 2?h post-prandial plasma insulin than healthy controls. A parallel reaction monitoring assay for dolphin serum adiponectin was developed based on tryptic peptides identified by mass spectrometry. Using identified post-translational modifications, a differential measurement was constructed. Total and unmodified adiponectin levels were measured in sera from dolphins with (n?=?4) and without (n?=?5) iron overload. This measurement yielded total adiponectin levels as well as site specific percent unmodified adiponectin that may inversely correlate with HMW adiponectin. Differences in insulin levels between iron overload cases and controls were observed 2?h post-prandial, but not during the fasting state. Thus, post-prandial as well as fasting serum adiponectin levels were measured to determine whether adiponectin and insulin would follow similar patterns. There was no difference in total adiponectin or percent unmodified adiponectin from case or control fasting animals. There was no difference in post-prandial total adiponectin levels between case and control dolphins (mean?±?SD) at 763?±?298 and 727?±?291?pmol/ml, respectively (p?=?0.91); however, percent unmodified adiponectin was significantly higher in post-prandial cases compared to controls (30.0?±?6.3 versus 17.0?±?6.6%, respectively; p?=?0.016). Interestingly, both total and percent unmodified adiponectin were correlated with glucagon levels in controls (r?=?0.999, p? adiponectin levels were not significantly different, the elevated percent unmodified adiponectin follows a trend similar to HMW adiponectin reported for humans with metabolic disorders.

Neely, Benjamin A.; Carlin, Kevin P.; Arthur, John M.; McFee, Wayne E.; Janech, Michael G.

2013-01-01

51

Cu(II) complexation of high molecular weight (HMW) fluorescent substances in root exudates from a wetland halophyte (Salicornia europaea L.).  

PubMed

High molecular weight (HMW) fractions are important components in root exudates. However, there is little available information concerning complexation of Cu(II) to the HMW fractions in root exudates. In the present study, complexation of root exudates from Salicornia europaea L. with Cu(II) was investigated using excitation emission matrix (EEM) fluorescence spectroscopy. Two protein-like fluorescence peaks were identified in the EEM spectra of root exudates. Fluorescence of both peaks was clearly quenched by Cu(II). The increase of conditional stability constant with increasing temperature indicates that the fluorescence quenching of the protein-like fluorescence by Cu(II) may be controlled by a dynamic process. The values of conditional stability constants (logK(a)) were in the range of 4.32-4.69, which were close to those of complexation of fulvic acid with Cu(II). This shows that the HMW fluorescent substances in root exudates from S. europaea L. were strong organic ligands for Cu(II). Our study suggests that the HMW fluorescent substances may affect chemical forms, mobility, and thus the fate of copper in wetland. PMID:21115394

Pan, Xiangliang; Yang, Jianying; Zhang, Daoyong; Chen, Xi; Mu, Shuyong

2010-11-05

52

The serum level of soluble CD26/dipeptidyl peptidase 4 increases in response to acute hyperglycemia after an oral glucose load in healthy subjects: association with high-molecular weight adiponectin and hepatic enzymes.  

PubMed

A soluble form of CD26/dipeptidyl peptidase 4 (sCD26/DPP4) is found in serum and it has DPP4 enzymatic activity. We investigated whether the serum level of sCD26/DPP4 was influenced by the oral glucose tolerance test (OGTT) in healthy subjects. The serum sCD26/DPP4 level increased significantly from 824.5 ng/mL (interquartile range, from 699.0 to 1050 ng/mL) at baseline to a peak of 985.0 ng/mL (interquartile range, from 796.5 to 1215 ng/mL) during the OGTT (P < 0.0001). The peak sCD26/DPP4 level correlated positively with the baseline age and body mass index, and fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), alanine aminotransferase, and ?-glutamyl transpeptidase (GGT) levels whereas it correlated negatively with high-density lipoprotein (HDL) cholesterol and the serum levels of total and high-molecular weight (HMW) adiponectin. Stepwise regression analysis was done with forward selection of variables, including age, FPG, HOMA-IR, TG, HDL cholesterol, uric acid, GGT, C-reactive protein, and HMW adiponectin. In a model that explained 57.5% of the variation of the peak sCD26/DPP4 level, GGT (? = 0.382, P = 0.007) and HOMA-IR (? = 0.307, P = 0.034) were independent determinants of the peak serum level of sCD26/DPP4. Serum HMW adiponectin decreased significantly from 4.43 ?g/mL (interquartile range, from 2.80 to 6.65 ?g/mL) at baseline to 4.17 ?g/mL (interquartile range, from 2.48 to 6.96 ?g/mL) 120 minutes after the oral glucose load (P < 0.0001). The baseline serum level of sCD26/DPP4 showed a significant negative correlation with the percent change of HMW adiponectin during the OGTT. In conclusion, the serum level of sCD26/DPP4 increased acutely after an oral glucose load in apparently healthy subjects. The abrupt increase of serum sCD26/DPP4 after a glucose load may be a marker of insulin resistance that could come from liver or muscle. PMID:23994650

Aso, Yoshimasa; Terasawa, Tomoko; Kato, Kanako; Jojima, Teruo; Suzuki, Kunihiro; Iijima, Toshie; Kawagoe, Yoshiaki; Mikami, Shigeru; Kubota, Yoshiro; Inukai, Toshihiko; Kasai, Kikuo

2013-08-30

53

DYSREGULATION OF MATERNAL SERUM ADIPONECTIN IN PRETERM LABOR  

PubMed Central

Objective Intra-amniotic and systemic infection/inflammation have been causally linked to preterm parturition and fetal injury. An emerging theme is that adipose tissue can orchestrate a metabolic response to insults, but also an inflammatory response via the production of adipocytokines, and that these two phenomenon are interrelated. Adiponectin, an insulin-sensitizing, anti-inflammatory adipocytokine, circulates in multimeric complexes including low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms. Each of these complexes can exert differential biological effects. The aim of this study was to determine whether spontaneous preterm labor (PTL) with intact membranes and intra-amniotic infection/inflammation (IAI) is associated with changes in maternal serum circulating adiponectin multimers. Study design This cross-sectional study included patients in the following groups: 1) normal pregnant women (n=158); 2) patients with an episode of preterm labor and intact membranes without IAI who delivered at term (n=41); 3) preterm labor without IAI who delivered preterm (n=27); and 4) preterm labor with IAI who delivered preterm (n=36). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results 1) Preterm labor leading to preterm delivery or an episode of preterm labor which does not lead to preterm delivery, was associated with a lower median maternal serum concentration of total and HMW adiponectin, a lower median HMW/total adiponectin ratio, and a higher median LMW/total adiponectin ratio than normal pregnancy; 2) among patients with preterm labor, those with IAI had the lowest median concentration of total and HMW adiponectin, as well as the lowest median HMW/total adiponectin ratio; 3) The changes in maternal adiponectin and adiponectin multimers remained significant after adjusting for confounding factors such as maternal age, BMI, gestational age at sampling, and parity. Conclusion 1) Preterm labor is characterized by a change in the profile of adiponectin multimers concentrations and their relative isoforms. These changes were observed in patients with an episode of preterm labor not leading to preterm delivery, in patients with intra-amniotic inflammation, or in those without evidence of intra-amniotic inflammation; 2) The changes in adiponectin multimer concentrations reported in preterm labor are different from those previously reported in spontaneous labor at term, suggesting that there is a fundamental difference between preterm labor and labor at term; 3) The findings reported herein, provide the first evidence for the participation of adiponectin multimer in preterm parturition. We propose that adiponectins and adipokines in general provide a mechanism to organize the metabolic demands generated by the process of preterm parturition regardless of the nature of the insult (intra-amniotic inflammation or not).

Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Gotsch, Francesca; Dong, Zhong; Nhan-Chang, Chia-Ling; Jodicke, Cristiano; Yoon, Bo Hyun; Hassan, Sonia S.; Kusanovic, Juan Pedro

2013-01-01

54

Adiponectin complexes composition in Japanese-Brazilians regarding their glucose tolerance status  

PubMed Central

Background Adiponectin circulates in different multimer complexes comprised of low molecular weight trimeric form (LMW), hexamer of middle molecular weight (MMW) and high molecular weight multimers (HMW). In Japanese-Brazilians, a population with high prevalence of glucose metabolism disturbances, we examined the associations of total adiponectin and its multimers with diabetes mellitus. Methods Two study groups were examined: 26 patients with diabetes mellitus (DM,14 women and 12 men, aged 55.3?±?8.6 years) and 27 age-matched control subjects with normal glucose tolerance (NGT,12 women and 15 men, aged 54.0?±?9.2 years). Results We found no significant differences in total [NGT: 6.90 ug/ml (4.38-13.43); DM: 5.38 ug/ml (3.76-8.56), p?=?0.35], MMW [NGT:2.34 ug/ml (1.38-3.25); DM: 1.80 ug/ml (1.18-2.84), p?=?0.48] or LMW adiponectin [NGT: 2.07 ug/ml (1.45-3.48), DM: 2.93 ug/ml (1.78-3.99), p?=?0.32] between groups. In contrast, HMW adiponectin levels were significantly lower in patients with DM [TGN: 2.39 ug/ml (1.20-4.75); DM: 1.04 ug/ml (0.42-1.60), p?=?0.001]. A logistic regression analysis was done to identify independent associations with diabetes mellitus. The results showed that HOMA-IR and HMW adiponectin in women were independently associated with diabetes mellitus. Conclusion The current investigation demonstrates that in Japanese-Brazilians HMW adiponectin is selectively reduced in individuals with type 2 diabetes, while no differences were found in MMW and LMW adiponectin isoforms.

2013-01-01

55

MATERNAL SERUM ADIPONECTIN MULTIMERS IN PATIENTS WITH A SMALL-FOR-GESTATIONAL-AGE NEWBORN  

PubMed Central

Objective Several mechanisms of disease have been implicated in the pathophysiology of SGA including an anti-angiogenic state, failure of physiologic transformation of spiral arteries, and an exaggerated intravascular pro-inflammatory response. Adiponectin, an insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic adipokine circulates in oligomeric complexes including low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms. Adiponectin plays a role in a wide range of biological activities including those that have been implicated in the pathophysiology SGA. Thus, the aim of this study was to determine if third trimester adiponectin concentrations differed between women with normal weight infants and those with an SGA neonate. Study design This cross-sectional study included women with: 1) a normal pregnancy (n=234); and 2) an SGA neonate (n=78). The study population was further stratified by first trimester BMI (normal weight <25 kg/m2 vs. overweight/obese ?25 kg/m2). Maternal serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results 1) The median maternal serum concentrations of total, HMW and MMW adiponectin were significantly lower in patients with an SGA neonate than in those with normal pregnancies; 2) patients with an SGA neonate had a significantly lower median HMW/total adiponectin ratio and higher median MMW/total adiponectin and LMW/total adiponectin ratios than those with a normal pregnancy; 3) among patients with an SGA neonate, neither maternal serum concentrations of adiponectin multimers, nor their relative distribution differ between normal weight and overweight/obese patients. Conclusion 1) Pregnancies complicated by an SGA neonate are characterized by a alterations in the maternal serum adiponectin multimers concentrations and their relative abundance; 2) in contrast to normal pregnancies, those complicated by an SGA neonate are not associated with low circulating adiponectin multimers in overweight/obese individuals suggesting altered regulation of this adipokine in the presence of an SGA neonate; 3) collectively, the findings reported herein suggest that maternal adipose tissue may play a role, in the pathogenesis of SGA.

Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Gotsch, Francesca; Dong, Zhong; Yoon, Bo Hyun; Hassan, Sonia S.; Kusanovic, Juan Pedro

2013-01-01

56

Correlation between change in body weight rather than current body weight and change in serum adiponectin levels in a Japanese population—the Funagata study  

Microsoft Academic Search

Serum adiponectin levels are decreased in obese subjects. We examined the association of current body weight (BW) and its change with a change in serum adiponectin levels. Serum adiponectin levels at the baseline (from 1995 to 1997) and the 5-year follow-up (from 2000 to 2002) examinations were evaluated in 1003 (M\\/F, 425\\/578; age at the baseline examinations, 58.3 ± 11.7\\/57.5

Nobuko Arawaka; Makoto Daimon; Toshihide Oizumi; Yumi Jimbu; Wataru Kameda; Hiroshi Yamaguchi; Hiroshi Ohnuma; Makoto Tominaga; Takeo Kato

2006-01-01

57

A3-3: Pre-Pregnancy Adiponectin Levels and Subsequent Risk of Gestational Diabetes Mellitus (GDM)  

PubMed Central

Background/Aims Adiponectin is an adipocyte-derived polypeptide with insulin-sensitizing properties that has been prospectively linked to the development of type 2 diabetes. Adiponectin levels decrease during the course of normal pregnancy. It is unknown whether pre-pregnancy adiponectin levels are related to risk of gestational diabetes mellitus (GDM), a common pregnancy complication and strong predictor of type 2 diabetes. Our study assessed prospectively whether serum total and high molecular weight (HMW) adiponectin concentrations measured before pregnancy are associated with subsequent risk of GDM. Methods We conducted a case-control study among normoglycemic women who took part in a multiphasic health checkup (MHC) exam at Kaiser Permanente Northern California between 1984–1996 and had a subsequent pregnancy before 2009 (255 GDM cases and 507 controls, matched on: year of exam, age at exam and age at pregnancy and number of intervening pregnancies). The MHC exam occurred on average 7 years before pregnancy. Results Pre-pregnancy total adiponectin and HMW concentrations were lower in women who developed GDM than controls (7.7 vs. 10.6 and 2.8 vs. 3.9 ?g/ml, respectively, P-values <0.001). Compared with women in the highest quartile of total adiponectin, women in the lowest quartile had an almost 4-fold increased risk of GDM after adjusting for insulin, hours since last food, race/ethnicity, family history of diabetes, education, BMI and parity (OR (95% CI): 3.83 (2.05–7.16)). Similar results were observed comparing the highest versus lowest quartile of HMW adiponectin (OR: 4.15 (2.20–7.83)). Conclusions The risk of GDM is increased among women with lower pre-pregnancy levels of adiponectin, suggesting decreased insulin sensitivity is present years before pregnancy. Measuring adiponectin may help identify women at high risk for GDM.

Hedderson, Monique; Darbinian, Jeanne; Ferrara, Assiamira

2013-01-01

58

Functional significance of skeletal muscle adiponectin production, changes in animal models of obesity and diabetes, and regulation by rosiglitazone treatment.  

PubMed

Endocrine effects of adipose-derived adiponectin on skeletal muscle have been shown to account, at least in part, for the anti-diabetic effects of this adipokine. Recently, the concept of myokines has gained credence, and the potential for skeletal muscle to produce adiponectin has been suggested. Here we demonstrated an increased level of adiponectin mRNA and protein expression as well as protein secretion in response to rosiglitazone treatment in L6 muscle cells. This correlated with the ability of rosiglitazone to enhance insulin sensitivity for stimulation of protein kinase B (Akt) phosphorylation and glucose transport; rosiglitazone also corrected high-glucose-induced insulin resistance in L6 cells. Overexpression of adiponectin confirmed the functional significance of local production of adiponectin in muscle cells via elevated glucose uptake and increased insulin sensitivity. In obese diabetic db/db mice, there was a change in the adiponectin expression profile in soleus and extensor digitorum longus (EDL) muscle with less high molecular weight (HMW) and more medium (MMW)/low (LMW) molecular weight species detected. Induction of obesity and insulin resistance in rats by feeding a high-fat high-sucrose diet also led to decreased muscle HMW adiponectin content that could be corrected by rosiglitazone treatment. In summary, we show the ability of skeletal muscle cells to produce adiponectin, which can mediate autocrine metabolic effects, thus establishing adiponectin as a bona fide myokine. We also demonstrate that skeletal muscle adiponectin production is altered in animal models of obesity and diabetes and that these changes can be corrected by rosiglitazone. PMID:19531641

Liu, Ying; Chewchuk, Simon; Lavigne, Charles; Brûlé, Sophie; Pilon, Genevieve; Houde, Vanessa; Xu, Aimin; Marette, Andre; Sweeney, Gary

2009-06-16

59

Adiponectin is regulated differently by chronic exercise than by weight-matched food restriction in hyperphagic and obese OLETF rats.  

PubMed

This study was intended to investigate the effects of chronic exercise on blood adiponectin level. Male Otsuka Long Evans Tokushima Fatty (OLETF) rats (26 weeks old) were divided to undergo either regular 12-week wheel running exercise (EX) or to have food restriction (FR) that resulted in body weight reduction similar to that in EX. Both EX and FR induced similar reductions in body weight, abdominal fat volume and plasma leptin concentration compared with ad libitum control. At the end of the study, although plasma adiponectin level was increased in FR, the adiponectin level did not change in EX. Plasma testosterone level was higher in EX than in either of the other two groups. A significant inverse relationship existed between plasma levels of adiponectin and testosterone for all groups. Our results suggested that 12-week voluntary wheel running exercise induces different effects on plasma adiponectin level than does food restriction, despite similar reduction in body weight, fat tissue mass and plasma leptin concentration. We speculate that the elevated plasma testosterone concentration might offset any hyperadiponectinemic effect of body weight and fat volume reduction in exercising rats. PMID:16889803

Kimura, Masaki; Shinozaki, Tomokazu; Tateishi, Naoto; Yoda, Emi; Yamauchi, Hideki; Suzuki, Masato; Hosoyamada, Makoto; Shibasaki, Toshiaki

2006-07-12

60

PLASMA ACYLATION STIMULATING PROTEIN, LEPTIN, ADIPONECTIN AND INSULIN BEFORE AND AFTER WEIGHT LOSS IN OVERWEIGHT AND OBESE WOMEN  

Technology Transfer Automated Retrieval System (TEKTRAN)

The purpose of this study was to determine the relationships between weight loss and plasma (ASP), leptin, adiponectin, and insulin. Thirty-five overweight and obese (BMI 28-39 kg/m**2), hyperlipidemic women aged between 35 and 60 years old participated in a 6-month weight loss study consisting in 3...

61

Interactions among Hageman factor (HG, Factor XII), plasma thromboplastin antecedent (PTA, Factor XI), plasma prekallikrein (PK, Fletcher factor) and high molecular weight kininogen (HMW-K, Fitzgerald factor) in blood coagulation.  

PubMed

Studies of plasmas from individuals with Hageman trait (factor XII deficiency), plasma thromboplastin antecedent (PTA, factor XI) deficiency, Fletcher trait (plasma prekallikrein deficiency) and Fitzgerald trait (high molecular weight-kininogen deficiency) have revealed the importance of these proteins in blood coagulation. The interactions among them, however, are not fully elucidated. We have studied these reactions by two different approaches. (1) In a purified system, high molecular weight kininogen was absolutely required for activation of PTA by HF and ellagic acid (EA). The yield of activated PTA was proportional to the amount of HF, HMW-K, and PTA in the mixtures, suggesting that these three proteins may form a complex in the presence of EA. (2) In experiments with whole plasma, we took advantage of the adsorption of EA to Sephadex gels. When normal plasma or plasma deficient in HF, PK, HMW-K or PTA was exposed to Sephadex-EA and was separated by centrifugation, each supernatant plasma except that deficient in HF shortened the prolonged partial thromboplastin time (PTT) of HF-deficient plasma. Plasma simultaneously depleted of HMW-K, PK and PTA also shortened the PTT of HF-deficient plasma and of plasma depleted of HF and PK, but had virtually no procoagulant effect upon the PTT of plasma depleted of HF and MHW-K. Thus, exposure of HF in plasma to Sephadex-EA appeared to generate a clot-promoting form of HF in the absence of other clotting factors, but its expression required the presence of HMW-K. PMID:517254

Saito, H; Ratnoff, O D

1979-01-01

62

Human milk adiponectin impacts infant weight trajectory during the second year of life  

PubMed Central

Objectives Serum adiponectin (APN) is associated with lower childhood obesity, and APN concentration in human milk is associated with slower growth during active breastfeeding. Here, we examine infant weight gain in the second year of life after exposure to high or low levels of mother’s milk APN. Methods Breastfeeding mother-infant pairs were recruited in Mexico City and followed for 2 years; 192 infants with ?12 months’ follow-up were analyzed. Monthly milk samples were assayed for APN; mothers were classified as producing high or low levels of milk APN. Infant and maternal serum APN were assessed during year 1. Infant anthropometry was measured monthly (year 1) or bi-monthly (year 2), and WHO Z-scores calculated. Longitudinal adjusted models assessed weight-for-age (WEI) and weight-for-length (WFL) Z-score trajectories from 1 to 2 years. Results Maternal serum APN modestly correlated with milk APN (r=0.37, p<0.0001) and infant serum APN (r=0.29, p=0.01). Infants exposed to high milk APN experienced increasing WEI and WFL Z-scores between age 1 and 2 years in contrast to low milk APN exposure (p for group*time=0.02 and 0.054, respectively), adjusting for growth in the first 6 months and other covariates. In contrast, infant serum APN in year 1 was not associated with rate of weight gain in year 2. Conclusions High human milk APN exposure was associated with accelerated weight trajectory during the second year of life suggesting its role in catch up growth after slower weight gain during the first year of life.

Woo, Jessica G; Guerrero, M Lourdes; Guo, Fukun; Martin, Lisa J; Davidson, Barbara S; Ortega, Hilda; Ruiz-Palacios, Guillermo M; Morrow, Ardythe L

2011-01-01

63

Correlation of circulating C1q and C1q-binding adiponectin concentrations with aging in males: a preliminary report  

PubMed Central

Background Atherosclerosis is an age-related disease. Adiponectin and C1q form a protein complex in human blood, and that serum C1q and C1q-binding adiponectin (C1q-APN) concentrations can be measured. We investigated circulating C1q and C1q-APN levels in Japanese men including elderly men. Findings The study subjects were 509 Japanese men including elderly men. Serum levels of total adiponectin (Total-APN), high-molecular weight-adiponectin (HMW-APN), C1q-APN and C1q were measured by enzyme-linked immunosorbent assay. Total-APN, HMW-APN and C1q-APN, but not C1q, correlated significantly and positively with aging (r=0.26, r=0.24, r=0.17, p<0.01, respectively). The HMW-APN/Total-APN ratio correlated significantly and positively with aging (r=0.14, p<0.01). The C1q-APN/Total-APN ratio and C1q-APN/HMW-APN ratio correlated significantly and negatively with aging (r=?0.17, p<0.01, r=?0.12, p=0.01). C1q-APN/C1q correlated significantly and positively with aging (r=0.09, p=0.03). Multiple regression analysis identified age and body mass index as significant determinants of C1q-APN. Conclusions The present study demonstrates that serum HMW-APN, C1q-APN, and Total-APN, but not C1q, correlated positively with aging. These preliminary results could form the basis for future research. Trial registration Clinical Trial Registration Number: UMIN000004318

2013-01-01

64

Weight Loss and Changes in Salivary Ghrelin and Adiponectin: Comparison Between Sleeve Gastrectomy and Roux-en-Y Gastric Bypass and Gastric Banding  

Microsoft Academic Search

Background  Weight loss is associated with increased levels of adiponectin with a greater increase observed following Roux-en-Y gastric\\u000a bypass (RYGB) compared to restrictive procedures. However, currently there are no data on changes in adiponectin following\\u000a laparoscopic sleeve gastrectomy (LSG). Ghrelin was reported to be also produced by the salivary glands. There are also no\\u000a data available regarding its changes following bariatric

Frank Benedix; Sabine Westphal; Robert Patschke; Dennis Granowski; Claus Luley; Hans Lippert; Stephanie Wolff

2011-01-01

65

Suppression of human melanoma tumor growth in SCID mice by a human high molecular weight-melanoma associated antigen (HMW-MAA) specific monoclonal antibody.  

PubMed

The lack of efficacy of available therapies for the treatment of malignant melanoma has emphasized the need to develop novel therapeutic strategies to prevent melanoma growth. We have tested whether the anti-HMW-MAA mAb 225.28S is able to inhibit human melanoma tumor growth in SCID mice because in vitro data suggested that this antigen plays a role in spreading, migration and invasion of melanoma cells. Tumors were established by subcutaneous injection of the human melanoma cell line 518A2 into SCID mice. When tumors reached a size of 5 mm, the mAb 225.28S was administered intravenously 4 times in 3 day intervals at 100 microg/injection. Within 14 days after the first administration of the mAb 225.28S, tumor growth was reduced by 52% as compared to control mice. Three hundred and seven genes of >20,000 genes contained on the GeneChip were changed in their expression level at least 2-fold after administration of the mAb 225.28S. The encoded proteins were mostly components or modifiers of the extracellular matrix, tumor suppressors, and melanogenesis associated proteins. Surprisingly, the administration of the control mAb that did not lead to a significant tumor growth inhibition in vivo resulted in the modulation of two-thirds of these genes. This is the first report of suppression of human melanoma tumor growth in SCID mice by the mAb 225.28S. Our results suggest that anti-HMW-MAA mAbs may represent useful reagents to apply passive immunotherapy to patients with malignant melanoma. PMID:15578703

Hafner, Christine; Breiteneder, Heimo; Ferrone, Soldano; Thallinger, Christiane; Wagner, Stefan; Schmidt, Wolfgang M; Jasinska, Joanna; Kundi, Michael; Wolff, Klaus; Zielinski, Christoph C; Scheiner, Otto; Wiedermann, Ursula; Pehamberger, Hubert

2005-04-10

66

AGRONOMIC, BIOCHEMICAL AND QUALITY CHARACTERISTICS OF WHEATS CONTAINING HMW-GLUTENIN TRANSGENES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Bread dough strength is primarily dependent on its composition of high-molecular-weight glutenin subunits (HMW-GS), a class of storage proteins that typically comprises 5-10% of flour proteins. We have made a set of transgenic wheats that differ both quantitatively and qualitatively in their HMW-GS ...

67

Human high molecular weight melanoma-associated antigen (HMW-MAA) mimicry by mouse anti-idiotypic monoclonal antibody MK2-23: induction of humoral anti-HMW-MAA immunity and prolongation of survival in patients with stage IV melanoma.  

PubMed Central

Twenty-five patients with stage IV melanoma were immunized with the mouse anti-idiotypic monoclonal antibody (mAb) MK2-23 (2 mg per injection), which bears the internal image of the determinant defined by anti-HMW-MAA mAb 763.74. Two patients were inevaluable, since they did not complete 4 weeks of therapy. Only 14 patients developed antibodies that were shown by serological and immunochemical assays to recognize the same or spatially close determinant as the anti-HMW-MAA mAb 763.74 and to express the idiotope defined by mAb MK2-23 in their antigen-combining sites. Side effects that are likely to be caused by bacillus Calmette-Guérin present in the immunogen consisted of erythema, induration, and ulceration at the sites of the injections. Occasionally, patients complained of flu-like symptoms, arthralgias, and myalgias. Three of the patients who developed anti-HMW-MAA antibodies achieved a partial response. It consisted of a decrease in the size of metastatic lesions and lasted 52 weeks in 1 patient and 93 weeks in the other 2 patients. Survival of the 14 patients who developed anti-HMW-MAA antibodies was significantly (P = 0.0003) longer than that of the 9 patients without detectable humoral anti-HMW-MAA immunity development. In the multivariate analysis, such an association between development of anti-HMW-MAA antibodies and survival prolongation was still significant (P = 0.001) after adjustment for difference in performance status, the only confounding factor found to be significantly related to survival. Lastly, a significant (P = 0.03 by likelihood ratio test) interaction between anti-HMW-MAA antibodies and patients' performance status was found, since the prolongation of survival associated with anti-HMW-MAA antibodies was more marked in patients with a performance status of less than or equal to 70% than in those with a higher one. These results suggest that anti-idiotypic mAb MK2-23 may represent a useful immunogen to implement active specific immunotherapy in patients with melanoma. Images

Mittelman, A; Chen, Z J; Yang, H; Wong, G Y; Ferrone, S

1992-01-01

68

The effect of moderate alcohol consumption on adiponectin oligomers and muscle oxidative capacity: a human intervention study  

Microsoft Academic Search

Aims\\/hypothesis  The aim of this study was to investigate whether moderate alcohol consumption increases plasma high molecular weight (HMW)\\u000a adiponectin and\\/or muscle oxidative capacity.\\u000a \\u000a \\u000a \\u000a Materials and methods  Eleven lean (BMI 18–25 kg\\/m2) and eight overweight (BMI ?27 kg\\/m2) men consumed 100 ml whisky (?32 g alcohol) or water daily for 4 weeks in a randomised, controlled, crossover trial. After\\u000a each treatment period, muscle biopsies and fasting blood

J. W. J. Beulens; L. J. C. van Loon; F. J. Kok; M. Pelsers; T. Bobbert; J. Spranger; A. Helander; H. F. J. Hendriks

2007-01-01

69

Plasma Acylation-Stimulating Protein, Adiponectin, Leptin, and Ghrelin before and after Weight Loss Induced by Gastric Bypass Surgery in Morbidly Obese Subjects  

Microsoft Academic Search

We examined fasting plasma insulin, acylation-stimulating protein (ASP), leptin, adiponectin, ghrelin, and metabolic\\/car- diovascular risk profile before and 15 6 months after iso- lated Roux-en-Y gastric bypass surgery in 50 morbidly obese subjects. Average preoperative plasma lipids were mostly nor- mal, whereas ASP, insulin, and leptin were elevated, and adi- ponectin and ghrelin were decreased. Postoperatively, body weight decreased significantly

MAY FARAJ; PETER J. HAVEL; STEVE PHELIS; DAVID BLANK; ALLAN D. SNIDERMAN; KATHERINE CIANFLONE

70

Serum C1q- binding adiponectin in maintenance hemodialysis patients  

PubMed Central

Background Patients on maintenance hemodialysis (HD) have much higher levels of adiponectin (Total-APN). Adiponectin and C1q form a protein complex in human blood, and serum C1q-binding adiponectin (C1q-APN) can be measured. We recently reported that C1q-APN/Total-APN ratio rather than Total-APN correlated with atherosclerosis in diabetics. However, the characteristics of C1q-APN in HD patients remain unclear. The preset study investigated the characteristics of the adiponectin parameters including C1q-APN and also to clarify the relationship between various serum adiponectin parameters and atherosclerotic cardiovascular diseases (ACVD) in HD patients. Methods The single cross-sectional study subjects were 117 Japanese patients (males/females?=?61/56) on regular HD. Blood Total-APN, high molecular weight-adiponectin (HMW-APN), C1q-APN and C1q concentrations were measured by enzyme-linked immunosorbent assays. ACVD were defined as stroke, coronary and peripheral artery diseases, thoracic and abdominal aneurysms. Results Stepwise regression analysis identified high-density lipoprotein-cholesterol (HDL-C) as the only significant and independent determinant of C1q-APN in males, and duration of HD as the only significant and independent determinant of C1q-APN in females. Stepwise regression analysis identified uric acid, low-density lipoprotein-cholesterol and triglyceride as significant and independent determinants of C1q-APN/Total-APN ratio in males, and leukocyte count and HDL-C as significant and independent determinants of C1q-APN/Total-APN ratio in females. Multiple logistic regression analysis identified inorganic phosphorus and C1q-APN or C1q-APN/C1q ratio as significant determinants of ACVD. Conclusions Low serum C1q-APN and C1q-APN/C1q ratio, but not C1q-APN/Total-APN ratio, correlated with ACVD in HD patients. Trial registration ClinicalTrials.gov: UMIN http://000004318

2013-01-01

71

Isolation of HMW DNA from sunflower ( Helianthus annuus L.) for BAC cloning  

Microsoft Academic Search

The cultivated sunflower (Helianthus annuus L.) is one of the most important oil crops in the world. The importance of sunflower oil in human nutrition and in the chemical\\u000a industry makes the sunflower a major research interest. An essential element for genomic libraries is the preparation of high\\u000a molecular weight (HMW) DNA. We developed 2 methods for isolating HMW sunflower

Nehir Özdemir; Renate Horn; Wolfgang Friedt

2002-01-01

72

Porcine Adiponectin Receptor 1 Transgene Resists High-fat/Sucrose Diet-Induced Weight Gain, Hepatosteatosis and Insulin Resistance in Mice.  

PubMed

Adiponectin and its receptors have been demonstrated to play important roles in regulating glucose and lipid metabolism in mice. Obesity, type II diabetes and cardiovascular disease are highly correlated with down-regulated adiponectin signaling. In this study, we generated mice overexpressing the porcine Adipor1 transgene (pAdipor1) to study its beneficial effects in metabolic syndromes as expressed in diet-induced obesity, hepatosteatosis and insulin resistance. Wild-type (WT) and pAdipor1 transgenic mice were fed ad libitum with a standard chow diet (Chow) or a high-fat/sucrose diet (HFSD) for 24 weeks, beginning at 6 to 7 weeks of age. There were 12 mice per genetic/diet/sex group. When challenged with HFSD to induce obesity, the pAdipor1 transgenic mice resisted development of weight gain, hepatosteatosis and insulin resistance. These mice had lowered plasma adiponectin, triglyceride and glycerol concentrations compared to WT mice. Moreover, we found that (indicated by mRNA levels) fatty acid oxidation was enhanced in skeletal muscle and adipose tissue, and liver lipogenesis was inhibited. The pAdipor1 transgene also restored HFSD-reduced phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose transporter 4 mRNA in the adipose tissues, implying that the increased Pck1 may promote glyceroneogenesis to reduce glucose intolerance and thus activate the flux of glyceride-glycerol to resist diet-induced weight gain in the adipose tissues. Taken together, we demonstrated that pAdipor1 can prevent diet-induced weight gain and insulin resistance. Our findings may provide potential therapeutic strategies for treating metabolic syndromes and obesity, such as treatment with an ADIPOR1 agonist or activation of Adipor1 downstream targets. PMID:24172199

Liu, Bing-Hsien; Lin, Yuan-Yu; Wang, Ya-Chin; Huang, Chao-Wei; Chen, Chih-Chien; Wu, Shinn-Chih; Mersmann, Harry J; Cheng, Winston T K; Ding, Shih-Torng

2013-01-01

73

TNF-? Antagonism with Etanercept Decreases Glucose and Increases the Proportion of High Molecular Weight Adiponectin in Obese Subjects with Features of the Metabolic Syndrome  

PubMed Central

Context and Objective: Obesity is associated with activation of the TNF-? system, increased inflammatory markers, and insulin resistance. Although studies in rodents suggest that attenuation of TNF activity improves glucose homeostasis, the effect of prolonged inhibition of TNF-? with etanercept on inflammation and glucose homeostasis in a human model of obesity is not known. Design and Participants: Forty obese subjects with features of metabolic syndrome were randomized to etanercept or placebo, 50 mg twice weekly for 3 months, followed by 50 mg once weekly for 3 months. Outcome Measures: Subjects underwent oral glucose tolerance testing and measurement of serum inflammatory biomarkers and adipokines. Subcutaneous fat biopsy was performed in a subset for measurement of adipokine and TNF-? mRNA expression. Results: Visceral adiposity was significantly associated with serum concentrations of TNF receptor 1 (TNFR1), TNFR2, and vascular cell adhesion molecule-1 and adipose tissue expression of TNF-? and SOCS-3 (all P < 0.05). Insulin resistance as assessed by homeostasis model assessment was significantly associated with TNFR1, C-reactive protein, IL-6, and soluble intracellular adhesion molecule-1 (sICAM-1) (all P < 0.05). Etanercept significantly improved fasting glucose (treatment effect vs. placebo over 6 months, ?10.8 ± 4.4%, P = 0.02). Etanercept also increased the ratio of high molecular weight adiponectin to total adiponectin (+22.1 ± 9.2% vs. placebo, P = 0.02), and decreased levels of sICAM-1 (?11 ± 2% vs. placebo, P < 0.0001). In contrast, body composition, lipids, C-reactive protein, and IL-6 were unchanged after 6 months. Conclusions: Prolonged therapy with etanercept improved fasting glucose, increased the ratio of high molecular weight to total adiponectin, and decreased sICAM-1 in obese subjects with abnormal glucose homeostasis and significant subclinical inflammation.

Stanley, Takara L.; Zanni, Markella V.; Johnsen, Stine; Rasheed, Sarah; Makimura, Hideo; Lee, Hang; Khor, Victor K.; Ahima, Rexford S.; Grinspoon, Steven K.

2011-01-01

74

ApoA-1 mimetic restores adiponectin expression and insulin sensitivity independent of changes in body weight in female obese mice  

PubMed Central

Background: We examined the ability of the apolipoprotein AI mimetic peptide L-4F to improve the metabolic state of female and male ob mice and the mechanisms involved. Methods: Female and male lean and obese (ob) mice were administered L-4F or vehicle for 6 weeks. Body weight was measured weekly. Fat distribution, serum cytokines and markers of cardiovascular dysfunction were determined at the end of treatment. Results: L-4F significantly decreased serum interleukin (IL)-6, tumor necrosis factor-? and IL-1?. L-4F improved vascular function, and increased serum adiponectin levels and insulin sensitivity compared with untreated mice. In addition, L-4F treatment increased heme oxygenase (HO)-1, pAKT and pAMPK levels in kidneys of ob animals. pAKT and pAMPK levels were significantly reduced in the presence of an HO inhibitor. Interestingly, L4F did not alter body weight in female mice, but caused a significant reduction in males. Conclusions: L-4F treatments reduced cardiovascular risk factors and improved insulin sensitivity in female ob mice independent of body fat changes. Reduced inflammatory cytokine levels accompanied by increased HO activity, serum adiponectin and improved insulin sensitivity suggest that L-4F may promote the conversion of visceral fat to a healthier phenotype. Therefore, L-4F appears to be a promising therapeutic strategy for treating both cardiovascular risk factors and insulin resistance in obese patients of either gender.

Marino, J S; Peterson, S J; Li, M; Vanella, L; Sodhi, K; Hill, J W; Abraham, N G

2012-01-01

75

Aerobic exercise training improves insulin sensitivity without changes in body weight, body fat, adiponectin, and inflammatory markers in overweight and obese girls.  

PubMed

The aim of this study was to examine the effect of aerobic exercise training on insulin sensitivity in overweight and obese girls. Nineteen overweight and obese girls (mean +/- SD: age, 13.1+/-1.8 years; body mass index, 26.8+/-3.9 kg/m(2)) volunteered for this study. Body composition (dual-energy x-ray absorptiometry), insulin sensitivity (oral glucose tolerance test and homeostasis model assessment estimate of insulin resistance; n=15), adiponectin, C-reactive protein (CRP), interleukin (IL) 6, insulin-like growth factor-1, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 serum levels, and blood lipids and lipoproteins were assessed before and after 12 weeks of aerobic training. Cardiorespiratory fitness increased by 18.8% (P<.05) as a result of training. The area under the insulin concentration curve (insulin area under the curve) decreased by 23.3% (12781.7+/-7454.2 vs 9799.0+/-4918.6 microU.min/mL before and after intervention, respectively; P=.03). Insulin sensitivity was improved without changes in body weight (pre-intervention, 67.9+/-14.5 kg; post-intervention, 68.3+/-14.0 kg) or percent body fat (pre-intervention, 41.4% +/- 4.8%; post-intervention, 40.7%+/-5.2%). The lower limb fat-free mass increased by 6.2% (P<.01) as a result of training, and changes in lower limb fat-free mass were correlated with changes in the insulin area under the curve (r= -.68; P< .01). Serum adiponectin, IL-6, and CRP concentrations did not change (pre-intervention vs post-intervention: adiponectin, 9.57+/-3.01 vs 9.08+/-2.32 microg/mL; IL-6, 1.67+/-1.29 vs 1.65+/-1.25 pg/mL, CRP, 3.21+/-2.48 vs 2.73+/-1.88 mg/L) whereas insulin-like growth factor-1 was lower after training (pre-intervention, 453.8 +/- 159.3 ng/mL; post-intervention, 403.2+/- 155.1 ng/mL; P<.05). In conclusion, 12 weeks of aerobic training improved insulin sensitivity in overweight and obese girls without change in body weight, percent body fat, and circulating concentrations of adiponectin, IL-6, CRP, and other inflammatory markers. These findings suggest that increased physical activity may ameliorate the metabolic abnormalities associated with obesity in children with a mechanism other than the parameters cited earlier. PMID:16253636

Nassis, George P; Papantakou, Katerina; Skenderi, Katerina; Triandafillopoulou, Maria; Kavouras, Stavros A; Yannakoulia, Mary; Chrousos, George P; Sidossis, Labros S

2005-11-01

76

Increased plasma isoprostane is associated with visceral fat, high molecular weight adiponectin, and metabolic complications in obese children  

Microsoft Academic Search

Oxidative stress is considered to be increased in obese subjects. However, the association of oxidative stress with visceral\\u000a adiposity and adiponectin level is not fully understood in children. Forty-four obese Japanese children and adolescents, 28\\u000a boys and 16 girls, with median age of 9.9 years [5.2–13.8 years], and the 28 age-matched non-obese healthy controls, 15 boys\\u000a and 13 girls, were enrolled in

Shunsuke Araki; Kazushige Dobashi; Yukiyo Yamamoto; Kohtaro Asayama; Koichi Kusuhara

2010-01-01

77

Cancer immunotherapy targeting the HMW-MAA protein results in a broad antitumor response and reduction of pericytes in the tumor vasculature  

PubMed Central

The high molecular weight melanoma-associated antigen (HMW-MAA), also known as melanoma chondroitin sulfate proteoglycan, has been used as a target for the immunotherapy of melanoma. This antigen is expressed on the cell surface and has a restricted distribution in normal tissues. Besides its expression in a broad range of transformed cells, this antigen is also found in pericytes, which are important for tumor angiogenesis. We generated a recombinant Listeria monocytogenes (Lm-LLO-HMW-MAA-C) that expresses and secretes a fragment of HMW-MAA (residues 2,160–2,258) fused to the first 441 residues of the listeriolysin O (LLO) protein. Immunization with Lm-LLO-HMW-MAA-C was able to impede the tumor growth of early established B16F10-HMW-MAA tumors in mice and both CD4+ and CD8+ T cells were required for therapeutic efficacy. Immune responses to a known HLA-A2 epitope present in the HMW-MAA2160–2258 fragment was detected in the HLA-A2/Kb transgenic mice immunized with Lm-LLO-HMW-MAA-C. Surprisingly, this vaccine also significantly impaired the in vivo growth of other tumorigenic cell lines, such as melanoma, renal carcinoma, and breast tumors, which were not engineered to express HMW-MAA. One hypothesis is that the vaccine could be targeting pericytes, which are important for tumor angiogenesis. In a breast tumor model, immunization with Lm-LLO-HMW-MAA-C caused CD8+ T-cell infiltration in the tumor stroma and a significant decrease in the number of pericytes in the tumor blood vessels. In conclusion, a Lm-based vaccine against HMW-MAA can trigger cell-mediated immune responses to this antigen that can target not only tumor cells but also pericytes in the tumor vasculature.

Maciag, Paulo Cesar; Seavey, Matthew; Pan, Zhen-Kun; Ferrone, Soldano; Paterson, Yvonne

2009-01-01

78

LOW CIRCULATING MATERNAL ADIPONECTIN IN PATIENTS WITH PYELONEPHRITIS: ADIPONECTIN AT THE CROSSROADS OF PREGNANCY AND INFECTION  

PubMed Central

Objective An emerging theme in modern biology is that adipose tissue can respond to metabolic stress, and to inflammatory stimuli, by regulating the secretion of a complex network of soluble mediators, termed adipokines. Adiponectin, the most prevalent circulating adipokine in human, has profound insulin-sensitizing and anti-inflammatory properties. Indeed, the notion that adiponectin plays an important role in the interactions between the metabolic and the immune systems has been strongly suggested. Thus, the aim of this study was to determine if pyelonephritis during pregnancy is associated with changes in maternal serum adiponectin concentrations. Study design This cross-sectional study included women in the following groups: 1) normal pregnant women (n=200); and 2) pregnant women with pyelonephritis (n=50). Maternal plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results 1) The median maternal plasma adiponectin concentration was lower in patients with pyelonephritis than in those with a normal pregnancy (p<0.001); 2) among pregnant women with a normal weight, patients with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (p<0.001); 3) similarly, among overweight/obese patients, those with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (p<0.001); and 4) the presence of pyelonephritis was independently associated with maternal plasma adiponectin concentrations after adjustment for maternal age, smoking, gestational age at sampling, and pre-gestational BMI. Conclusion 1) The findings that acute pyelonephritis in pregnancy is characterized by low maternal plasma concentrations of adiponectin in both lean and overweight/obese patients are novel and concur with the anti-inflammatory properties of adiponectin; and 2) the results of this study support the notion that adiponectin may play a role in the intricate interface between inflammation and metabolism during pregnancy.

Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Erez, Offer; Mittal, Pooja; Kim, Sun Kwon; Gotsch, Francesca; Lamont, Ronald; Ogge, Giovanna; Pacora, Percy; Goncalves, Luis; Kim, Chong Jai; Gomez, Ricardo; Espinoza, Jimmy; Hassan, Sonia S.; Kusanovic, Juan Pedro

2009-01-01

79

Serum Adiponectin Levels in Advanced-Stage Parkinson's Disease Patients  

PubMed Central

Patients with advanced Parkinson's disease (PD) experience body weight loss and reductions in the most common cardiovascular risk factors. At present, the pathogenetic mechanisms involved have not been elucidated. Increased serum concentrations of adiponectin, which possesses antiatherogenic and anti-inflammatory properties, are associated with a reduction in cardiovascular risk. The objective of this study was to determine adiponectin serum concentrations in PD patients. Thirty PD patients underwent a full nutritional status assessment, including the determination of adiponectin serum concentrations. Mean ± SD adiponectin concentrations were 9.59 ± 5.9??g/mL (interquartile range: 5.92–12.9??g/mL). In PD patients, adiponectin serum levels were similar to those in normal-weight, healthy, young subjects and significantly higher than that in an aged-matched group of morbidly obese subjects. Further studies are warranted to establish the role of adiponectin in the management of PD patients.

Cassani, Erica; Cancello, Raffaella; Cavanna, Ferruccio; Maestrini, Sabrina; Di Blasio, Anna Maria; Liuzzi, Antonio; Pezzoli, Gianni; Barichella, Michela

2011-01-01

80

CIRCULATING CONCENTRATIONS OF HIGH MOLECULAR WEIGHT ADIPONECTIN MULTIMERS INCREASE FOLLOWING ROUX-EN-Y GASTRIC BYPASS SURGERY  

Technology Transfer Automated Retrieval System (TEKTRAN)

In addition to weight loss, bariatric surgery for severe obesity has been reported to rapidly improve insulin sensitivity, often leading to a sustained resolution of type-2 diabetes mellitus 1. This effect has been proposed to result from the marked early restriction of food intake and/or increased ...

81

Relationship between Thyroid Volume and Iodine, Leptin, and Adiponectin in Obese Women before and after Weight Loss  

Microsoft Academic Search

Objective: To investigate whether or not reduction of thyroid volume during weight loss is related to adipocytokines and urinary iodine excretion in obese women. Subjects and Methods: 98 obese and 31 non-obese women consecutively admitted to the endocrinology and metabolism outpatient clinic of the School of Medicine, Akdeniz University were included in the study. Thyroid volume, thyroid function tests, leptin

Esin Eray; Funda Sari; Sabahat Ozdem; Ramazan Sari

2011-01-01

82

Allelic variation of the HMW glutenin subunits in Aegilops tauschii accessions detected by sodium dodecyl sulphate (SDS-PAGE), acid polyacrylamide gel (A-PAGE) and capillary electrophoresis  

Microsoft Academic Search

Summary Variability of high molecular weight glutenin subunits (HMW-GS) was studied in 198 accessions of Ae. tauschii (2n=2x=14, DD) by sodium dodecyl sulphate (SDS-PAGE) and acid polyacrylamide gel electrophoresis (A-PAGE) and capillary electrophoresis (CE). A high allelic variation of HMW-GS, including some novel x- and y-type subunits and variable subunit combinations were observed. One accession (TD159) showed a x-type null

Yueming Yan; S. L. K. Hsam; Jianzhong Yu; F. J. Zeller

2003-01-01

83

Genetics of adiponectin.  

PubMed

Anti-inflammatory, anti-atherogenic and anti-diabetic properties of adiponectin make this adipokine an attractive target in the metabolism research. Given its biological role, genetic variation in adiponectin affecting its function might consequently play a role in the pathophysiology of various metabolic disorders. In this light, genetic aspects of adiponectin including its gene structure, heritability of serum concentrations and the role of genetic variation have been addressed in multiple genetic studies. Here, we provide a brief summary of adiponectin genetics with focus on gene structure and genetic variation controlling circulating adiponectin levels. We summarize the main findings from genome-wide linkage and association studies that have revealed the major genetic determinants of serum adiponectin. Beside genetic variants in the adiponectin gene, several other genes/loci (ARL15, CDH13, KNG1, FER, ETV5) contributing to the variability in circulating adiponectin have been identified. The majority of these variants are significantly associated with metabolic phenotypes relevant to metabolic diseases (e.g. obesity or type 2 diabetes (T2D)). Considering the protective properties of adiponectin in diseases such as T2D, comprehensive analyses of genetic variants including rare as well as frequent polymorphisms might provide insights on the specific role of adiponectin in the pathophysiology of metabolic diseases. PMID:22449616

Breitfeld, Jana; Stumvoll, Michael; Kovacs, Peter

2012-03-15

84

The Role of Adiponectin in Cancer: A Review of Current Evidence  

PubMed Central

Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies.

Dalamaga, Maria; Diakopoulos, Kalliope N.

2012-01-01

85

Changes in body weight, C-reactive protein, and total adiponectin in non-obese women after 12 months of a small-volume, home-based exercise program  

PubMed Central

OBJECTIVE: Our objective was to evaluate the effects of small-volume, home-based exercise combined with slight caloric restriction on the inflammatory markers C-reactive protein and adiponectin. METHODS: In total, 54 women were randomly assigned to one of two groups for exercise intervention: the control or home-based exercise groups. Weight, waist and hip circumferences, and inflammatory markers were measured at baseline and after 6 and 12 months. Women allocated to the home-based exercise group received a booklet explaining the physical exercises to be practiced at home at least 3 times per week, 40 minutes per session, at low-to-moderate intensity. All participants received dietary counseling aimed at reducing caloric intake by 100-300 calories per day, with a normal distribution of macro-nutrients (26-28% of energy as fat). Clinicaltrials.gov: NCT01206413 RESULTS: The home-based exercise group showed a significantly greater reduction in weight and body mass index at six months, but no difference between groups was observed thereafter. With regard to the inflammatory markers, a greater but non-statistically significant reduction was found for C-reactive protein in the home-based exercise group at six months; however, this difference disappeared after adjusting for weight change. No differences in adiponectin were found at the 6- or 12-month follow-up. CONCLUSION: Small-volume, home-based exercise did not promote changes in inflammatory markers independent of weight change.

Mediano, Mauro Felippe Felix; Neves, Fabiana Alves; de Souza Rodrigues Cunha, Alessandra Cordeiro; de Souza, Erica Patricia Garcia; Moura, Anibal Sanchez; Sichieri, Rosely

2013-01-01

86

Effects of Body Composition, Leptin, and Adiponectin on Bone Mineral Density in Prepubertal Girls  

Microsoft Academic Search

Body weight is positively associated with bone mineral density but the relationship between obesity and bone mineral density is unclear. Leptin and adiponectin are potential independent contributors to bone mineral density. We assessed the correlations of body composition, leptin and adiponectin with bone mineral density, and whether leptin, adiponectin and body composition determine bone mineral density independently in prepubertal girls.

Young Jun Rhie; Kee Hyoung Lee; So Chung Chung; Ho Seong Kim; Duk Hee Kim

2010-01-01

87

The Actinobacillus pleuropneumoniae HMW1C-Like Glycosyltransferase Mediates N-Linked Glycosylation of the Haemophilus influenzae HMW1 Adhesin  

PubMed Central

The Haemophilus influenzae HMW1 adhesin is an important virulence exoprotein that is secreted via the two-partner secretion pathway and is glycosylated at multiple asparagine residues in consensus N-linked sequons. Unlike the heavily branched glycans found in eukaryotic N-linked glycoproteins, the modifying glycan structures in HMW1 are mono-hexoses or di-hexoses. Recent work demonstrated that the H. influenzae HMW1C protein is the glycosyltransferase responsible for transferring glucose and galactose to the acceptor sites of HMW1. An Actinobacillus pleuropneumoniae protein designated ApHMW1C shares high-level homology with HMW1C and has been assigned to the GT41 family, which otherwise contains only O-glycosyltransferases. In this study, we demonstrated that ApHMW1C has N-glycosyltransferase activity and is able to transfer glucose and galactose to known asparagine sites in HMW1. In addition, we found that ApHMW1C is able to complement a deficiency of HMW1C and mediate HMW1 glycosylation and adhesive activity in whole bacteria. Initial structure-function studies suggested that ApHMW1C consists of two domains, including a 15-kDa N-terminal domain and a 55-kDa C-terminal domain harboring glycosyltransferase activity. These findings suggest a new subfamily of HMW1C-like glycosyltransferases distinct from other GT41 family O-glycosyltransferases.

Choi, Kyoung-Jae; Grass, Susan; Paek, Seonghee; St. Geme, Joseph W.; Yeo, Hye-Jeong

2010-01-01

88

Adiponectin and Resistin in the Neonatal Rat  

PubMed Central

Hypoxia is a common neonatal stress that induces insulin resistance and a decrease in body weight gain. Dexamethasone is often used to treat neonatal cardiopulmonary disease, and also leads to insulin resistance and a decrease in body weight gain. The current study addressed the hypothesis that serum concentrations of the adipokines adiponectin and/or resistin are altered during hypoxia and/or dexamethasone therapy in neonatal rats. Rat pups with their lactating dams were exposed to hypoxia (11% O2) from birth and treated with a tapering regimen of dexamethasone from postnatal day (PD) 3–6. Serum adiponectin and resistin were measured on PD7. Hypoxia and dexamethasone independently decreased body weight gain and increased adiponectin levels. The combination of hypoxia and dexamethasone did not further increase adiponectin. Dexamethasone caused a small increase in resistin in normoxic pups, which may facilitate the hyperinsulemic-normoglycemic state we previously described. We also conclude that adiponectin is increased during hypoxia in response to a decrease in the sensitivity to insulin.

Raff, Hershel; Bruder, Eric D.

2006-01-01

89

Effects of marked weight loss on plasma levels of adiponectin, markers of chronic subclinical inflammation and insulin resistance in morbidly obese women  

Microsoft Academic Search

OBJECTIVE:Obesity is linked to the insulin resistance syndrome (IRS), type 2 diabetes (T2D) and cardiovascular disease. Markers of chronic subclinical inflammation such as high-sensitive C-reactive protein (hs-CRP) and interleukin 6 (IL-6) are closely related to insulin resistance and obesity. Recent evidence suggests that adiponectin, a protein whose circulating levels are decreased in obesity, has anti-inflammatory properties, and also appears to

H-P Kopp; K Krzyzanowska; M Möhlig; J Spranger; A F H Pfeiffer; G Schernthaner

2005-01-01

90

Short-Term Overfeeding Increases Circulating Adiponectin Independent of Obesity Status  

PubMed Central

Background Adiponectin is an adipose tissue derived hormone which strengthens insulin sensitivity. However, there is little data available regarding the influence of a positive energy challenge (PEC) on circulating adiponectin and the role of obesity status on this response. Objective The purpose of this study was to investigate how circulating adiponectin will respond to a short-term PEC and whether or not this response will differ among normal-weight(NW), overweight(OW) and obese(OB). Design We examined adiponectin among 64 young men (19-29 yr) before and after a 7-day overfeeding (70% above normal energy requirements). The relationship between adiponectin and obesity related phenotypes including; weight, percent body fat (%BF), percent trunk fat (%TF), percent android fat (%AF), body mass index (BMI), total cholesterol, HDLc, LDLc, glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR) and ?-cell function (HOMA-?) were analyzed before and after overfeeding. Results Analysis of variance (ANOVA) and partial correlations were used to compute the effect of overfeeding on adiponectin and its association with adiposity measurements, respectively. Circulating Adiponectin levels significantly increased after the 7-day overfeeding in all three adiposity groups. Moreover, adiponectin at baseline was not significantly different among NW, OW and OB subjects defined by either %BF or BMI. Baseline adiponectin was negatively correlated with weight and BMI for the entire cohort and %TF, glucose, insulin and HOMA-IR in OB. However, after controlling for insulin resistance the correlation of adiponectin with weight, BMI and %TF were nullified. Conclusion Our study provides evidence that the protective response of adiponectin is preserved during a PEC regardless of adiposity. Baseline adiponectin level is not directly associated with obesity status and weight gain in response to short-term overfeeding. However, the significant increase of adiponectin in response to overfeeding indicates the physiological potential for adiponectin to attenuate insulin resistance during the development of obesity.

Cahill, Farrell; Amini, Peyvand; Wadden, Danny; Khalili, Sammy; Randell, Edward; Vasdev, Sudesh; Gulliver, Wayne; Sun, Guang

2013-01-01

91

Granulocyte elastase cleaves human high molecular weight kininogen and destroys its clot-promoting activity  

PubMed Central

Purified human granulocyte elastase cleaved purified human high molecular weight (HMW) kininogen into multiple low molecular weight fragments, and destroyed the clot-promoting activity of the HMW kininogen. Elastase digestion did not release kinin or destroy the bradykinin portion of the HMW kininogen molecule; kallikrein could release kinin from the elastase-induced low molecular weight digestion products of HMW kininogen. Purified alpha 1-antitrypsin prevented the destruction of the clot-promoting activity of HMW kininogen by elastase; it also delayed the clotting of normal plasma. Elastase may play a significant role in altered hemostasis as well as fibrinolysis, in areas of inflammation to which polymorphonuclear leukocytes have been attracted.

1988-01-01

92

ldentification of an Enhancer Element for the Endosperm-Specific Expression of High Molecular Weight Glutenin  

Microsoft Academic Search

Genes encoding high molecular weight (HMW) glutenin, a wheat seed storage protein, are expressed only in the developing endosperm. It was previously demonstrated that sequences essential for endosperm-specific transcrip- tion reside within 436 base pairs upstream of the initiation codon for HMW glutenin translation. We have further analyzed this region by testing the ability of a series of truncated HMW

Mark S. Thomas; Richard B. Flavel

1990-01-01

93

Structural Insights into the Glycosyltransferase Activity of the Actinobacillus pleuropneumoniae HMW1C-like Protein*  

PubMed Central

Glycosylation of proteins is a fundamental process that influences protein function. The Haemophilus influenzae HMW1 adhesin is an N-linked glycoprotein that mediates adherence to respiratory epithelium, an essential early step in the pathogenesis of H. influenzae disease. HMW1 is glycosylated by HMW1C, a novel glycosyltransferase in the GT41 family that creates N-glycosidic linkages with glucose and galactose at asparagine residues and di-glucose linkages at sites of glucose modification. Here we report the crystal structure of Actinobacillus pleuropneumoniae HMW1C (ApHMW1C), a functional homolog of HMW1C. The structure of ApHMW1C contains an N-terminal all ?-domain (AAD) fold and a C-terminal GT-B fold with two Rossmann-like domains and lacks the tetratricopeptide repeat fold characteristic of the GT41 family. The GT-B fold harbors the binding site for UDP-hexose, and the interface of the AAD fold and the GT-B fold forms a unique groove with potential to accommodate the acceptor protein. Structure-based functional analyses demonstrated that the HMW1C protein shares the same structure as ApHMW1C and provided insights into the unique bi-functional activity of HMW1C and ApHMW1C, suggesting an explanation for the similarities and differences of the HMW1C-like proteins compared with other GT41 family members.

Kawai, Fumihiro; Grass, Susan; Kim, Youngchang; Choi, Kyoung-Jae; St. Geme, Joseph W.; Yeo, Hye-Jeong

2011-01-01

94

Allelic variation of the HMW glutenin subunits in Aegilops tauschii accessions detected by sodium dodecyl sulphate (SDS-PAGE), acid polyacrylamide gel (A-PAGE) and capillary electrophoresis  

Microsoft Academic Search

Variability of high molecular weight glutenin subunits (HMW-GS) was studied in198 accessions of Ae. Tauschii (2n=2x=14, DD) by sodium dodecyl sulphate(SDS-PAGE) and acid polyacrylamide gel electrophoresis (A-PAGE) and capillary electrophoresis\\u000a (CE). A high allelic variation of HMW-GS, including some novel x- and y-type subunits and variable subunit combinations were\\u000a observed. One accession(TD159) showed a x-type null form. The results by

Yueming Yan; S. L. K. Hsam; Jianzhong Yu; Yi Jiang; F. J. Zeller

2003-01-01

95

Detection and characterization of human high molecular weight B cell growth factor receptors on leukemic B cells in chronic lymphocytic leukemia.  

PubMed Central

Human high molecular weight-B cell growth factor (HMW-BCGF) (60 kD) stimulates activated normal B cells, B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells, hairy cell leukemia (HCL) cells, prolymphocytic leukemia (PLL) cells, and chronic lymphocytic leukemia (CLL) cells. The expression of human high molecular weight B cell growth factor (HMW-BCGF) receptors (R) on clonal populations of leukemic B cells in CLL was studied by ligand binding assays using 125I-labeled HMW-BCGF as well as by immunofluorescence/flow cytometry and Scatchard analyses using an anti-HMW-BCGF R monoclonal antibody (MAb), designated BA-5. There was a high correlation between HMW-BCGF R expression and responsiveness to HMW-BCGF. 60% of CLL cases constitutively expressed HMW-BCGF R and showed a marked proliferative response to HMW-BCGF in [3H]TdR incorporation assays as well as colony assays. Similarly, HCL cells, PLL cells, and activated normal B cells expressed functional HMW-BCGF R, as determined by ligand binding assays using 125I-HMW-BCGF, [3H]TdR incorporation assays, and reactivity with BA-5 MAb. Scatchard analyses indicated the existence of approximately 3,000 HMW-BCGF R/cell on HMW-BCGF responsive CLL cells with an apparent Ka value of 4.6 X 10(7) M-1. The concentrations of HMW-BCGF required for maximum stimulation of CLL cells were two to three orders of magnitude lower than those needed for half maximal receptor occupancy, indicating that only a small fraction of HMW-BCGF R need to be occupied to stimulate leukemic CLL B cells. Crosslinking of surface bound 125I-HMW-BCGF (60 kD) with the bivalent crosslinker DTSSP to its binding site on fresh CLL cells identified a 150-kD HMW-BCGF/HMW-BCGF R complex, suggesting an apparent molecular weight of 90 kD for the receptor protein. The growth stimulatory effects of HMW-BCGF on clonogenic CLL cells did not depend on accessory cells or costimulant factors. The anti-HMW-BCGF R monoclonal antibody BA-5 disrupted HMW-BCGF/HMW-BCGF R interactions at the level of clonogenic CLL cells and inhibited HMW-BCGF-stimulated CLL colony formation in vitro. To our knowledge, this study represents the first detailed analysis of expression, function, and structure of HMW-BCGF R on B lineage CLL cells. Images

Uckun, F M; Fauci, A S; Chandan-Langlie, M; Myers, D E; Ambrus, J L

1989-01-01

96

Impact of adiponectin deficiency on pulmonary responses to acute ozone exposure in mice.  

PubMed

Obese mice have increased responses to acute ozone (O(3)) exposure. T-cadherin is a binding protein for the high-molecular weight isoforms of adiponectin, an anti-inflammatory hormone that declines in obesity. The objective of the present study was to determine whether adiponectin affects pulmonary responses to O(3), and whether these effects are mediated through T-cadherin. We performed bronchoalveolar lavage (BAL) and measured pulmonary responsiveness to methacholine after acute air or O(3) exposure (2 ppm for 3 h) in adiponectin-deficient (Adipo(-/-)) or T-cadherin-deficient (T-Cad(-/-)) mice. O(3) increased pulmonary responses to methacholine and increased BAL neutrophils and protein to a greater extent in wild-type than in Adipo(-/-) mice, whereas T-cadherin deficiency had no effect. O(3)-induced increases in BAL IL-6 and keratinocyte-derived chemokine (KC), which contribute to O(3)-induced pulmonary neutrophilia, were also greater in wild-type than in Adipo(-/-) mice. In contrast, responses to O(3) were not altered by transgenic overexpression of adiponectin. To determine which adiponectin isoforms are present in the lung, Western blotting was performed. The hexameric isoform of adiponectin dominated in serum, whereas BAL was dominated by the high-molecular weight isoform of adiponectin. Interestingly, serum adiponectin was greater in T-Cad(-/-) versus wild-type mice, whereas BAL adiponectin was lower in T-Cad(-/-) versus wild-type mice, suggesting that T-cadherin may be important for transit of high-molecular weight adiponectin from the blood to the lung. Our results indicate that adiponectin deficiency inhibits pulmonary inflammation induced by acute O(3) exposure, and that T-cadherin does not mediate the effects of adiponectin responsible for these events. PMID:19915153

Zhu, Ming; Hug, Christopher; Kasahara, David I; Johnston, Richard A; Williams, Alison S; Verbout, Norah G; Si, Huiqing; Jastrab, Jordan; Srivastava, Amit; Williams, Erin S; Ranscht, Barbara; Shore, Stephanie A

2009-11-13

97

Adiponectin and body composition in cystic fibrosis  

Microsoft Academic Search

The aim of the study was to evaluate adiponectin (AD) serum concentrations in 43 stable CF patients and 27 healthy subjects and to correlate them with their nutritional status. Body Composition (Bioelectrical Impedance), visceral\\/subcutaneous adipose tissue (VAT-SAT) in CF patients (CT-scan at L4), insulin resistance (HOMA-IR) and AD serum concentrations (ELISA) were studied. CF patients and controls had comparable weight,

Paraskevi Panagopoulou; Maria Fotoulaki; Alexandros Manolitsas; Ekaterini Pavlitou-Tsiontsi; Ioannis Tsitouridis; Sanda Nousia-Arvanitakis

2008-01-01

98

Role of the Adiponectin Binding Protein, T-Cadherin (Cdh13), in Allergic Airways Responses in Mice  

PubMed Central

Adiponectin is an adipose derived hormone that declines in obesity. We have previously shown that exogenous administration of adiponectin reduces allergic airways responses in mice. T-cadherin (T-cad; Cdh13) is a binding protein for the high molecular weight isoforms of adiponectin. To determine whether the beneficial effects of adiponectin on allergic airways responses require T-cad, we sensitized wildtype (WT), T-cadherin deficient (T-cad?/?) and adiponectin and T-cad bideficient mice to ovalbumin (OVA) and challenged the mice with aerosolized OVA or PBS. Compared to WT, T-cad?/? mice were protected against OVA-induced airway hyperresponsiveness, increases in BAL inflammatory cells, and induction of IL-13, IL-17, and eotaxin expression. Histological analysis of the lungs of OVA-challenged T-cad?/? versus WT mice indicated reduced inflammation around the airways, and reduced mucous cell hyperplasia. Combined adiponectin and T-cad deficiency reversed the effects of T-cad deficiency alone, indicating that the observed effects of T-cad deficiency require adiponectin. Compared to WT, serum adiponectin was markedly increased in T-cad?/? mice, likely because adiponectin that is normally sequestered by endothelial T-cad remains free in the circulation. In conclusion, T-cad does not mediate the protective effects of adiponectin. Instead, mice lacking T-cad have reduced allergic airways disease, likely because elevated serum adiponectin levels act on other adiponectin signaling pathways.

Williams, Alison S.; Kasahara, David I.; Verbout, Norah G.; Fedulov, Alexey V.; Zhu, Ming; Si, Huiqing; Wurmbrand, Allison P.; Hug, Christopher; Ranscht, Barbara; Shore, Stephanie A.

2012-01-01

99

Characterization and comparative analysis of HMW glutenin 1Ay alleles with differential expressions  

PubMed Central

Background High-molecular-weight glutenin subunits (HMW-GSs) have been considered as most important seed storage proteins for wheat flour quality. 1Ay subunits are of great interest because they are always silent in common wheat. The presence of expressed 1Ay subunits in diploid and tetraploid wheat genotypes makes it possible to investigate molecular information of active 1Ay genes. Results We identified 1Ay subunits with different electrophoretic mobility from 141 accessions of diploid and tetraploid wheats, and obtained the complete ORFs and 5' flanking sequences of 1Ay genes including 6 active and 3 inactive ones. Furthermore, the 5' flanking sequences were characterized from 23 wild diploid species of Triticeae. All 6 active 1Ay possess a typical HMW-GS primary structure and some novel characteristics. The conserved cysteine residue within the repetitive domain of y-type subunits was replaced by phenylalanine residue in subunits of 1Ay (Tu-e1), 1Ay (Tu-e2), 1Ay (Ta-e2) and 1Ay (Td-e). Particularly, 1Ay (Ta-e3) has an unusual large molecular weight of 2202 bp and was one of the known largest y-type HMW-GSs. The translations of 1Ay (Tu-s), 1Ay (Ta-s) and 1Ay (Td-s) were disrupted by premature stop codons in their coding regions. The 5' flanking sequences of active and inactive 1Ay genes differ in a few base substitutions and insertions or deletions. The 85 bp deletions have been found in promoter regions of all 1Ay genes and the corresponding positions of 6 species from Aegilops and Hordeum. Conclusion The possession of larger molecular weight and fewer conserved cysteine residues are unique structural features of 1Ay genes; it would be interested to express them in bread wheat and further to examine their impact to processing quality of wheat. The 1Ay genes from T. urartu are closer to the genes from T. turgidum dicoccon and T. aestivum, than those from T. monococcum aegilopoides. The 85 bp deletion and some variations in the 5'flanking region, have not interrupted expression of 1Ay genes, whereas the defects in the coding regions could be responsible to the silence of the 1Ay genes. Some mutational events in more distant distal promoter regions are also possible causes for the inactivation of 1Ay genes.

Jiang, Qian-Tao; Wei, Yu-Ming; Wang, Feng; Wang, Ji-Rui; Yan, Ze-Hong; Zheng, You-Liang

2009-01-01

100

Adiponectin and traumatic brain injury.  

PubMed

Adiponectin, a circulating adipose-derived hormone regulating inflammation and energy metabolism, has beneficial actions on cardiovascular disorders. Recent studies have suggested that adiponectin might be a potential molecular target for ischemic stroke therapy; however, little is known about the effects of adiponectin on traumatic brain injury. The present study examined the immunoactivity of adiponectin.Adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury using the Dragonfly device. Immuno-histochemical studies showed that the adiponectin expression was increased in the cerebral cortex at 24 h after injury and in the hippocampus at 72 h after injury. Our findings suggest that adiponectin might participate in the pathophysiological process occurring after traumatic brain injury. PMID:23564114

Takeuchi, Satoru; Wada, Kojiro; Nawashiro, Hiroshi; Uozumi, Yoichi; Otani, Naoki; Osada, Hideo; Nagatani, Kimihiro; Kobayashi, Hiroaki; Suzuki, Takamoto; Shima, Katsuji

2013-01-01

101

Separation and Quantification of HMW Glutenin Subunits by Capillary Electrophoresis 1  

Microsoft Academic Search

Cereal Chem. 78(6):737-742 The use of capillary electrophoresis in SDS (SDS-CE) for separation and quantification of HMW glutenin subunits (HMW-GS) was investi- gated. HMW-GS were precipitated with 40% acetone from 50% 1-pro- panol extract of flour under reducing conditions after removal of mono- meric proteins with 50% 1-propanol. Poly (ethylene oxide) was used in the running buffer (3% w\\/v) for

J. Zhu; K. Khan

2001-01-01

102

Elevated Serum Adiponectin Level in Patients with Mycobacterium avium-intracellulare Complex Pulmonary Disease  

Microsoft Academic Search

Background: Patients with Mycobacterium avium-intracellulare complex (MAC) pulmonary disease often suffer from weight loss. Adipokines are factors secreted by adipocytes, including leptin and adiponectin, as well as some inflammatory cytokines, tumor necrosis factor-? (TNF-?) and interleukin 6 (IL-6). Body mass index (BMI) is known to be inversely correlated with adiponectin and positively with leptin, TNF-?, and IL-6. Objective: We aimed

Sadatomo Tasaka; Naoki Hasegawa; Tomoyasu Nishimura; Wakako Yamasawa; Hirofumi Kamata; Hiromi Shinoda; Yoshifumi Kimizuka; Hiroshi Fujiwara; Hiroshi Hirose; Akitoshi Ishizaka

2010-01-01

103

Objectively Measured Physical Activity Is Negatively Associated with Plasma Adiponectin Levels in Minority Female Youth  

PubMed Central

Objective. To evaluate the relationship between adiponectin and physical activity (PA) in minority female youth. Methods. Plasma adiponectin was measured in 39 females (mean age 9.2 ± 0.9 years; 30 Latina, 9 African-American; 56% overweight). PA was assessed by accelerometry. Mean minutes per day spent in daily PA (DPA) (?3 metabolic equivalents (METs)), moderate PA (MPA)(4–7 METs), vigorous PA (VPA)(?7 METs), and moderate-to-vigorous PA (MVPA)(?4 METs) were calculated. The association between adiponectin and PA, controlling for age, fat weight, lean weight, and insulin sensitivity (SI) was analyzed using linear regression. Results. Adiponectin correlated with fat weight (r = ?0.43, P < .01) and SI (r = 0.52, P < .01). Minutes spent in DPA (? = ?0.40, P = .02), MPA (? = ?0.36, P = .04), or MVPA (? = ?0.37, P = .03) were predictors of adiponectin in the adjusted model. Conclusions. Higher PA levels were related to lower adiponectin levels. Potential mechanisms include upregulation of adiponectin receptors or an increase in high-molecular weight adiponectin with increasing PA.

Emken, B. Adar; Richey, Joyce; Belcher, Britni; Hsu, Ya-Wen; Spruijt-Metz, Donna

2010-01-01

104

Composition of HMW and LMW Glutenin Subunits and Their Effects on Dough Properties, Pan Bread, and Noodle Quality of Chinese Bread Wheats  

Microsoft Academic Search

Cereal Chem. 82(4):345-350 Knowledge of composition of high molecular weight glutenin subunits (HMW-GS) and low molecular weight glutenin subunits (LMW-GS) and their associations with pan bread and noodle quality will contribute to gen- etically improving processing quality of Chinese bread wheats. Two trials including a total of 158 winter and facultative cultivars and advanced lines were conducted to detect the

Z. H. He; L. Liu; X. C. Xia; J. J. Liu; R. J. Peña

2005-01-01

105

Presence and prognostic significance of melanoma-associated antigens CYT-MAA and HMW-MAA in serum of patients with melanoma.  

PubMed

With the goal of finding serological markers to monitor patients with early- as well as late-stage melanoma, we compared the levels of the cytoplasmic melanoma-associated antigens (CYT-MAA) and high-molecular-weight melanoma-associated antigen (HMW-MAA) in the sera of melanoma patients and controls. Using double-sandwich ELISA, we measured levels of both antigens in 117 patients and in 62 age- and sex-matched controls. Patients were stratified into four risk group based on stage of the disease. Serum levels of both markers were significantly higher in melanoma patients than in controls. CYT-MAA was the more sensitive marker, with 61% of patients showing elevated levels regardless of the stage of disease. HMW-MAA was elevated in 29%. Elevated CYT-MAA was also significantly correlated with poorer clinical outcome. By multivariate analysis (adjusting for stage and age), patients who had elevated CYT-MAA were 81% more likely to recur than patients with undetectable levels (hazard ratio=1.81, 95% CI=[1.07, 3.06], p-value=0.03). Elevated levels of HMW-MAA did not correlate with poor prognosis. These results suggest that both CYT-MAA and HMW-MAA are serum markers for residual melanoma in patients with resected disease. Furthermore, CYT-MAA appears to be a prognostic marker of clinical outcome in melanoma vaccine-treated patients. PMID:16117794

Vergilis, Irene J; Szarek, Michael; Ferrone, Soldano; Reynolds, Sandra R

2005-09-01

106

Glucocorticoid Effects on Adiponectin Expression  

PubMed Central

Maintenance of energy metabolism and glucose homeostasis is achieved by the regulatory effects of many hormones and their interactions. Glucocorticoids produced from adrenal cortex and adiponectin produced by adipose tissue play important roles in the production, distribution, storage, and utilization of energy substrates. Glucocorticoids are involved in the activation of a number of catabolic processes by affecting the expression of a plethora of genes, while adiponectin acts primarily as an insulin sensitizer. Both are regulated by a number of physiological and pharmacological factors. Although the effects of glucocorticoids on adiponectin expression have been extensively studied in different in vitro, animal and clinical study settings, no consensus has been reached. This report reviews the primary literature concerning the effects of glucocorticoids on adiponectin expression and identifies potential reasons for the contradictory results between different studies. In addition, methods to gain better insights pertaining to the regulation of adiponectin expression are discussed.

Sukumaran, Siddharth; DuBois, Debra C.; Jusko, William J.; Almon, Richard R.

2013-01-01

107

Role of leptin and adiponectin in insulin resistance.  

PubMed

Adipose tissue is a major source of energy for the human body. It is also a source of major adipocytokines adiponectin and leptin. Insulin resistance is a condition in which insulin action is impaired in adipose tissue and is more strongly linked to intra-abdominal fat than to fat in other depots. The expression of adiponectin decreases with increase in the adiposity. Adiponectin mediates insulin-sensitizing effect through binding to its receptors AdipoR1 and AdipoR2, leading to activation of adenosine monophosphate dependent kinase (AMPK), PPAR-?, and presumably other yet-unknown signalling pathways. Weight loss significantly elevates plasma adiponectin levels. Reduction of adiponectin has been associated with insulin resistance, dyslipidemia, and atherosclerosis in humans. The other major adipokine is leptin. Leptin levels increase in obesity and subcutaneous fat has been a major determinant of circulating leptin levels. The leptin signal is transmitted by the Janus kinase, signal transducer and activator of transcription ((JAK-STAT) pathway. The net action of leptin is to inhibit appetite, stimulate thermogenesis, enhance fatty acid oxidation, decrease glucose, and reduce body weight and fat. PMID:23266767

Yadav, Amita; Kataria, Megha A; Saini, Vandana; Yadav, Anil

2012-12-22

108

Human Antibodies Specific for the High-Molecular-Weight Adhesion Proteins of Nontypeable Haemophilus influenzae Mediate Opsonophagocytic Activity  

PubMed Central

The HMW1- and HMW2-like adhesion proteins of nontypeable Haemophilus influenzae are expressed by 75% of these strains, and antibodies directed against these proteins are protective in animal models of infection. The purpose of the present study was to define the functional activity of human antibodies specific for these proteins in an in vitro complement-dependent opsonophagocytic assay. Human promyelocytic cell line HL-60 served as the source of phagocytic cells, and a commercial preparation of intravenous immunoglobulin (IVIG) served as the source of human antibodies. High-molecular-weight (HMW) proteins were purified from four prototype nontypeable H. influenzae strains and used to prepare solid-phase affinity columns. IVIG was adsorbed on each column to remove strain-specific anti-HMW antibodies and to allow recovery of affinity-purified anti-HMW antibody fractions. Unadsorbed IVIG killed each of the prototype strains at titers of 1:80 to 1:320. HMW-adsorbed sera demonstrated fourfold decreases in opsonophagocytic titer against the homologous strains compared to unadsorbed IVIG. Affinity-purified anti-HMW antibody preparations demonstrated opsonophagocytic titers of 1:20 to 1:80 against the respective homologous strains and opsonophagocytic titers as high as 1:80 against heterologous strains. None of the affinity-purified anti-HMW antibody preparations was opsonophagocytic for a representative nontypeable H. influenzae strain that did not express HMW1- or HMW2-like proteins. These data demonstrate that human antibodies specific for the HMW1/HMW2-like adhesion proteins of nontypeable H. influenzae are opsonophagocytic and that such antibodies recognize epitopes shared by the HMW proteins of unrelated nontypeable H. influenzae strains. These results argue for continued investigation of the HMW1/HMW2-like proteins as potential vaccine candidates for prevention of disease due to nontypeable H. influenzae.

Winter, Linda E.; Barenkamp, Stephen J.

2003-01-01

109

Ubiquitous occurrence of high molecular weight hydrocarbons in crude oils  

Microsoft Academic Search

For many years the presence of waxes in crude oils has been associated with organic matter derived from terrigenous sources. High temperature gas chromatography (HTGC) has been used to establish the ubiquitous presence of high molecular weight (HMW) hydrocarbons, extending as high as C120, in crude oils. HMW hydrocarbons (>C40+) have been observed in crude oils derived from terrigenous, lacustrine,

Michael Hsieh; R. Paul Philp

2001-01-01

110

Transposon mutagenesis reinforces the correlation between Mycoplasma pneumoniae cytoskeletal protein HMW2 and cytadherence.  

PubMed Central

A new genetic locus associated with Mycoplasma pneumoniae cytadherence was previously identified by transposon mutagenesis with Tn4001. This locus maps approximately 160 kbp from the genes encoding cytadherence-associated proteins HMW1 and HMW3, and yet insertions therein result in loss of these proteins and a hemadsorption-negative (HA-) phenotype, prompting the designation cytadherence-regulatory locus (crl). In the current study, passage of transformants in the absence of antibiotic selection resulted in loss of the transposon, a wild-type protein profile, and a HA+ phenotype, underscoring the correlation between crl and M. pneumoniae cytadherence. Nucleotide sequence analysis of crl revealed open reading frames (ORFs) orfp65, orfp216, orfp41, and orfp24, arranged in tandem and flanked by a promoter-like and a terminator-like sequence, suggesting a single transcriptional unit, the P65 operon. The 5' end of orfp65 mRNA was mapped by primer extension, and a likely promoter was identified just upstream. The product of each ORF was identified by using antisera prepared against fusion proteins. The previously characterized surface protein P65 is encoded by orfp65, while the 190,000 Mr cytadherence-associated protein HMW2 is a product of orfp216. Proteins with sizes of 47,000 and 41,000 Mr and unknown function were identified for orfp41 and orfp24, respectively. Structural analyses of HMW2 predict a periodicity highly characteristic of a coiled-coil conformation and five leucine zipper motifs, indicating that HMW2 probably forms dimers in vivo, which is consistent with a structural role in cytadherence. Each transposon insertion mapped to orfp216 but affected the levels of all products of the P65 operon. HMW2 is thought to form a disulfide-linked dimer, formerly designated HMW5, and examination of an hmw2 deletion mutant confirms that HMW5 is a product of the hmw2 gene.

Krause, D C; Proft, T; Hedreyda, C T; Hilbert, H; Plagens, H; Herrmann, R

1997-01-01

111

Molecular Characterization of a HMW Glutenin Subunit Allele Providing Evidence for Silencing of x-type Gene on Glu-B1  

Microsoft Academic Search

Understanding the molecular structure of high-molecular-weight glutenin subunit (HMW-GS) may provide useful evidence for the study on the improvement of quality of cultivated wheat and the evolution of Glu-1 alleles. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) shows that the subunits encoded by Glu-B1 were null, named 1Bxm, in a Triticum turgidum var. dicoccoides line PI94640. Primers based on the conserved

Zu-Jun YANG; Guang-Rong LI; Chang LIU; Juan FENG; Jian-Ping ZHOU; Zheng-Long REN

2006-01-01

112

Interstitial-tissue localization of high-molecular-weight kininogen in guinea-pig skin.  

PubMed

A rabbit antibody against the light-chain of guinea-pig high-molecular-weight (HMW) kininogen, which was specific to HWM kininogen and did not recognize low-molecular-weight kininogen, was prepared. This antibody demonstrated the presence of HMW kininogen antigen at the interstitial-tissue space in the guinea-pig skin by means of immunohistochemistry. The interstitial-tissue HMW kininogen antigen was extracted from the skin. This antigen molecule in the skin extract behaved identically as HWM kininogen of plasma in slab-polyacrylamide gel electrophoresis under the presence of sodium dodecyl sulfate followed by immunoblotting. Therefore, it was concluded that HMW kininogen was present in the interstitial-tissue fluid in the skin. The amount of HMW kininogen in the skin extract was quantified by a sandwich enzyme-linked immunosorbent assay with the anti-light-chain antibody and a goat anti-guinea-pig HMW kininogen antibody. On the assumption that the interstitial-tissue volume is 50 ml/100 g wet skin tissue, the average concentration of HMW kininogen in the interstitial-tissue fluid of the skin was calculated to be 23% of the plasma concentration. On the other hand, the proportion of intravascular HMW kininogen (derived from blood remaining in the vessels of the harvested skin) in relation to the total HMW kininogen in the skin extract was quantified by measuring the radio-labelled HMW kininogen which had been injected intravenously as a tracer of the intravascular HMW kininogen. About 5% of the total HMW kininogen in the skin extract was calculated to be derived from the intravascular blood volume of the skin, indicating that the majority of the HMW kininogen in the skin extract was derived from the extravascular-tissue space. PMID:3120776

Yamamoto, T; Tsuruta, J; Kambara, T

1987-12-18

113

Mycoplasma pneumoniae Cytoskeletal Protein HMW2 and the Architecture of the Terminal Organelle?  

PubMed Central

The terminal organelle of Mycoplasma pneumoniae mediates cytadherence and gliding motility and functions in cell division. The defining feature of this complex membrane-bound cell extension is an electron-dense core of two segmented rods oriented longitudinally and enlarging to form a bulb at the distal end. While the components of the core have not been comprehensively identified, previous evidence suggested that the cytoskeletal protein HMW2 forms parallel bundles oriented lengthwise to yield the major rod of the core. In the present study, we tested predictions emerging from that model by ultrastructural and immunoelectron microscopy analyses of cores from wild-type M. pneumoniae and mutants producing HMW2 derivatives. Antibodies specific for the N or C terminus of HMW2 labeled primarily peripheral to the core along its entire length. Furthermore, truncation of HMW2 did not correlate specifically with core length. However, mutant analysis correlated specific HMW2 domains with core assembly, and examination of core-enriched preparations confirmed that HMW2 was a major component of these fractions. Taken together, these findings yielded a revised model for HMW2 in terminal organelle architecture.

Bose, Stephanie R.; Balish, Mitchell F.; Krause, Duncan C.

2009-01-01

114

Plasma adiponectin distribution in a Mediterranean population and its association with cardiovascular risk factors and metabolic syndrome  

Microsoft Academic Search

Adiponectin may play an important role in the regulation of body weight, insulin resistance, and cardiovascular disease. The aim of this study was to evaluate the distribution of adiponectin in a Mediterranean adult population and its relationship with cardiovascular risk factors and metabolic syndrome. A cross-sectional study was performed in a representative sample of 1023 subjects from a Spanish Mediterranean

Jordi Salas-Salvadó; Marisa Granada; Mònica Bulló; Augusto Corominas; Patricia Casas; Màrius Foz

2007-01-01

115

Secretion of adiponectin from mouse aorta and its role in cold storage-induced vascular dysfunction.  

PubMed

Availability of adiponectin plays a crucial role in cardiovascular function. The present study was conducted to evaluate the presence, alterations and impact of the various adiponectin isoforms in vascular tissue under clinically relevant in vitro conditions (cold storage). Presence of various adiponectin isoforms in vascular smooth muscle cells and their regulation during cold storage was evaluated by PCR, western blot, ELISA and immunohistochemistry. The impact of the various isoforms for vessel preservation was assessed using isometric force measurement as an in vitro assay for vascular function. Adiponectin is expressed in smooth muscle cells from murine aortae and human saphenous veins. Following 2 days of cold storage adiponectin mRNA expression in mouse aorta is reduced, which appears to be regulated indirectly by miR-292-3p. Despite the reduced mRNA expression, adiponectin accumulated in cold storage supernatant over 2 days indicating a net release of adiponectin. Two days of cold storage resulted in an impairment of endothelium-dependent relaxation which was prevented by addition of full-length adiponectin in concentrations similar to normal plasma levels during storage. In contrast, addition of recombinant adiponectin which is unable to form high order multimers failed to improve vessel function. High concentrations (20 ?g/mL) of this trimeric isoform even reduced the vasorelaxation response and facilitated uncoupling of endothelial nitric oxide synthase. Endothelial injury by cold storage may partly be prevented by addition of high-molecular-weight adiponectin. This effect may support graft patency to avoid coagulation- and atherosclerosis-associated impairment of perfusion. PMID:24121466

Ebner, Annette; Poitz, David M; Alexiou, Konstantin; Deussen, Andreas

2013-10-11

116

Adiponectin, leptin, and yoga practice.  

PubMed

To address the mechanisms underlying hatha yoga's potential stress-reduction benefits, we compared adiponectin and leptin data from well-matched novice and expert yoga practitioners. These adipocytokines have counter-regulatory functions in inflammation; leptin plays a proinflammatory role, while adiponectin has anti-inflammatory properties. Fifty healthy women (mean age=41.32, range=30-65), 25 novices and 25 experts, provided fasting blood samples during three separate visits. Leptin was 36% higher among novices compared to experts, P=.008. Analysis of adiponectin revealed a borderline effect of yoga expertise, P=.08; experts' average adiponectin levels were 28% higher than novices across the three visits. In contrast, experts' average adiponectin to leptin ratio was nearly twice that of novices, P=.009. Frequency of self-reported yoga practice showed significant negative relationships with leptin; more weeks of yoga practice over the last year, more lifetime yoga sessions, and more years of yoga practice were all significantly associated with lower leptin, with similar findings for the adiponectin to leptin ratio. Novices and experts did not show even marginal differences on behavioral and physiological dimensions that might represent potential confounds, including BMI, central adiposity, cardiorespiratory fitness, and diet. Prospective studies addressing increased risk for type II diabetes, hypertension, and cardiovascular disease have highlighted the importance of these adipocytokines in modulating inflammation. Although these health risks are clearly related to more extreme values then we found in our healthy sample, our data raise the possibility that longer-term and/or more intensive yoga practice could have beneficial health consequences by altering leptin and adiponectin production. PMID:22306535

Kiecolt-Glaser, Janice K; Christian, Lisa M; Andridge, Rebecca; Hwang, Beom Seuk; Malarkey, William B; Belury, Martha A; Emery, Charles F; Glaser, Ronald

2012-01-27

117

Racial differences in adiponectin and leptin in healthy premenopausal women.  

PubMed

The aim of this article is to longitudinally investigate racial differences in serum adiponectin and leptin in European-American (EA) and African-American (AA) women in the overweight and weight-reduced states. Sixty-two EA and 58 AA premenopausal women were weight reduced from body mass index (BMI) 27-30 kg/m(2) to BMI ? 24. Fasting serum adiponectin and leptin were determined; body composition and intra-abdominal adipose tissue (IAAT) were measured with dual-energy X-ray absorptiometry and computed tomography, respectively. In repeated-measure MANOVA, there was a significant race effect for IAAT and total fat mass; compared to AA women, EA women had higher IAAT and total fat mass (p < 0.0001 and p = 0.027, respectively). In the mixed-model for adiponectin that adjusted for IAAT, limb fat, and total fat, race was significantly associated with adiponectin (p = 0.046). AA women had significantly lower adjusted adiponectin compared to EA women at baseline [7.67 (6.85, 8.60) vs. 9.32 (8.34, 10.4) ?g/ml, p < 0.05] and following weight loss [9.75 (8.70, 10.9) vs. 11.8 (10.6, 13.2) ?g/ml, p < 0.05]. In a mixed-model for leptin that adjusted for insulin, estradiol, and fat mass, race was significantly associated with leptin (p < 0.0001). AA women had significantly higher adjusted leptin compared to EA women at baseline [24.7 (22.3, 27.4) vs. 19.9 (18.1, 21.8) ng/dl, p < 0.05] and following weight loss [11.7 (10.2, 13.3) vs. 8.48 (7.50, 9.57) ng/dl, p < 0.05]. Despite having a more favorable body fat distribution, AA women had lower adjusted adiponectin and higher leptin. Differences in body composition and fat distribution do not appear to be significant factors in explaining lower adiponectin and higher leptin in AA women. PMID:22983832

Azrad, Maria; Gower, Barbara A; Hunter, Gary R; Nagy, Tim R

2012-09-15

118

Dietary fish oil did not prevent sleep deprived rats from a reduction in adipose tissue adiponectin gene expression  

PubMed Central

Sleep deprivation in humans has been related to weight gain and consequently, increased risk for insulin resistance. In contrast, there is a significant loss of weight in sleep deprived rats suggesting a state of insulin resistance without obesity interference. Thus, we aimed to assess the effects of a rich fish oil dietetic intervention on glucose tolerance, serum insulin and adiponectin, and adipose tissue gene expression of adiponectin and TNF-? of paradoxically sleep deprived (PSD) rats. The study was performed in thirty day-old male Wistar randomly assigned into two groups: rats fed with control diet (soybean oil as source of fat) and rats fed with a fish oil rich diet. After 45 days of treatment, the animals were submitted to PSD or maintained as home cage control group for 96 h. Body weight and food intake were carefully monitored in all groups. At the end of PSD period, a glucose tolerance test was performed and the total blood and adipose tissues were collected. Serum insulin and adiponectin were analyzed. Adipose tissues were used for RT-PCR to estimate the gene expression of adiponectin and TNF-?. Results showed that although fish oil diet did not exert any effect upon these measurements, PSD induced a reduction in adiponectin gene expression of retroperitoneal adipose tissues, with no change in serum adiponectin concentration or in adiponectin and TNF-? gene expression of epididymal adipose tissue. Thus, the stress induced by sleep deprivation lead to a desbalance of adiponectin gene expression.

de Mattos, Ana Barbosa Marcondes; Pinto, Monica Jordao S; Oliveira, Cristiane; Biz, Carolina; Ribeiro, Eliane Beraldi; do Nascimento, Claudia Maria Oller; Andersen, Monica Levy; Tufik, Sergio; Oyama, Lila Missae

2008-01-01

119

Adiponectin: Identification, physiology and clinical relevance in metabolic and vascular disease  

Microsoft Academic Search

Adiponectin is the most abundant adipose-specific protein. Its expression is reduced in obesity, insulin resistance and type 2 diabetes, and plasma concentrations are inversely related to body weight, especially visceral adiposity. Adiponectin is also inversely associated with other traditional cardiovascular risk factors, such as blood pressure, low-density lipoprotein cholesterol and triglyceride levels, and is positively related to high-density lipoprotein cholesterol

Yuji Matsuzawa

2005-01-01

120

Adiponectin gene therapy ameliorates high-fat, high-sucrose diet-induced metabolic perturbations in mice  

PubMed Central

Background and Design: Adiponectin is an adipokine secreted primarily from adipose tissue that can influence circulating plasma glucose and lipid levels through multiple mechanisms involving a variety of organs. In humans, reduced plasma adiponectin levels induced by obesity are associated with insulin resistance and type 2 diabetes, suggesting that low adiponectin levels may contribute the pathogenesis of obesity-related insulin resistance. Methods and Results: The objective of the present study was to investigate whether gene therapy designed to elevate circulating adiponectin levels is a viable strategy for ameliorating insulin resistance in mice fed a high-fat, high-sucrose (HFHS) diet. Electroporation-mediated gene transfer of mouse adiponectin plasmid DNA into gastrocnemius muscle resulted in elevated serum levels of globular and high-molecular weight adiponectin compared with control mice treated with empty plasmid. In comparison to HFHS-fed mice receiving empty plasmid, mice receiving adiponectin gene therapy displayed significantly decreased weight gain following 13 weeks of HFHS diet associated with reduced fat accumulation, and exhibited increased oxygen consumption and locomotor activity as measured by indirect calorimetry, suggesting increased energy expenditure in these mice. Consistent with improved whole-body metabolism, mice receiving adiponectin gene therapy also had lower blood glucose and insulin levels, improved glucose tolerance and reduced hepatic gluconeogenesis compared with control mice. Furthermore, immunoblot analysis of livers from mice receiving adiponectin gene therapy showed an increase in insulin-stimulated phosphorylation of insulin signaling proteins. Conclusion: Based on these data, we conclude that adiponectin gene therapy ameliorates the metabolic abnormalities caused by feeding mice a HFHS diet and may be a potential therapeutic strategy to improve obesity-mediated impairments in insulin sensitivity.

Kandasamy, A D; Sung, M M; Boisvenue, J J; Barr, A J; Dyck, J R B

2012-01-01

121

Adiponectin and Resistin in Human Cerebrospinal Fluid and Expression of Adiponectin Receptors in the Human Hypothalamus  

Microsoft Academic Search

Context: The adipokine leptin has critical importance in central appetite regulation. In contrast to some suggestion of adiponectin influencing energy homeostasis in rodents, there is no evidence for adiponectin or resistin entering the human blood-brain barrier. Objective: The objective was to establish the presence of adiponectin or resistin in human cerebrospinal fluid (CSF) and to compare their distribution with leptin.

Katarina Kos; Alison L. Harte; Nancy F. da Silva; Anton Tonchev; Georgi Chaldakov; Sean James; David R. Snead; Barbara Hoggart; Joseph P. O'Hare; Philip G. McTernan; Sudhesh Kumar

122

Opposite Changes in Circulating Adiponectin in Women With Bulimia Nervosa or Binge Eating Disorder  

Microsoft Academic Search

Adiponectin is a recently discovered peripheral peptide that is secreted exclusively by differentiated adipocytes. It has been shown to enhance insulin sensitivity, control body weight, regulate lipid homeostasis, and prevent atheroscle- rosis. Dysregulation of both lipid and glucose metabolism and changes in body weight and body fat mass have been reported in bulimia nervosa (BN) and\\/or binge eating disorder (BED);

PALMIERO MONTELEONE; MICHELE FABRAZZO; VASSILIS MARTIADIS; ANTONIO FUSCHINO; CRISTINA SERRITELLA; NICOLA MILICI; MARIO MAJ

123

Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts  

SciTech Connect

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.

Kitahara, Kanako [Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541 (Japan); Department of Immunology, Toho University School of Medicine, Tokyo (Japan); Kusunoki, Natsuko [Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541 (Japan); Kakiuchi, Terutaka [Department of Immunology, Toho University School of Medicine, Tokyo (Japan); Suguro, Toru [Department of Orthopaedic Surgery, Toho University School of Medicine, Tokyo (Japan); Kawai, Shinichi [Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541 (Japan)], E-mail: skawai@med.toho-u.ac.jp

2009-01-09

124

Adipocyte iron regulates adiponectin and insulin sensitivity.  

PubMed

Iron overload is associated with increased diabetes risk. We therefore investigated the effect of iron on adiponectin, an insulin-sensitizing adipokine that is decreased in diabetic patients. In humans, normal-range serum ferritin levels were inversely associated with adiponectin, independent of inflammation. Ferritin was increased and adiponectin was decreased in type 2 diabetic and in obese diabetic subjects compared with those in equally obese individuals without metabolic syndrome. Mice fed a high-iron diet and cultured adipocytes treated with iron exhibited decreased adiponectin mRNA and protein. We found that iron negatively regulated adiponectin transcription via FOXO1-mediated repression. Further, loss of the adipocyte iron export channel, ferroportin, in mice resulted in adipocyte iron loading, decreased adiponectin, and insulin resistance. Conversely, organismal iron overload and increased adipocyte ferroportin expression because of hemochromatosis are associated with decreased adipocyte iron, increased adiponectin, improved glucose tolerance, and increased insulin sensitivity. Phlebotomy of humans with impaired glucose tolerance and ferritin values in the highest quartile of normal increased adiponectin and improved glucose tolerance. These findings demonstrate a causal role for iron as a risk factor for metabolic syndrome and a role for adipocytes in modulating metabolism through adiponectin in response to iron stores. PMID:22996660

Gabrielsen, J Scott; Gao, Yan; Simcox, Judith A; Huang, Jingyu; Thorup, David; Jones, Deborah; Cooksey, Robert C; Gabrielsen, David; Adams, Ted D; Hunt, Steven C; Hopkins, Paul N; Cefalu, William T; McClain, Donald A

2012-09-10

125

Adiponectin gene polymorphisms may not be associated with idiopathic premature ovarian failure.  

PubMed

Premature ovarian failure (POF) is a syndrome characterized by loss of ovarian function before the age of 40 years. Adiponectin, a protein secreted by adipose tissue, exerts beneficial effects on glucose and lipid metabolism. Transcription of adiponectin and its receptor gene is correlated with follicular development. POF, as a type of pathological ovarian aging, is associated with an increase in fat mass and body weight, in which adiponectin may be involved. The present study aimed to investigate the relationship between adiponectin gene polymorphisms and idiopathic POF in Chinese women. We examined DNA samples of the variant SmaI (rs2241766) and BsmI (rs1501299) loci of the adiponectin gene in 120 POF patients and 104 controls. Polymerase chain reaction and restriction fragment length polymorphism were used to assess these genotype variants. Our results showed that the genotype distributions of the SmaI and BsmI polymorphisms did not significantly differ between the patients with idiopathic POF and the controls. Moreover, no significant difference was found between the controls and POF patients in the haplotype analysis. This suggests that the SmaI and BsmI polymorphisms of adiponectin gene might not be responsible for idiopathic POF, at least, in the Chinese population. More researches are required to determine whether these findings can be extrapolated to other populations. PMID:23370338

Ye, Yuqin; Pu, Danhua; Liu, Jiayin; Li, Fanghong; Cui, Yugui; Wu, Jie

2013-01-28

126

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity  

PubMed Central

Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte–derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, “anhedonia,” and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic–pituitary–adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressant-like behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders.

Liu, Jing; Guo, Ming; Zhang, Di; Cheng, Shao-Ying; Liu, Meilian; Ding, Jun; Scherer, Philipp E.; Liu, Feng; Lu, Xin-Yun

2012-01-01

127

Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism  

PubMed Central

The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA sequencing. Compared with WT mice, adiponectin KO mice fed a chow diet exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty-acid activation and synthesis, triglyceride synthesis, and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weight compared with WT mice. When fed a high-fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the liver. These lipogenic defects are consistent with the down-regulation of lipogenic genes in the KO mice.

Liu, Qingqing; Yuan, Bingbing; Lo, Kinyui Alice; Patterson, Heide Christine; Sun, Yutong; Lodish, Harvey F.

2012-01-01

128

Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.  

PubMed

The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA sequencing. Compared with WT mice, adiponectin KO mice fed a chow diet exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty-acid activation and synthesis, triglyceride synthesis, and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weight compared with WT mice. When fed a high-fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the liver. These lipogenic defects are consistent with the down-regulation of lipogenic genes in the KO mice. PMID:22904186

Liu, Qingqing; Yuan, Bingbing; Lo, Kinyui Alice; Patterson, Heide Christine; Sun, Yutong; Lodish, Harvey F

2012-08-16

129

Plasma Adiponectin Levels Correlate Positively with an Increasing Number of Components of Frailty in Male Elders  

PubMed Central

Objective Frailty is an important geriatric syndrome. Adiponectin is an important adipokine that regulates energy homeostasis. The aim of this study is to investigate the relationship between plasma adiponectin levels and frailty in elders. Methods The demographic data, body weight, metabolic and inflammatory parameters, including plasma glucose, total cholesterol, triglyceride, tumor necrosis factor alpha (TNF-?), c-reactive protein (CRP) and adiponectin levels, were assessed. The frailty score was assessed using the Fried Frailty Index (FFI). Results The mean (SD) age of the 168 participants [83 (49.4%) men and 85 (50.6%) women] was 76.86 (6.10) years. Judged by the FFI score, 42 (25%) elders were robust, 92 (54.7%) were pre-frail, and 34 (20.3%) were frail. The mean body mass index was 25.19 (3.42) kg/m2. The log-transformed mean (SD) plasma adiponectin (µg/mL) level was 1.00 (0.26). The log-transformed mean plasma adiponectin (µg/mL) levels were 0.93 (0.23) in the robust elders, 1.00 (0.27) in the pre-frail elders, and 1.10 (0.22) in the frail elders, and the differences between these values were statistically significant (p ?=?0.012). Further analysis showed that plasma adiponectin levels rose progressively with an increasing number of components of frailty in all participants as a whole (p for trend ?=?0.024) and males (p for trend ?=?0.037), but not in females (p for trend ?=?0.223). Conclusion Plasma adiponectin levels correlate positively with an increasing number of components of frailty in male elders. The difference between the sexes suggests that certain sex-specific mechanisms may exist to affect the association between adiponectin levels and frailty.

Tsai, Jaw-Shiun; Wu, Chih-Hsun; Chen, Su-Chiu; Huang, Kuo-Chin; Chen, Chin-Ying; Chang, Ching-I; Chuang, Lee-Ming; Chen, Ching-Yu

2013-01-01

130

IFN? primes macrophages for inflammatory activation by high molecular weight hyaluronan  

PubMed Central

The objective was to assess outcomes of IFN?-priming upon macrophage activation by the synovial macromolecule high-molecular-weight hyaluronan [HMW-HA] in the context of rheumatoid arthritis inflammation. Human macrophages primed by IFN? and activated by HMW-HA were evaluated for cytokine secretion by ELISA and Milliplex assay and activation profiles by nuclear transcription factor EIA. IFN?-primed, HMW-HA-activated macrophages produced elevated levels of TNF and secreted the TH1 cytokine IL-12p70, while IFN? suppressed HMW-HA-induced secretion of the regulatory cytokine IL-10 and activation of the transcription factor c-Jun. IFN? modulates the HMW-HA-induced cytokine response profile promoting macrophage activation and inflammatory TH1 cytokine secretion.

Wallet, Mark A.; Wallet, Shannon M.; Guiulfo, Giorgio; Sleasman, John W.; Goodenow, Maureen M.

2010-01-01

131

High molecular weight hyaluronan decreases UVB-induced apoptosis and inflammation in human epithelial corneal cells  

PubMed Central

Purpose The aim of this study was to investigate high molecular weight hyaluronan (HMW-HA) protection on human corneal epithelial (HCE) cells against ultraviolet B (UVB) radiation-induced toxic effects. Methods The HCE cell line was incubated with HMW-HA or phosphate-buffered salt solution (PBS), rinsed, and exposed to UVB radiation. Cell viability, reactive oxygen species (ROS) and glutathione (GSH) levels, 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) release, p53 phosphorylation, caspase-3, -8, -9 activation, and interleukin (IL)-6 and -8 production were assessed to evaluate and to compare UVB-induced toxicity between cells treated with HMW-HA and cells treated with PBS. Results Data indicate that HMW-HA had significant protective effects against UVB radiation. HMW-HA increased HCE cell viability, decreased IL-6 and -8 production, and decreased caspase-3 and -8 activation. However, HMW-HA had no significant effect on ROS and GSH levels, 8-oxo-dG release, and p53 phosphorylation. Conclusions To our knowledge, we report for the first time the ability of HMW-HA to protect cells against UV irradiation. According to our results, HMW-HA provides anti-inflammatory and anti-apoptotic signals to cells exposed to UVB.

Pauloin, Thierry; Dutot, Melody; Joly, Francine; Warnet, Jean-Michel

2009-01-01

132

Purification of High Molecular Weight Kininogen and the Role of This Agent in Blood Coagulation  

PubMed Central

Recent studies of individuals with high molecular weight (HMW) kininogen deficiency established the importance of this plasma protein for in vitro initiation of blood coagulation. In the present study, HMW-kininogen was highly purified from human plasma by monitoring its clot-promoting activity, using Fitzgerald trait plasma as a substrate. This preparation of HMW-kininogen revealed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (mol wt: 120,000) and released 1% of its weight as bradykinin upon incubation with plasma kallikrein. HMW-kininogen specifically repaired impaired surface-mediated plasma reactions of Fitzgerald trait plasma, but did not affect those of Hageman trait and Fletcher trait plasma. Kinin release from HMW-kininogen by trypsin, but not by plasma kallikrein, resulted in total loss of clot-promoting activity. No inhibitors of coagulation were found when all kinin activity was removed from HMW-kininogen by trypsin. The roles of HMW-kininogen, Hageman factor (HF, Factor XII), plasma prekallikrein (Fletcher factor), and plasma thromboplastin antecedent (PTA, Factor XI) in blood coagulation were studied in a purified system. HMW-kininogen was absolutely required for activation of PTA by HF and ellagic acid. The yield of activated PTA was proportional to the amount of HF, HMW-kininogen, and PTA in the mixtures, suggesting that, to activate PTA, these three proteins might form a complex in the presence of ellagic acid. No fragmentation of HF was found under these conditions. In contrast to HF, HF-fragments (mol wt: 30,000) activated PTA in the absence of HMW-kininogen and ellagic acid. Thus, it appears that in the present study PTA was activated in two distinct ways. Which pathway is the major one in whole plasma remains to be determined. Images

Saito, Hidehiko

1977-01-01

133

Purification of high molecular weight kininogen and the role of this agent in blood coagulation.  

PubMed

Recent studies of individuals with high molecular weight (HMW) kininogen deficiency established the importance of this plasma protein for in vitro initiation of blood coagulation. In the present study, HMW-kininogen was highly purified from human plasma by monitoring its clot-promoting activity, using Fitzgerald trait plasma as a substrate. This preparation of HMW-kininogen revealed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (mol wt: 120,000) and released 1% of its weight as bradykinin upon incubation with plasma kallikrein. HMW-kininogen specifically repaired impaired surface-mediated plasma reactions of Fitzgerald trait plasma, but did not affect those of Hageman trait and Fletcher trait plasma. Kinin release from HMW-kininogen by trypsin, but not by plasma kallikrein, resulted in total loss of clot-promoting activity. No inhibitors of coagulation were found when all kinin activity was removed from HMW-kininogen by trypsin. The roles of HMW-kininogen, Hageman factor (HF, Factor XII), plasma prekallikrein (Fletcher factor), and plasma thromboplastin antecedent (PTA, Factor XI) in blood coagulation were studied in a purified system. HMW-kininogen was absolutely required for activation of PTA by HF and ellagic acid. The yield of activated PTA was proportional to the amount of HF, HMW-kininogen, and PTA in the mixtures, suggesting that, to activate PTA, these three proteins might form a complex in the presence of ellagic acid. No fragmentation of HF was found under these conditions. In contrast to HF, HF-fragments (mol wt: 30,000) activated PTA in the absence of HMW-kininogen and ellagic acid. Thus, it appears that in the present study PTA was activated in two distinct ways. Which pathway is the major one in whole plasma remains to be determined. PMID:893664

Saito, H

1977-09-01

134

Adiponectin: good, bad, or just plain ugly?  

Microsoft Academic Search

It has been suggested that adiponectin has antiatherogenic, anti-inflammatory, and insulin-sensitizing properties. However, studies in humans have reported inverse as well as positive associations between adiponectin concentrations and disease states. This Commentary discusses the apparent conflict in the literature.

Tina Costacou; Trevor J Orchard

2008-01-01

135

Adipocytokines and aging: adiponectin and leptin.  

PubMed

Adipose tissue is an active metabolic organ secreting adipocytokines which are involved in the energy homeostasis and regulation of glucose and lipid metabolism. Aging is associated with fat redistribution, which is characterized by loss of peripheral subcutaneous fat and accumulation of visceral fat. Visceral adipose tissue is more involved in the developement of metabolic diseases than subcutaneous adipose tissue. Aging also alters the function, proliferation, size, and number of adipose cells which leads to alterations in the secretion, synthesis and function of the adipocytokines. Adiponectin is an insulin sensitizing, anti-inflammatory, and antiathoregenic adipokine. Centarians have higher adiponectin levels associated with longevity. However, in older individuals ? age 65 or more ? adiponectin is associated with higher mortality. Dysregulation of adiponectin in older individuals may be due to loss of function of circulating adiponectin or a response to increased inflammatory process. Longitidunal increase in adiponectin levels 5with aging rather than genetically high adiponectin levels may translate to increased mortality in older patients. The adipocytokine leptin is traditionally viewed as a product of adipocytes that can exert endocrine effects. There have been conflicting reports of not only the effects of aging on leptin, but also the effects of leptin on age-related diseases including sarcopenia, Alzheimer's disease and cardiovascular diseases. Aging is also associated with resistance to leptin and/or to a decrease of receptors for this hormone. In this review, we briefly discuss the role of two major adipocytokines adiponectin and leptin in the aging process and age-related diseases. PMID:23732375

Gulcelik, N E; Halil, M; Ariogul, S; Usman, A

2013-06-01

136

Characterization of high molecular weight glutenin subunits in Thinopyrum intermedium, Th. bessarabicum, Lophopyrum elongatum, Aegilops markgrafii, and their addition lines in wheat  

Technology Transfer Automated Retrieval System (TEKTRAN)

High molecular weight (HMW) glutenin subunits (GSs) play an important role in determining dough viscoelastic properties and end-use quality in cultivated wheat, and they are also excellent protein markers for genotype identification. The HMW-GSs in wheat species (Triticum ssp.) and Aegilops tauschii...

137

Adiponectin, a key adipokine in obesity related liver diseases  

PubMed Central

Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis, non-alcoholic steatohepatitis (NASH), and progressive liver fibrosis is considered the most common liver disease in western countries. Fatty liver is more prevalent in overweight than normal-weight people and liver fat positively correlates with hepatic insulin resistance. Hepatic steatosis is regarded as a benign stage of NAFLD but may progress to NASH in a subgroup of patients. Besides liver biopsy no diagnostic tools to identify patients with NASH are available, and no effective treatment has been established. Visceral obesity is a main risk factor for NAFLD and inappropriate storage of triglycerides in adipocytes and higher concentrations of free fatty acids may add to increased hepatic lipid storage, insulin resistance, and progressive liver damage. Most of the adipose tissue-derived proteins are elevated in obesity and may contribute to systemic inflammation and liver damage. Adiponectin is highly abundant in human serum but its levels are reduced in obesity and are even lower in patients with hepatic steatosis or NASH. Adiponectin antagonizes excess lipid storage in the liver and protects from inflammation and fibrosis. This review aims to give a short survey on NAFLD and the hepatoprotective effects of adiponectin.

Buechler, Christa; Wanninger, Josef; Neumeier, Markus

2011-01-01

138

Leptin to adiponectin ratio in preeclampsia.  

PubMed

The aim of the present study was to assess leptin/adiponectin ratio in preeclamptic patients compared with normal pregnant women. A cross-sectional study was designed. The study population consisted of 30 preeclamptic patients and 30 healthy pregnant women. Serum levels of total leptin and adiponectin were assessed using commercially available enzyme-linked immunosorbent assay methods. The one-way ANOVA and Student's t tests and Pearson's correlation analysis were used for statistical calculations. Levels of leptin and adiponectin were also adjusted for BMI. A p-value < 0.05 was considered statistically significant. The leptin/adiponectin ratio was increased significantly in preeclamptic patients. The leptin/adiponectin ratio was significantly higher in severe preeclamptic patient than in mild preeclampsia. Adjusted leptin/adiponectin ratio was also significantly increased in preeclamptic patients than in normal pregnant women. The findings of the present study suggest that the leptin/adiponectin ratio was increased in preeclamsia and imbalance between the adipocytokines could be involved in the pathogenesis of preeclampsia. PMID:23923407

Khosrowbeygi, A; Ahmadvand, H

2013-04-01

139

Associations of Insulin Resistance and Adiponectin With Mortality in Women With Breast Cancer  

PubMed Central

Purpose Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients. This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity. Here, we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality. Patients and Methods We measured glucose, insulin, and adiponectin levels in fasting serum samples from 527 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between adiponectin and insulin and glucose levels (expressed as the Homeostatic Model Assessment [HOMA] score) represented as continuous measures and median split categories, along with breast cancer mortality and all-cause mortality, using Cox proportional hazards models. Results Increasing HOMA scores were associated with reduced breast cancer survival (hazard ratio [HR], 1.12; 95% CI, 1.05 to 1.20) and reduced all-cause survival (HR, 1.09; 95% CI, 1.02 to 1.15) after adjustment for possible confounders. Higher levels of adiponectin (above the median: 15.5 ?g/mL) were associated with longer breast cancer survival (HR, 0.39; 95% CI, 0.15 to 0.95) after adjustment for covariates. A continuous measure of adiponectin was not associated with either breast cancer–specific or all-cause mortality. Conclusion Elevated HOMA scores and low levels of adiponectin, both associated with obesity, were associated with increased breast cancer mortality. To the best of our knowledge, this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors.

Duggan, Catherine; Irwin, Melinda L.; Xiao, Liren; Henderson, Katherine D.; Smith, Ashley Wilder; Baumgartner, Richard N.; Baumgartner, Kathy B.; Bernstein, Leslie; Ballard-Barbash, Rachel; McTiernan, Anne

2011-01-01

140

The Interactive Effects of Transgenically Overexpressed 1Ax1 with Various HMW-GS Combinations on Dough Quality by Introgression of Exogenous Subunits into an Elite Chinese Wheat Variety.  

PubMed

Seed storage proteins in wheat endosperm, particularly high-molecular-weight glutenin subunits (HMW-GS), are primary determinants of dough properties, and affect both end-use quality and grain utilization of wheat (Triticum aestivum L). In order to investigate the interactive effects between the transgenically overexpressed 1Ax1 subunit with different HMW-GS on dough quality traits, we developed a set of 8 introgression lines (ILs) overexpressing the transgenic HMW-glutenin subunit 1Ax1 by introgression of this transgene from transgenic line B102-1-2/1 into an elite Chinese wheat variety Chuanmai107 (C107), using conventional crossing and backcrossing breeding technique. The donor C107 strain lacks 1Ax1 but contains the HMW-GS pairs 1Dx2+1Dy12 and 1Bx7+1By9. The resultant ILs showed robust and stable expression of 1Ax1 even after five generations of self-pollination, and crossing/backcrossing three times. In addition, overexpression of 1Ax1 was compensated by the endogenous gluten proteins. All ILs exhibited superior agronomic performance when compared to the transgenic parent line, B102-1-2/1. Mixograph results demonstrated that overexpressed 1Ax1 significantly improved dough strength, resistance to extension and over-mixing tolerance, in the targeted wheat cultivar C107. Further, comparisons among the ILs showed the interactive effects of endogenous subunits on dough properties when 1Ax1 was overexpressed: subunit pair 17+18 contributed to increased over-mixing tolerance of the dough; expression of the Glu-D1 allele maintained an appropriate balance between x-type and y-type subunits and thereby improved dough quality. It is consistent with ILs C4 (HMW-GS are 1, 17+18, 2+12) had the highest gluten index and Zeleny sedimentation value. This study demonstrates that wheat quality could be improved by using transgenic wheat overexpressing HMW-GS and the feasibility of using such transgenic lines in wheat quality breeding programs. PMID:24167625

Mao, Xiang; Li, Yin; Zhao, Shasha; Zhang, Jian; Lei, Qian; Meng, Dandan; Ma, Fengyun; Hu, Wei; Chen, Mingjie; Chang, Junli; Wang, Yuesheng; Yang, Guangxiao; He, Guangyuan

2013-10-22

141

The Interactive Effects of Transgenically Overexpressed 1Ax1 with Various HMW-GS Combinations on Dough Quality by Introgression of Exogenous Subunits into an Elite Chinese Wheat Variety  

PubMed Central

Seed storage proteins in wheat endosperm, particularly high-molecular-weight glutenin subunits (HMW-GS), are primary determinants of dough properties, and affect both end-use quality and grain utilization of wheat (Triticum aestivum L). In order to investigate the interactive effects between the transgenically overexpressed 1Ax1 subunit with different HMW-GS on dough quality traits, we developed a set of 8 introgression lines (ILs) overexpressing the transgenic HMW-glutenin subunit 1Ax1 by introgression of this transgene from transgenic line B102-1-2/1 into an elite Chinese wheat variety Chuanmai107 (C107), using conventional crossing and backcrossing breeding technique. The donor C107 strain lacks 1Ax1 but contains the HMW-GS pairs 1Dx2+1Dy12 and 1Bx7+1By9. The resultant ILs showed robust and stable expression of 1Ax1 even after five generations of self-pollination, and crossing/backcrossing three times. In addition, overexpression of 1Ax1 was compensated by the endogenous gluten proteins. All ILs exhibited superior agronomic performance when compared to the transgenic parent line, B102-1-2/1. Mixograph results demonstrated that overexpressed 1Ax1 significantly improved dough strength, resistance to extension and over-mixing tolerance, in the targeted wheat cultivar C107. Further, comparisons among the ILs showed the interactive effects of endogenous subunits on dough properties when 1Ax1 was overexpressed: subunit pair 17+18 contributed to increased over-mixing tolerance of the dough; expression of the Glu-D1 allele maintained an appropriate balance between x-type and y-type subunits and thereby improved dough quality. It is consistent with ILs C4 (HMW-GS are 1, 17+18, 2+12) had the highest gluten index and Zeleny sedimentation value. This study demonstrates that wheat quality could be improved by using transgenic wheat overexpressing HMW-GS and the feasibility of using such transgenic lines in wheat quality breeding programs.

Zhang, Jian; Lei, Qian; Meng, Dandan; Ma, Fengyun; Hu, Wei; Chen, Mingjie; Chang, Junli; Wang, Yuesheng; Yang, Guangxiao; He, Guangyuan

2013-01-01

142

Expression of Adiponectin and Adiponectin Receptors in Human Pituitary Gland and Brain  

Microsoft Academic Search

Background\\/Aims: Adiponectin and its receptors, AdipoR1 and AdipoR2, constitute integral components of energy homeostatic mechanism in peripheral tissues. Recent studies have implicated adiponectin in central neural networks regulating food intake and energy expenditure. The present study aimed at investigating the possible expression and distribution of adiponectin and its receptors in human pituitary gland, hypothalamus and different brain areas. Methods: Sections

Aristea Psilopanagioti; Helen Papadaki; Elena F. Kranioti; Theodore K. Alexandrides; John N. Varakis

2009-01-01

143

Adiponectin Receptor Expression in Human Malignant Tissues  

Microsoft Academic Search

Adiponectin has been proposed to be a mediator of obesity-associated malignancies and to have direct antineoplastic effects\\u000a acting via adiponectin receptors AdipoR1 and AdipoR2. We describe herein the expression of AdipoR1 and AdipoR2 in several\\u000a cancers not previously studied. We used immunohistochemistry to assess expression of adiponectin receptors in archival specimens\\u000a of renal cell carcinoma (n?=?64), hepatocellular carcinoma (n?=?123), melanoma

Sharon H. Chou; Sofia Tseleni-Balafouta; Hyun-Seuk Moon; John P. Chamberland; Xiaowen Liu; Nikolaos Kavantzas; Christos S. Mantzoros

2010-01-01

144

The associations between plasma adiponectin, ghrelin levels and cardiovascular risk factors  

Microsoft Academic Search

Objective: Ghrelin is a recently discovered peptide, which is produced primarily in the stomach. This orexigenic peptide participates not only in the induction of mealtime hunger but also in long-term body weight regulation and energy homeostasis. Adiponectin is a protein secreted by adipocytes, and has been proposed to mediate obesity-related insulin resistance. Moreover, concentrations of adi- ponectin are reduced in

K M Choi; J Lee; K W Lee; J A Seo; S G Kim; N H Kim; D S Choi; S H Baik

2004-01-01

145

Adiponectin: saving the starved and the overfed.  

PubMed

The incidence of the metabolic syndrome, type 2 diabetes and cardio- and cerebrovascular disease is increasing in the Western world. The adipocyte derived protein adiponectin is thought to have a protective role against these conditions. But why is it so? Is it reasonable to believe that we have adiponectin to gain protection from welfare related diseases? Humans have had a far deadlier foe throughout history than obesity and sedentariness and that is starvation. During starvation, the body is catabolic in order to provide fuel. Catabolism is also seen in patients with advanced cardiac or renal failure, type 1 diabetes and anorexia. These subjects have higher adiponectin levels than controls. In this article, I will put forward the hypothesis that the adiponectin system evolved in order to help us to survive periods of malnourishment. PMID:17509773

Behre, C J

2007-05-16

146

The Roles of Leptin and Adiponectin  

PubMed Central

Although leptin is a key adipokine promoting liver fibrosis, adiponectin may prevent liver injury. To determine the role of these adipokines in liver fibrosis and to understand their expression in vivo, fa/fa rats and their lean littermates were subjected to bile duct ligation (BDL). Histomorphometry for collagen and ?-smooth muscle actin (?-SMA) revealed that lean rats, but not fa/fa littermates, had significant fibrosis with abundant hepatic stellate cell (HSC) activation. The lean-BDL rats had significantly higher leptin concentrations in the hepatic vein than lean sham-operated, fa/fa BDL, or fa/fa sham-operated rats. Co-localization of leptin and ?-SMA in activated HSCs was observed by immunohistochemistry. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis confirmed the presence of leptin and ?-SMA in activated, but not quiescent, HSCs, whereas only quiescent HSCs synthesized adiponectin mRNA and protein. Adiponectin overexpression in activated HSCs reduced proliferation, augmented apoptosis, and reduced expression of ?-SMA and proliferating cell nuclear antigen. Adiponectin receptors (AdipoR1 and AdipoR2) were detected in both activated and quiescent HSCs, but only activated HSCs produced significant apoptosis after treatment with either globular or full-length adiponectin. Adiponectin may act to reverse HSC activation, maintain HSC quiescence, or significantly, may have important therapeutic implications in liver fibrosis.

Ding, Xiaokun; Saxena, Neeraj K.; Lin, Songbai; Xu, Amin; Srinivasan, Shanthi; Anania, Frank A.

2005-01-01

147

A Comparative Study on the Expression, Purification and Functional Characterization of Human Adiponectin in Pichia pastoris and Escherichia coli.  

PubMed

Adiponectin is one of the most bioactive substances secreted by adipose tissue and is involved in the protection against metabolic syndrome, artherosclerosis and type II diabetes. Research into the use of adiponectin as a promising drug for metabolic syndromes requires production of this hormone in high quantities considering its molecular isoforms. The objective of this study is to produce recombinant human adiponectin by Pichia pastoris (P-ADP) as a cheap and convenient eukaryotic expression system for potential application in pharmaceutical therapy. For comparison, adiponectin was also expressed using the Escherichia coli (E-ADP) expression system. Adiponectin was constructed by overlap-extension PCR, and cloned in standard cloning vector and hosts. Recombinant expression vectors were cloned in the P. pastoris and E. coli host strains, respectively. SDS-PAGE and western blotting were used to detect and analyse expressed recombinant protein in both systems. Adiponectin was purified by affinity chromatography and quantified using the Bradford Assay. The results of this study indicated that P-ADP quantity (0.111 mg/mL) was higher than that of E-ADP (0.04 mg/mL) and both were produced in soluble form. However, P-ADP was able to form high molecular weights of adiponectin molecules, whilst E-ADP was not able to form isoforms higher than trimer. In addition, P-ADP was more active in lowering blood glucose compared with E-ADP. The two types of proteins were equally efficient and significantly decreased blood triglyceride and increased high density lipoprotein. We conclude that P. pastoris is able to produce high quantity of bioactive adiponectin for potential use in treatment of metabolic syndromes. PMID:22489167

Rothan, Hussin A; Teh, Ser Huy; Haron, Kamariah; Mohamed, Zulqarnain

2012-03-15

148

Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen.  

PubMed

Flaujeac trait is the functional deficiency of a plasma protein of the intrinsic coagulation, kinin-forming, and plasma fibrinolytic pathways. The Flaujeac factor in man has been isolated and tentatively identified as a kininogen of high molecular weight (HMW). Highly purified bovine HMW-kininogen, but not bovine low molecular weight kininogen, repaired Flaujeac factor deficiency. The two subspecies of this molecule, HMW-kininogen a and HMW-kininogen b, also corrected Flaujeac factor deficiency. When bovine HMW-kininogen was incubated with bovine plasma kallikrein, kinin-free HMW-kininogen, bradykinin, and a glycopeptide fragment (peptide 1-2; 12,584 daltons) were rapidly released. None of these fragmentation products corrected Flaujeac factor deficiency alone or in mixtures. The function of HMW-kininogen appeared to depend upon the structural integrity of the native molecule. When injected in concentrations of 2 pmol-8 nmol/0.1 ml, peptide 1-2 caused increased vascular permeability in rabbits, rats, or guinea pigs. The enhanced permeability was maximal within 1-2 min and terminated in 5-10 min, differing from that of bradykinin or histamine. Injected together in equimolar amounts, peptide 1-2 and bradykinin produced a synergistic permeability response which was immediate in onset as well as prolonged in duration. Peptide 1-2 is a rapidly acting, highly basic glyco-peptide which mediates increased vascular permeability in a complementary and synergistic manner with bradykinin. PMID:993350

Matheson, R T; Miller, D R; Lacombe, M J; Han, Y N; Iwanaga, S; Kato, H; wuepper, K D

1976-12-01

149

Relationship between Changes in Plasma Adiponectin Concentration and Insulin Sensitivity after Niacin Therapy  

PubMed Central

Background Niaspan® (extended-release niacin) is a nicotinic acid formulation used to treat dyslipidemia in obese subjects. Niaspan binds to the GPR109A receptor in adipose tissue and stimulates adiponectin secretion, which should improve insulin sensitivity. However, Niaspan therapy often causes insulin resistance. The purpose of this study was to evaluate whether Niaspan-induced changes in plasma adiponectin concentration are associated with a blunting of Niaspan's adverse effect on insulin action in obese subjects with non-alcoholic fatty liver disease (NAFLD). Methods A hyperinsulinemic-euglycemic clamp procedure was used to assess muscle insulin sensitivity before and after 16 weeks of Niaspan therapy in 9 obese subjects with NAFLD [age 43 ± 5 years; BMI 35.1 ± 1.3 (means ± SEM)]. Results Niaspan therapy did not affect body weight (99.1 ± 4.2 vs. 100 ± 4.4 kg) or percent body fat (37.8 ± 2.5 vs. 37.0 ± 2.5%). However, Niaspan therapy caused a 22% reduction in insulin-mediated glucose disposal (p < 0.05). The deterioration in glucose disposal was inversely correlated with the Niaspan-induced increase in plasma adiponectin concentration (r = 0.67, p = 0.05). Conclusions These results demonstrate that Niaspan causes skeletal muscle insulin resistance, independent of changes in body weight or body fat, and the Niaspan-induced increase in plasma adiponectin concentration might partially ameliorate Niaspan's adverse effect on insulin action in obese subjects with NAFLD.

Fraterrigo, Gemma; Fabbrini, Elisa; Mittendorfer, Bettina; O'Rahilly, Stephen; Scherer, Philipp E.; Patterson, Bruce W.; Klein, Samuel

2012-01-01

150

Cloning of adiponectin receptors that mediate antidiabetic metabolic effects  

Microsoft Academic Search

Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and

Toshimasa Yamauchi; Junji Kamon; Yusuke Ito; Atsushi Tsuchida; Takehiko Yokomizo; Shunbun Kita; Takuya Sugiyama; Makoto Miyagishi; Kazuo Hara; Masaki Tsunoda; Koji Murakami; Toshiaki Ohteki; Shoko Uchida; Sato Takekawa; Hironori Waki; Nelson H. Tsuno; Yoichi Shibata; Yasuo Terauchi; Philippe Froguel; Kazuyuki Tobe; Shigeo Koyasu; Kazunari Taira; Toshio Kitamura; Takao Shimizu; Ryozo Nagai; Takashi Kadowaki

2003-01-01

151

Comparison of adiponectin concentration between pancreatic cancer and colorectal cancer  

PubMed Central

Introduction Adiponectin (ADP) is an adipocytokine secreted by the adipose tissue which can be a useful marker in oncogenesis. Preliminary studies suggest that adiponectin rates differ according to the type of cancer. Aim of study Compare ADP plasma levels in pancreatic cancer (PC) and colorectal cancer (CRC) in a prospective monocentric study. Patients and methods The study included all the incident cases of PC gathered from a university hospital in France from January 2006 till September 2007. A control population of incident cases of colorectal cancer (CRC), matching on age, gender, and tumor staging was set in the same period. In addition to demographic data, the other parameters analyzed were: ADP rate, insulinoresistance (Homa-test), presence of a dysmetabolic syndrome, evolution of weight and data concerning the tumor (staging, tumor markers: ACE, CA19.9). Results 33 CRC and 53 PC were analyzed. Type 2 diabetes was found in 18.2% of the CRC cases and 39.6% of the PC (p = 0.037). The mean ADP level was significantly higher in PC versus CRC (20.9 microgram/l versus 15.9 microgram/l; p = 0.03). In multivariate analysis , after adjusting for gender, age, bilirubinemia and weigth loss, the variables independently associated with a high level of ADP (> 10 microG/L) were type 2 diabetes (OR = 0.05, p = 0.01), insulinoresistance (OR = 0.42, p = 0.05) and PC (OR = 12.03, p = 0.047). Conclusion ADP concentration is higher in PC patients than in CRC patients. ADP concentration > 10 microgram/l was independently associated with pancreatic cancer. Our data confirm that adiponectin rates differ strongly according to the type of cancer.

Phelip, Jean Marc; Bageacu, Serban; Baconnier, Mathieu; Barabino, Gabriele; Del Tedesco, Emilie; Benhamou, Pierre Yves

2011-01-01

152

Postprandial Adiponectin Levels Are Associated with Improvements in Postprandial Triglycerides After Roux-en-Y Gastric Bypass in Type 2 Diabetic Patients.  

PubMed

Abstract Background: Postprandial hypertrygliceridemia is a known factor for cardiovascular disease and is often observed in patients with type 2 diabetes mellitus (T2DM) and visceral adiposity. Adiponectin is a hormone with antiatherogenic and anti-inflammatory effects, which decreases in obesity and T2DM subjects. The weight loss induced by diet or bariatric surgery could be restoring adiponectin levels. Objective: The aim of the study was to evaluate the impact of weight loss induced by bariatric surgery, which could restore adiponectin and triglycerides (TG) levels in obese and diabetic patients. Methods: Ten patients with T2DM (BMI 39.3+2.44) were evaluated before and at 7 and 90 days after Roux-en-Y gastric bypass (RYGB). A meal test was performed and plasma insulin, glucagon-like peptide-1 (GLP-1), glucose, TG, and adiponectin levels were measured at fasting and at 30, 60, 90, and 120?min postprandial. Results: Seven days after surgery, significant reductions in the insulin resistance were observed, while TG and adiponectin levels remained unchanged during the meal test. Ninety days after surgery, TG and glucose levels decreased significantly at fasting, and postprandial, adiponectin, GLP-1, and insulin curves increased significantly after meal ingestion. Both changes in the area under the curve (AUC) of adiponectin correlated with changes in the AUC of TG (R=-0.64, P=0.003) and changes in AUC of adiponectin correlated with changes in total fat mass. No correlation was found between changes in insulin, GLP-1, and TG levels. Conclusions: The adiponectin levels may be involved in the mechanism responsible for high TG levels in obese and diabetic patients. These abnormalities can be reversed by RYGB. PMID:23745620

Umeda, Luciana M; Pereira, Andrea Z; Carneiro, Glaucia; Arasaki, Carlos H; Zanella, Maria Teresa

2013-06-07

153

Circulating Adiponectin Levels and Expression of Adiponectin Receptors in Relation to Lung Cancer: Two Case-Control Studies  

Microsoft Academic Search

Background: Decreased circulating levels of adiponectin, an adipocyte-secreted hormone and endogenous insulin sensitizer, have been associated with several obesity-related malignancies. Thiazolidinedione administration, which increases adiponectin levels, decreases risk for lung cancer. Whether circulating adiponectin levels are associated with lung cancer and\\/or whether adiponectin receptors are expressed in lung cancer remains unknown. Methods: We conducted a case-control study of 85 patients

Eleni T. Petridou; Nicholas Mitsiades; Spyros Gialamas; Miltiadis Angelopoulos; Alkistis Skalkidou; Nick Dessypris; Alex Hsi; Nikolaos Lazaris; Aristidis Polyzos; Constantinos Syrigos; Aoife M. Brennan; Sofia Tseleni-Balafouta; Christos S. Mantzoros

2007-01-01

154

Adiponectin Upregulates Ferritin Heavy Chain in Skeletal Muscle Cells  

PubMed Central

OBJECTIVE—Adiponectin is an adipocyte-derived protein that acts to reduce insulin resistance in the liver and muscle and also inhibits atherosclerosis. Although adiponectin reportedly enhances AMP-activated protein kinase and inhibits tumor necrosis factor-? action downstream from the adiponectin signal, the precise physiological mechanisms by which adiponectin acts on skeletal muscles remain unknown. RESEARCH DESIGN AND METHODS—We treated murine primary skeletal muscle cells with recombinant full-length human adiponectin for 12 h and searched, using two-dimensional electrophoresis, for proteins upregulated more than threefold by adiponectin compared with untreated cells. RESULTS—We found one protein that was increased 6.3-fold with adiponectin incubation. MALDI-TOF (matrix-assisted laser desorption/ionization?top of flight) mass spectrometric analysis identified this protein as ferritin heavy chain (FHC). When murine primary skeletal muscle cells were treated with adiponectin, I?B-? phosphorylation was observed, suggesting that adiponectin stimulates nuclear factor (NF)-?B activity. In addition, FHC upregulation by adiponectin was inhibited by NF-?B inhibitors. These results suggest NF-?B activation to be involved in FHC upregulation by adiponectin. Other NF-?B target genes, manganese superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS), were also increased by adiponectin treatment. We performed a reactive oxygen species (ROS) assay using CM-H2DCFDA fluorescence and found that ROS-reducing effects of adiponectin were abrogated by FHC or MnSOD small-interfering RNA induction. CONCLUSIONS—We have demonstrated that adiponectin upregulates FHC in murine skeletal muscle tissues, suggesting that FHC elevation might partially explain how adiponectin protects against oxidative stress in skeletal muscles.

Ikegami, Yuichi; Inukai, Kouichi; Imai, Kenta; Sakamoto, Yasushi; Katagiri, Hideki; Kurihara, Susumu; Awata, Takuya; Katayama, Shigehiro

2009-01-01

155

APPL1: role in adiponectin signaling and beyond  

PubMed Central

Adiponectin, an adipokine secreted by the white adipose tissue, plays an important role in regulating glucose and lipid metabolism and controlling energy homeostasis in insulin-sensitive tissues. A decrease in the circulating level of adiponectin has been linked to insulin resistance, type 2 diabetes, atherosclerosis, and metabolic syndrome. Adiponectin exerts its effects through two membrane receptors, AdipoR1 and AdipoR2. APPL1 is the first identified protein that interacts directly with adiponectin receptors. APPL1 is an adaptor protein with multiple functional domains, the Bin1/amphiphysin/rvs167, pleckstrin homology, and phosphotyrosine binding domains. The PTB domain of APPL1 interacts directly with the intracellular region of adiponectin receptors. Through this interaction, APPL1 mediates adiponectin signaling and its effects on metabolism. APPL1 also functions in insulin-signaling pathway and is an important mediator of adiponectin-dependent insulin sensitization in skeletal muscle. Adiponectin signaling through APPL1 is necessary to exert its anti-inflammatory and cytoprotective effects on endothelial cells. APPL1 also acts as a mediator of other signaling pathways by interacting directly with membrane receptors or signaling proteins, thereby playing critical roles in cell proliferation, apoptosis, cell survival, endosomal trafficking, and chromatin remodeling. This review focuses mainly on our current understanding of adiponectin signaling in various tissues, the role of APPL1 in mediating adiponectin signaling, and also its role in the cross-talk between adiponectin/insulin-signaling pathways.

Deepa, Sathyaseelan S.; Dong, Lily Q.

2009-01-01

156

Plasma adiponectin levels and left ventricular remodeling in hypertrophic cardiomyopathy.  

PubMed

Adiponectin, which is an adipose-derived protein with antiatherosclerogenic activities, has been reported to be elevated in patients with heart failure. However, there are no reports on the significance of adiponectin in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to elucidate the clinical significance of plasma adiponectin levels in HCM patients. Clinical characteristics, echocardiographic parameters, and levels of plasma B-type natriuretic peptide (BNP) and adiponectin were evaluated in 106 HCM patients. The plasma adiponectin levels were 10.8 +/- 6.3 (range, 2.7-37.3) microg/mL. Plasma adiponectin levels were positively related to age and inversely related to body mass index (BMI). Among echocardiographic parameters, % fractional shortening (r = -0.20, P = 0.03) and maximum LV wall thickness (r = -0.23, P = 0.02) were inversely related to plasma adiponectin levels. A significant correlation between plasma adiponectin levels and BNP levels was also observed (r = 0.27, P = 0.005). In multivariate analysis, BMI, % fractional shortening, and plasma BNP levels were independent predictors of plasma adiponectin levels. Plasma adiponectin levels are associated with impaired LV systolic function in HCM patients, but not with the LV outflow gradient. Together with BNP, adiponectin can be a useful biomarker for assessing disease severity in HCM patients. PMID:20145352

Kitaoka, Hiroaki; Kubo, Toru; Okawa, Makoto; Yamasaki, Naohito; Matsumura, Yoshihisa; Nishinaga, Masanori; Doi, Yoshinori L

2010-01-01

157

Effects of Body Composition, Leptin, and Adiponectin on Bone Mineral Density in Prepubertal Girls  

PubMed Central

Body weight is positively associated with bone mineral density but the relationship between obesity and bone mineral density is unclear. Leptin and adiponectin are potential independent contributors to bone mineral density. We assessed the correlations of body composition, leptin and adiponectin with bone mineral density, and whether leptin, adiponectin and body composition determine bone mineral density independently in prepubertal girls. Forty-eight prepubertal girls were classified into obese and control groups by body mass index. Serum leptin and adiponectin levels were determined by enzyme immunoassay. Bone mineral density was measured using dual energy radiography absorptiometry and body composition was measured using bioelectrical impedance analysis. Lean and fat mass, and leptin were positively correlated with bone mineral density. Lean mass was a positive independent predictor of femoral and L-spine bone mineral density. Serum leptin was a postivie independent predictor of femoral bone mineral density. Fat mass was a negative independent predictor of femoral bone mineral density. In prepubertal girls, lean mass has a favorable effect on bone mineral density. Fat mass seems not to protect the bone structure against osteoporosis, despite increased mechanical loading. Serum leptin may play a biological role in regulating bone metabolism.

Rhie, Young Jun; Lee, Kee Hyoung; Chung, So Chung; Kim, Ho Seong

2010-01-01

158

Human High-Molecular-Weight Melanoma-associated Antigen Mimicry by Mouse Antiidiotypic Monoclonal Antibody TK7-3711  

Microsoft Academic Search

Since the human high-molecular-weight melanoma-associated antigen (HMW-MAA) represents a useful target to implement active specific immunotherapy with mouse antiidiotypic monoclonal antibody (mAh), the present study is aimed at developing and characterizing mouse antiidiotypic inAhs which bear the mirror image of the determinant defined by the anti-HMW-MAA mAb TP61.5. To this end, a BALB\\/c mouse was immunized with the syngeneic mAb

Zhi Jian Chen; Hong Yang; Toshiro Kageshita; Soldano Terrone

159

Homology modeling and molecular dynamics simulations of the N-terminal domain of wheat high molecular weight glutenin subunit 10  

Microsoft Academic Search

High molecular weight glutenin subunits (HMW-GS) are of a particular interest because of their biome- chanical properties, which are important in many food systems such as breadmaking. Using fold-recognition techniques, we identified a fold compatible with the N-terminal domain of HMW-GS Dy10. This fold corresponds to the one adopted by proteins belonging to the cereal inhibitor family. Starting from three

ROLAND CAZALIS; THIERRY AUSSENAC; LARBI RHAZI; ANTOINE MARIN; JEAN-FRANÇOIS GIBRAT

2003-01-01

160

Safflomide increases the expression of adiponectin in vitro and in vivo: potential implication for hypoadiponectemia, visceral obesity, and insulin resistance.  

PubMed

Safflomide (N-caffeoyltryptamine) is a phenolic amide with serotonin receptor antagonist and antioxidant activities. We investigated the potential effects of safflomide on the expression of adipokines in vitro and in vivo. Safflomide did not affect the expressions of TNF-?, IL-6, and MCP-1/CCL2 in hypertrophic 3T3-L1 cells but upregulated adiponectin mRNA 1-5-fold at concentrations between 1 and 20 ?M (p < 0.05). Because safflomide is a non-selective 5-HT receptor antagonist and because the expression of 5-HT2A receptor is often inversely correlated to adiponectin expression, the potential effects of 5-HT receptor antagonist activity of safflomide on the expression of adiponectin was further investigated in 3T3-L1 cells. At the concentration of 10 ?M, safflomide was able to increase adiponectin protein production in 3T3-L1 cells more than 4-fold (p < 0.05), which was greater than the 5-HT2A antagonist ketanserin. The upregulation was partially suppressed by treatment with 5-HT2A agonists (serotonin and ?-Me-5-HT), suggesting that safflomide may upregulate adiponectin expression more than by blocking 5-HT2A receptors in 3T3-L1 cells. Likely, the upregulation was also attributed to the antioxidant activity of safflomide because two safflomide analogues (N-cinnamoyltryptamine and N-coumaroyltryptamine) with less antioxidant activity were not as potent as safflomide. Rats supplemented with safflomide (3 mg/day) in a high-fat diet showed a significant plasma adiponectin increase (more than 30%) with a significant reduction in body weight, visceral fat, and improved insulin resistance compared to non-supplemented rats, demonstrating the in vivo activity of safflomide. These data suggest that safflomide may have beneficial effects on obesity-related conditions, such as low adiponectin, visceral obesity, and insulin resistance. PMID:22428927

Park, Jae B; Wang, Thomas T Y

2012-04-11

161

[Adiponectin: an anti-carcinogenic adipokine?].  

PubMed

Adipose tissue has long been considered as an « organ » of energy storage. Although many works had previously identified the secretory nature of adipocyte, it was only in 1994, when the leptin gene was cloned, that adipose tissue earned the status of endocrine tissue. It was the first demonstration that an adipose tissue-derived hormone was able to communicate with the central nervous system to control satiety and energy balance. In fact, it is almost at the same time that another major adipokine produced by adipocytes, adiponectin, has been discovered. It took several years to identify the insulin-sensitizing, anti-inflammatory and anti-atherogenic properties of this hormone. More recently, several epidemiological, genetic and experimental findings suggest an anti-carcinogenic role for adiponectin. In this brief review we will present the arguments supporting a protective role of adiponectin in tumor progression, particularly in the context of breast cancer. Adiponectin deficiency commonly observed in obesity may contribute to the natural history of several cancers, as well as the elevation of leptin and other hormonal disturbances associated with excessive adiposity. PMID:23570813

Fève, Bruno

2013-04-06

162

Association analysis of adiponectin and somatostatin polymorphisms on BTA1 with growth and carcass traits in Angus cattle  

Microsoft Academic Search

Summary This study tested positional candidate genes adiponectin (ADIPOQ) and somatostatin (SST) for effects on carcass traits in a commercially relevant cattle population. Both genes are located within a region of BTA1 previously reported to harbour quantitative trait loci (QTL) that affect marbling, quality grade, yield grade, ribeye area and weaning weight in Bos tau- rus · Bos indicus crosses.

N. S. Morsci; R. D. Schnabel; J. F. Taylor

2006-01-01

163

Low-molecular-weight polyethylenimine as a non-viral vector for DNA delivery: comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine  

Microsoft Academic Search

Low-molecular-weight polyethylenimine (LMW-PEI) was synthesized by the acid-catalyzed, ring-opening polymerization of aziridine and compared with commercially available high-molecular-weight PEI (HMW-PEI) of 25 kDa. Molecular weights were determined by size-exclusion chromatography in combination with multi-angle laser light scattering. The weight average molecular weight (Mw) of synthesized LMW-PEI was determined as 5.4±0.5 kDa, whereas commercial HMW-PEI showed a Mw of 48±2 kDa.

Klaus Kunath; Anke von Harpe; Dagmar Fischer; Holger Petersen; Ulrich Bickel; Karlheinz Voigt; Thomas Kissel

2003-01-01

164

Systemic Fate of the Adipocyte-Derived Factor Adiponectin  

PubMed Central

OBJECTIVE The adipocyte-derived secretory protein adiponectin has been widely studied and shown to have potent insulin-sensitizing, antiapoptotic, and anti-inflammatory properties. While its biosynthesis is well understood, its fate, once in circulation, is less well established. RESEARCH DESIGN AND METHODS Here, we examine the half-life of adiponectin in circulation by tracking fluorescently labeled recombinant adiponectin in the circulation, following it to its final destination in the hepatocyte. RESULTS Despite its abundant presence in plasma, adiponectin is cleared rapidly with a half-life of ?75 min. A more bioactive version carrying a mutation at cysteine 39 is cleared within minutes. Even though steady-state levels of adiponectin differ between male and female mice, we failed to detect any differences in clearance rates, suggesting that differences in plasma are mostly due to differential production rates. In a metabolically challenged state (high-fat diet exposure or in an ob/ob background), adiponectin levels are reduced in plasma and clearance is significantly prolonged, reflecting a dramatic drop in adiponectin production levels. CONCLUSIONS Combined, these results show a surprisingly rapid turnover of adiponectin with multiple fat pads contributing to the plasma levels of adiponectin and clearance mediated primarily by the liver. It is surprising that despite high-level production and rapid clearance, plasma levels of adiponectin remain remarkably constant.

Halberg, Nils; Schraw, Todd D.; Wang, Zhao V.; Kim, Ja-Young; Yi, James; Hamilton, Mark P.; Luby-Phelps, Kate; Scherer, Philipp E.

2009-01-01

165

Modulation of skeletal muscle performance and SERCA by exercise and adiponectin gene therapy in insulin-resistant rat.  

PubMed

This study addresses the potential application of adiponectin gene therapy and exercise in protection against skeletal muscle dysfunction in type 2 diabetes mellitus (T2DM) while focusing on the role of sarco and endoplasmic reticulum Ca(+2) ATPase (SERCA) and Glut4. 50 rats were divided into five groups: control, T2DM, T2DM treated with either adiponectin gene or exercise or a combination of both. Serum glucose, insulin, HOMA index, triglycerides, and cholesterol were measured. Weight gain%, muscle contractile parameters {(peak twitch tension (Pt), peak tetanic tension (PTT), half relaxation time (HRT)}, and gene expression of SERCA, Glut4, and adiponectin were assessed in gastrocnemius muscle. Diabetic rats treated with either adiponectin gene or exercise showed significant reduction in all serum parameters and wt gain%. There was significant elevation in Pt and PTT with shortening in HRT. Furthermore, a significant increase in SERCA, Glut4, and adiponectin gene expression was noticed in both groups. Combination therapy caused marked gene expression of SERCA, GLUT4, and greater improvement in muscle contractility than either of the monotherapies. Skeletal muscle dysfunction in T2DM is mediated via impaired SERCA and Glut 4. Combination therapy offered best protection against muscle dysfunction and provides a novel promising strategy for a complete cure of muscle dysfunction in T2DM. PMID:23815341

Safwat, Yasmeen; Yassin, Nadia; Gamal El Din, Maha; Kassem, Lobna

2013-05-13

166

Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis  

PubMed Central

Obesity is rapidly becoming a pandemic and is associated with increased carcinogenesis. Obese populations have higher circulating levels of leptin in contrast to low concentrations of adiponectin. Hence, it is important to evaluate the dynamic role between adiponectin and leptin in obesity-related carcinogenesis. Recently, we reported the oncogenic role of leptin including its potential to increase tumor invasiveness and migration of hepatocellular carcinoma (HCC) cells. In the present study, we investigated whether adiponectin could antagonize the oncogenic actions of leptin in HCC. We employed HCC cell-lines HepG2 and Huh7, nude mice-xenograft model of HCC and immunohistochemistry-data from tissue-microarray to demonstrate the antagonistic role of adiponectin on the oncogenic actions of leptin. Adiponectin treatment inhibited leptin-induced cell proliferation of HCC cells. Using scratch-migration and electric cell-substrate impedance-sensing based migration assays, we found that adiponectin inhibited leptin-induced migration of HCC cells. Adiponectin treatment effectively blocked leptin-induced invasion of HCC cells in matrigel invasion assays. While leptin inhibited apoptosis in HCC cells, we found that adiponectin treatment induced apoptosis even in the presence of leptin. Analysis of the underlying molecular mechanisms revealed that adiponectin treatment reduced leptin-induced Stat3 and Akt phosphorylation. Adiponectin also increased suppressor of cytokine signaling (SOCS3), a physiologic negative regulator of leptin signal transduction. Importantly, adiponectin significantly reduced leptin-induced tumor burden in nude mice. In HCC samples, leptin expression significantly correlated with HCC proliferation as evaluated by Ki-67 while adiponectin expression correlated significantly with increased disease-free-survival and inversely with tumor size and local recurrence. Conclusion Collectively, these data demonstrate that adiponectin has the molecular potential to inhibit the oncogenic actions of leptin by blocking downstream effector molecules.

Sharma, Dipali; Wang, Jason; Fu, Ping P.; Sharma, Shvetank; Nagalingam, Arumugam; Mells, Jamie; Handy, Jeffrey; Page, Andrew J.; Cohen, Cynthia; Anania, Frank A.; Saxena, Neeraj K.

2010-01-01

167

Isolation of high molecular weight DNA from marine sponge bacteria for BAC library construction.  

PubMed

Metagenomics is a powerful tool for mining the genetic repositories from environmental microorganisms. Bacteria associated with marine sponges (phylum Porifera) are rich sources of biologically active natural products. However, to date, few compounds are discovered from the sponge metagenomic libraries, and the main reason might be the difficulties in recovery of high molecular weight (HMW) DNA from sponge symbionts to construct large insert libraries. Here, we describe a method to recover HMW bacterial DNA from diverse sponges with high quality for bacterial artificial chromosome (BAC) library construction. Microorganisms concentrated from sponges by differential centrifugation were embedded in agarose plugs to lyse out the HMW DNA for recovery. DNA fragments over 436 kb size were recovered from three different types of sponges, Halichondria sp., Haliclona sp., and Xestospongia sp. To evaluate the recovered DNA quality, the diversity of bacterial DNA comprised in the HMW DNA derived from sponge Halichondria sp. was analyzed, and this HMW DNA sample was also cloned into a shuttle BAC vector between Escherichia coli and Streptomyces sp. The results showed that more than five types of bacterial DNA, i.e., Proteobacteria, Nitrospirae, Cyanobacteria, Planctomycetes, and unidentified bacteria, had been recovered by this method, and an average 100 kb size insert DNA in a constructed BAC library demonstrated that the recovered HMW DNA is suitable for metagenomic library construction. PMID:19685098

Ouyang, Yongchang; Dai, Shikun; Xie, Lianwu; Ravi Kumar, M S; Sun, Wei; Sun, Huimin; Tang, Danling; Li, Xiang

2009-08-15

168

Isoleucine epimerization and amino acid composition in molecular-weight separations of Pleistocene Genyornis eggshell  

NASA Astrophysics Data System (ADS)

This study explores the geochronological utility and analytical reproducibility of separating the high-molecular-weight fraction (HMW) from eggshells of the extinct late Pleistocene ratite, Genyornis, using disposable, prepacked gel-filtration columns. The superior integrity of ratite eggshell for the retention of amino acids indicates that this biomineral is better suited for this type of investigation than previously studied molluscan shell. To evaluate the reproducibility of the gel-filtration technique, we analyzed triplicate subsamples of three eggshells of different ages. The reproducibility, based on the average intrashell variation (coefficient of variation; CV) in the extent of isoleucine epimerization (aIle/Ile) in the HMW (enriched in molecules ca. >10,000 MW) is 3%, well within the range appropriate for geochronological purposes. The average intrashell variation in the total amino acid concentration (?[aa]) of the HMW is 5%, somewhat better than for the total acid hydrolysate (TOTAL) of the same samples (7%). To evaluate the relation between molecular weight and the rate of isoleucine epimerization, three molecular-weight fractions were separated using gel filtration, plus the naturally hydrolyzed free fraction (FREE), for each of four fossil eggshells. AIle/Ile increases with decreasing molecular weight in all shells, with a ca. sixfold to ninefold difference in ratios between the HMW andFREE, and a ca. fivefold difference between the HMW andTOTAL. Although linear correlations between aIle/Ile measured in each molecular-weight fraction and in theTOTAL are all highly significant (r ? 0.951), the relation between the extent of epimerization in the HMW and in the TOTAL is best expressed as an exponential function (r = 0.951). This relation is consistent with the idea that, as the epimerization reaction approaches equilibrium in theTOTAL (ca. aIle/Ile > 1.1), its rate decreases beyond that of the HMW. The amino acid composition (relative percent of eight amino acids or combinations of amino acids) is more uniform in the HMW of the four samples compared to lower-molecular-weight fractions. The greater "compositional stability" of the HMW indicates that it contains a residuum of macromolecules that have not been affected by the diagenetically driven changes observed in lower-molecular-weight fractions.

Kaufman, Darrell S.; Miller, Gifford H.

1995-07-01

169

Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice  

SciTech Connect

We previously demonstrated that adiponectin has anti-fibrogenic and anti-inflammatory effects in the liver of mouse models of various liver diseases. However, its role in liver regeneration remains unclear. The aim of this study was to determine the role of adiponectin in liver regeneration. We assessed liver regeneration after partial hepatectomy in wild-type (WT) and adiponectin knockout (KO) mice. We analyzed DNA replication and various signaling pathways involved in cell proliferation and metabolism. Adiponectin KO mice exhibited delayed DNA replication and increased lipid accumulation in the regenerating liver. The expression levels of peroxisome proliferator-activated receptor (PPAR) {alpha} and carnitine palmitoyltransferase-1 (CPT-1), a key enzyme in mitochondrial fatty acid oxidation, were decreased in adiponectin KO mice, suggesting possible contribution of altered fat metabolism to these phenomena. Collectively, the present results highlight a new role for adiponectin in the process of liver regeneration.

Ezaki, Hisao; Yoshida, Yuichi; Saji, Yukiko; Takemura, Takayo; Fukushima, Juichi; Matsumoto, Hitoshi; Kamada, Yoshihiro; Wada, Akira; Igura, Takumi [Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2, K1, Yamadaoka, Suita, Osaka 565-0871 (Japan); Kihara, Shinji; Funahashi, Tohru; Shimomura, Iichiro [Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, 2-2, B5, Yamadaoka, Suita, Osaka 565-0871 (Japan); Tamura, Shinji [Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2, K1, Yamadaoka, Suita, Osaka 565-0871 (Japan); Kiso, Shinichi [Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2, K1, Yamadaoka, Suita, Osaka 565-0871 (Japan)], E-mail: kiso@gh.med.osaka-u.ac.jp; Hayashi, Norio [Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2, K1, Yamadaoka, Suita, Osaka 565-0871 (Japan)

2009-01-02

170

Association of adiponectin gene polymorphism (+T45G) with acute coronary syndrome and circulating adiponectin levels.  

PubMed

We investigated the association of adiponectin gene polymorphisms (+T45G and +G276T) and adiponectin levels with acute coronary syndrome (ACS) among Arabs in Qatar. A case-control study was performed in 142 Arab patients with ACS and 122 controls. Genotypes were determined using TaqMan real-time polymerase chain reaction assay. The TT, TG, and GG genotype frequencies of the T45G variant were significantly different among cases and controls (P = .023) but not significant for G276T genotypic frequencies. It was found that only the +45G allele was significantly associated with 3-fold increased risk of ACS (odds ratio = 2.77; 1.03-6.96; P = .043) among patients, using the genetic recessive model. Carriers of GG alleles had significantly lower adiponectin levels compared to TT/TG carriers of T45G in patients with ACS. The present study suggests that only T45G single-nucleotide polymorphism in the adiponectin gene is associated with higher odds for ACS events and has an effect on serum adiponectin levels among Arab populations. PMID:22887729

Rizk, Nasser M; El-Menyar, Ayman; Marei, Isra; Sameer, Maha; Musad, Tasneem; Younis, Dima; Farag, Fathi; Basem, Nora; Al-Ali, Khalid; Al Suwaidi, Jassim

2012-08-09

171

Tissue levels of adiponectin in breast cancer patients  

Microsoft Academic Search

Background  Adiponectin is a new adipocyte-secreted protein and associated with insulin-resistant status, such as type 2 diabetes mellitus\\u000a and obesity. The inverse correlation between serum adiponectin levels and breast cancer risk was recently documented. On the\\u000a other hand, the association of tissue adiponectin levels with breast cancer has not been previously reported. Thus, in the\\u000a present study, the relationship between tissue

Mehmet Karaduman; Ahmet Bilici; Ahmet Ozet; Ali Sengul; Ugur Musabak; Melih Alomeroglu

2007-01-01

172

The leptin\\/adiponectin ratio: Potential implications for peritoneal dialysis  

Microsoft Academic Search

Leptin and adiponectin are adipokines with respective pro-atherogenic and anti-atherogenic properties, defining the plasma leptin\\/adiponectin ratio as a novel marker for atherosclerosis. In non-renal patients, both hyperleptinemia and hypoadiponectinemia are associated with cardiovascular complications. In peritoneal dialysis (PD) patients, the leptin\\/adiponectin ratio is markedly elevated, which is consistent with their increased cardiovascular risk. As glucose metabolism regulates adipokines, we hypothesized

D Teta; M Maillard; G Halabi; M Burnier

2008-01-01

173

Microencapsulation of linoleic acid with low- and high-molecular-weight components of soluble soybean polysaccharide and its oxidation process.  

PubMed

Soluble soybean polysaccharide (SSPS) was fractionated into its low- (LMW) and high-molecular-weight (HMW) components to test their antioxidative and emulsifying properties. Linoleic acid was emulsified with an aqueous solution of SSPS, HMW, a mixture of LMW or HMW with maltodextrin, or maltodextrin alone. The emulsions prepared with SSPS, HWM and the mixture of HMW with maltodextrin were stable. These emulsions were spay-dried to produce microcapsules. The encapsulated linoleic acid was oxidized at 37 degrees C and at various levels of relative humidity. Linoleic acid encapsulated with the mixture of LMW with maltodextrin or HMW was stable to oxidation, and this stability increased as the weight fraction of LMW in the mixture was increased. The LMW components also had high DPPH-radical scavenging activity. These results indicate that LMW played an important role in suppressing or retarding the oxidation of linoleic acid encapsulated with SSPS. The oxidative stability of linoleic acid encapsulated with a mixture of the LMW and HMW components was high at low and high relative humidity, but not at intermediate levels of relative humidity. PMID:14519968

Fang, Xu; Watanabe, Yoshiyuki; Adachi, Shuji; Matsumura, Yasuki; Mori, Tomohiko; Maeda, Hirokazu; Nakamura, Akihiro; Matsuno, Ryuichi

2003-09-01

174

Adiponectin Reduces Lipid Accumulation in Macrophage Foam Cells  

PubMed Central

Adiponectin is one of several, important metabolically active cytokines secreted from adipocytes. Low circulating levels of this adipokine have been associated epidemiologically with obesity, insulin resistance, type II diabetes, and cardiovascular disease. To determine if adiponectin can modulate lipid metabolism in macrophages, we expressed the adiponectin gene in human THP-1 macrophage foam cells using a lentiviral vector expression system and demonstrated that macrophages transduced with the adiponectin gene had decreased lipid accumulation compared with control macrophages transduced with the LacZ gene. Macrophages transduced with the adiponectin gene also exhibited decreased oxidized low-density lipoprotein (oxLDL) uptake and increased HDL-mediated cholesterol efflux. Additional studies suggest two potential mechanisms for the reduced lipid accumulation in these adiponectin-transduced macrophage foam cells. The first mechanism involves the PPAR? and LXR signaling pathways which up-regulate the expression of ABCA1 and promote lipid efflux from these cells. The second mechanism involves decreased lipid uptake and increased lipid hydrolysis which may result from decreased SR-AI and increased SR-BI and HSL gene activities in the transformed macrophage foam cells. We demonstrated also that the expression of two proatherogenic cytokines, MCP-1 and TNF?, were decreased in the adiponectin transduced macrophage foam cells. These results suggest that adiponectin may modulate multiple pathways of lipid metabolism in macrophages. Our studies provide new insights into potential mechanisms of adiponectin-mediated alterations in lipid metabolism and macrophage foam cell formation which may impact the development of atherosclerosis.

Tian, Ling; Luo, Nanlan; Klein, Richard L.; Chung, B Hong; Garvey, W. Timothy; Fu, Yuchang

2009-01-01

175

The cardio-protective signaling and mechanisms of adiponectin  

PubMed Central

Adiponectin is an endogenous insulin-sensitizing hormone which has been found to regulate energy metabolism throughout the body, including the heart. However, low levels of adiponectin are found in patients with diabetes, hypertension and cardiovascular diseases. Thus it has been suggested to be an independent predictor for cardiovascular risk. Paradoxically, recent studies have also determined that adiponectin has cardioprotective effects against various cardiac related pathologies which lead to heart failure. These cardioprotective effects of adiponectin are attributed to its anti-inflammatory, anti-oxidant and anti-apoptotic properties. Further findings suggest that locally produced adiponectin in cardiomyocytes are functional and biologically significant. This ectopic derived adiponectin exerts its protective effects through an autocrine mechanism. These data suggest adiponectin may serve as a potential therapeutic target against the development of pathologies which develop into heart failure. The current manuscript has summarized the key findings to date which explore the cardioprotective mechanisms of adiponectin against various cardiac pathologies. Further we explore the roles of both circulating and endogenous heart specific adiponectin and their physiological importance in various heart diseases.

Nanayakkara, Gayani; Kariharan, Thiruchelvan; Wang, Lili; Zhong, Juming; Amin, Rajesh

2012-01-01

176

Resistance training improves cardiovascular risk factors in obese women despite a significative decrease in serum adiponectin levels.  

PubMed

Increased circulating adiponectin and insulin sensitivity are usually observed after body fat loss induced by a weight-loss diet. Progressive resistance training (PRT) without a concomitant weight-loss diet significantly decreases visceral fat, thus improving insulin sensitivity. Therefore, the purpose of this study was to ascertain the effects of combined 16-week PRT and weight-loss diet on circulating adiponectin and insulin sensitivity index. Thirty-four obese (BMI: 30-40 kg/m(2)) women, aged 40-60 year, were randomized to three groups: a control group (C; n = 9); a diet group (WL; n = 12) with a caloric restriction of 500 kcal/d; and a diet plus resistance training group (WL+RT; n = 13) with the same caloric restriction as group WL and a 16-week supervised whole body PRT of two sessions/week. Both WL and WL+RT groups showed similar decreases in body mass (-6.3% and -7.7%) and visceral fat (-19.9% and -20.5%). WL resulted in an expected increase in circulating levels of adiponectin (P = 0.07) and insulin sensitivity. However, circulating total adiponectin decreased (P < 0.05) in WL+RT group, whereas an improvement in different cardiovascular risk factors (insulin sensitivity, low-density lipoprotein cholesterol (LDL-C), etc.) was observed. In conclusion, in obese women a 16-week combined PRT and weight-loss diet is accompanied by significant improvements in different cardiovascular risk factors in spite of a significant decrease of circulating adiponectin. PMID:19713947

Ibáñez, Javier; Izquierdo, Mikel; Martínez-Labari, Cristina; Ortega, Francisco; Grijalba, Ana; Forga, Luis; Idoate, Fernando; García-Unciti, Marisol; Fernández-Real, José M; Gorostiaga, Esteban M

2009-08-27

177

Characterization of Human Anti-High Molecular Weight-Melanoma-associated Antigen Single-Chain Fv Fragments Isolated from a Phage Display Antibody Library1  

Microsoft Academic Search

The human high molecular weight-melanoma-associated antigen (HMW- MAA) meets the criteria to be used as an immunogen for immunotherapy of malignant melanoma, because it is expressed by a large percentage of mela noma lesions with limited heterogeneity and has a restricted distribution in normal tissues. The high immunogenicity of the HMW-MAA in BALB\\/c mice has resulted in the development of

Smruti A. Desai; Xinhui Wang; Elvyra J. Noronha; Toshiro Kageshita; Soldano Ferrone

178

B-cell Chronic Lymphocytic Leukemia risk in association with serum leptin and adiponectin levels: a case-control study in Greece  

PubMed Central

Aim Leptin and adiponectin are two well studied adipokines in relation to malignancies. In this study, we examined the association between leptin/adiponectin and risk of B-cell chronic lymphocytic leukemia (B-CLL), as well as the relationships between adipokines and several established prognostic factors of B-CLL. Methods Ninety-five patients with incident B-CLL and 95 hospital controls matched on age and gender were studied between 2001 and 2007, and blood samples were collected. Leptin, total and high molecular weight adiponectin and prognostic markers of B-CLL were determined. Results Cases had a higher body mass index (BMI) than controls (p=0.01) and lower levels of leptin (p<0.01). Significantly more cases than controls presented a family history of lymphohematopoietic cancer (LHC) (p=0.01). Higher serum leptin levels were associated with lower risk of B-CLL adjusting for age, gender, family history of LHC, BMI and serum adiponectin; the multivariate odds ratio comparing highest to lowest tertile was 0.05 (95% CI 0.01–0.29, p trend <0.001); Adiponectin was not significantly different between cases and controls. Conclusion Leptin was found to be inversely associated with risk of CLL but in contrast to prior studies of CLL and hematologic malignancies, this study found no significant association between CLL and adiponectin.

Dalamaga, Maria; Crotty, Bradley H.; Fargnoli, Jessica; Papadavid, Evangelia; Lekka, Antigoni; Triantafilli, Maria; Karmaniolas, Konstantinos; Migdalis, Ilias; Dionyssiou-Asteriou, Amalia; Mantzoros, Christos S.

2011-01-01

179

Anthropometric measures, plasma adiponectin, and breast cancer risk  

Microsoft Academic Search

Adiponectin is a peptide hormone secreted exclusively by adipocytes, and obesity is an established risk factor for breast cancer. We have, thus, evaluated the associations of anthropometric measures of adiposity and adiponectin with the development of breast cancer in a case-control study. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 244 incident cases with breast cancer,

Yu-Feng Tian; Chi-Hong Chu; Mei-Hsuan Wu; Chia-Lin Chang; Tsan Yang; Yu-Ching Chou; Giu-Cheng Hsu; Cheng-Ping Yu; Jyh-Cherng Yu; Chien-An Sun

180

Adiponectin Inhibits Allograft Rejection in Murine Cardiac Transplantation  

PubMed Central

Background Low levels of plasma adiponectin, an adipocytokine that possesses anti-inflammatory and anti-atherogenic properties, frequently observed among obese subjects correlate with higher prevalence of several cardiovascular diseases. This study investigated whether adiponectin modulates allograft rejection in MHC class II—mismatched cardiac transplants. Methods We heterotopically transplanted Bm12 allografts into adiponectin-deficient (APN?/?, C57BL/6 background) or wild-type (APN+/+) mice. Some APN?/? mice received adiponectin reconstitution by adenovirus. Histological analyses assessed allograft rejection, and real-time RT-PCR evaluated the genes for cytokines/chemokines associated with the immune and inflammatory responses. In addition, we tested the effect of adiponectin on proliferation and cytokine/chemokine production in mouse T lymphocytes stimulated in vitro with anti-CD3 antibodies. Results Allografts transplanted to APN?/? mice showed severe acute rejection relative to transplants in APN+/+ hosts accompanied by increased accumulation of CD4- and CD8-positive T lymphocytes and Mac3-positive macrophages. Adiponectin provision by adenovirus in APN?/? mice reversed these exacerbated responses to allografting. The rejected allografts in APN?/? mice contained significantly higher levels of TNF?, IFN?, and RANTES. Moreover, adiponectin significantly suppressed proliferation and production of TNF?, IFN?, RANTES, MCP-1, and IP-10 in mouse T lymphocytes stimulated in vitro with anti-CD3 antibodies. Conclusions These observations provide new mechanistic insight into immunoregulation in allograft recipients relative to obesity, an increasingly prevalent risk factor. Adiponectin may offer a new therapeutic target for allograft rejection after cardiac transplantation.

Okamoto, Yoshihisa; Christen, Thomas; Shimizu, Koichi; Asano, Ken-ichi; Kihara, Shinji; Mitchell, Richard N.; Libby, Peter

2009-01-01

181

Linkage analysis of circulating levels of adiponectin in hispanic children  

Technology Transfer Automated Retrieval System (TEKTRAN)

Adiponectin, a hormone produced exclusively by adipose tissue, is inversely associated with insulin resistance and pro-inflammatory conditions. The aim of this study was to find quantitative trait loci (QTLs) that affect circulating levels of adiponectin in Hispanic children participating in the VVA...

182

Adiponectin receptors in energy homeostasis and obesity pathogenesis.  

PubMed

Adipokines, that is factors secreted by adipose tissue, act through a network of autocrine, paracrine, and endocrine pathways to regulate several aspects of physiology, including glucose and lipid metabolism, neuroendocrine function, reproduction, and cardiovascular function. In particular, adiponectin, a 30-kDa protein, is associated with the regulation of insulin sensitivity, and its levels in serum are affected by altered metabolic homeostasis. Adiponectin effects are mediated by adiponectin receptors, which occur as two isoforms (AdipoR1 and AdipoR2). Transcriptional regulation of adiponectin is by the peroxisome proliferator-activated receptor-gamma (PPAR-?). However, acting through AdipoR1 and AdipoR2, adiponectin enhances 5' adenosine monophosphate-activated protein kinase (AMPK) and the PPAR?-mediated pathways in the liver and skeletal muscles. Adiponectin receptors mediate a wide spectrum of metabolic reactions, including gluconeogenesis and fatty-acid oxidation. Altogether, adiponectin deficiency and/or decreased adiponectin receptor-mediated activity possibly contribute to insulin resistance in metabolic syndromes, coronary heart disease, and liver disease. PMID:23317789

Akingbemi, Benson T

2013-01-01

183

Preparation and application of low molecular weight poly(vinyl chloride). III mechanical properties of blended poly(vinyl chloride)  

SciTech Connect

The blending effect of poly(vinyl chloride) with relatively higher molecular weight (HMW-PVC) and relatively lower molecular weight (LMW-PVC) has been investigated by measuring various mechanical properties: melt properties, tensile strength, tensile modulus, and impact strength. The blended PVC has slightly improved melt properties in comparison with the HMW-PVC used. The tensile strength of the blended PVC is related to the weight-average polymerization degree (Pw) of LMW-PVC and the LMW-PVC content. At the LMW-PVC content of 20%, the tensile strength of blended PVC is a maximum: approximately 58 MPa.

Yamamoto, Kikuo; Maehala, Takashi; Mitani, Katsuo; Mizutani, Yukio (Tokuyama Soda Co., Ltd., Tokuyama-city (Japan))

1993-11-05

184

Mechanisms of adiponectin regulation and use as a pharmacological target.  

PubMed

Adiponectin is an insulin-sensitizing and anti-inflammatory fat cell hormone that has immense potential as a therapeutic target for a multitude of obesity-associated diseases, including type 2 diabetes, NASH and atherosclerosis (Chandran M, Phillips SA, Ciaraldi T, Henry RR: Adiponectin: more than just another fat cell hormone?Diabetes Care 2003, 26:2442-2450). The adiponectin gene is located in chromosome 3q27, a susceptibility locus for T2DM and metabolic disorders (Saito K, Tobe T, Minoshima S, Asakawa S, Sumiya J, Yoda M, Nakano Y, Shimizu N, Tomita M: Organization of the gene for gelatin-binding protein (GBP28). Gene 1999, 229:67-73). Increased circulating levels of adiponectin are associated with improvement in the metabolic syndrome and reductions are strongly predictive of diabetes risk (Li S, Shin HJ, Ding EL, van Dam RM: Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 2009, 302:179-188. Extensive efforts have been made to understand how adiponectin levels can be elevated. The complex post-translational processing and secretion of adiponectin provides a rich area where pharmacologic manipulation may be developed to increase adiponectin levels in humans. Circulating adiponectin levels are increased by many commonly used drugs, such as statins, angiotensin converting enzyme (ACE) inhibitors, and thiazolidinediones (TZDs) providing an important opportunity to gain insight into the mechanisms underlying their effects. This review describes the cellular processes by which adiponectin is synthesized and secreted, current therapeutics known to affect this pathway and the potential for therapeutic manipulation in human subjects. PMID:20810317

Phillips, Susan A; Kung, Jacqueline T

2010-12-01

185

Ghrelin, leptin and adiponectin as possible predictors of the hedonic value of odors.  

PubMed

Several lines of evidence point to a close relationship between the hormones of energy homeostasis and the olfactory system. Examples are the localization of leptin and adiponectin receptors in the olfactory system or increased activation of brain regions related to the palatability and the hedonic value of food in response to food pictures after application of ghrelin. In this preliminary study, we tested in 31 subjects (17 male and 14 female) if and to what extent the peripheral blood concentrations of "satiety" hormones, such as leptin, adiponectin, and ghrelin (acyl and total), are correlated with the self-ratings of odor pleasantness and with the objective olfactory and gustatory ability. The hedonic values of some odors were found to be differently rated between donors depending on gender and body weight. The concentrations of leptin, adiponectin and total ghrelin were significantly associated with the hedonic value of pepper black oil, but failed to show significant correlations for 5 other odors tested. Except for a significant association between leptin and odor identification, hormone concentrations were not linked to the abilities of smell and taste. Peripheral adipokines and gut hormones may alter the perception and pleasantness of specific odors, presumably either directly through their receptors in the olfactory system or indirectly through central interfaces between the regulation systems of olfaction, appetite control, memory and motivation. PMID:21185875

Trellakis, Sokratis; Tagay, Sefik; Fischer, Cornelia; Rydleuskaya, Alena; Scherag, André; Bruderek, Kirsten; Schlegl, Sandra; Greve, Jens; Canbay, Ali E; Lang, Stephan; Brandau, Sven

2010-12-24

186

Effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels in mice.  

PubMed

Lifestyle-related diseases are associated with overeating and lack of exercise. The purpose of this study was to investigate the effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels. Mice were housed for 4 weeks in 4 groups, which included the non-exercise and normal diet (SN), exercise and normal diet (EN), non-exercise and high-fat diet (SF) and the exercise and high-fat diet (EF) group. The mice in the exercise groups were housed in cages with a running wheel and were subjected to voluntary exercise. The food intake (Kcal) of the mice in the exercise groups increased compared to that of the mice in the non-exercise groups (P<0.01). Body weight and visceral fat decreased in the mice in the EF group compared to the mice in the SF group (P<0.01 and P<0.05). The temperature of the mice in the EF group increased compared to that of the mice in the SN group (P<0.05). Blood glucose, insulin (P<0.01), cholesterol (P<0.01) and triglyceride concentrations (P<0.01) increased in the SF group compared to the normal diet groups. Furthermore, plasma insulin and cholesterol concentrations increased in the SF group compared to the exercise groups (P<0.01). Plasma adiponectin and nesfatin-1 levels in the SF group decreased compared to the SN group (P<0.05). Exercise under a high-fat diet antagonized the significant decrease in the nesfatin-1 level. Exercise together with a high-fat diet affected the plasma levels of adiponectin and nesfatin. It is therefore suggested that exercise together with a high-fat diet can affect various diseases via adiponectin and nesfatin. PMID:22977512

Chaolu, Huhe; Asakawa, Akihiro; Ushikai, Miharu; Li, Ying-Xiao; Cheng, Kai-Chun; Li, Jiang-Bo; Zoshiki, Takahiro; Terashi, Mutsumi; Tanaka, Chie; Atsuchi, Kaori; Sakoguchi, Takeo; Tsai, Minglun; Amitani, Haruka; Horiuchi, Masahisa; Takeuchi, Toru; Inui, Akio

2011-01-19

187

Effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels in mice  

PubMed Central

Lifestyle-related diseases are associated with overeating and lack of exercise. The purpose of this study was to investigate the effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels. Mice were housed for 4 weeks in 4 groups, which included the non-exercise and normal diet (SN), exercise and normal diet (EN), non-exercise and high-fat diet (SF) and the exercise and high-fat diet (EF) group. The mice in the exercise groups were housed in cages with a running wheel and were subjected to voluntary exercise. The food intake (Kcal) of the mice in the exercise groups increased compared to that of the mice in the non-exercise groups (P<0.01). Body weight and visceral fat decreased in the mice in the EF group compared to the mice in the SF group (P<0.01 and P<0.05). The temperature of the mice in the EF group increased compared to that of the mice in the SN group (P<0.05). Blood glucose, insulin (P<0.01), cholesterol (P<0.01) and triglyceride concentrations (P<0.01) increased in the SF group compared to the normal diet groups. Furthermore, plasma insulin and cholesterol concentrations increased in the SF group compared to the exercise groups (P<0.01). Plasma adiponectin and nesfatin-1 levels in the SF group decreased compared to the SN group (P<0.05). Exercise under a high-fat diet antagonized the significant decrease in the nesfatin-1 level. Exercise together with a high-fat diet affected the plasma levels of adiponectin and nesfatin. It is therefore suggested that exercise together with a high-fat diet can affect various diseases via adiponectin and nesfatin.

CHAOLU, HUHE; ASAKAWA, AKIHIRO; USHIKAI, MIHARU; LI, YING-XIAO; CHENG, KAI-CHUN; LI, JIANG-BO; ZOSHIKI, TAKAHIRO; TERASHI, MUTSUMI; TANAKA, CHIE; ATSUCHI, KAORI; SAKOGUCHI, TAKEO; TSAI, MINGLUN; AMITANI, HARUKA; HORIUCHI, MASAHISA; TAKEUCHI, TORU; INUI, AKIO

2011-01-01

188

High-molecular-weight hyaluronan is a novel inhibitor of pulmonary vascular leakiness.  

PubMed

Endothelial cell (EC) barrier dysfunction results in increased vascular permeability, a perturbation observed in inflammatory states, tumor angiogenesis, atherosclerosis, and both sepsis and acute lung injury. Therefore, agents that enhance EC barrier integrity have important therapeutic implications. We observed that binding of high-molecular-weight hyaluronan (HMW-HA) to its cognate receptor CD44 within caveolin-enriched microdomains (CEM) enhances human pulmonary EC barrier function. Immunocytochemical analysis indicated that HMW-HA promotes redistribution of a significant population of CEM to areas of cell-cell contact. Quantitative proteomic analysis of CEM isolated from human EC demonstrated HMW-HA-mediated recruitment of cytoskeletal regulatory proteins (annexin A2, protein S100-A10, and filamin A/B). Inhibition of CEM formation [caveolin-1 small interfering RNA (siRNA) and cholesterol depletion] or silencing (siRNA) of CD44, annexin A2, protein S100-A10, or filamin A/B expression abolished HMW-HA-induced actin cytoskeletal reorganization and EC barrier enhancement. To confirm our in vitro results in an in vivo model of inflammatory lung injury with vascular hyperpermeability, we observed that the protective effects of HMW-HA on LPS-induced pulmonary vascular leakiness were blocked in caveolin-1 knockout mice. Furthermore, targeted inhibition of CD44 expression in the mouse pulmonary vasculature significantly reduced HMW-HA-mediated protection from LPS-induced hyperpermeability. These data suggest that HMW-HA, via CD44-mediated CEM signaling events, represents a potentially useful therapeutic agent for syndromes of increased vascular permeability. PMID:20709728

Singleton, Patrick A; Mirzapoiazova, Tamara; Guo, Yurong; Sammani, Saad; Mambetsariev, Nurbek; Lennon, Frances E; Moreno-Vinasco, Liliana; Garcia, Joe G N

2010-08-13

189

Biomarkers of Adiponectin: Plasma Protein Variation and Genomic DNA Polymorphisms  

PubMed Central

Adiponectin is secreted by white adipose tissue and exists as the most abundant adipokine in the human plasma. Recent research has indicated that plasma adiponectin levels are inversely correlated with body mass index (BMI) and insulin resistance. Reduction of plasma adiponectin levels is commonly observed in the patients with type 2 diabetes (T2D) and/or in those who are obese in comparison with healthy control individuals. The adiponectin (AdipoQ) gene has a moderate linkage disequilibrium (LD), but two small LD blocks are observed, respectively, in the promoter region and the boundary of exon 2-intron 2. Genetic association studies have demonstrated that single nucleotide polymorphisms (SNPs) +45G15G(T/G) in exon 2 and +276G/T in intron 2 of the AdipoQ gene confer the risk susceptibility to the development of T2D, obesity and diabetic nephropathy (DN). The SNPs in the promoter region, including ?11426A/G, ?11377C/G and ?11391G/A, are found to be associated with T2D and DN. Recent research has indicated that the promoter polymorphisms interfere with the AdipoQ promoter activity. The haplotypes constructed by the promoter polymorphisms and SNP +276G/T in intron 2 are associated with circulating adiponectin levels. This review summarises genetic and pathophysiological relevancies of adiponectin and discusses about the biomarkers of adiponectin plasma protein variation and genomic DNA polymorphisms.

Gu, Harvest F.

2009-01-01

190

Genome-wide association study for adiponectin levels in Filipino women identifies CDH13 and a novel uncommon haplotype at KNG1-ADIPOQ.  

PubMed

Adiponectin is an adipocyte-secreted protein involved in a variety of metabolic processes, including glucose regulation and fatty acid catabolism. We conducted a genome-wide association study to investigate the genetic loci associated with plasma adiponectin in 1776 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). Our strongest signal for adiponectin mapped to the gene CDH13 (rs3865188, P ? 7.2 × 10(-16)), which encodes a receptor for high-molecular-weight forms of adiponectin. Strong association was also detected near the ADIPOQ gene (rs864265, P = 3.8 × 10(-9)) and at a novel signal 100 kb upstream near KNG1 (rs11924390, P = 7.6 × 10(-7)). All three signals were also observed in 1774 young adult CLHNS offspring and in combined analysis including all 3550 mothers and offspring samples (all P ? 1.6 × 10(-9)). An uncommon haplotype of rs11924390 and rs864265 (haplotype frequency = 0.050) was strongly associated with lower adiponectin compared with the most common C-G haplotype in both CLHNS mothers (P = 1.8 × 10(-25)) and offspring (P = 8.7 × 10(-32)). Comprehensive imputation of 2653 SNPs in a 2 Mb region using as reference combined CHB, JPT and CEU haplotypes from the 1000 Genomes Project revealed no variants that perfectly tagged this haplotype. Our findings provide the first genome-wide significant evidence of association with plasma adiponectin at the CDH13 locus and identify a novel uncommon KNG1-ADIPOQ haplotype strongly associated with adiponectin levels in Filipinos. PMID:20876611

Wu, Ying; Li, Yun; Lange, Ethan M; Croteau-Chonka, Damien C; Kuzawa, Christopher W; McDade, Thomas W; Qin, Li; Curocichin, Ghenadie; Borja, Judith B; Lange, Leslie A; Adair, Linda S; Mohlke, Karen L

2010-09-27

191

Adiponectin levels and expression of adiponectin receptors in isolated monocytes from overweight patients with coronary artery disease  

PubMed Central

Background Adiponectin has insulin-sensitizing and anti-atherosclerotic effects, partly mediated through its action on monocytes. We aimed to determine adiponectin levels and expression of its receptors (AdipoR1 and AdipoR2) in peripheral monocytes from overweight and obese patients with coronary artery disease (CAD). Methods Fifty-five overweight/obese patients, suspected for CAD, underwent coronary angiography: 31 were classified as CAD patients (stenosis ? 50% in at least one main vessel) and 24 as nonCAD. Quantitative RT-PCR and flow cytometry were used for determining mRNA and protein surface expression of adiponectin receptors in peripheral monocytes. A high sensitivity multiplex assay (xMAP technology) was used for the determination of plasma adiponectin and interleukin-10 (IL-10) secreted levels. Results Plasma adiponectin levels were decreased in CAD compared to nonCAD patients (10.9 ± 3.1 vs. 13.8 ± 5.8 ?g/ml respectively, p = 0.033). In multivariable analysis, Matsuda index was the sole independent determinant of adiponectin levels. AdipoR1 and AdipoR2 protein levels were decreased in monocytes from CAD compared to nonCAD patients (59.5 ± 24.9 vs. 80 ± 46 and 70.7 ± 39 vs. 95.6 ± 47.8 Mean Fluorescence Intensity Arbitrary Units respectively, p < 0.05). No significant differences were observed concerning the mRNA levels of the adiponectin receptors between CAD and nonCAD patients. AdipoR2 protein levels were positively correlated with plasma adiponectin and Matsuda index (r = 0.36 and 0.31 respectively, p < 0.05 for both). Furthermore, basal as well as adiponectin-induced IL-10 release was reduced in monocyte-derived macrophages from CAD compared to nonCAD subjects. Conclusions Overweight patients with CAD compared to those without CAD, had decreased plasma adiponectin levels, as well as decreased surface expression of adiponectin receptors in peripheral monocytes. This fact together with the reduced adiponectin-induced IL-10 secretion from CAD macrophages could explain to a certain extent, an impaired atheroprotective action of adiponectin.

2011-01-01

192

Adiponectin modulates NK-cell function.  

PubMed

Adiponectin (APN) has been shown to exert antiinflammatory effects in various disease models but little is known concerning its regulation of NK-cell function. Here, we show that the majority of human CD56(dim) NK cells express surface Adiponectin receptor (AdipoR) 1 and 2 while most CD56(high) NK cells are AdipoR-negative. Toll-like receptor (TLR) ligand-induced IFN-? production was diminished by APN while it had no influence on NK-cell cytotoxicity. In contrast only a small subpopulation of murine NK cells expresses surface AdipoRs, but about 90% store them intracellularly. APN-deficient knockout (KO) mice had elevated frequencies of NK cells. However, cytotoxic degranulation of NK cells was decreased in APN knockout (APN-KO) animals. Accordingly, frequencies of CD11b(high) CD27(high) and CD94(high) effector NK cells and expression of NKG2D were lower in APN-KO mice. Upon CVB3 infection NK-cell function was restored in APN-KO mice. Our data suggest that in addition to its antiinflammatory effects APN also influences the numerical and differentiation status of NK cells, which may further impact the outcome of immune-mediated diseases in APN-KO mice. PMID:23401034

Wilk, Sabrina; Jenke, Alexander; Stehr, Jenny; Yang, Chin-An; Bauer, Sandra; Göldner, Katrin; Kotsch, Katja; Volk, Hans-Dieter; Poller, Wolfgang; Schultheiss, Heinz-Peter; Skurk, Carsten; Scheibenbogen, Carmen

2013-03-01

193

The Relationships of Leptin, Adiponectin Levels and Paraoxonase Activity with Metabolic and Cardiovascular Risk Factors in Females Treated with Psychiatric Drugs  

PubMed Central

OBJECTIVES The aim of this study was to investigate serum leptin, adiponectin and paraoxonase1 levels in adult females receiving pharmacotherapy for various psychiatric disorders. METHODS The study group consisted of 32 obese females (mean age 40.53 ± 11.00 years, mean body mass index 35.44 ± 5.33 kg/m2) who were receiving treatment for psychiatric disorders, and the control group included 22 obese females (mean age 35.95 ± 9.16 years, mean body mass index 30.78 ± 3.33 kg/m2) who were free of psychiatric disorders. Analyses were performed using a bioelectrical impedance device. Fasting blood samples were obtained for complete blood count and various biochemical tests, including determination of leptin, adiponectin and paraoxonase1 activity. RESULTS Body mass index, waist and hip circumference, body fat percentage, fasting blood glucose, insulin, glycosylated hemoglobin, homeostasis model assesment of insulin resistance, alanine transaminase, aspartate tarnsaminase, and leptin levels were significantly higher in the study group than in controls. Although body weight was positively correlated with leptin levels in both groups, body weight was negatively correlated with adiponectin levels in the control group and positively correlated with adiponectin levels in the study group. In the study group, body mass index and hip circumference correlated positively with leptin levels, hip circumference correlated positively with adiponectin levels, and waist to hip ratio correlated positively with paraoxonase levels. In the control group, body mass index as well as waist and hip circumferences were positively correlated with leptin levels. Weight, body mass index, and hip circumference were also negatively correlated with the adiponectin/leptin ratio in the control group. CONCLUSION This study indicates a higher risk for obesity-related disorders, particularly metabolic syndrome, diabetes and cardiovascular disease, in patients treated with psychiatric drugs.

Ozenoglu, Aliye; Balci, Huriye; Ugurlu, Serdal; Caglar, Erkan; Uzun, Hafize; Sarkis, Cihat; Gunay, Can; Eker E, Engin

2008-01-01

194

Adiponectin Promotes Monocyte-to-Fibroblast Transition in Renal Fibrosis.  

PubMed

Bone marrow-derived fibroblasts may contribute substantially to the pathogenesis of renal fibrosis through the excessive production and deposition of extracellular matrix. However, the mechanisms underlying the accumulation and activation of these fibroblasts are not understood. Here, we used a mouse model of tubulointerstitial fibrosis to determine whether adiponectin, which is elevated in CKD and is associated with disease progression, regulates monocyte-to-fibroblast transition and fibroblast activation in injured kidneys. In wild-type mice, the expression of adiponectin and the number of bone marrow-derived fibroblasts in the kidney increased after renal obstruction. In contrast, the obstructed kidneys of adiponectin-knockout mice had fewer bone marrow-derived fibroblasts. Adiponectin deficiency also led to a reduction in the number of myofibroblasts, the expression of profibrotic chemokines and cytokines, and the number of procollagen-expressing M2 macrophages in injured kidneys. Consistent with these findings, adiponectin-deficiency reduced the expression of collagen I and fibronectin. Similar results were observed in wild-type and adiponectin-knockout mice after ischemia-reperfusion injury. In cultured bone marrow-derived monocytes, adiponectin stimulated the expression of ?-smooth muscle actin (SMA) and extracellular matrix proteins and activated AMP-activated protein kinase (AMPK) in a time- and dose-dependent manner. Furthermore, specific activation of AMPK increased the expression of ?-SMA and extracellular matrix proteins, while inhibition of AMPK attenuated these responses. Taken together, these findings identify adiponectin as a critical regulator of monocyte-to-fibroblast transition and renal fibrosis, suggesting that inhibition of adiponectin/AMPK signaling may represent a novel therapeutic target for fibrotic kidney disease. PMID:23833260

Yang, Jun; Lin, Song-Chang; Chen, Gang; He, Liqun; Hu, Zhaoyong; Chan, Lawrence; Trial, Joann; Entman, Mark L; Wang, Yanlin

2013-07-05

195

Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes.  

PubMed

Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics-based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26-0.35) increase in fasting insulin, a 0.34-SD (0.30-0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47-2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI -0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (-0.20 SD; 95% CI -0.38 to -0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75-1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: -0.03 SD; 95% CI -0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95-1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes. PMID:23835345

Yaghootkar, Hanieh; Lamina, Claudia; Scott, Robert A; Dastani, Zari; Hivert, Marie-France; Warren, Liling L; Stancáková, Alena; Buxbaum, Sarah G; Lyytikäinen, Leo-Pekka; Henneman, Peter; Wu, Ying; Cheung, Chloe Y Y; Pankow, James S; Jackson, Anne U; Gustafsson, Stefan; Zhao, Jing Hua; Ballantyne, Christie M; Xie, Weijia; Bergman, Richard N; Boehnke, Michael; El Bouazzaoui, Fatiha; Collins, Francis S; Dunn, Sandra H; Dupuis, Josee; Forouhi, Nita G; Gillson, Christopher; Hattersley, Andrew T; Hong, Jaeyoung; Kähönen, Mika; Kuusisto, Johanna; Kedenko, Lyudmyla; Kronenberg, Florian; Doria, Alessandro; Assimes, Themistocles L; Ferrannini, Ele; Hansen, Torben; Hao, Ke; Häring, Hans; Knowles, Joshua W; Lindgren, Cecilia M; Nolan, John J; Paananen, Jussi; Pedersen, Oluf; Quertermous, Thomas; Smith, Ulf; Lehtimäki, Terho; Liu, Ching-Ti; Loos, Ruth J F; McCarthy, Mark I; Morris, Andrew D; Vasan, Ramachandran S; Spector, Tim D; Teslovich, Tanya M; Tuomilehto, Jaakko; van Dijk, Ko Willems; Viikari, Jorma S; Zhu, Na; Langenberg, Claudia; Ingelsson, Erik; Semple, Robert K; Sinaiko, Alan R; Palmer, Colin N A; Walker, Mark; Lam, Karen S L; Paulweber, Bernhard; Mohlke, Karen L; van Duijn, Cornelia; Raitakari, Olli T; Bidulescu, Aurelian; Wareham, Nick J; Laakso, Markku; Waterworth, Dawn M; Lawlor, Debbie A; Meigs, James B; Richards, J Brent; Frayling, Timothy M

2013-07-08

196

Adiponectin, driver or passenger on the road to insulin sensitivity?  

PubMed Central

Almost 20 years have passed since the first laboratory evidence emerged that an abundant message encoding a protein with homology to the C1q superfamily is highly specifically expressed in adipocytes. At this stage, we refer to this protein as adiponectin. Despite more than 10,000 reports in the literature since its initial description, we seem to have written only the first chapter in the textbook on adiponectin physiology. With every new aspect we learn about adiponectin, a host of new questions arise with respect to the underlying molecular mechanisms. Here, we aim to summarize recent findings in the field and bring the rodent studies that suggest a causal relationship between adiponectin levels in plasma and systemic insulin sensitivity in perspective with the currently available data on the clinical side.

Ye, Risheng; Scherer, Philipp E.

2013-01-01

197

Regulation of adiponectin in adipocytes upon exposure to HIV-1  

Technology Transfer Automated Retrieval System (TEKTRAN)

Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose...

198

Lower Serum Adiponectin Levels in African-American Boys  

Microsoft Academic Search

Objective: To examine adiponectin, an adipocyte-secreted hormone with anti-inflammatory and insulin-sensitizing effects, in relation to race or gender in younger subjects.Research Methods and Procedures: The relationship of adiponectin, quantitated by radioimmunoassay, to anthropometric and metabolic factors (fasting insulin, glucose, and leptin) and reproductive hormones was examined in 46 healthy African Americans (25 girls\\/21 boys) and 40 whites (20 girls\\/20 boys)

Mikako Degawa-Yamauchi; Jason R. Dilts; Jason E. Bovenkerk; Chandan Saha; J. Howard Pratt; Robert V. Considine

2003-01-01

199

Adiponectin and inflammatory markers in peripheral arterial occlusive disease  

Microsoft Academic Search

This study was designed to examine the plasma levels of adiponectin as well as markers of inflammation and endothelial function in peripheral arterial occlusive disease (PAOD), and to investigate the pathophysiological significance of adiponectin in this disease. Eighty-eight subjects with (n=40) and without PAOD (n=48) were enrolled. Multiple regression analysis including age, sex, body mass index, hypertension, diabetes, triglycerides, high-density

Yoshio Iwashima; Takeshi Horio; Yoshihiko Suzuki; Shinji Kihara; Hiromi Rakugi; Kenji Kangawa; Tohru Funahashi; Toshio Ogihara; Yuhei Kawano

2006-01-01

200

Adiponectin Enhances the Responsiveness of the Olfactory System  

PubMed Central

The peptide hormone adiponectin is secreted by adipose tissue and the circulating concentration is reversely correlated with body fat mass; it is considered as starvation signal. The observation that mature sensory neurons of the main olfactory epithelium express the adiponectin receptor 1 has led to the concept that adiponectin may affect the responsiveness of the olfactory system. In fact, electroolfactogram recordings from olfactory epithelium incubated with exogenous adiponectin resulted in large amplitudes upon odor stimulation. To determine whether the responsiveness of the olfactory sensory neurons was enhanced, we have monitored the odorant-induced expression of the immediate early gene Egr1. It was found that in an olfactory epithelium incubated with nasally applied adiponectin the number of Egr1 positive cells was significantly higher compared to controls, suggesting that adiponectin rendered the olfactory neurons more responsive to an odorant stimulus. To analyze whether the augmented responsiveness of sensory neurons was strong enough to elicit a higher neuronal activity in the olfactory bulb, the number of activated periglomerular cells of a distinct glomerulus was determined by monitoring the stimulus-induced expression of c-fos. The studies were performed using the transgenic mOR256-17-IRES-tauGFP mice which allowed to visualize the corresponding glomerulus and to stimulate with a known ligand. The data indicate that upon exposure to 2,3-hexanedione in adiponectin-treated mice the number of activated periglomerular neurons was significantly increased compared to controls. The results of this study indicate that adiponectin increases the responsiveness of the olfactory system, probably due to a higher responsiveness of olfactory sensory neurons.

Loch, Diana; Heidel, Christian; Breer, Heinz; Strotmann, Jorg

2013-01-01

201

Adiponectin Independently Predicts Metabolic Syndrome in Overweight Latino Youth  

Microsoft Academic Search

Context: Adiponectin may be important in the pathogenesis of in- sulin resistance and the metabolic syndrome in youth. Objective: The objective of the study was to determine the unique effect of adiponectin on the metabolic syndrome in overweight Latino youth. Participants: Participants included 175 overweight children (aged 11.1 1.7 yr, body mass index percentile 97.3 2.9) with a family history

Gabriel Q. Shaibi; Martha L. Cruz; Marc J. Weigensberg; Claudia M. Toledo-Corral; Louise A. Kelly; Jaimie N. Davis; Corinna Koebnick; Emily E. Ventura; Christian K. Roberts; Michael I. Goran

202

Variant high-molecular-weight glutenin subunits arising from biolistic transformation of wheat  

Technology Transfer Automated Retrieval System (TEKTRAN)

Genetic transformation via the biolistic method has been used to introduce genes encoding natural and novel high-molecular-weight glutenin subunits (HMW-GS) into wheat. The appearance of new seed proteins of sizes not predicted by the transgene coding sequences has been noted in some of these exper...

203

A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome.  

PubMed

Adiponectin is a protein secreted by adipocytes that modulates insulin action. To assess whether variants of this gene contribute to the prevalence of insulin resistance in Caucasians, we genotyped 413 nondiabetic individuals for two single nucleotide polymorphisms (SNPs) at this locus. The two SNPs (45T-->G and 276G-->T) were chosen because of their association with type 2 diabetes in Japanese. Whereas each polymorphism was significantly associated with some correlate of insulin resistance, the haplotype defined by the two together was strongly associated with many components of the insulin resistance syndrome. Homozygotes for the risk haplotype had higher body weight (P = 0.03), waist circumference (P = 0.004), systolic (P = 0.01) and diastolic (P = 0.003) blood pressure, fasting glucose (P = 0.02) and insulin (P = 0.005) levels, homeostasis model assessment (HOMA) for insulin resistance (P = 0.003), and total to HDL cholesterol ratio (P = 0.01). Homozygotes also had significantly lower plasma levels of adiponectin (P = 0.03), independent of sex, age, and body weight. In an independent study group of 614 Caucasians, including 310 with type 2 diabetes, the risk haplotype was confirmed to be associated with increased body weight (P = 0.03) but not with type 2 diabetes per se. We conclude that variability at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome, but given the nature of the two SNPs, the risk haplotype is most probably a marker in linkage disequilibrium with an as yet unidentified polymorphism that affects plasma adiponectin levels and insulin sensitivity. PMID:12086965

Menzaghi, Claudia; Ercolino, Tonino; Di Paola, Rosa; Berg, Anders H; Warram, James H; Scherer, Philipp E; Trischitta, Vincenzo; Doria, Alessandro

2002-07-01

204

Serum leptin, adiponectin and endometrial cancer risk in Chinese women  

PubMed Central

Objective To investigate the relationship between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women. Methods We conducted a case-control study of a total of 516 Chinese women to detect the relationships between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women. The study subject constituted 206 cases of endometrial cancer and 310 normal controls. Results Patients with endometrial carcinoma had higher serum leptin concentrations than controls (28.8±2.2 ug/L vs. 19.8±1.4 ug/L; p<0.001). The adiponectin levels in patients were lower than in controls with borderline statistical significance (2,330.7±180.5 ug/L vs. 2,583.9±147.2 ug/L; p=0.078). Logistic regression analysis confirmed the associations between leptin or adiponectin, and endometrial carcinoma after adjustment for age, body mass index, fasting insulin, serum glucose, cholesterol, triglycerides, and high-density lipoprotein cholesterol (odds ratio for the top tertile vs. the bottom tertile: leptin 2.05; 95% confidence interval [CI], 1.28 to 3.29; p<0.001; adiponectin 0.52; 95% CI, 0.32 to 0.83; p<0.001). Conclusion Increased leptin or decreased adiponectin levels are associated with endometrial carcinoma.

Ma, Yu; Liu, Zhiwei; Zhang, Yan

2013-01-01

205

Influence of adiponectin gene polymorphisms on adiponectin serum level and insulin resistance index in taiwanese metabolic syndrome patients.  

PubMed

Although mounting evidences have revealed an association between the gene coding for adiponectin and serum adiponectin levels, much controversy still surrounds the association of the adiponectin gene with metabolic traits such as insulin resistance in obesity and type 2 diabetes (T2DM). On the other hand, very few studies have looked into the relations between adiponectin genetic variants and risks of metabolic syndromes (Mets). The present study assessed the influence of two common adiponectin single-nucleotide polymorphisms (SNPs), rs266729 (C-11377G) and rs1501299 (G276T) in the risk of Mets. A community-based population of 137/110 case/control was genotyped by PCR-RFLP, and the levels of serum adiponectin, fasting serum glucose, fasting serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), uric acid and C-reactive protein of each subject were measured. The distribution of genotypic and allelic frequencies of C-11377G or G276T was not statistically different between the Mets and control groups. However, among the patients with Mets, those carrying GG at C-11377G had a lower level of serum adiponectin (P < 0.001), higher levels of fasting serum glucose (P = 0.0142), fasting serum insulin (P < 0.001) and HOMA-IR (P < 0.001) compared with those carrying the CC or CG genotype. Our data suggest that subjects who carry the homologous GG genotype at C-11377G of the adiponectin gene may be of higher risk of Mets and should be monitored more closely with other serum biochemical indexes. PMID:23286448

Lin, Chih-Hsueh; Ho, Chien-Yi; Liu, Chiu-Shong; Lin, Wen-Yuan; Li, Chia-Ing; Yang, Chuan-Wei; Bau, Da-Tian; Li, Tsai-Chung; Lin, Cheng-Chieh

2012-12-31

206

Common polymorphisms in the adiponectin and its receptor genes, adiponectin levels and the risk of prostate cancer  

PubMed Central

Background Adiponectin, an insulin-sensitizing adipokine, is inversely associated with adiposity and prostate cancer risk and progression. However, the role of genetic variation in the adiponectin (ADIPOQ) and receptor genes (ADIPOR1/R2) in prostate cancer is largely unknown. Methods In a nested case-control study of 1286 cases and 1267 controls within the Physicians' Health Study, we evaluated 29 common single nucleotide polymorphisms (SNPs) in ADIPOQ (n=13), ADIPOR1(n=5) and ADIPOR2(n=11) in relation to the risk of prostate cancer. In subgroups, we also evaluated the association of genotype and circulating adiponectin levels (n=951) and prostate tumor expression of insulin receptor (IR) and insulin-like growth factor 1 (IGF-1R) receptor (n=181). Results Among the 12 tagging polymorphisms in ADIPOQ, four (rs266729, rs182052, rs822391, rs2082940) were significantly associated (p<0.05) with overall prostate cancer risk, with no significant difference by tumor grade or clinical stage. Two of the risk SNPs (rs266729, rs182052) plus four other SNPs (rs16861209, rs17366568, rs3774261, rs7639352) were also associated with plasma adiponectin levels and three of these (rs1686109, rs17366568, rs3774261) were also significantly associated with IR expression in prostate tumor tissue. One additional SNP was associated with IGF1-R tumor tissue expression (rs16861205). None of the 16 variants in ADIPOR1/R2 were related to cancer risk or circulating adiponectin levels. Conclusions Common variants in the adiponectin gene were associated with prostate cancer risk, plasma adiponectin levels, and IR or IGF-1R expression in the prostate tumor. Impact These genotype-phenotype associations support the biological relevance of adiponectin for prostate carcinogenesis, particularly in earlier stages of development.

Dhillon, Preet K.; Penney, Kathryn L.; Schumacher, Fredrick; Rider, Jennifer R.; Sesso, Howard D.; Pollak, Michael; Fiorentino, Michelangelo; Finn, Stephen; Loda, Massimo; Rifai, Nader; Mucci, Lorelei A.; Giovannucci, Edward; Stampfer, Meir J.; Ma, Jing

2013-01-01

207

Associations between perinatal factors and adiponectin and leptin in 9-year-old Mexican-American children.  

PubMed

What is already known about this subject Mexican-American children are at particularly high risk of obesity. Features of the perinatal environment, including maternal nutrition, anthropometry, glucose tolerance and growth rate during infancy are implicated in programming of obesity in the offspring. What this study adds Greater rate of weight or length gain in the first 6 months of life is associated with lower 9-year child adiponectin levels, adjusting for 9-year child BMI. Nine-year-old child adipokine levels are strongly related to those of their mothers'. OBJECTIVES: To (i) determine whether perinatal factors (including maternal anthropometry and nutrition and early life growth measures) are associated with adiponectin and leptin levels in 9-year-old children, and (ii) assess relationships between adiponectin, leptin and concurrent lipid profile in these children. METHODS: We measured plasma adiponectin and leptin for 146 mothers-9-year-old child pairs from the ongoing longitudinal birth cohort followed by the Center for the Health Assessment of Mothers and Children of Salinas. Data on perinatal factors, including sociodemographics, maternal anthropometry and nutrition, and early life child growth were collected during pregnancy, birth and 6-month visits. RESULTS: Greater rate of weight and length gain during the first 6 months of life were associated with lower adiponectin in 9-year-olds (??=?-2.0, P?=?0.04; ??=?-8.2, P?=?0.02, respectively) adjusting for child body mass index (BMI). We found no associations between child adipokine levels and either maternal calorie, protein, total fat, saturated fat, fibre, sugar-sweetened beverage consumption during pregnancy or children's concurrent sugar-sweetened beverage and fast food intake. Lipid profile in 9-year-old children closely reflected adiponectin but not leptin levels after adjustment for child BMI. Additionally, we report that child adipokine levels were closely related to their mothers' levels at the 9-year visit. CONCLUSION: Overall, our results support the hypothesis that early life factors may contribute to altered adipokine levels in children. PMID:23325579

Volberg, Vitaly; Harley, Kim G; Aguilar, Raul S; Rosas, Lisa G; Huen, Karen; Yousefi, Paul; Davé, Veronica; Phan, Nguyet; Lustig, Robert H; Eskenazi, Brenda; Holland, Nina

2013-01-16

208

Non-self-discrimination as a driving concept in the identification of an immunodominant HMW-MAA epitopic peptide sequence by autoantibodies from melanoma cancer patients.  

PubMed

We analyzed the sera of patients with melanoma to define the human humoral autoantibody profile towards HMW-MAA. Computational proteome scanning using the non-self-discrimination principle as a guide led to the individuation of the low-similarity HMW-MAA781-789RATVWMLRL peptide fragment as an immunodominant B-cell epitope. Linear B-cell determinant individuation was experimentally validated by dot blot immunoassay and NMR spectroscopy analysis. Regulation of physiologic self-reactivity by the non-self-discrimination principle is discussed. PMID:15252841

Dummer, Reinhard; Mittelman, Abraham; Fanizzi, Francesco P; Lucchese, Guglielmo; Willers, Jörg; Kanduc, Darja

2004-09-20

209

Adiponectin and inflammatory markers in peripheral arterial occlusive disease.  

PubMed

This study was designed to examine the plasma levels of adiponectin as well as markers of inflammation and endothelial function in peripheral arterial occlusive disease (PAOD), and to investigate the pathophysiological significance of adiponectin in this disease. Eighty-eight subjects with (n=40) and without PAOD (n=48) were enrolled. Multiple regression analysis including age, sex, body mass index, hypertension, diabetes, triglycerides, high-density lipoprotein cholesterol, creatinine, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cellular adhesion molecules-1 (sVCAM-1), von Willebrand factor, and high-sensitive C reactive protein (Hs-CRP) showed that adiponectin concentration was significantly lower in PAOD subjects (PAOD: 7.9+/-0.7 microg/mL versus without PAOD: 9.5+/-0.6 microg/mL, F=4.94, p<0.03). Furthermore, concentrations of adiponectin (F=8.5, p<0.01) as well as sICAM-1 (F=5.8, p<0.02), sVCAM-1 (F=5.9, p<0.02), and Hs-CRP (F=3.8, p=0.05) were independently associated with ankle-brachial index. In 27 subjects (10 with PAOD and 17 without PAOD), adiponectin levels in the femoral artery and saphenous vein were measured. A significant step-up of adiponectin from the artery to the vein was observed in subjects without PAOD (+13.0%, p<0.01), but not in subjects with PAOD (+0.4%, NS). Plasma adiponectin as well as Hs-CRP were followed before and after percutaneous transluminal angioplasty (PTA) in eight patients. Adiponectin showed a tendency to decrease after PTA (day 6, -30.6%), although Hs-CRP significantly increased. Adiponectin is decreased in patients with PAOD in proportion to the severity of the disease. Adiponectin concentration could be a marker of the existence of atherosclerosis, and measurement of its concentration may be helpful in assessment of the progress of atherosclerosis. PMID:16321391

Iwashima, Yoshio; Horio, Takeshi; Suzuki, Yoshihiko; Kihara, Shinji; Rakugi, Hiromi; Kangawa, Kenji; Funahashi, Tohru; Ogihara, Toshio; Kawano, Yuhei

2006-10-01

210

Effects of sugar-sweetened beverages on plasma acylation stimulating protein, leptin, and adiponectin: Relationships with Metabolic Outcomes.  

PubMed

OBJECTIVE: The effects of fructose and glucose consumption on plasma acylation stimulating protein (ASP), adiponectin, and leptin concentrations relative to energy intake, body weight, adiposity, circulating triglycerides, and insulin sensitivity were determined. DESIGN AND METHODS: Thirty two overweight/obese adults consumed glucose- or fructose-sweetened beverages (25% energy requirement) with their ad libitum diets for 8 weeks, followed by sweetened beverage consumption for 2 weeks with a standardized, energy-balanced diet. Plasma variables were measured at baseline, 2, 8, and 10 weeks, and body adiposity and insulin sensitivity at baseline and 10 weeks. RESULTS: Fasting and postprandial ASP concentrations increased at 2 and/or 8 weeks. ASP increases correlated with changes in late-evening triglyceride concentrations. At 10 weeks, fasting adiponectin levels decreased in both groups, and decreases were inversely associated with baseline intra-abdominal fat volume. Sugar consumption increased fasting leptin concentrations; increases were associated with body weight changes. The 24-h leptin profiles increased during glucose consumption and decreased during fructose consumption. These changes correlated with changes of 24-h insulin levels. CONCLUSIONS: The consumption of fructose and glucose beverages induced changes in plasma concentrations of ASP, adiponectin, and leptin. Further study is required to determine if these changes contribute to the metabolic dysfunction observed during fructose consumption. PMID:23512943

Rezvani, Reza; Cianflone, Katherine; McGahan, John P; Berglund, Lars; Bremer, Andrew A; Keim, Nancy L; Griffen, Steven C; Havel, Peter J; Stanhope, Kimber L

2013-03-20

211

Extraction of High Molecular Weight DNA from Microbial Mats  

PubMed Central

Successful and accurate analysis and interpretation of metagenomic data is dependent upon the efficient extraction of high-quality, high molecular weight (HMW) community DNA. However, environmental mat samples often pose difficulties to obtaining large concentrations of high-quality, HMW DNA. Hypersaline microbial mats contain high amounts of extracellular polymeric substances (EPS)1 and salts that may inhibit downstream applications of extracted DNA. Direct and harsh methods are often used in DNA extraction from refractory samples. These methods are typically used because the EPS in mats, an adhesive matrix, binds DNA2,3 during direct lysis. As a result of harsher extraction methods, DNA becomes fragmented into small sizes4,5,6. The DNA thus becomes inappropriate for large-insert vector cloning. In order to circumvent these limitations, we report an improved methodology to extract HMW DNA of good quality and quantity from hypersaline microbial mats. We employed an indirect method involving the separation of microbial cells from the background mat matrix through blending and differential centrifugation. A combination of mechanical and chemical procedures was used to extract and purify DNA from the extracted microbial cells. Our protocol yields approximately 2 ?g of HMW DNA (35-50 kb) per gram of mat sample, with an A260/280 ratio of 1.6. Furthermore, amplification of 16S rRNA genes7 suggests that the protocol is able to minimize or eliminate any inhibitory effects of contaminants. Our results provide an appropriate methodology for the extraction of HMW DNA from microbial mats for functional metagenomic studies and may be applicable to other environmental samples from which DNA extraction is challenging.

Bey, Benjamin S.; Fichot, Erin B.; Norman, R. Sean

2011-01-01

212

Regulation of obesity-associated inflammation and colon tumorigenesis by resveratrol and adiponectin  

Microsoft Academic Search

Obesity is characterized by decreased production of the anti-inflammatory hormone, adiponectin, increased secretion of pro-inflammatory cytokines and chemokines, and increased risk of colon cancer. Although adiponectin has been negatively associated with colorectal cancer development in human population, the role of adiponectin in colon tumorigenesis is unknown. The anti-inflammatory dietary polyphenol, resveratrol (RSV), increases circulating adiponectin concentrations in vivo, and has

Rebecca L. Boddicker

2011-01-01

213

Effect of adiponectin on bovine granulosa cell steroidogenesis, oocyte maturation and embryo development  

Microsoft Academic Search

BACKGROUND: Adiponectin is an adipokine, mainly produced by adipose tissue. It regulates several reproductive processes. The protein expression of the adiponectin system (adiponectin, its receptors, AdipoR1 and AdipoR2 and the APPL1 adaptor) in bovine ovary and its role on ovarian cells and embryo, remain however to be determined. METHODS: Here, we identified the adiponectin system in bovine ovarian cells and

Virginie Maillard; Svetlana Uzbekova; Florence Guignot; Christine Perreau; Christelle Ramé; Stéphanie Coyral-Castel; Joëlle Dupont

2010-01-01

214

Modulation of Adiponectin and Leptin during Refeeding of Female Anorexia Nervosa Patients  

Microsoft Academic Search

Context: Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is limited and contradicting. Objective: Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in

Dalit Modan-Moses; Daniel Stein; Clara Pariente; Amit Yaroslavsky; Anka Ram; Michal Faigin; Ron Loewenthal; Eleanor Yissachar; Rina Hemi; Hannah Kanety

215

Genome-wide Linkage and Association Analyses to Identify Genes Influencing Adiponectin Levels: The GEMS Study  

Microsoft Academic Search

Adiponectin has a variety of metabolic effects on obesity, insulin sensitivity, and atherosclerosis. To identify genes influencing variation in plasma adiponectin levels, we performed genome-wide linkage and association scans of adiponectin in two cohorts of subjects recruited in the Genetic Epidemiology of Metabolic Syndrome Study. The genome-wide linkage scan was conducted in families of Turkish and southern European (TSE, n

Hua Ling; Dawn M. Waterworth; Heide A. Stirnadel; Toni I. Pollin; Philip J. Barter; Y. Antero Kesäniemi; Robert W. Mahley; Ruth McPherson; Gérard Waeber; Thomas P. Bersot; Jonathan C. Cohen; Scott M. Grundy; Vincent E. Mooser; Braxton D. Mitchell

2009-01-01

216

Role of adiponectin in regulating ovarian theca and granulosa cell function  

Microsoft Academic Search

Adiponectin is an adipokine that has been implicated in insulin resistance, a condition associated with polycystic ovarian syndrome in humans, but whether adiponectin can directly affect ovarian theca or granulosa cell function is unknown. Therefore, to determine the effects of adiponectin on proliferation, steroidogenesis and gene expression of large-follicle theca and granulosa cells, experiments were conducted using bovine ovarian cell

Dana V. Lagaly; Pauline Y. Aad; Juan A. Grado-Ahuir; Laura B. Hulsey; Leon J. Spicer

2008-01-01

217

Adiponectin and Peak Bone Mass in Men: A Cross-Sectional, Population-Based Study  

Microsoft Academic Search

Adiponectin, a protein classically known to be secreted by adipocytes, is also secreted by bone-forming cells. Results of previous studies have been contradictory as to whether serum adiponectin and bone mineral density (BMD) are associated. The aim of this study was to investigate a possible association between serum adiponectin and BMD in young, healthy men at a time of peak

M. Frost; B. Abrahamsen; T. L. Nielsen; J. Frystyk; A. Flyvbjerg; C. Hagen; M. Andersen; K. Brixen

2010-01-01

218

Adiponectin Suppresses Pathological Microvessel Formation in Retina Through Modulation of Tumor Necrosis Factor Expression  

Microsoft Academic Search

The fat-derived hormone adiponectin has been shown to have a protective role in macrovascular disorders. However, nothing is known about the function of adiponectin in retinal microvessel disease. Here, we investigated the causal role of adiponectin in retinal vessel formation and inflammation under conditions of hypoxia. When neonatal mice were subjected to ischemia-induced retinopathy, pathological retinal neovascularization during ischemia was

Akiko Higuchi; Koji Ohashi; Shinji Kihara; Kenneth Walsh; Noriyuki Ouchi

219

Leucine-rich glioma inactivated 3 associates negatively with adiponectin.  

PubMed

Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of LGI/epitempin family. We previously reported that LGI3 was expressed in adipose tissues and suppressed adipogenesis through its receptor, ADAM23. We proposed that LGI3 may be a candidate adipokine with pro-inflammatory activity. To investigate the role of LGI3 in adipose tissues, we analyzed cytokine profile in LGI3 knockout mice. Protein array analysis showed that adiponectin was significantly increased in adipose tissues and plasma of LGI3 knockout mice. SiRNA-mediated knockdown of LGI3 increased adiponectin in 3T3-L1 preadipocytes. Treatment of differentiating 3T3-L1 cells with LGI3 protein decreased adiponectin in a dose-dependent manner. High fat diet (HFD)-fed mice showed expression of LGI3 in adipose tissue macrophages in addition to adipocytes that expressed LGI3 in both normal chow-fed and HFD-fed mice. The 60-kDa LGI3 was selectively increased in adipose tissues of HFD mice in which adiponectin was downregulated. Taken together, these results suggested that LGI3 may participate in adipose tissue homeostasis by negatively regulating adiponectin. PMID:23548727

Kim, Hyun A; Kwon, Nyoun Soo; Baek, Kwang Jin; Kim, Dong-Seok; Yun, Hye-Young

2013-03-30

220

DIFFERENTIATION OF ALLELIC VARIATIONS OF THE HMW GLUTENIN SUBUNITS OF WHEAT FLOURS BY USE OF MIXING PARAMETERS AND POLYMERIC PROTEIN CONTENT  

Technology Transfer Automated Retrieval System (TEKTRAN)

The mixing parameters and polymeric proteins (PP) of two different wheat cultivars, Centurk and OK102, each with four different lines of differing HMW-GS composition were analyzed. The mixing parameters from a 10-g mixograph were utilized to discriminate among different cultivars as well as differen...

221

EFFECTS OF OVER-EXPRESSION OF HIGH MOLECULAR WEIGHT GLUTENIN SUBUNIT 1Dy10 ON WHEAT TORTILLA PROPERTIES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Wheat (Triticum aestivum L.) flour properties necessary for optimal tortilla production have not been identified. Transgenic wheats (Triticum aestivum L.) over-expressing high molecular weight glutenin subunit (HMW-GS) 1Dy10 were used to produce tortillas and their quality evaluated. The level of HM...

222

Metabolic profiling of transgenic wheat over-expressing the high-molecular weight Dx5 glutenin subunit  

Technology Transfer Automated Retrieval System (TEKTRAN)

The primary aim of this work was to evaluate potential changes in the metabolic network of transgenic wheat grain due to over-expression of the gene encoding the high-molecular-weight (HMW) glutenin Dx5-subunit. We used GC-MS and multivariate analyses to compare the metabolite profiles of developing...

223

The effects of BADGE and caffeine on the time-course response of adiponectin and lipid oxidative enzymes in high fat diet-fed C57BL/6J mice: correlation with reduced adiposity and steatosis.  

PubMed

Adiponectin, which is expressed exclusively in adipose tissue, has been shown to increase fatty acid oxidation via activation of AMP-activated kinase (AMPK) and phosphorylation of acetyl CoA carboxylase (ACC). ACC phosphorylation and carnitine palmitoyl-transferase-1 (CPT1) activity have been shown to be rate controlling factors in fatty acid oxidation. In high fat diet (HFD)-induced obese mice, we analyzed the time-course of changes in the expression of adiponectin and lipid oxidative enzymes induced by treatment with bisphenol A diglycidyl ether (BADGE) or caffeine for 8 weeks, and investigated whether the changes of adiponectin and lipid oxidative enzymes expression correlated with reduced adiposity or steatosis after 8 weeks of treatment. After 8 weeks of treatment, BADGE and caffeine had reduced body weight and epididymal adipose tissue weight in mice fed HFD, and markedly reduced the number of fatty droplets in the liver. Interestingly, the expression of adiponectin and lipid oxidative enzymes significantly increased after 2 weeks of treatment. These results indicate that the expression of adiponectin and lipid oxidative enzymes in the early stages of BADGE or caffeine treatment correlated well with the long-term anti-obesity effects. PMID:18946183

Yun, Jun-Won; Shin, Eui-Seok; Cho, Si-Young; Kim, Shin-Hyoung; Kim, Chae-Wook; Lee, Tae-Ryong; Kim, Bae-Hwan

2008-10-01

224

T-cadherin Supports Angiogenesis and Adiponectin Association with the Vasculature in a Mouse Mammary Tumor Model  

PubMed Central

T-cadherin delineates endothelial, myoepithelial and ductal epithelial cells in the normal mouse mammary gland, and becomes progressively restricted to the vasculature during mammary tumorigenesis. To test the function of T-cadherin in breast cancer, we inactivated the T-cadherin gene in mice and evaluated tumor development and pathology after crossing the mutation into the MMTV-polyoma virus middle T (PyV-mT) transgenic model. We report that T-cadherin deficiency limits mammary tumor vascularization and reduces tumor growth. Tumor transplantation experiments confirm T-cadherin's stromal role in tumorigenesis. In comparison with wild type MMTV-PyV-mT controls, T-cadherin-deficient tumors are pathologically advanced and metastasize to the lungs. T-cadherin is a suggested binding partner for high molecular weight forms of the circulating fat-secreted hormone adiponectin. We discern adiponectin in association with the T-cadherin-positive vasculature in the normal and malignant mammary gland and report that this interaction is lost in the T-cadherin null condition. This work establishes a role for T-cadherin in promoting tumor angiogenesis and raises the possibility that vascular T-cadherin - adiponectin association may contribute to the molecular cross-talk between tumor cells and the stromal compartment in breast cancer.

Hebbard, Lionel. W.; Garlatti, Michelle; Young, Lawrence J.T.; Cardiff, Robert D.; Oshima, Robert G.; Ranscht, Barbara

2009-01-01

225

A Study of Adiponectin in Children with Diabetes Mellitus  

PubMed Central

Objectives: Adiponectin is a hormone produced by adipose tissue. It is secreted exclusively by adipocytes and appears to play a role in the pathophysiology of obesity, diabetes mellitus (DM), and its comorbidities. The aim of this study was to assess adiponectin levels in diabetic children with type 1 DM (T1DM) and type 2 DM (T2DM), and to detect its prognostic role in them. Methods: This study was undertaken from April to July 2011 at Minia University Children’s Hospital, Egypt, and included 314 children aged 2–18 years divided into two patient groups. Group I consisted of 164 pre-diagnosed diabetic patients, further subdivided into Group Ia which included 142 patients with T1DM and Group Ib, 22 patients with T2DM; Group 2 included 150 apparently healthy children as a controls; they were age- and sex-matched to the diseased group. Patients were subjected to a thorough history taking, clinical examination, and laboratory investigations including assessment of HbA1c percentages, fasting C-peptide levels, lipid profiles and fasting serum adiponectin levels. Results: Adiponectin levels did not differ significantly between patients with T1DM and T2DM, but it was significantly higher in diabetic patients than in the controls. In T1DM, adiponectin had positive significant correlations with the duration of the disease and waist circumference, while in T2DM, it had a positive significant correlation with the dose of insulin given and negative significant associations with diastolic blood pressure, cholesterol, and C-peptide levels. Conclusion: The results of the study suggest that adiponectin can play a protective role against the metabolic complications of DM.

Ali, Basma A.; Mahrous, Doaa M.; Abdallah, Ahlam M.; Fikri, Mina

2013-01-01

226

Absence of high molecular weight proteins 1 and/or 2 is associated with decreased adherence among non-typeable Haemophilus influenzae clinical isolates.  

PubMed

High molecular weight (Hmw) proteins 1 and 2, type IV pilin protein (PilA), outer-membrane protein P5 (OmpP5), Haemophilus protein D (Hpd) and Haemophilus adhesive protein (Hap) are surface proteins involved in the adherence of non-typeable Haemophilus influenzae. One hundred clinical isolates were evaluated for the presence of the genes encoding these proteins by PCR and for their adherence capacity (AC) to Detroit 562 nasopharyngeal cells (D562). The majority of isolates were from blood (77/100); other sites were also represented. Confluent D562 monolayers (1.2×10(5) cells per well) were inoculated with standardized minimal infective doses (m.o.i.) of 10(2), 10(3) or 10(4) c.f.u. per well. The AC was categorized as low (<10?%) or high (?10?%) depending on the percentage of c.f.u. adhering per well. All the isolates evaluated showed adherence: 69/100 (69?%) demonstrated high adherence, while 31/100 (31?%) showed low adherence. Of all the genes evaluated, hmw1A and/or hmw2A were detected in 69/100 (69?%) of isolates. The presence of hmw1A and/or hmw2A was associated with increased adherence to D562 cells (P?0.001). Dot immunoblots were performed to detect protein expression using mAbs 3D6, AD6 and 10C5. Among the high-adherence isolates (n?=?69), 72?% reacted with 3D6 and 21?% with 10C5. Our data indicate that the absence of Hmw1 and/or Hmw2 was associated with decreased adherence to D562 cells. PMID:23988628

Vuong, Jeni; Wang, Xin; Theodore, Jordan M; Whitmon, Jennifer; Gomez de Leon, Patricia; Mayer, Leonard W; Carlone, George M; Romero-Steiner, Sandra

2013-08-29

227

The role of adiponectin in reproduction: from polycystic ovary syndrome to assisted reproduction  

PubMed Central

Objective To summarize the effects of the adipokine adiponectin on the reproductive endocrine system, from the hypothalamic-pituitary axis to the gonads and target tissues of the reproductive system. Design A Medline computer search was performed to identify relevant articles. Setting Research institution. Intervention(s) None. Result(s) Adiponectin is a hormone secreted by adipose tissue that acts to reduce insulin resistance and atherogenic damage, but it also exerts actions in other tissues. Adiponectin mediates its actions in the periphery mainly via two receptors, AdipoR1 and AdipoR2. Adiponectin receptors are present in many reproductive tissues, including the central nervous system, ovaries, oviduct, endometrium, and testes. Adiponectin influences gonadotropin release, normal pregnancy, and assisted reproduction outcomes. Conclusion(s) Adiponectin, a beneficial adipokine, represents a major link between obesity and reproduction. Higher levels of adiponectin are associated with improved menstrual function and better outcomes in assisted reproductive cycles.

Michalakis, Konstantinos G.; Segars, James H.

2011-01-01

228

Immunochemical characterization of a human high molecular weight — melanoma associated antigen identified with monoclonal antibodies  

Microsoft Academic Search

Sodium dodecyl sulfate polyacrylamide gel analysis of a high molecular weight (HMW) human melanoma associated antigen (MAA) defined by murine monoclonal antibodies revealed a number of distinct polypeptides ranging from 80,000 up to 280,000 daltons, in addition to an extremely heterogeneous group of components distributed over a wide range in apparent molecular weight (300,000–700,000 daltons). The 280,000 dalton and the

Barry S. Wilson; Giovanna Ruberto; Soldano Ferrone

1983-01-01

229

Lactobacillus rhamnosus GG improves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production.  

PubMed

Recently, a probiotic Lactobacillus rhamnosus GG (LGG) has shown several beneficial effects, including improved insulin sensitivity. To clarify the mechanism underlying the insulin-sensitizing effect of LGG, mice were orally administrated with LGG for 13 weeks, and their body weight, insulin sensitivity, and expression of genes related to glucose and lipid metabolism were examined. LGG-treated mice showed attenuated weight gain and enhanced insulin sensitivity in high fat diet group, while no change was observed in normal diet-fed group. The expression of fatty acid oxidative genes in the liver was increased and gluconeogenic genes were decreased. GLUT4 mRNA expression in skeletal muscle and adiponectin production in adipose tissue were significantly increased. This was corroborated with the increased activation of AMPK in skeletal muscle and adipose tissue. Taken together, these results indicate that LGG treatment improves insulin sensitivity and reduces lipid accumulation by stimulating adiponectin secretion and consequent activation of AMPK. PMID:23313485

Kim, Sun-Woo; Park, Kun-Young; Kim, Bobae; Kim, Eunha; Hyun, Chang-Kee

2013-01-09

230

Measurement of salivary resistin, visfatin and adiponectin levels.  

PubMed

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). PMID:22108712

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

2011-11-11

231

Adiponectin and metabolic syndrome in women at menopause  

Microsoft Academic Search

Obesity is associated with premature atherosclerosis, as well as with many metabolic alterations including insulin resistance, dyslipidemia and hypertension. Visceral fat accumulation, particularly, is closely associated with the development of metabolic syndrome. The menopause transition, as well as the early postmenopausal period, is associated with increase in total and central obesity. Among adipocytokines secreted by the adipose tissue adiponectin is

Aneta Mankowska; Lena Nowak; Grazyna Sypniewska

232

Adiponectin protects hippocampal neurons against kainic acid-induced excitotoxicity  

Microsoft Academic Search

Neuronal damage after seizure is correlated with blood–brain barrier (BBB) leakage. Adiponectin (Ad) has shown protective effects on endothelial function. In this study, we investigated the effects of Ad on cell survival and BBB integrity in the mouse hippocampus after kainic acid (KA) treatment. Twenty-four hours after intracerebroventricular injection of recombinant Ad, mice were treated with KA, and then sacrificed

Byeong Tak Jeon; Hyun Joo Shin; Jeong Bin Kim; Yu Kyeung Kim; Dong Hoon Lee; Kyu Hong Kim; Hyun Joon Kim; Sang Soo Kang; Gyeong Jae Cho; Wan Sung Choi; Gu Seob Roh

2009-01-01

233

Evaluating vaspin and adiponectin in postmenopausal women with endometrial cancer.  

PubMed

Insulin resistance is a well-documented risk factor for the development of endometrial cancer. Adiponectin and vaspin are insulin-sensitizing proteins that are secreted from adipose tissue. A clear association between serum levels of adipokines and endometrial cancer has yet to be established. The study group consisted of postmenopausal women with confirmed endometrial cancer, whereas patients with benign endometrial conditions constituted the control group. The two groups were compared in terms of insulin resistance and serum levels of adiponectin and vaspin. A total of 60 patients with confirmed endometrial cancer and 70 controls with benign endometrial conditions (polyps and atrophy) were enrolled. Median homeostasis model assessment of insulin resistance value was significantly higher in the study group compared with the control group (2.93 vs 1.27, P<0.0001), whereas mean quantitative insulin sensitivity check index value was significantly lower (0.33±0.02 vs 0.37±0.37, P<0.0001). Median values for both adiponectin and vaspin were significantly lower in patients with endometrial cancer compared with the control group (4.09 vs 17.13??g/ml, P<0.0001 and 0.21 vs 0.39?ng/ml, P<0.0001 respectively). Low levels of both adiponectin and vaspin were found to be significantly associated with an increased risk for endometrial cancer. Following adjustment for confounding factors, the respective odds ratios for endometrial cancer in patients in the first tertile compared with those in the third tertile were 10.80 (2.76-42.24; P=0.001) and 13.23 (2.94-59.64; P=0.001). Our results show that lower levels of circulating adiponectin and vaspin levels are associated with an increased risk of developing endometrial cancer. PMID:23896633

Erdogan, Serpil; Sezer, Sevilay; Baser, Eralp; Gun-Eryilmaz, Ozlem; Gungor, Tayfun; Uysal, Sema; Yilmaz, Fatma Meric

2013-08-21

234

Serum adiponectin and leptin levels in patients with lipodystrophies.  

PubMed

Lipodystrophies are characterized by selective but variable loss of body fat and metabolic complications of insulin resistance. We hypothesized that reduced synthesis and secretion of adipocyte-specific proteins may be related to the metabolic complications of lipodystrophy. Therefore, we compared fasting serum concentrations of adiponectin and leptin, in 18 patients with congenital generalized lipodystrophy (CGL), 11 with acquired generalized lipodystrophy (AGL), 46 with familial partial lipodystrophy-Dunnigan variety (FPLD) and 18 with acquired partial lipodystrophy (APL) and studied their relationship to metabolic parameters. Patients with CGL and AGL had markedly reduced serum adiponectin levels compared to those with FPLD and APL (median [range]: 1.5 [0.4-7.5], 3.2 [0.6-7.7], 6.9 [1.9-23.2] and 7.9 [3.1-13.3] microg/mL, respectively, p < 0.0001); the same trend was noted for serum leptin levels (0.63 [0.05-3.7], 2.18 [0.05-11.30], 2.86 [0.23-9.00] and 6.24 [1.21-10.4] ng/mL, respectively, p < 0.0001). Serum adiponectin levels correlated negatively with fasting serum triglycerides (r = -0.6, p < 0.001) and insulin levels (r = -0.5, p < 0.0001) and positively with serum high-density lipoprotein cholesterol levels (r = 0.5, p < 0.001). Serum adiponectin levels were lower in patients with diabetes compared to non-diabetic subjects (3.0 vs. 7.1 microg/mL, p < 0.001). Our results indicate that serum adiponectin and leptin levels are extremely low in patients with generalized lipodystrophies and may be related to severe insulin resistance and its metabolic complications in lipodystrophies. PMID:11994394

Haque, Wasim A; Shimomura, Iichiro; Matsuzawa, Yuji; Garg, Abhimanyu

2002-05-01

235

Metabolic Risk Susceptibility in Men Is Partially Related to Adiponectin/Leptin Ratio  

PubMed Central

Background. High adiponectin/leptin ratio may be protective from metabolic risks imparted by high triglyceride, low HDL, and insulin resistance. Methods. This cross-sectional study examines plasma adipokine levels in 428 adult men who were subgrouped according to low (<6.5??g/mL)and high (?6.5??g/mL)adiponectin levels or a low or high ratio of adiponectin/leptin. Results. Men with high adiponectin/leptin ratio had lower plasma triglyceride and higher HDL cholesterol than those with low ratio. Similarly, those with high adiponectin/leptin ratio had lower TG/HDL cholesterol ratio and HOMA2-IR than those with low ratio. In contrast, levels of adiponectin or the ratio of adiponectin/leptin did not associate with systolic blood pressure. But the ratio of adiponectin/leptin decreased progressively with the increase in the number of risk factors for metabolic syndrome. Conclusion. Adipokine levels may reflect adipose tissue triglyceride storage capacity and insulin sensitivity. Leptin is an index of fat mass, and adiponectin is a biomarker of triglyceride metabolism and insulin sensitivity. Men with high adiponectin/leptin ratios have better triglyceride profile and insulin sensitivity than men with a low ratio regardless of waist girth.

Vega, Gloria Lena; Grundy, Scott M.

2013-01-01

236

Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway  

SciTech Connect

Adipocytes can highly and specifically express adiponectin, and the adiponectin receptor (AdipoR) has been detected in bone-forming cells. The present study was undertaken to investigate the action of adiponectin on osteoblast proliferation and differentiation. AdipoR1 protein was detected in human osteoblasts. Adiponectin promoted osteoblast proliferation and resulted in a dose- and time-dependent increase in alkaline phosphatase (ALP) activity, osteocalcin and type I collagen production, and an increase in mineralized matrix. Suppression of AdipoR1 with small-interfering RNA (siRNA) abolished the adiponectin-induced cell proliferation and ALP expression. Adiponectin induces activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal Kinase (JNK), but not ERK1/2 in osteoblasts, and these effects were blocked by suppression of AdipoR1 with siRNA. Furthermore, pretreatment of osteoblasts with the JNK inhibitor SP600125 abolished the adiponectin-induced cell proliferation. p38 inhibitor SB203580 blocked the adiponectin-induced ALP activity. These data indicate that adiponectin induces human osteoblast proliferation and differentiation, and the proliferation response is mediated by the AdipoR/JNK pathway, while the differentiation response is mediated via the AdipoR/p38 pathway. These findings suggest that osteoblasts are the direct targets of adiponectin.

Luo Xianghang [Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, 86 Middle Renmin Road, Changsha, Hunan 410011 (China); Guo Lijuan [Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, 86 Middle Renmin Road, Changsha, Hunan 410011 (China); Yuan Lingqing [Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, 86 Middle Renmin Road, Changsha, Hunan 410011 (China); Xie Hui [Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, 86 Middle Renmin Road, Changsha, Hunan 410011 (China); Zhou Houde [Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, 86 Middle Renmin Road, Changsha, Hunan 410011 (China); Wu Xianping [Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, 86 Middle Renmin Road, Changsha, Hunan 410011 (China); Liao Eryuan [Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, 86 Middle Renmin Road, Changsha, Hunan 410011 (China)]. E-mail: eyliao1207@21cn.com

2005-09-10

237

Association of adiponectin gene G276T polymorphism with atherogenic indicators in obese children.  

PubMed

Adiponectin plays a protective role against atherosclerosis. Genetic investigation has revealed that G276T adiponectin gene polymorphism is related to adiponectin concentration and metabolic disturbances. The aim of the present study was to investigate the association of adiponectin gene G276T polymorphism with indices of atherosclerosis in obese children. We examined 159 children (125 obese and 34 non-obese). G276T of adiponectin gene polymorphism was identified using a PCR-RFLP method. The intima media thickness (IMT) was evaluated in 82 patients. In all children, the anthropometric indices, fasting plasma total cholesterol (TC), HDL and LDL cholesterol, triglycerydes (TG), C-reactive protein (CRP), and adiponectin were measured. Oral glucose tolerance test (OGTT) also was performed. We found that the obese patients presented with higher values of atherogenic indicators than the non-obese patients. The indicators positively correlated with CRP and lipid concentrations. Ninety one percent of obese children presented with elevated IMT which correlated with CRP. The children with GG genotype (GG + GT allele) had lower values of BMI, TC, and TG but higher adiponectin concentrations. The mean level of adiponectin was statistically decreased in the compared with the homozygous TT children. The other anthropometric and atherogenic indicators did not differ between these two sets of obese children. We conclude that adiponectin concentrations were decreased in children with polymorphism G276T in adiponectin gene. The study, however, failed to show significant associations between carotid IMT, lipid markers, blood pressure, or HOMA-IR in obese children. PMID:22836642

Pyrzak, Beata; Ruminska, Malgorzata; Czerwonogrodzka-Senczyna, Aneta; Majcher, Anna; Wisniewska, Alicja; Brzewski, Michal; Demkow, Urszula

2013-01-01

238

Effect of Adiponectin Gene Polymorphisms on Circulating Adiponectin and Insulin Resistance Indexes in Women with Polycystic Ovary Syndrome  

Microsoft Academic Search

Background: We examined the possible association of adiponectin gene polymorphisms with polycystic ovary syndrome (PCOS) and their influence on serum adi- ponectin and insulin resistance indexes in Greek women with PCOS. Methods: We genotyped samples from 100 women with PCOS characterized with respect to body mass index (BMI), glucose and insulin concentrations during an oral glucose tolerance test (OGTT), lipid

Nectaria Xita; Ioannis Georgiou; Anthoula Chatzikyriakidou; Maria Vounatsou; Gerasimos-Peter Papassotiriou; Ioannis Papassotiriou; Agathocles Tsatsoulis

239

Tracing inputs of terrestrial high molecular weight dissolved organic matter within the Baltic Sea ecosystem  

NASA Astrophysics Data System (ADS)

To test the hypothesis whether high molecular weight dissolved organic matter (HMW-DOM) in a high latitude marginal sea is dominated by terrestrial derived matter, 10 stations were sampled along the salinity gradient of the central and northern Baltic Sea and were analyzed for concentrations of dissolved organic carbon as well as ?13C values of HMW-DOM. Different end-member-mixing models were applied to quantify the influence of terrestrial DOM and to test for conservative versus non-conservative behavior of the terrestrial DOM in the different Baltic Sea basins. The share of terrestrial DOM to the total HMW-DOM was calculated for each station, ranging from 43 to 83%. This shows the high influence of terrestrial DOM inputs for the Baltic Sea ecosystem. The data also suggest that terrestrial DOM reaching the open Baltic Sea is not subject to substantial removal anymore. However compared to riverine DOM concentrations, our results indicate that substantial amounts of HMW-DOM (> 50%) seem to be removed near the coastline during estuarine mixing. A budget approach yielded residence times for terrestrial DOM of 2.8, 3.0, and 4.5 yr for the Bothnian Bay, the Bothnian Sea and the Baltic Proper.

Deutsch, B.; Alling, V.; Humborg, C.; Korth, F.; Mörth, C. M.

2012-11-01

240

The fragments of bovine high molecular weight kininogen promote osteoblast proliferation in vitro.  

PubMed

High molecular weight (HMW) kininogen is known to be a large plasma protein and cleaved by plasma proteinase kallikrein, then it generates four fragments in the blood coagulation cascade: heavy chain, bradykinin, fragment 1.2, and light chain. The fragment 1.2 has also been found in the basic protein fraction of bovine milk as a bioactive protein which promotes osteoblast proliferation. The milk basic protein has been shown to be a multi functional edible protein which promotes bone formation and inhibits bone resorption. In the present study, we purified the fragment 1.2 from bovine plasma and assessed it could promote osteoblast proliferation and posses the activity after pepsin digestion. Purified plasma HMW kininogen did not promote the proliferation, however, the kallikrein-cleaved HMW kininogen promoted the proliferation. The fragment 1.2, purified from the proteolysate, also promoted the proliferation. The pepsin digestion was performed according to the method of the assessment of allergenesity of genetically modified crops. After pepsin digestion, the fragment 1.2 generated resistant fragments and showed the promoting activity of osteoblast proliferation. These results suggest that the enzymatically-digested fragments of bovine HMW kininogen are able to be a naturally occurred active protein that promotes the bone formation by oral administration. PMID:17071946

Yamamura, Jun-ichi; Morita, Yoshikazu; Takada, Yukihiro; Kawakami, Hiroshi

2006-10-28

241

Adiponectin is associated with risk of the metabolic syndrome and insulin resistance in women.  

PubMed

The purpose of this study was to examine insulin resistance, markers of the metabolic syndrome, cardiovascular disease (CVD) risk, and serum adiponectin concentrations in pre-menopausal Hispanic and non-Hispanic White (NHW) women. This cross-sectional study examined 119 pre-menopausal women (76 Hispanic, 45 NHW) for markers of the metabolic syndrome (ATP III criteria), level of insulin resistance (HOMA-IR), CVD risk factors, and serum total adiponectin concentrations. Relationships between variables were assessed using Student's t-tests, Pearson's and Spearman's Rho correlations, and stepwise multiple regression analysis. Hispanic women had significantly lower adiponectin concentrations than NHW women, even after controlling for body fat (%) (P < 0.01). Number of markers of the metabolic syndrome was inversely related to total adiponectin concentration for all women combined and for NHW women (P ? 0.04), but not for Hispanic women. Insulin resistance was inversely related to adiponectin for all women and for NHW women (P < 0.01), but not significantly associated in Hispanic women. Adiponectin concentration was not significantly associated with number of CVD risk factors for these women. While adiponectin was associated with markers of metabolic syndrome and insulin resistance for all women of this study and despite lower adiponectin concentrations for Hispanic women than NHW women, the role of adiponectin to these conditions among Hispanics remains unclear. There was no significant association between adiponectin and CVD risk for these women. Future research should focus on understanding mechanisms for up-regulating adiponectin secretion and if ethnicity affects adiponectin gene expression and secretion given the beneficial effects derived from elevated adiponectin levels. PMID:20454813

King, George A; Deemer, Sarah E; Thompson, Dixie L

2010-05-08

242

Heme oxygenase-2/adiponectin protein-protein interaction in metabolic syndrome.  

PubMed

Insulin resistance with adipose tissue dysfunction and dysregulation in the production and secretion of adipokines is one of the hallmarks of metabolic syndrome. We have previously reported that increased levels of the heme oxygenase (HO) system, HO-1/HO-2 results in increased levels of adiponectin. Despite documentation of the existence of the anti-inflammatory axis HO-adiponectin, a possible protein-protein interaction between HO and adiponectin has not been examined. Here, we investigated the existence of protein interactions between HO-2 and adiponectin in the maintenance of adipocyte function during metabolic syndrome by integrating phenotypic and in silico studies. Compared to WT animals, HO-2 null mice displayed an increase in both visceral and subcutaneous fat content and reduced circulating adiponectin levels. The decrease in adiponectin was reversed by upregulation of HO-1. HO-2 depletion was associated with increased adipogenesis in cultured mesenchymal stem cells (MSCs) and decreased adiponectin levels in the culture media. In addition, HO-1 siRNA decreased adiponectin release. HO-2 was found to bind to the monomeric form of adiponectin, according to poses and calculated energies. HO-2-adiponectin interactions were validated by the two-hybrid system assay. In conclusion, protein-protein interactions between HO-2 and adiponectin highlight the role of HO-2 as a molecular chaperone for adiponectin assembly, while HO-1 increases adiponectin levels. Thus, crosstalk between HO-2 and HO-1 could be manipulated in a therapeutic approach to ameliorate the deleterious effects of obesity and the metabolic syndrome. PMID:23438433

Vanella, Luca; Li Volti, Giovanni; Guccione, Salvatore; Rappazzo, Giancarlo; Salvo, Eliana; Pappalardo, Morena; Forte, Stefano; Schwartzman, Michal L; Abraham, Nader G

2013-02-21

243

Association between novel adipocytokines adiponectin, vaspin, visfatin, and thyroid: An experimental and clinical update.  

PubMed

Adipose tissue secretes a variety of active biological substances, called adipocytokines, that act in an autocrine, paracrine, and endocrine manner. They have roles in appetite control, thermogenesis, and thyroid and reproductive functions. All these molecules may lead to local and generalized inflammation, mediating obesity-associated vascular disorders including hypertension, diabetes, atherosclerosis, and insulin resistance. Thyroid dysfunction is associated with changes in body weight, thermogenesis, and energy expenditure. The connections between cardiovascular risk factors such as dyslipidemia, impaired glucose tolerance, insulin resistance, atherosclerosis, and thyroid dysfunction have been reported in several studies. The adipocytokines serve as causative or protective factors in the development of these disorders in the states of thyroid dysfunction. Abnormal levels of adipocytokines (adiponectin (ADP), leptin, resistin, vaspin, and visfatin) in hypo- and hyperthyroidism have been reported with controversial results. This review aims to update the implication of novel adipokines ADP, vaspin, and visfatin in thyroid dysfunction. PMID:24145612

Cinar, Nese; Gurlek, Alper

2013-10-24

244

Chronic maternal infusion of full-length adiponectin in pregnant mice down-regulates placental amino acid transporter activity and expression and decreases fetal growth  

PubMed Central

Maternal adiponectin levels are inversely correlated to birth weight, suggesting that maternal adiponectin limits fetal growth. We hypothesized that full-length adiponectin (fADN) infusion in pregnant mice down-regulates placental amino acid transporters and decreases fetal growth. Starting at embryonic day (E) 14.5, fADN (0.62 ± 0.02 ?g (g body weight)?1 day?1, n= 7) or vehicle (control, n= 9) were infused in pregnant C57/BL6 mice by mini-osmotic pump. At E18.5, dams were killed and placental homogenates and trophoblast plasma membrane (TPM) vesicles were prepared. Infusion of fADN elevated maternal serum fADN by 4-fold and decreased fetal weights by 18%. Adiponectin receptor 2, but not adiponectin receptor 1, was expressed in TPM. fADN infusion decreased TPM System A (–56%, P < 0.001) and System L amino acid transporter activity (–50%, P < 0.03). TPM protein expression of SNAT1, 2 and 4 (System A amino acid transporter isoforms) and LAT1 and LAT2, but not CD98, (System L amino acid transporter isoforms) was down-regulated by fADN infusion. To identify possible mechanisms underlying these changes we determined the phosphorylation of proteins in signalling pathways known to regulate placental amino acid transporters. fADN decreased phosphorylation of insulin receptor substrate-1 (Tyr-608), Akt (Thr-308 and Ser-473), S6 kinase 1 (Thr-389), eukaryotic initiation factor 4E binding protein 1 (Thr-37/46 and Thr-70) and ribosomal protein S6 (Ser-235/236) and increased the phosphorylation of peroxisome proliferator-activated receptor ? (PPAR?) (Ser-21) in the placenta. These data suggest that maternal adiponectin decreases fetal growth by down-regulation of placental amino acid transporters, which limits fetal nutrient availability. This effect may be mediated by inhibition of insulin/IGF-I and mTOR signalling pathways, which are positive regulators of placental amino acid transporters. We have identified a novel physiological mechanism by which the endocrine functions of maternal adipose tissue influence fetal growth.

Rosario, Fredrick J; Schumacher, Michael A; Jiang, Jean; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

2012-01-01

245

Effect of gliadins and HMW and LMW subunits of glutenin on dough properties in the F 6 recombinant inbred lines from a bread wheat cross  

Microsoft Academic Search

The storage proteins of 64 F2-derived F6 recombinant inbred lines (RILs) from the bread wheat cross ‘Prinqual’\\/‘Marengo’ were analyzed. Parents differed at four loci: Gli-B1 (coding for gliadins), Glu-B1 (coding for HMW glutenin subunits), Glu-A3\\/Gli-A1 (coding for LMW glutenin subunits\\/gliadins) and Glu-D3 (coding for LMW glutenin subunits). The effect of allelic variation at these loci on tenacity, extensibility and dough

M. T. Nieto-Taladriz; M. R. Perretant; M. Rousset

1994-01-01

246

The cumulative effect of allelic variation in LMW and HMW glutenin subunits on dough properties in the progeny of two bread wheats  

Microsoft Academic Search

The effects of allelic variation at Gli-A1, GluA3 and Glu-A1 loci coding for gliadins, LMW glutenin subunits and HMW glutenin subunits on dough resistance and extensibility was analysed in 56 F2-derived F6 families from a cross between bread wheats MKR(111\\/8) and ‘Kite’. Extensograph data from two sites giving widely different flour protein levels (approximately 7% and 14%) revealed that the

R. B. Gupta; N. K. Singh; K. W. Shepherd

1989-01-01

247

The model high molecular weight DOC compound, dextran, is ingested by the benthic ciliate Uronema marinum but does not supplement ciliate growth  

Microsoft Academic Search

Phagotrophic ciliates are capable of growth solely on dissolved compounds in laboratory cultures. Whether ciliates use dissolved compounds in the environment for growth is unclear. We investigated the ability of the marine benthic ciliate Uronema marinum to ingest a model high molecular weight dissolved organic carbon (HMW-DOC) compound, dextran, at concentrations typical for coastal salt marsh sediments (3 µM to

M R First; J T Hollibaugh

2009-01-01

248

Lipoprotein (a) levels in those with high molecular weight apo (a) isoforms may remain low in a significant proportion of patients with end-stage renal disease  

Microsoft Academic Search

Background. Studies have reported an increase in median Lipoprotein (Lp) (a) in patients with high molecular weight (HMW) apolipoprotein (apo) (a) isoforms and renal impairment. Some studies identify Lp (a) levels as a risk factor for vascular disease in renal failure whilst others have demonstrated an association with apo (a) isoform type and vascular disease. Methods. A total of 239

Darren S. Parsons; David A. Reaveley; Darrell V. Pavitt; Madhukar Misra; Edwina A. Brown

249

Identification of monoclonal anti-HMW-MAA antibody linear peptide epitope by proteomic database mining.  

PubMed

An efficient strategy is presented for the identification of antigenic sequences in the context of given MHC molecules of interest. The proteomic analysis of the antigenic peptide repertoire is described and demonstrated by using high-molecular weight melanoma-associated antigen. The identification of the epitopic sequence of a monoclonal antibody raised against the 250 kDa tumor associated antigen was reached by using only seven short synthetic peptide fragments, instead of the 155 non-overlapping 15-mer peptides theoretically necessary as minimum screening library. The present result has been obtained by applying as driving criteria the analysis of the peptide affinity to MHC class II molecules and the non-self discrimination concept. PMID:15373771

Mittelman, Abraham; Tiwari, Raj; Lucchese, Guglielmo; Willers, Jörg; Dummer, Reinhard; Kanduc, Darja

2004-10-01

250

What is the role of adiponectin in obesity related non-alcoholic fatty liver disease?  

PubMed Central

Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries. Insulin resistance is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of insulin resistance or obesity. Adiponectin is the most abundant adipose-specific adipokine. There is evidence that adiponectin decreases hepatic and systematic insulin resistance, and attenuates liver inflammation and fibrosis. Adiponectin generally predicts steatosis grade and the severity of NAFLD; however, to what extent this is a direct effect or related to the presence of more severe insulin resistance or obesity remains to be addressed. Although there is no proven pharmacotherapy for the treatment of NAFLD, recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications. In this adiponectin-focused review, the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are analyzed systematically.

Finelli, Carmine; Tarantino, Giovanni

2013-01-01

251

Low Adiponectin Levels in Adolescent Obesity: A Marker of Increased Intramyocellular Lipid Accumulation  

Microsoft Academic Search

found between adiponectin and triglyceride levels (r 0.80, P < 0.001) and IMCL (r 0.73, P < 0.001). Triglycerides (partial r2 0.52; P < 0.0002) and IMCL (partial r2 0.10; P < 0.05) were the most significant predictors of adiponectin lev- els, explaining 62% of the variation. In conclusion, plasma adiponectin levels are reduced in adolescent obesity and re- lated

RAM WEISS; SYLVIE DUFOUR; AIDA GROSZMANN; KITT PETERSEN; JAMES DZIURA; SARA E. TAKSALI; GERALD SHULMAN; SONIA CAPRIO

252

Production and Secretion of Adiponectin from 3T3–L1 Adipocytes: Comparison of Antihypertensive Drugs  

Microsoft Academic Search

BackgroundAdiponectin is an important vascular protective adipocytokine that possesses antidiabetic, antiatherogenic, and anti-inflammatory properties. The aim of this study was to evaluate the effect of various antihypertensive drugs on the production and secretion of adiponectin from adipocytes.Methods3T3–L1 adipocytes were incubated for 6 h with increased doses of the following drugs: hydrochlorothiazide, atenolol, losartan, telmisartan, captopril, and nifedipine. Adiponectin levels, as

Raphaelle Brody; Edna Peleg; Ehud Grossman; Yehonatan Sharabi

2009-01-01

253

Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell  

Microsoft Academic Search

Recently, it was reported that reduction in serum adiponectin levels is correlated with the incidence of breast cancer. As\\u000a an effort to explain this, we screened various human breast cancer cell lines to identify those in which proliferation is\\u000a directly controlled by adiponectin. Among the five tested cell lines, proliferation of MDA-MB-231 cancer cell was significantly\\u000a suppressed by adiponectin within

Jee Hyun Kang; Yoon Young Lee; Byung Yeon Yu; Beom-Seok Yang; Kyung-Hwan Cho; Do Kyoung Yoon; Yong Kyun Roh

2005-01-01

254

Plasma Concentrations of a Novel, Adipose-Specific Protein, Adiponectin, in Type 2 Diabetic Patients  

Microsoft Academic Search

Adiponectin is a novel, adipose-specific protein abundantly present in the circulation, and it has antiatherogenic properties. We analyzed the plasma adiponectin concentrations in age- and body mass index (BMI)-matched nondiabetic and type 2 diabetic subjects with and without coronary artery disease (CAD). Plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in nondiabetic subjects (6.660.4

Kikuko Hotta; Tohru Funahashi; Yukio Arita; Masahiko Takahashi; Morihiro Matsuda; Yoshihisa Okamoto; Hiromi Iwahashi; Hiroshi Kuriyama; Noriyuki Ouchi; Kazuhisa Maeda; Makoto Nishida; Shinji Kihara; Naohiko Sakai; Tadahisa Nakajima; Kyoichi Hasegawa; Masahiro Muraguchi; Yasukazu Ohmoto; Tadashi Nakamura; Shizuya Yamashita; Toshiaki Hanafusa; Yuji Matsuzawa

2010-01-01

255

The effect of exercise training on adiponectin receptor expression in KKAy obese\\/diabetic mice  

Microsoft Academic Search

Adiponectin is an adipocyte-derived factor that plays a pivotal role in lipid and glucose metabolism. Recently, two types of adiponectin receptors (AdipoR1 and AdipoR2) were identified. We investigated whether ex- ercise training (ET) or dietary restriction (DR) affects the expression of adiponectin receptors in skeletal muscle and liver, thereby improving glucose and lipid metabolism in KKAy mice. KKAy mice were

Hu Huang; Kaoruko Tada Iida; Hirohito Sone; Tomotaka Yokoo; Nobuhiro Yamada; Ryuichi Ajisaka

2006-01-01

256

Effect of adiponectin on bovine granulosa cell steroidogenesis, oocyte maturation and embryo development  

PubMed Central

Background Adiponectin is an adipokine, mainly produced by adipose tissue. It regulates several reproductive processes. The protein expression of the adiponectin system (adiponectin, its receptors, AdipoR1 and AdipoR2 and the APPL1 adaptor) in bovine ovary and its role on ovarian cells and embryo, remain however to be determined. Methods Here, we identified the adiponectin system in bovine ovarian cells and embryo using RT-PCR, immunoblotting and immunohistochemistry. Furthermore, we investigated in vitro the effects of recombinant human adiponectin (10 micro g/mL) on proliferation of granulosa cells (GC) measured by [3H] thymidine incorporation, progesterone and estradiol secretions measured by radioimmunoassay in the culture medium of GC, nuclear oocyte maturation and early embryo development. Results We show that the mRNAs and proteins for the adiponectin system are present in bovine ovary (small and large follicles and corpus luteum) and embryo. Adiponectin, AdipoR1 and AdipoR2 were more precisely localized in oocyte, GC and theca cells. Adiponectin increased IGF-1 10(-8) M-induced GC proliferation (P < 0.01) but not basal or insulin 10(-8) M-induced proliferation. Additionally, adiponectin decreased insulin 10(-8) M-induced, but not basal or IGF-1 10(-8) M-induced secretions of progesterone (P < 0.01) and estradiol (P < 0.05) by GC. This decrease in insulin-induced steroidogenesis was associated with a decrease in ERK1/2 MAPK phosphorylation in GC pre-treated with adiponectin. Finally, addition of adiponectin during in vitro maturation affected neither the percentage of oocyte in metaphase-II nor 48-h cleavage and blastocyst day 8 rates. Conclusions In bovine species, adiponectin decreased insulin-induced steroidogenesis and increased IGF-1-induced proliferation of cultured GC through a potential involvement of ERK1/2 MAPK pathway, whereas it did not modify oocyte maturation and embryo development in vitro.

2010-01-01

257

Plasma Adiponectin Increases Postprandially in Obese, but not in Lean, Subjects  

Microsoft Academic Search

Objective: We investigated the acute responses of plasma adiponectin levels to a test meal in lean and obese subjects.Research Methods and Procedures: We studied 13 lean and 11 obese subjects after a 10-hour overnight fast. Glucose, insulin, and adiponectin concentrations were measured at baseline and 15, 30, 60, 120, and 180 minutes after a fixed breakfast.Results: At baseline, fasting adiponectin

Patrick J. English; Steven R. Coughlin; Katharine Hayden; Iqbal A. Malik; John P. H. Wilding

2003-01-01

258

Adiponectin in Patients with Obstructive Sleep Apnea Syndrome: Course and Physiological Relevance  

Microsoft Academic Search

Background: Adiponectin is an adipocyte-derived hormone with anti-inflammatory and insulin-sensitizing properties. Insulin resistance is a typical feature of the obstructive sleep apnea syndrome (OSAS). Objectives: Since nasal continuous positive airway pressure (nCPAP) treatment improves insulin sensitivity in patients with OSAS, we investigated serum adiponectin levels before and during nCPAP treatment to clarify possible interactions between the adiponectin levels and insulin

I. A. Harsch; H. Wallaschofski; C. Koebnick; S. Pour Schahin; E. G. Hahn; J. H. Ficker; T. Lohmann

2004-01-01

259

Association of Plasma Adiponectin Concentrations with Chronic Lymphocytic Leukemia and Myeloproliferative Diseases  

Microsoft Academic Search

Adiponectin, an adipocyte-secreted hormone, is an important negative regulator in the immune system and hematopoiesis. In\\u000a this study, we investigated the association of adiponectin levels with chronic lymphocytic leukemia (CLL) and myeloproliferative\\u000a diseases (MPDs). We measured adiponectin levels in 19 patients with CLL and 30 patients with MPD (chronic myelogenous leukemia,\\u000a 15; polycythemia vera, 9; myelofibrosis, 4; essential thrombocythemia, 2).

Ferit Avcu; A. Ugur Ural; M. Ilker Yilmaz; Necati Bingol; Oral Nevruz; Kayser Caglarc

2006-01-01

260

Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration  

Microsoft Academic Search

Aims\\/hypothesis  A decrease in plasma adiponectin levels has been shown to contribute to the development of diabetes. However, it remains uncertain\\u000a whether adiponectin plays a role in the regulation of insulin secretion. In this study, we investigated whether adiponectin\\u000a may be involved in the regulation of insulin secretion in vivo and in vitro.\\u000a \\u000a \\u000a \\u000a Methods  The effect of adiponectin on insulin secretion was

M. Okamoto; M. Ohara-Imaizumi; N. Kubota; S. Hashimoto; K. Eto; T. Kanno; T. Kubota; M. Wakui; R. Nagai; M. Noda; S. Nagamatsu; T. Kadowaki

2008-01-01

261

Relationship between Adiponectin Level, Insulin Sensitivity, and Metabolic Syndrome in Type 1 Diabetic Patients  

PubMed Central

Objective. Adiponectin is known to be decreased in insulin resistance (IR) and metabolic syndrome (MS) which can be present in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the relationship between adiponectin level, MS, and insulin sensitivity in T1DM. Research Design and Methods. The study included 77 T1DM patients divided into two groups based on the total plasma adiponectin median value. Insulin sensitivity was calculated with the equation for eGDR, and MS was defined according to International Diabetes Federation criteria. Results. Patients with higher adiponectin level (n = 39) had significantly lower waist circumference (P < 0.002), fasting venous glucose levels (P < 0.001), higher HDL3-cholesterol (P = 0.011), and eGDR (P = 0.003) in comparison to the group with lower adiponectin who showed higher prevalence of MS (P = 0.045). eGDR increased for 1.09?mg/kg?1?min?1 by each increase of 1?µg/mL total fasting plasma adiponectin (P = 0.003). In the logistic regression model, adiponectin was inversely associated with the presence of MS (P = 0.014). Conclusion. Higher adiponectin concentration is associated with lower prevalence of MS in T1DM. Whether higher adiponectin concentration has a protective role in the development of the MS in T1DM needs to be clarified in future follow-up studies.

Blaslov, Kristina; Zibar, Karin; Duvnjak, Lea

2013-01-01

262

Biglycan Deletion Alters Adiponectin Expression in Murine Adipose Tissue and 3T3-L1 Adipocytes  

PubMed Central

Obesity promotes increased secretion of a number of inflammatory factors from adipose tissue. These factors include cytokines and very lately, extracellular matrix components (ECM). Biglycan, a small leucine rich proteoglycan ECM protein, is up-regulated in obesity and has recently been recognized as a pro-inflammatory molecule. However, it is unknown whether biglycan contributes to adipose tissue dysfunction. In the present study, we characterized biglycan expression in various adipose depots in wild-type mice fed a low fat diet (LFD) or obesity-inducing high fat diet (HFD). High fat feeding induced biglycan mRNA expression in multiple adipose depots. Adiponectin is an adipokine with anti-inflammatory and insulin sensitizing effects. Due to the importance of adiponectin, we examined the effect of biglycan on adiponectin expression. Comparison of adiponectin expression in biglycan knockout (bgn?/0) and wild-type (bgn+/0) reveals higher adiponectin mRNA and protein in epididymal white adipose tissue in bgn?/0 mice, as well higher serum concentration of adiponectin, and lower serum insulin concentration. On the contrary, knockdown of biglycan in 3T3-L1 adipocytes led to decreased expression and secretion of adiponectin. Furthermore, treatment of 3T3-L1 adipocytes with conditioned medium from biglycan treated macrophages resulted in an increase in adiponectin mRNA expression. These data suggest a link between biglycan and adiponectin expression. However, the difference in the pattern of regulation between in vivo and in vitro settings reveals the complexity of this relationship.

Ward, Meliza G.; Ajuwon, Kolapo M.

2012-01-01

263

Globular adiponectin induces LKB1/AMPK-dependent glucose uptake via actin cytoskeleton remodeling.  

PubMed

Previous studies have shown that many metabolic actions of adiponectin are mediated via the activation of AMP kinase and that adiponectin stimulates GLUT4 translocation and glucose uptake in the muscle. In this study, we demonstrate that adiponectin stimulates actin cytoskeleton remodeling, with increased phosphorylation of cofilin, and that blocking of cytoskeletal remodeling with cytochalasin D prevents adiponectin-stimulated AMPK phosphorylation in L6 myoblasts. LKB1 is an upstream kinase of AMPK, and we observed the colocalization of LKB1 with filamentous actin in response to adiponectin. Adiponectin-stimulated translocation of LKB1 from a nuclear to a cytoplasmic location to activate AMPK was also dependent on actin cytoskeleton remodeling. Cytoskeletal remodeling visualized by rhodamine-phalloidin immunofluorescence indicated that adiponectin-stimulated reorganization resulted in the formation membrane ruffles, which were also clearly visible by scanning electron microscopy in L6-GLUT4(myc) myoblasts. The stimulation of glucose uptake, but not of GLUT4-myc translocation to the cell surface, by adiponectin was also dependent on actin cytoskeleton remodeling. These results suggest that actin remodeling induced by adiponectin is essential for mediating LKB1/AMPK signaling and glucose uptake in skeletal muscle cells. PMID:23709749

Vu, Vivian; Bui, Phuong; Eguchi, Megumi; Xu, Aimin; Sweeney, Gary

2013-06-29

264

Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.  

PubMed

Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases. PMID:23691032

Sun, Yiyi; Zang, Zhihe; Zhong, Ling; Wu, Min; Su, Qing; Gao, Xiurong; Zan, Wang; Lin, Dong; Zhao, Yan; Zhang, Zhonglin

2013-05-14

265

Identification of Adiponectin Receptor Agonist Utilizing a Fluorescence Polarization Based High Throughput Assay  

PubMed Central

Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.

Sun, Yiyi; Zang, Zhihe; Zhong, Ling; Wu, Min; Su, Qing; Gao, Xiurong; Zan, Wang; Lin, Dong; Zhao, Yan; Zhang, Zhonglin

2013-01-01

266

Adiponectin Deficiency Promotes Tumor Growth in Mice by Reducing Macrophage Infiltration  

PubMed Central

Adiponectin is an adipocyte-derived plasma protein that has been implicated in regulating angiogenesis, but the role of adiponectin in regulating this process is still controversial. In this study, in order to determine whether adiponectin affects tumor growth and tumor induced vascularization, we implanted B16F10 melanoma and Lewis Lung Carcinoma cells subcutaneously into adiponectin knockout and wild-type control mice, and found that adiponectin deficiency markedly promoted the growth of both tumors. Immunohistochemical analyses indicated that adiponectin deficiency reduced macrophage recruitment to the tumor, but did not affect cancer cell mitosis, apoptosis, or tumor-associated angiogenesis. In addition, treatment with recombinant adiponectin did not affect the proliferation of cultured B16F10 tumor cells. Importantly, the restoration of microphage infiltration at an early stage of tumorigenesis by means of co-injection of B16F10 cells and macrophages reversed the increased tumor growth in adiponectin knockout mice. Thus, we conclude that the enhanced tumor growth observed in adiponectin deficient mice is likely due to the reduction of macrophage infiltration rather than enhanced angiogenesis.

Sun, Yutong; Lodish, Harvey F.

2010-01-01

267

Adiponectin promotes syncytialisation of BeWo cell line and primary trophoblast cells  

PubMed Central

Background In human pregnancy, a correct placentation depends on trophoblast proliferation, differentiation, migration and invasion. These processes are highly regulated by placental hormones, growth factors and cytokines. Recently, we have shown that adiponectin, an adipokine, has anti-proliferative effects on trophoblastic cells. Here, we complete this study by demonstrating that adiponectin modulates BeWo and human villous cytotrophoblast cell differentiation. Results We showed that hCG secretion was up-regulated by adiponectin treatment in both BeWo cells and human cytotrophoblasts from very early placentas (5-6 weeks). The expression of two trophoblast differentiation markers, leptin and syncytin 2, was also up-regulated by adiponectin in BeWo cells. Moreover, adiponectin treatment induced a loss of E-cadherin staining in these cells. In parallel, we demonstrated that AdipoR1 and AdipoR2 are up-regulated during forskolin induced BeWo cell differentiation, reinforcing the role of adiponectin in trophoblast syncytialization. SiRNA mediated down-regulation of AdipoR1 and AdipoR2 was used to demonstrate that adiponectin effects on differentiation were essentially mediated by these receptors. Finally, using a specific inhibitor, we demonstrated that the PKA signalling pathway could be one pathway involved in adiponectin effects on trophoblast differentiation. Conclusion Adiponectin enhances the differentiation process of trophoblast cells and could thus be involved in functional syncytiotrophoblast formation.

2010-01-01

268

Adiponectin promotes endothelial cell differentiation from human peripheral CD14+ monocytes in vitro.  

PubMed

Adiponectin was revealed to have anti-atherogenic and anti-inflammatory properties and has been recently found to stimulate angiogenesis in vivo and in vitro. However, the role of adiponectin in endothelial differentiation remains unclear. The objective of this study was to investigate whether adiponectin can promote peripheral CD14(+) monocytes differentiation into endothelial cells (ECs). Human peripheral blood CD14(+) monocytes were cultured with or without adiponectin (10 microg/ml) for 10 days. Adiponectin significantly promoted EC morphology formation from CD14(+) monocytes. By flow cytometery analysis, cells treated with adiponection substantially increased mean fluorescence intensity of vascular endothelial growth factor receptor-2 (VEGFR-2) and endothelial nitric oxide synthase (eNOS), two specific endothelial markers, by 49.2 % and 53.9 %, respectively, as compared to control cells. By real time PCR analysis, the mRNA level of eNOS in adiponectin-treated cells was also increased by 31.9 % of that of the control cells. However, the mRNA levels of calponin and SMMHC, two specific SMC markers, in adiponectin-treated cells were decreased by 81.1 % and 79.7 % of that of the control cells, respectively. These data demonstrated that adiponectin could promote endothelial differentiation from peripheral blood CD14(+) monocytes by morphology change, upregulation of EC markers and downregulation of SMC markers. Adiponectin-promoted EC differentiation may contribute to vascular healing and angiogenesis. PMID:16796811

Yang, Hui; Zhang, Rongxin; Mu, Hong; Li, Min; Yao, Qizhi; Chen, Changyi

269

Human genetics of adiponectin in the metabolic syndrome  

Microsoft Academic Search

Adiponectin, an adipose-derived plasma protein, has been well established to be an important biomarker for metabolic syndrome\\u000a and its complications after exhausted studies in humans. Animal and cell culture experiments also support most claims from\\u000a human observations of its roles in the metabolic syndrome. Reproducible results of human genetic studies of diverse ethnic\\u000a origin and by different investigators may provide

Wei-Shiung Yang; Lee-Ming Chuang

2006-01-01

270

Adiponectin SNP45TG is associated with gestational diabetes mellitus  

Microsoft Academic Search

Introduction  Diabetes and pregnancy can be associated in two ways: pregnancy that occurs in women who are already diabetic (diabetes of\\u000a pre-gestational origin); and diabetes that occur in women who are already pregnant [gestational diabetes mellitus (GDM) (O’sullivan\\u000a 1961)]. Patients with previous GDM history have higher risk of developing diabetes outside of pregnancy. Accumulating literature\\u000a had suggested that adiponectin plays a

Chen Fei Low; Eusni Rahayu Mohd Tohit; Pei Pei Chong; Faridah Idris

2011-01-01

271

Molecular pathways: adiponectin and leptin signaling in cancer.  

PubMed

The increasing percentage of obese individuals in the population and its independent association of increased risk for the development of cancer have heightened the necessity to understand the molecular mechanisms that underlie this connection. The deregulation of adipokines in the setting of obesity and their impact on cancer progression and metastasis is one such area of research. Adipokines are bioactive proteins that mediate metabolism, inflammation, angiogenesis, and proliferation. Altered levels of adipokines or their cognate receptors in cancers can ultimately lead to an imbalance in downstream molecular pathways. Discovery of adipokine receptors in various cancers has highlighted the potential for novel therapeutic targets. Leptin and adiponectin represent two adipokines that elicit generally opposing molecular effects. Epidemiologic studies have highlighted associations between increased serum leptin levels and increased tumor growth, whereas adiponectin exhibits an inverse correlation with cancer development. This review addresses the current level of understanding of molecular pathways activated by adiponectin and leptin to identify the areas of intervention and facilitate advancement in the field. PMID:23355630

Vansaun, Michael N

2013-01-25

272

Associations of BMI and insulin resistance with leptin, adiponectin, and the leptin to adiponectin ratio across ethnic groups: The Multi-Ethnic Study of Atherosclerosis (MESA)  

PubMed Central

Purpose Associations of adiponectin and leptin and their ratio with BMI and HOMA-IR have been investigated in different ethnic groups but variability in both assays and statistical methods have made cross-study comparisons difficult. We examined associations among these variables across four ethnic groups in a single study. Methods Adiponectin and leptin were measured in a subset of MESA participants. We calculated associations (using both partial correlations and adjusted linear regression) in each ethnic group and then compared the magnitude of these associations across groups. Results After excluding individuals with type 2 diabetes there were 714 White, 219 Chinese, 332 African American, and 405 Hispanic individuals, in the study sample. Associations of BMI with adiponectin and leptin differed significantly (P < 0.05) across the ethnic groups in regression analyses, while associations of HOMA-IR with adiponectin and leptin did not differ across ethnic groups. The leptin to adiponectin ratio was not associated with a greater amount of adiposity or HOMA-IR variance than leptin or adiponectin in any ethnic group. Conclusions Given the consistency of HOMA-IR and adipokine associations, the differing means of adiponectin and leptin across ethnic groups may help to explain ethnic differences in mean insulin resistance.

Rasmussen-Torvik, Laura J.; Wassel, Christina L.; Ding, Jingzhong; Carr, Jeffery; Cushman, Mary; Jenny, Nancy; Allison, Matthew A.

2012-01-01

273

Effect of exercise on chemically-induced colitis in adiponectin deficient mice  

PubMed Central

Background Inflammatory bowel diseases are associated with increased adiponectin (APN) levels, which may exert pro-inflammatory effects in these individuals. Since habitual exercise may increase APN, the aim of this study was to determine how exercise training affects mice with acute colitis. Methods Male adiponectin knock out (APNKO) and wild type (WT) mice (C57BL/6) were randomly assigned to 4 different groups: 1) Sedentary (SED); 2) Exercise trained (ET); 3) Sedentary with dextran sodium sulfate (DSS) treatment (SED?+?DSS); and 4) Exercise trained with DSS (ET?+?DSS). Exercise-trained mice ran at 18 m/min for 60 min, 5d/wk for 4 weeks. Subsequently, the ET?+?DSS and the SED?+?DSS mice received 2% DSS in their drinking water for 5 days (d), followed by 5d of regular water. Results The clinical symptoms of acute colitis (diarrhea, stool haemoccult, and weight loss) were unaffected by exercise and there was no difference between the APNKO and WT mice (p?>?0.05) except on day 39. However, the clinical symptoms of the DSS-treated APNKO mice were worse than WT mice treated with DSS and had increased susceptibility to intestinal inflammation due to increased local STAT3 activation, higher IL-6, TNF-?, IL-1? and IL-10 levels, and as a result had increased intestinal epithelial cell proliferation (p?

2012-01-01

274

Adiponectin: an adipocyte-derived hormone, and its gene encoding in children with chronic kidney disease  

PubMed Central

Background The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with chronic kidney disease (CKD). Adiponectin (ADPN) is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD. Methods On seventy eight advanced CKD (stages 4 and 5) pediatric patients undergoing maintenance hemodialysis( MHD) or conservative treatment (CT) the following parameters were studied: body mass index, left ventricular mass index(LVMI), serum adiponectin , cholesterol, HDL-cholesterol, high sensitivity C-reactive protein (hs CRP),interleukin 6(IL6) and single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene at positions 45, and 276. Seventy age-and gender-matched healthy subjects served as control subjects. Results Markedly (P?=?0.01) elevated plasma adiponectin levels were observed in CKD patients, especially CT patients, compared to control subjects. The wild type of ADIPOQ 45T > G (T) allele is the main gene for patients and controls. MHD and CT patients had significantly higher frequency of the TT genotypes of +276G > T gene (P?=?0.04) compared with control subjects. A significant positive correlation was observed between plasma adiponectin and IL6 level, whereas negative correlations were found between adiponectin level, cholesterol, HDL cholesterol and hs CRP. In a stepwise backward multiple regression model only IL6 (P?=?0.001) was independently associated with plasma adiponectin levels. The adiponectin gene the 276 GT+TT genotypes were associated with a higher level of adiponectin . Conclusions The present study demonstrated that ADPN is related to several metabolic and inflammatory CV risk factors in a manner consistent with the hypothesis that this protein might have a protective role against these factors. We observed an association between the +276G>T SNP in the adiponectin gene and CKD in children. Genetic variation of +276 gene seemed to have a positive impact on circulating adiponectin levels in CKD patients.

2012-01-01

275

Adiponectin and Its Receptors in Chronic Hepatitis B Patients With Steatosis in China  

PubMed Central

Background HBV infection is a serious public health problem worldwide, which can contribute to the incidence of chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC). Objectives In the present report, we assessed the association between adiponectin, its receptors and hepatic steatosis, fibrosis, and inflammation with hepatitis B virus. Patients and Methods Liver biopsies from 89 patients with untreated chronic hepatitis B (34 steatosis vs. 55 without steatosis) were analyzed; liver biopsies from 50 healthy adults were used as control. The liver biopsies were subjected to routine histological examination, and stained immunohistochemically for adiponectin and adiponectin receptor2 (adipoR2). Results The two groups were found to be comparable with respect to demographic, biochemical, metabolic, histological, and viral characteristics. BMI, ?-GT, FPG, insulin, and insulin sensitivity estimated by the HOMA index were significantly higher in patients with steatosis. The viral load of HBV and HBeAg positivity was higher in patients with steatosis than those without steatosis. High serum adiponectin levels were significantly correlated with abnormal serum ALT level (vs. normal ALT, P = 0.000), and HBV genotype C (vs. genotype B, P = 0.018). In patients with chronic HBV, the insulin sensitizing adipokine adiponectin, and its receptor AdipoR2were associated with steatosis. While adiponectin may becorrelated with inflammation, adiponectin, and its receptors were not associated with viral factors. Conclusions Our results suggest that the role of adiponectin might be impaired in chronic hepatitis B with steatosis. Reduced hepatic expression of adiponectin and adipoR2 might be of pathophysiological relevance in CHB patients with steatosis. These findings indicated that reduced liver adiponectin expression may play an important role in the pathogenesis, and progression of CHB patients with steatosis. However, hepatic expression of adiponectin, and adipoR2 was not associated with various measures of HBV infection.

Wu, Di; Li, Hongqi; Xiang, Guoan; Zhang, Liwei; Li, Lihong; Cao, Yongmei; Zhang, Jinqian

2013-01-01

276

Adiponectin ameliorates iron-overload cardiomyopathy through the PPAR?-PGC-1-dependent signaling pathway.  

PubMed

Adiponectin is a circulating adipose-derived cytokine that may act as an antioxidative and anti-inflammatory protein. Although adiponectin has been reported to exert cytoprotective effects in acute cardiac diseases, its effects on chronic heart failure are less clear. Therefore, we aimed to investigate whether adiponectin would have a beneficial effect in iron-induced chronic heart failure and to elucidate its regulation in cardiomyocytes. Mice were first treated with iron dextran for 4 weeks to induce iron-overload cardiomyopathy. They exhibited decreased survival with impaired left ventricle contractility and decreased serum adiponectin levels. In vivo cardiac adiponectin gene (ADIPOQ) overexpression with adenoassociated virus (AAV)-ADIPOQ ameliorated cardiac iron deposition and restored cardiac function in iron-overloaded mice. In addition, AAV-ADIPOQ-treated iron-overload mice had lower expression of inflammatory markers, including myeloperoxidase activity, monocyte chemotactic protein-1, tumor necrosis factor-?, interleukin-6, and intercellular adhesion molecule-1, than iron-overloaded mice not treated with AAV-ADIPOQ. Our in vitro study showed that adiponectin induced heme oxygenase-1 (HO-1) expression through the peroxisome proliferator-activated receptor (PPAR)?-HO-1 signaling pathway. Furthermore, the adiponectin-mediated beneficial effects were PPAR?-dependent as the adiponectin-mediated attenuation of iron deposition was abolished in PPAR?-knockout mice. Finally, PPAR?-HO-1 signaling involved PPAR? and peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) binding and nuclear translocation, and their levels were increased by adiponectin therapy. Together, these findings suggest that adiponectin acts as an anti-inflammatory signaling molecule and induces the expression of HO-1 through the PPAR?-PGC-1 complex-dependent pathway in cardiomyocytes, resulting in the attenuation of iron-induced cardiomyopathy. Using adiponectin for adjuvant therapies in iron-overload cardiac dysfunction may be an option in the future. PMID:23723143

Lin, Heng; Lian, Wei-Shiung; Chen, Hsi-Hsien; Lai, Pei-Fang; Cheng, Ching-Feng

2013-05-30

277

Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies.  

PubMed

Obesity is a risk factor for breast cancer development. A recent hypothesis suggests that the adipokines, adiponectin and leptin, are involved in breast cancer development. This prompted us to investigate the role of adiponectin and leptin in mammary carcinogenesis. Adiponectin receptors (AdipoR1 and AdipoR2) and leptin receptor (Ob-Rt, representing all the isoforms of Ob-R) proteins were detected by immunohistochemistry in in situ ductal carcinoma, invasive ductal malignancy, and healthy adjacent tissue. In addition, mRNA expression of adiponectin, AdipoR1, AdipoR2, leptin, Ob-Rt, and Ob-Rl (the long isoform of Ob-R) was observed in MCF-7 breast cancer cells. Interestingly, leptin mRNA expression was 34.7-fold higher than adiponectin mRNA expression in the MCF-7 cell line. Moreover, adiponectin (10 microg/ml) tended to decrease the mRNA expression of leptin (-36%) and Ob-Rl (-28%) and significantly decreased Ob-Rt mRNA level (-26%). In contrast, leptin treatment (1 microg/ml) significantly decreased AdipoR1 mRNA (-23%). Adiponectin treatment (10 microg/ml) inhibited the proliferation of MCF-7 cells, whereas leptin (1 microg/ml) stimulated the growth of cancer cells. In addition, adiponectin inhibited leptin-induced cell proliferation (both 1 microg/ml). Using microarray analysis, we found that adiponectin reduced the mRNA levels of genes involved in cell cycle regulation (mitogen-activated protein kinase 3 and ATM), apoptosis (BAG1, BAG3, and TP53), and potential diagnosis/prognosis markers (ACADS, CYP19A1, DEGS1, and EVL), whereas leptin induced progesterone receptor mRNA expression. In conclusion, the current study indicates an interaction of leptin- and adiponectin-signaling pathways in MCF-7 cancer cells whose proliferation is stimulated by leptin and suppressed by adiponectin. PMID:19661131

Jardé, T; Caldefie-Chézet, F; Goncalves-Mendes, N; Mishellany, F; Buechler, C; Penault-Llorca, F; Vasson, M P

2009-08-06

278

Structural and genetical studies on the high-molecular-weight subunits of wheat glutenin  

Microsoft Academic Search

Summary  The high-molecular-weight (HMW) subunits of glutenin from about 185 varieties were fractionated by sodium dodecyl sulphate\\u000a polyacrylamide gel electrophoresis (SDS-PAGE). About 20 different, major subunits were distinguished by this technique although\\u000a each variety contained, with only a few exceptions, between 3 and 5 subunits. Further inter-varietal substitution lines to\\u000a those already described (Payne et al. 1980) were analysed and the

P. I. Payne; L. M. Holt; C. N. Law

1981-01-01

279

Individual Characteristics and Quitting in Apprentices Exposed to High-molecular-weight Agents  

Microsoft Academic Search

To determine whether specific immunological sensitization (SIS) and symptoms of allergy are associated with quitting apprentice- ships with exposure to high-molecular-weight (HMW) agents. In a cohort study of 769 apprentices starting career programs in ani- mal health technology (AHT), pastry-making (PM), and dental hy- giene technology (DHT), health status was assessed at baseline and yearly for up to 44 mo.

EDUARD MONSÓ; JEAN-LUC MALO; CLAIRE INFANTE-RIVARD; HEBERTO GHEZZO; MICHÈLE MAGNAN; CAROLE TRUDEAU; DENYSE GAUTRIN

280

Construction of adiponectin-encoding plasmid DNA and overexpression in mice in vivo.  

PubMed

The effects of elevated adiponectin (ADN) plasma levels on food intake, body weight, and lipid deposition of wild-type mice through ADN gene transfer using hydrodynamic based-gene delivery (HD) were investigated. The administration of pTarget/ADN significantly increased the blood ADN levels on days 1, 3, and 7 as well as food intake and body weight. Reverse transcription polymerase chain reaction (RT-PCR) was used to investigate the key-function genes involved in lipid deposition on epididymal fat, gastrocnemius, and extensor digitorum longus on days 1 and 7. The amounts of adipose triglyceride lipase, hormone-sensitive lipase, and lipoprotein lipase mRNA in the three samples significantly increased. We determined sirtuin 1 (SIRT1), forkhead box O3 (FOXO3a), and peroxisome proliferator-activated receptor-? coactivator-1? (PGC-1?) gene expression and protein level in these samples. The amounts of SIRT1, FOXO3a, and PGC-1? mRNA in epididymal fat, gastrocnemius, and extensor digitorum longus remarkably increased. However, a significant increase in SIRT1 and PGC-1? protein levels was only observed in extensor digitorum longus. These results suggest that high doses of ADN can increase food intake and body weight. Elevated ADN levels may also affect fat deposition on the adipose tissue and skeletal muscles of wild-type mice via SIRT1, FOXO3a, and its downstream targets, including PGC-1?. PMID:22561699

Huang, Yan-Na; Qi, Jian-Hua; Xiang, Lan; Wang, Yi-Zhen

2012-04-25

281

Antidiabetic treatment restores adiponectin serum levels and APPL1 expression, but does not improve adiponectin-induced vasodilation and endothelial dysfunction in Zucker diabetic fatty rats  

PubMed Central

Background Adiponectin is able to induce NO-dependent vasodilation in Zucker lean (ZL) rats, but this effect is clearly alleviated in their diabetic littermates, the Zucker diabetic fatty (ZDF) rats. ZDF rats also exhibit hypoadiponectinemia and a suppressed expression of APPL1, an adaptor protein of the adiponectin receptors, in mesenteric resistance arteries. Whether an antidiabetic treatment can restore the vasodilatory effect of adiponectin and improve endothelial function in diabetes mellitus type 2 is not known. Methods During our animal experiment from week 11 to 22 in each case seven ZDF rats received an antidiabetic treatment with either insulin (ZDF+I) or metformin (ZDF+M). Six normoglycemic ZL and six untreated ZDF rats served as controls. Blood glucose was measured at least weekly and serum adiponectin levels were quantified via ELISA in week 11 and 22. The direct vasodilatory response of their isolated mesenteric resistance arteries to adiponectin as well as the endothelium-dependent and -independent function was evaluated in a small vessel myograph. Additionally, the expression of different components of the adiponectin signaling pathway in the resistance arteries was quantified by real-time RT-PCR. Results In ZDF rats a sufficient blood glucose control could only be reached by treatment with insulin, but both treatments restored the serum levels of adiponectin and the expression of APPL1 in small resistance arteries. Nevertheless, both therapies were not able to improve the vasodilatory response to adiponectin as well as endothelial function in ZDF rats. Concurrently, a downregulation of the adiponectin receptors 1 and 2 as well as endothelial NO-synthase expression was detected in insulin-treated ZDF rats. Metformin-treated ZDF rats showed a reduced expression of adiponectin receptor 2. Conclusions An antidiabetic treatment with either insulin or metformin in ZDF rats inhibits the development of hypoadiponectinemia and downregulation of APPL1 in mesenteric resistance arteries, but is not able to improve adiponectin induced vasodilation and endothelial dysfunction. This is possibly due to alterations in the expression of adiponectin receptors and eNOS.

2013-01-01

282

Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells  

Microsoft Academic Search

BACKGROUND: Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation. Adiponectin and its receptors are known to be expressed in osteoblasts, but their actions with regard to bone metabolism are still unclear. In this study, we investigated the effects of adiponectin on the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. RESULTS: Adiponectin

Ippei Kanazawa; Toru Yamaguchi; Shozo Yano; Mika Yamauchi; Masahiro Yamamoto; Toshitsugu Sugimoto

2007-01-01

283

Secretion of the Adipocyte-Specific Secretory Protein Adiponectin Critically Depends on Thiol-Mediated Protein Retention? †  

PubMed Central

Adiponectin is a secretory protein abundantly secreted from adipocytes. It assembles into a number of different higher-order complexes. Adipocytes maintain tight control over circulating plasma levels, suggesting the existence of a complex, highly regulated biosynthetic pathway. However, the critical mediators of adiponectin maturation within the secretory pathway have not been elucidated. Previously, we found that a significant portion of de novo-synthesized adiponectin is not secreted and retained in adipocytes. Here, we show that there is an abundant pool of properly folded adiponectin in the secretory pathway that is retained through thiol-mediated retention, as judged by the release of adiponectin in response to treatment of adipocytes with reducing agents. Adiponectin is covalently bound to the ER chaperone ERp44. An adiponectin mutant lacking cysteine 39 fails to stably interact with ERp44, demonstrating that this residue is the primary site mediating the covalent interaction. Another ER chaperone, Ero1-L?, plays a critical role in the release of adiponectin from ERp44. Levels of both of these proteins are highly regulated in adipocytes and are influenced by the metabolic state of the cell. While less critical for the secretion of trimers, these chaperones play a major role in the assembly of higher-order adiponectin complexes. Our data highlight the importance of posttranslational events controlling adiponectin levels and the release of adiponectin from adipocytes. One mechanism for increasing circulating levels of specific adiponectin complexes by peroxisome proliferator-activated receptor gamma agonists may be selective upregulation of rate-limiting chaperones.

Wang, Zhao V.; Schraw, Todd D.; Kim, Ja-Young; Khan, Tayeba; Rajala, Michael W.; Follenzi, Antonia; Scherer, Philipp E.

2007-01-01

284

Blockade of Sympathetic Nervous System Activity by Rilmenidine Increases Plasma Adiponectin Concentration in Patients With Essential Hypertension  

Microsoft Academic Search

Background: Adiponectin is an adipose tissue-specific protein with antiatherogenic and insulin-sensitizing properties. In patients with essential hypertension plasma adiponectin levels are lower than in healthy subjects. It is hypothetized that low plasma adiponectin concentration may be involved in the pathogenesis of vascular complications in hypertension. The aim of the study was to evaluate the effect of 6 months of antihypertensive

?ukasz Nowak; Marcin Adamczak; Andrzej Wi?cek

2005-01-01

285

Serum adiponectin is positively associated with lung function in young adults, independent of obesity: The CARDIA study  

Microsoft Academic Search

RATIONALE: Adipose tissue produces adiponectin, an anti-inflammatory protein. Adiponectin deficiency in mice is associated with abnormal post-natal alveolar development. OBJECTIVE: We hypothesized that lower serum adiponectin concentrations are associated with lower lung function in humans, independent of obesity. We explored mediation of this association by insulin resistance and systemic inflammation. METHODS AND MEASUREMENTS: Spirometry testing was conducted at years 10

Bharat Thyagarajan; David R Jacobs Jr; Lewis J Smith; Ravi Kalhan; Myron D Gross; Akshay Sood

2010-01-01

286

Adiponectin Is Associated with Brain Natriuretic Peptide and Left Ventricular Hypertrophy in Hemodialysis Patients with Type 2 Diabetes Mellitus  

Microsoft Academic Search

Background: Adiponectin, an adipocyte-derived hormone, has been shown to prevent the progression of left ventricular hypertrophy (LVH). However, recent studies have demonstrated increased levels of adiponectin according to the severity of chronic heart failure. We therefore investigated the relationships between adiponectin, brain natriuretic peptide (BNP), and LVH in type 2 diabetic patients on hemodialysis. Methods: The study population comprised 41

Hirotaka Komaba; Naoya Igaki; Shunsuke Goto; Kazuki Yokota; Toshiyuki Takemoto; Yoshiaki Hirosue; Takeo Goto

2007-01-01

287

Changes in adiponectin and the risk of sudden death, stroke, myocardial infarction, and mortality in hemodialysis patients  

Microsoft Academic Search

Adiponectin is an adipocyte-specific cytokine that has a protective role in the development of cardiovascular morbidities. As chronic kidney disease progresses, adiponectin levels increase and cardiovascular risk profiles change. Here we determined the association of baseline and longitudinal changes in adiponectin with different cardiovascular outcomes in 1255 type 2 diabetic hemodialysis patients in the German Diabetes and Dialysis Study. Within

Christiane Drechsler; Vera Krane; Karl Winkler; Friedo W Dekker; Christoph Wanner

2009-01-01

288

Association of Plasma Adiponectin Levels with Oxidative Stress in Hemodialysis Patients  

Microsoft Academic Search

Background: Recent evidence suggests that oxidative stress may be an instigator of the metabolic syndrome, and adiponectin, an adipocyte-derived polypeptide, may modulate oxidative stress, ameliorating the atherosclerotic process. Aim: Oxidative stress is increased in hemodialysis (HD) patients. We hypothesize that a relationship between plasma levels of adiponectin and markers of inflammation and oxidative stress exists. Methods and Results: In 124

Paik-Seong Lim; Shun-Liang Chen; Ming-Ying Wu; Chuen-Yuh Hu; Tsai-Kun Wu

2007-01-01

289

Knockdown of RyR3 enhances adiponectin expression through an atf3-dependent pathway.  

PubMed

Adiponectin is an important adipose-specific protein, which possesses insulin (INS)-sensitizing, antiinflammatory, and antiatherosclerotic functions. However, its regulation remains largely unknown. In this study, we identified that ryanodine receptor (RyR)3 plays an important role in the regulation of adiponectin expression. RyR3 was expressed in 3T3-L1 preadipocytes, and its level was decreased upon adipogenesis. Silencing of RyR3 expression in 3T3-L1 preadipocytes resulted in up-regulated adiponectin promoter activity, enhanced adiponectin mRNA expression, and more adiponectin protein secreted into the medium. An inverse relation between RyR3 and adiponectin mRNA levels was also observed in adipose tissues of db/db mice. In addition, knockdown of RyR3 with small interfering RNA (siRNA) in db/db mice and high-fat diet-fed obese mice increased serum adiponectin level, improved INS sensitivity, and lowered fasting glucose levels. These effects were in parallel with decreased mitochondrial Ca(2+), increased mitochondrial mass, and reduced activating transcription factor 3 (atf3) expression. Overexpression of atf3 in 3T3-L1 preadipocytes blocked the effect of RyR3 silencing on adiponectin expression, indicating that an atf3-dependent pathway mediates the effect downstream of RyR3 silencing. Our data suggest that RyR3 may be a new therapeutic target for improving INS sensitivity and related metabolic disorders. PMID:23389954

Tsai, Shu-Huei; Chang, Emily Yun-Chia; Chang, Yi-Cheng; Hee, Siow-Wey; Tsai, Yun-Chih; Chang, Tien-Jyun; Chuang, Lee-Ming

2013-02-06

290

The adipose tissue production of adiponectin is increased in end-stage renal disease.  

PubMed

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6?mg/ml in cases compared with 8.4?mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis factor ?, interleukin 6, and high-sensitivity C-reactive protein were significantly higher in cases compared with controls. Adiponectin mRNA and protein expression in visceral and subcutaneous fat were significantly higher in cases than controls, while adiponectin receptor-1 mRNA expression was significantly increased in peripheral blood cells, muscle, and adipose tissue in cases compared with controls. Thus, our study suggests that adipose tissue production of adiponectin contributes to the high plasma levels seen in end-stage renal disease. PMID:23283133

Martinez Cantarin, Maria P; Waldman, Scott A; Doria, Cataldo; Frank, Adam M; Maley, Warren R; Ramirez, Carlo B; Keith, Scott W; Falkner, Bonita

2013-01-02

291

The adipose tissue production of adiponectin is increased in end stage renal disease  

PubMed Central

Adiponectin has anti-diabetic properties and patients with obesity, diabetes and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end stage renal disease. Here we determine if adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared to 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis factor ?, interleukin 6 and high sensitivity C-reactive protein were significantly higher in cases compared to controls. Adiponectin mRNA and protein expression in visceral and subcutaneous fat was significantly higher in cases than controls while adiponectin receptor 1 mRNA expression was significantly increased in peripheral blood cells, muscle and adipose tissue in cases compared to controls. Thus, our study suggests that adipose tissue production of adiponectin contributes to the high plasma levels seen in end stage renal disease.

Cantarin, Maria P Martinez; Waldman, Scott; Doria, Cataldo; Frank, Adam M.; Maley, Warren R.; Ramirez, Carlo B.; Keith, Scott W.; Falkner, Bonita

2012-01-01

292

Relationship of Plasma Adiponectin With Sex Hormone and Insulin-like Growth Factor Levels  

Microsoft Academic Search

Objective: Recent studies have suggested that a relationship between adiponectin and sex hormone, prolactin, and insulin-like growth factor levels could be important for breast cancer risk and insulin sensitivity. Therefore, we assessed the relationship of adiponectin with plasma concentrations of estrone; estradiol; estrone sulfate; testosterone; androstenedione; dehydroepiandrosterone (DHEA); dehydroepiandrosterone sulfate (DHEAS); sex hormone binding globulin (SHBG); prolactin; insulin-like growth factor

Shelley S. Tworoger; Christos Mantzoros; Susan E. Hankinson

2007-01-01

293

Bisphenol A at Environmentally Relevant Doses Inhibits Adiponectin Release from Human Adipose Tissue Explants and Adipocytes  

Microsoft Academic Search

Background: The incidence of obesity has risen dramatically over the last few decades. This epidemic may be affected by exposure to xenobiotic chemicals. Bisphenol A (BPA), an endocrine disruptor, is detectable at nanomolar levels in human serum worldwide. Adiponectin is an adipocyte-specific hormone that increases insulin sensitivity and reduces tissue inflammation. Thus, any factor that suppresses adiponectin release could lead

Eric R. Hugo; Terry D. Brandebourg; Jessica G. Woo; Jean Loftus; J. Wesley Alexander; Nira Ben-Jonathan

2008-01-01

294

Role of adiponectin and leptin on body development in infants during the first year of life  

Microsoft Academic Search

BACKGROUND: The control of growth and nutritional status in the foetus and neonate is a complex mechanism, in which also hormones produced by adipose tissue, such as adiponectin and leptin are involved. The aim of this study was to evaluate levels of adiponectin, leptin and insulin in appropriate (AGA) and small for gestational age (SGA) children during the 1st year

Elena Bozzola; Cristina Meazza; Marica Arvigo; Paola Travaglino; Sara Pagani; Mauro Stronati; Antonella Gasparoni; Carolina Bianco; Mauro Bozzola

2010-01-01

295

Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin  

Microsoft Academic Search

Background & Aims: Obesity is one of the risk factors for liver fibrosis, in which plasma adiponectin, an adipocytokine, levels are decreased. Hepatic stellate cells play central roles in liver fibrosis. When they are activated, they undergo transformation to myofibroblast-like cells. Adiponectin suppresses the proliferation and migration of vascular smooth muscle cells, whose characteristics are similar to those of hepatic

Yoshihiro Kamada; Shinji Tamura; Shinichi Kiso; Hitoshi Matsumoto; Yukiko Saji; Yuichi Yoshida; Koji Fukui; Norikazu Maeda; Hitoshi Nishizawa; Hiroyuki Nagaretani; Yoshihisa Okamoto; Shinji Kihara; Jun-ichiro Miyagawa; Yasuhisa Shinomura; Tohru Funahashi; Yuji Matsuzawa

2003-01-01

296

Relationship of Adiponectin with Insulin Sensitivity in Humans, Independent of Lipid Availability  

Microsoft Academic Search

Objective: To test in humans the hypothesis that part of the association of adiponectin with insulin sensitivity is independent of lipid availability.Research Methods and Procedures: We studied relationships among plasma adiponectin, insulin sensitivity (by hyperinsulinemic-euglycemic clamp), total adiposity (by DXA), visceral adiposity (VAT; by magnetic resonance imaging), and indices of lipid available to muscle, including circulating and intramyocellular lipid (IMCL;

Stuart M. Furler; Seng Khee Gan; Ann M. Poynten; Donald J. Chisholm; Lesley V. Campbell; Adamandia D. Kriketos

2006-01-01

297

Adiponectin: an independent risk factor for coronary heart disease in men in the Framingham Offspring Study  

Technology Transfer Automated Retrieval System (TEKTRAN)

Our aim was to determine whether plasma adiponectin levels were an independent predictor of coronary heart disease (CHD) risk. Plasma adiponectin levels were measured in 3,188 male and female participants from cycle 6 of the Framingham Offspring Study (mean age: 57 years in both men and women; BMI:...

298

Acute exercise increases adipose tissue interstitial adiponectin concentration in healthy overweight and lean subjects  

Microsoft Academic Search

Objective: We studied how an acute bout of exercise influences expression and concentration of adiponectin and regulators of adiponectin in adipose tissue and plasma. Design and methods: Eight overweight and eight lean males were examined by large-pore microdialysis in s.c. abdominal adipose tissue (SCAAT) and had arterialized blood sampled. On one day subjects rested for 3 h, exercised for 1

L. Hojbjerre; Mary Rosenzweig; Flemming Dela; Jens M Bruun; Bente Stallknecht

2007-01-01

299

Adiponectin Modulates the Glycogen Synthase Kinase3B\\/B-Catenin Signaling Pathway and Attenuates Mammary Tumorigenesis of MDA-MB-231 Cells in Nude Mice  

Microsoft Academic Search

Adiponectin is an adipokine that has pleiotropic beneficial roles in systemic insulin resistance and inflammation. Several recent clinical studies suggest that low serum levels of adiponectin are associated with increased risks of breast cancer. Here, we investigated the direct effects of adiponectin on breast cancer development in vitro and in vivo. Our results showed that adiponectin significantly attenuated the prolif-

Yu Wang; Janice B. Lam; Jing Liu; Michael C. Lam; Donghai Wu; Garth J. S. Cooper; Aimin Xu

300

Gene expression pattern of adiponectin and adiponectin receptors in dominant and atretic follicles and oocytes screened based on brilliant cresyl blue staining.  

PubMed

Adiponectin and its receptors (AdipoR1 and AdipoR2) are novel endocrine systems that act at various levels to control male and female fertility. The aim of this study was to determine whether adiponectin and its receptors gene expression levels differ between dominant follicle (DF) and atretic follicle (AF) and also between oocytes which were stained positively and negatively with brilliant cresyl blue (BCB(+) and BCB(-)). Based on estradiol/progesterone ratio, follicles from ovaries were classified as AFs and DFs. The stages of estrous cycle (follicular or luteal phases) were defined by macroscopic observation of the ovaries and the uterus. Oocytes were stained with BCB for 90 min. The relative expression of adiponectin, AdipoR1 and AdipoR2 mRNA in theca and cumulus cells and oocytes of different follicles were determined by quantitative real time PCR. Adiponectin and its receptors genes were clearly expressed higher (P<0.05) in theca and cumulus cells and oocytes of DFs than those of AFs during the follicular and luteal phases. BCB(+) oocytes showed a higher (P<0.05) expression of adiponectin and its receptors compared with their BCB(-) counterparts. Positive correlation (r>0.725, P<0.001) was observed between adiponectin mRNA level in ovarian cells of DFs and follicular fluid E2 concentration in follicular phase. Adiponectin mRNA abundance in ovarian cells of AFs showed a significant negative correlation with follicular fluid progesterone concentration in follicular and luteal phases (r<-0.731, P<0.001). This work has revealed the novel association of adiponectin and its receptors genes with follicular dominance and oocyte competence, thereby opening several new avenues of research into the mechanisms of dominance and competence in animal and human. PMID:22391295

Tabandeh, M R; Golestani, N; Kafi, M; Hosseini, A; Saeb, M; Sarkoohi, P

2012-02-11

301

Adiponectin inhibits leptin signaling via multiple mechanisms to exert protective effects against hepatic fibrosis  

PubMed Central

SYNOPSIS Adiponectin is protective against hepatic fibrosis, while leptin promotes fibrosis. In hepatic stellate cells (HSCs), leptin signals via a Janus Kinase 2/Signal Transducers and Activators of Transcription 3 (Jak2/Stat3) pathway, producing effects that enhance extracellular matrix deposition. Suppressors of Cytokine Signaling-3 (SOCS-3) and Protein Tyrosine Phosphatase-1B (PTP1B) are both negative regulators of Jak/Stat signaling, and recent studies demonstrated a role for adiponectin in regulating SOCS-3 expression. In this study we investigated mechanisms whereby adiponectin dampens leptin signaling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad?/?) and wild-type mice with leptin and/or carbon tetrachloride (CCl4), or saline. We analyzed Jak2 and Ob-Rb phosphorylation, and PTP1B expression and activity. We also explored potential mechanisms through which adiponectin regulates SOCS-3/Ob-Rb association. Adiponectin inhibited leptin-stimulated Jak2 activation and Ob-Rb phosphorylation in HSCs, while both were increased in Ad?/? mice. Adiponectin stimulated PTP1B expression and activity, in vitro, while PTP1B expression was lower in Ad?/?mice than in wild-type mice. Adiponectin also promoted SOCS-3/Ob-R association, and blocked leptin-stimulated formation of extracellular TIMP-1/MMP-1 complexes, in vitro. These data suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: by promoting binding of SOCS-3 to Ob-Rb, and stimulating PTP1B expression and activity, thus inhibiting Jak2-Stat3 signaling at multiple points.

HANDY, Jeffrey A.; FU, Ping P.; KUMAR, Pradeep; MELLS, Jamie E.; SHARMA, Shvetank; SAXENA, Neeraj K.; ANANIA, Frank A.

2011-01-01

302

GnRH decreases adiponectin expression in pituitary gonadotropes via the calcium and PKA pathways.  

PubMed

As endocrinologically active cells, adipocytes are capable of secreting various adipocytokines such as leptin, resistin, and adiponectin to impact metabolic function. Although adipocytes remain to be the primary site of synthesis and secretion, there is now growing evidence that supports the presence of adiponectin and its receptors within the hypothalamic-pituitary-gonadal axis, providing a possible link between obesity and abnormal reproductive physiology. It has been demonstrated that adiponectin may reduce gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus as well as modulate gonadal steroid hormone production. Furthermore, prior data indicate that adiponectin may play a role in decreasing luteinizing hormone secretion from pituitary gonadotropes. We aimed to identify the hormonal regulators of adiponectin and its receptors, AdipoR1 and AdipoR2, in pituitary gonadotropes using immortalized gonadotropic L?T2 cells and primary rat pituitary cells. Our study shows significant alterations in adiponectin expression across the estrous cycle. In addition, we present a novel finding that GnRH suppresses pituitary adiponectin expression via the calcium and protein kinase A intracellular pathways in both cultured rat primary pituitary cells and the L?T2 gonadotrope cell line. The GnRH did not alter expression of the adiponectin receptors, AdipoR1 and AdipoR2, in cultured gonadotropes. Expression of the adiponectin receptors, AdipoR1 and AdipoR2, was not altered by GnRH in cell culture but in vivo or in vitro. Our data suggest that gonadotrope function may be modulated by GnRH-mediated changes in adiponectin expression. PMID:23239819

Kim, Jonathan; Zheng, Weiming; Grafer, Constance; Mann, Merry Lynn; Halvorson, Lisa M

2012-12-13

303

Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease  

PubMed Central

Background Disorders of endocrine substances in epicardial adipose tissue are known causes of coronary artery disease (CAD). Adiponectin is associated with cardiovascular disease. However, expression of adiponectin in epicardial adipose tissue and its function in CAD pathogenesis is unclear. This study investigates adiponectin expression in epicardial adipose tissue in CAD patients. Methods Vessels or adipose tissue samples collected from CAD patients and non-CAD controls were examined after immunochemical staining. Adiponectin, cytokines of interleukin-6 (IL-6) and necrosis factor-? (TNF-?) and toll-like receptor 4 (TLR4) expression level in adipose tissue were measured using real-time quantitative RT-PCR. Adiponectin concentrations in peripheral and coronary sinus vein plasma were measured with enzyme-linked immunosorbent assay. Peripheral vein plasma biochemistries were performed with routine laboratory techniques. Monocytes were collected from blood using lymphocyte separation medium. Expression level of cytokines and transcription factor NF-?B were measured to learn the effect of adiponectin on stearic acid-stimulated monocytes. Percentage of TLR4 positive monocytes was analyzed using flow cytometry. Results Histological examination revealed increased macrophage infiltration into epicardial adipose tissue of CAD patients. Decreased adiponectin displayed by real-time quantitative RT-PCR was associated with enhanced cytokines of IL-6 and TNF-? or TLR4 expression level in epicardial adipose tissue, suggesting decreased circulating adiponectin may be useful as a more sensitive predictor for coronary atherosclerosis than routine laboratory examinations. Adiponectin suppressed secretion of IL-6 and TNF-? in stimulated monocytes and TLR4 was expressed on cell surfaces. Conclusions Endocrine disorders in epicardial adipose tissue are strongly linked to CAD, and adiponectin has a protective effect by inhibiting macrophage-mediated inflammation.

2011-01-01

304

Adiponectin inhibits leptin signalling via multiple mechanisms to exert protective effects against hepatic fibrosis.  

PubMed

Adiponectin is protective against hepatic fibrosis, whereas leptin promotes fibrosis. In HSCs (hepatic stellate cells), leptin signals via a JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) pathway, producing effects that enhance ECM (extracellular matrix) deposition. SOCS-3 (suppressor of cytokine signalling-3) and PTP1B (protein tyrosine phosphatase 1B) are both negative regulators of JAK/STAT signalling, and recent studies have demonstrated a role for adiponectin in regulating SOCS-3 expression. In the present study we investigate mechanisms whereby adiponectin dampens leptin signalling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad-/-) and wild-type mice with leptin and/or carbon tetrachloride (CCl4) or saline. We analyse JAK2 and Ob-Rb (long form of the leptin receptor) phosphorylation, and PTP1B expression and activity. We also explore potential mechanisms through which adiponectin regulates SOCS-3-Ob-Rb association. Adiponectin inhibits leptin-stimulated JAK2 activation and Ob-Rb phosphorylation in HSCs, whereas both were increased in Ad-/- mice. Adiponectin stimulates PTP1B expression and activity in vitro, whereas PTP1B expression was lower in Ad-/-mice than in wild-type mice. Adiponectin also promotes SOCS-3-Ob-R association and blocks leptin-stimulated formation of extracellular TIMP-1 (tissue inhibitor of metalloproteinases-1)-MMP-1 (matrix metalloproteinase-1) complexes in vitro. These results suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: (i) by promoting binding of SOCS-3 to Ob-Rb, and (ii) by stimulating PTP1B expression and activity, thus inhibiting JAK2/STAT3 signalling at multiple points. PMID:21846328

Handy, Jeffrey A; Fu, Ping P; Kumar, Pradeep; Mells, Jamie E; Sharma, Shvetank; Saxena, Neeraj K; Anania, Frank A

2011-12-15

305

The Helix-Loop-Helix Factors Id3 and E47 are Novel Regulators of Adiponectin  

PubMed Central

Adiponectin is an adipocyte-derived cytokine with beneficial effects on insulin sensitivity and the development of atherosclerosis. Id3 is a helix-loop-helix (HLH) factor that binds to E-proteins such as E47 and inhibits their binding to DNA. While the bHLH factor SREBP-1c is a known activator of adiponectin transcription, this study provides the first evidence of a role for Id3 and E47 in adiponectin expression. Decreased Id3 in differentiating adipocytes correlates with increased adiponectin expression and forced expression of Id3 inhibits adiponectin expression. Moreover, Id3 null mice have increased adiponectin expression in visceral fat tissue and in serum. We demonstrate that E47 potentiates SREBP-1c-mediated adiponectin promoter activation and that Id3 can dose-dependently inhibit this action via interaction with E47. Mutation of a consensus E47 binding site results in nearly complete loss of promoter activation. Further, we demonstrate E47 binding to the endogenous adiponectin promoter both in vitro and in vivo by ChIP analysis. Binding is not detected in undifferentiated cells which express Id3 but peaks during differentiation in parallel with Id3 decline. This promoter binding can be completely abolished by the overexpression of Id3 and is enhanced in adipose tissue null for Id3. These data establish Id3 and E47 as novel regulators of SREBP-1c-mediated adiponectin expression in differentiating adipocytes and provide evidence that Id3 regulates adiponectin expression in vivo.

Doran, Amanda C.; Meller, Nahum; Cutchins, Alexis; Deliri, Hamid; Slayton, R. Parker; Oldham, Stephanie N.; Kim, Jae B.; Keller, Susanna R.; McNamara, Coleen A.

2009-01-01

306

Evidence that an N-terminal S-layer protein fragment triggers the release of a cell-associated high-molecular-weight amylase in Bacillus stearothermophilus ATCC 12980.  

PubMed Central

During growth on starch medium, the S-layer-carrying Bacillus stearothermophilus ATCC 12980 and an S-layer-deficient variant each secreted three amylases, with identical molecular weights of 58,000, 122,000, and 184,000, into the culture fluid. Only the high-molecular-weight amylase (hmwA) was also identified as cell associated. Extraction and reassociation experiments showed that the hmwA had a high-level affinity to the peptidoglycan-containing layer and to the S-layer surface, but the interactions with the peptidoglycan-containing layer were stronger than those with the S-layer surface. For the S-layer-deficient variant, no changes in the amount of cell-associated and free hmwA could be observed during growth on starch medium, while for the S-layer-carrying strain, cell association of the hmwA strongly depended on the growth phase of the cells. The maximum amount of cell-associated hmwA was observed 3 h after inoculation, which corresponded to early exponential growth. The steady decrease in cell-associated hmwA during continued growth correlated with the appearance and the increasing intensity of a protein with an apparent molecular weight of 60,000 on sodium dodecyl sulfate gels. This protein had a high-level affinity to the peptidoglycan-containing layer and was identified as an N-terminal S-layer protein fragment which did not result from proteolytic cleavage of the whole S-layer protein but seems to be a truncated copy of the S-layer protein which is coexpressed with the hmwA under certain culture conditions. During growth on starch medium, the N-terminal S-layer protein fragment was integrated into the S-layer lattice, which led to the loss of its regular structure over a wide range and to the loss of amylase binding sites. Results obtained in the present study provide evidence that the N-terminal part of the S-layer protein is responsible for the anchoring of the subunits to the peptidoglycan-containing layer, while the surface-located C-terminal half could function as a binding site for the hmwA.

Egelseer, E M; Schocher, I; Sleytr, U B; Sara, M

1996-01-01

307

Induction of human adiponectin gene transcription by telmisartan, angiotensin receptor blocker, independently on PPAR-{gamma} activation  

SciTech Connect

Adiponectin, an adipose tissue-specific plasma protein, has been shown to ameliorate insulin resistance and inhibit the process of atherosclerosis. Recently, several reports have stated that angiotensin type 1 receptor blockers (ARBs), increase adiponectin plasma level, and ameliorate insulin resistance. Telmisartan, a subclass of ARBs, has been shown to be a partial agonist of the peroxisome proliferator-activated receptor (PPAR)-{gamma}, and to increase the plasma adiponectin level. However, the transcriptional regulation of the human adiponectin gene by telmisartan has not been determined yet. To elucidate the effect of telmisartan on adiponectin, the stimulatory regulation of human adiponectin gene by telmisartan was investigated in 3T3-L1 adipocytes, utilizing adenovirus-mediated luciferase reporter gene-transferring technique. This study indicates that telmisartan may stimulate adiponectin transcription independent of PPAR-{gamma}.

Moriuchi, Akie [Department of Endocrinology and Metabolism, Unit of Translational Medicine, Graduate School of Biomedical Science, Nagasaki University (Japan)]|[Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University, Hospital of Medicine and Dentistry, Nagasaki (Japan); Yamasaki, Hironori [Department of Endocrinology and Metabolism, Unit of Translational Medicine, Graduate School of Biomedical Science, Nagasaki University (Japan)]|[Health Center, Nagasaki University (Japan)]. E-mail: f1195@cc.nagasaki-u-ac.jp; Shimamura, Mika [Course of Pharmaceutical Sciences, Graduate School of Biomedical Science, Nagasaki University (Japan); Kita, Atsushi; Kuwahara, Hironaga; Satoh, Tsuyoshi; Satoh, Tsuyoshi [Department of Endocrinology and Metabolism, Unit of Translational Medicine, Graduate School of Biomedical Science, Nagasaki University (Japan); Fujishima, Keiichiro; Fukushima, Keiko [Department of Endocrinology and Metabolism, Unit of Translational Medicine, Graduate School of Biomedical Science, Nagasaki University (Japan)]|[Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University, Hospital of Medicine and Dentistry, Nagasaki (Japan); Fukushima, Tetsuya; Abiru, Norio; Eguchi, Katsumi [Department of Endocrinology and Metabolism, Unit of Translational Medicine, Graduate School of Biomedical Science, Nagasaki University (Japan); Hayakawa, Takao; Mizuguchi, Hiroyuki [Project III, National Institute of Health Sciences, Osaka Branch, Fundamental Research Laboratories for Development of Medicine (Japan); Nagayama, Yuji [Department of Medical Gene Technology, Atomic Bomb Disease Institute, Graduate School of Biochemical Sciences, Nagasaki University (Japan); Kawasaki, Eiji [Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University, Hospital of Medicine and Dentistry, Nagasaki (Japan)

2007-05-18

308

RNA-Directed DNA Polymerase from Human Leukemic Blood Cells and from Primate Type-C Virus-Producing Cells: High and Low-Molecular-Weight Forms with Variant Biochemical and Immunological Properties  

Microsoft Academic Search

RNA-directed DNA polymerase (reverse transcriptase) from leukocytes of individual leukemic patients can be grouped by velocity gradient analyses into two distinct classes, a low-molecular-weight (LMW) class of approximately 70,000 and a high-molecular-weight (HMW) class of 130,000 to 140,000. The reverse transcriptases from mammalian type-C viruses have with one exception (see text) been isolated as enzymes with molecular weights of 70,000.

H. Mondal; R. E. Gallagher; R. C. Gallo

1975-01-01

309

Genetic Polymorphisms of the Main Transcription Factors for Adiponectin Gene Promoter in Regulation of Adiponectin Levels: Association Analysis in Three European Cohorts  

PubMed Central

Adiponectin serum concentrations are an important biomarker in cardiovascular epidemiology with heritability etimates of 30–70%. However, known genetic variants in the adiponectin gene locus (ADIPOQ) account for only 2%–8% of its variance. As transcription factors are thought to play an under-acknowledged role in carrying functional variants, we hypothesized that genetic polymorphisms in genes coding for the main transcription factors for the ADIPOQ promoter influence adiponectin levels. Single nucleotide polymorphisms (SNPs) at these genes were selected based on the haplotype block structure and previously published evidence to be associated with adiponectin levels. We performed association analyses of the 24 selected SNPs at forkhead box O1 (FOXO1), sterol-regulatory-element-binding transcription factor 1 (SREBF1), sirtuin 1 (SIRT1), peroxisome-proliferator-activated receptor gamma (PPARG) and transcription factor activating enhancer binding protein 2 beta (TFAP2B) gene loci with adiponectin levels in three different European cohorts: SAPHIR (n?=?1742), KORA F3 (n?=?1636) and CoLaus (n?=?5355). In each study population, the association of SNPs with adiponectin levels on log-scale was tested using linear regression adjusted for age, sex and body mass index, applying both an additive and a recessive genetic model. A pooled effect size was obtained by meta-analysis assuming a fixed effects model. We applied a significance threshold of 0.0033 accounting for the multiple testing situation. A significant association was only found for variants within SREBF1 applying an additive genetic model (smallest p-value for rs1889018 on log(adiponectin)?=?0.002, ? on original scale?=??0.217 µg/ml), explaining ?0.4% of variation of adiponectin levels. Recessive genetic models or haplotype analyses of the FOXO1, SREBF1, SIRT1, TFAPB2B genes or sex-stratified analyses did not reveal additional information on the regulation of adiponectin levels. The role of genetic variations at the SREBF1 gene in regulating adiponectin needs further investigation by functional studies.

Kiesslich, Tobias; Kapur, Karen; Bergmann, Sven; Waterworth, Dawn; Heid, Iris M.; Wichmann, H.-Erich; Kedenko, Igor; Kronenberg, Florian; Paulweber, Bernhard

2012-01-01

310

Adiponectin: merely a bystander or the missing link to cardiovascular disease?  

PubMed

Adiponectin, a newly discovered adipose-tissue secreting hormone, is a major regulator of a wide spectrum of physiological processes, such as energy metabolism, inflammation and vascular homeostasis. Emerging data suggest that adiponectin is the link between obesity and obesity-related disorders with cardiovascular disease. Adiponectin is a dominant insulin-sensitive adipokine and, in contrast to other adipose-tissue derived cytokines, it has major anti-diabetic, antiatherogenic and anti-inflammatory properties. Adiponectin has been extensively studied in the context of several aspects and risk factors of cardiovascular disease such as obesity, diabetes type I and II, coronary heart disease, hypertension, heart failure, cerebrovascular disease and smoking. The aim of this article is to summarize the acquired so far knowledge on adiponectin in relation to cardiovascular disease, to review its main biological and biochemical characteristics, to highlight the main mechanisms of adiponectin-driven beneficial effects on vasculature and briefly to refer to the basic correlations of adiponectin with the important aforementioned aspects of cardiovascular disease. PMID:23470075

Hatzis, Georgios; Deftereos, Spyridon; Tousoulis, Dimitris; Bouras, Georgios; Giannopoulos, Georgios; Anatoliotakis, Nikolaos; Tsounis, Dimitrios; Stefanadis, Christodoulos

2013-01-01

311

Is adiponectin associated with acute myocardial infarction in Iranian non obese patients?  

PubMed Central

Backgrounds Adiponectin is an adipose tissue-derived mediator with significant anti-atherogenic properties. A few studies were done in acute phase of myocardial infarction especially in non obese patients. We design a study to investigate the association between adiponectin concentration and acute phase of myocardial infarction in non obese patients. Methods This case-control study was done in Paymaneah Hospital (Jahrom, Iran) from Feb 2007 to May 2008. Plasma adiponectin levels were measured in 43 patients with AMI (mean age: 62.7 ± 13.3 years, male: 67.4%) at the first 24 hours of admission and 43 normal controls (mean age: 62.1 ± 12.3 years, male: 55.8%) matched for age, sex and other CAD risk factors. Results Adiponectin levels in patients with AMI (3.36 ?g/mL) were significantly lower than that of the control group (5.03 ?g/mL) (p < 0.0001). Lower adiponectin were independently associated with higher risk of AMI (odds ratio = 8.97; 95% CIs: 2.3–34.5; p = 0.001). Adiponectin levels negatively correlated with triglyceride (r = -0.46, p = 0.002) and total cholesterol (r = -0.32, p = 0.03) in the case group and with body mass index (BMI) in control subjects. Conclusion The present study showed that adiponectin was associated with AMI in non obese patients but it is not related to sex, age and other CAD risk factors.

Shojaie, Mohammad; Sotoodah, Abdoreza; Shafaie, Ghafar

2009-01-01

312

Effects of spa therapy on serum leptin and adiponectin levels in patients with knee osteoarthritis.  

PubMed

Adipocytokine, including leptin and adiponectin, may play an important role in the pathophysiology of osteoarthritis (OA). Spa therapy is one of the most commonly used non-pharmacological approaches for OA, but its mechanisms of action are not completely known. The aim of the present study was to assess whether spa therapy modified plasma levels of leptin and adiponectin in thirty patients with knee OA treated with a cycle of a combination of daily locally applied mud-packs and bicarbonate-sulphate mineral bath water. Leptin and adiponectin plasma levels were assessed at baseline and after 2 weeks, upon completion of the spa treatment period. The concentrations of leptin and adiponectin were measured by ELISA. At basal time, plasma leptin levels were significantly correlated with body mass index (BMI) and gender, but no significant correlation was found with patient age, duration of disease, radiographic severity of knee OA, VAS score or Lequesne index. There was no correlation between plasma adiponectin level and BMI, gender and age, duration of the disease, radiographic severity of knee OA and VAS score. A significant correlation of plasma adiponectin levels was found only with the Lequesne index. At the end of the mud-bath therapy cycle, serum leptin levels showed a slight but not significant increase, while a significant decrease (P < 0.05) in serum adiponectin levels was found. However, leptin and adiponectin concentrations after treatment were not correlated with other clinical parameters. In conclusion, our data show that spa therapy can modify plasma levels of the adipocytokines leptin and adiponectin, important mediators of cartilage metabolism. Whether this effect may play a potential role in OA needs further investigations. PMID:20237929

Fioravanti, Antonella; Cantarini, Luca; Bacarelli, Maria Romana; de Lalla, Arianna; Ceccatelli, Linda; Blardi, Patrizia

2010-03-18

313

Mitochondria dysfunction contributes to the increased vulnerabilities of adiponectin knockout mice to liver injury  

PubMed Central

Adiponectin is an adipocyte-derived hormone with a wide range of beneficial effects on obesity-related medical complications. Numerous epidemiological investigations in diverse ethnic groups have identified lower adiponectin level as an independent risk factor for non-alcoholic fatty liver diseases and liver dysfunctions. Animal studies have demonstrated that replenishment of adiponectin protects against various forms of hepatic injuries, suggesting it to be a potential drug candidate for the treatment of liver diseases. This study was designed to investigate the cellular and molecular mechanisms underlying the hepato-protective effects of adiponectin. Our results demonstrated that in adiponectin knockout (ADN-KO) mice, there was a pre-existing condition of hepatic steatosis and mitochondria dysfunction, which might contribute to the increased vulnerabilities of these mice to secondary liver injuries induced by obesity and other conditions. Adenovirus-mediated replenishment of adiponectin depleted lipid accumulation, restored the oxidative activities of mitochondria respiratory chain (MRC) complexes and prevented the accumulation of lipid peroxidation products in ADN-KO mice, but had no obvious effects on mitochondria biogenesis. The gene and protein levels of uncoupling protein 2 (UCP2), a mitochondria membrane transporter, were decreased in ADN-KO mice and could be significantly up-regulated by adiponectin treatment. Moreover, the effects of adiponectin on mitochondria activities and on protection against endotoxin-induced liver injuries were significantly attenuated in UCP2 knockout mice. These results suggest that the hepatoprotective properties of adiponectin are mediated, at least in part, by enhancing the activities of MRC complexes through a mechanism involving UCP2.

Zhou, Mingyan; Xu, Aimin; Tam, Paul KH; Lam, Karen SL; Chan, Lawrence; Hoo, Ruby LC; Liu, Jing; Chow, Kim HM; Wang, Yu

2008-01-01

314

Rosiglitazone inhibits monocyte/macrophage adhesion through de novo adiponectin production in human monocytes.  

PubMed

Rosiglitazone (RSG) has a variety of actions on both insulin sensitization and anti-atherogenic effects. The molecular effect of RSG on monocyte/macrophage function in terms of de novo synthesis of adiponectin is not fully understood. Here, we examined the regulation of adiponectin expression in human monocytes/macrophages by RSG and its function on monocyte adhesion during initiation of atherosclerosis. Adiponectin expression in monocytes and macrophages was studied by RT-PCR, quantitative real-time PCR, Western blot, and immunocytochemistry. Signal transduction and adhesion molecules were studied in order to describe the function of de novo synthesized adiponectin in monocyte adhesion. Adiponectin was expressed and upregulated during monocyte differentiation. The expression of adiponectin was enhanced, albeit at a much lesser degree, by a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist RSG, which was similar to what was found in adipocytes. Monocyte adhesion was remarkably reduced when the cells were treated with RSG for 12 h. This inhibitory effect of RSG was abolished by specific anti-adiponectin antibodies but not by non-immune immunoglobulin G in a serum-free condition. Adiponectin-induced suppression on monocyte adhesion was inhibited by a selective AMP-activated protein kinase (AMPK) inhibitor compound C. The reduced expression and/or function of adhesion molecule integrins may underlie the mechanism contributing to reduced monocyte adhesion upon AMPK activation. Our data suggest that the inhibitory effect of RSG on monocyte adhesion might be at least in part through de novo adiponectin expression and activation of an AMPK-dependent pathway, which might play an important role in atherogenesis. PMID:20506517

Tsai, Jaw-Shiun; Chen, Ching-Yu; Chen, Yuh-Lien; Chuang, Lee-Ming

2010-08-15

315

Genetic Architecture of Plasma Adiponectin Overlaps With the Genetics of Metabolic Syndrome-Related Traits  

PubMed Central

OBJECTIVE Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome–related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs). RESEARCH DESIGN AND METHODS We made use of a family-based population, the Erasmus Rucphen Family study (1,258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model. RESULTS Plasma adiponectin showed a heritability of 55.1%. Genetic correlations between plasma adiponectin HDL cholesterol and plasma insulin ranged from 15 to 24% but were not significant for fasting glucose, triglycerides, blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), and C-reactive protein. A significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. A nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjustment for plasma adiponectin. CONCLUSIONS The significant genetic correlation between plasma adiponectin and HDL cholesterol and plasma insulin should be taken into account in the interpretation of genome-wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR.

Henneman, Peter; Aulchenko, Yurii S.; Frants, Rune R.; Zorkoltseva, Irina V.; Zillikens, M. Carola; Frolich, Marijke; Oostra, Ben A.; van Dijk, Ko Willems; van Duijn, Cornelia M.

2010-01-01

316

Bacterial Diversity of a Consortium Degrading High-Molecular-Weight Polycyclic Aromatic Hydrocarbons in a Two-Liquid Phase Biosystem  

Microsoft Academic Search

High-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs) are pollutants that persist in the environment due to\\u000a their low solubility in water and their sequestration by soil and sediments. Although several PAH-degrading bacterial species\\u000a have been isolated, it is not expected that a single isolate would exhibit the ability to degrade completely all PAHs. A consortium\\u000a composed of different microorganisms can better

Isabelle Lafortune; Pierre Juteau; Eric Déziel; François Lépine; Réjean Beaudet; Richard Villemur

2009-01-01

317

Preparation of high molecular weight poly(methyl methacrylate) with high yield by room temperature suspension polymerization of methyl methacrylate  

Microsoft Academic Search

To obtain high molecular weight (HMW) poly(methyl methacrylate) (PMMA) with high conversion, methyl methacrylate (MMA) was\\u000a polymerized in suspension using a room temperature initiator, 2,2?-azobis(2,4-dimethylvaleronitrile) (ADMVN), and the effects\\u000a of polymerization conditions on the polymerization behavior of MMA and the molecular parameters of PMMA were investigated.\\u000a On the whole, the experimental results well corresponded to the theoretically predicted tendencies. These

Won Seok Lyoo; Seok Kyun Noh; Jeong Hyun Yeum; Gu Chan Kang; Han Do Ghim; Jinwon Lee; Byung Chul Ji

2004-01-01

318

High-intensity endurance training improves adiponectin mRNA and plasma concentrations  

Microsoft Academic Search

Adiponectin is an anti-inflammatory protein that reduced in obesity. Exercise training may reduce the adipose tissue (AT),\\u000a although it is not well known whether exercise-induced change in AT, increases the adiponectin mRNA expression and plasma\\u000a concentrations or not; therefore, the purpose of this study was to investigate the adiponectin mRNA and plasma concentrations\\u000a in middle-aged men after 12 weeks high-intensity exercise

Mehrzad MoghadasiHamid Mohebbi; Hamid Mohebbi; Farhad Rahmani-Nia; Sadegh Hassan-Nia; Hamid Noroozi; Nazanin Pirooznia

319

Dose dependency of aflatoxin B/sub 1/ binding on human high molecular weight DNA in the activation of proto-oncogene  

SciTech Connect

The binding of aflatoxin B/sub 1/, AFB/sub 1/, a potent hepatocarcinogen, to various high molecular weight (HMW) DNAs from human normal liver and two liver cancer cell lines, Alexander primary liver carcinoma (PLC) and Mahlavu hepatocellular carcinoma (hHC) and from NIH/3T3 cell have been investigated. The kinetics of AFB/sub 1/ binding to these DNAs showed similar initial rates but the extents of binding to the PLC and hHC DNAs seemed to be slightly higher. Preferential AFB/sub 1/ bindings were identified in both PLC and hHC DNAs compared to normal liver DNA. A critical AFB/sub 1/ binding dosage, ranging 100 to 460 fmole/..mu..g DNA, was found to activate the carcinogenic effect of the Mahlavu hHC HMW DNA, but not normal liver HMW DNA, rendering it capable of inducting focal transformation in NIH/3T3 cell. Excessive AFB/sub 1/ binding on the hHC and PLC HMW DNAs resulted in an over-kill of both cell transformation capability and templating activity of the DNA.

Yang, S.S.; Taub, J.V.; Modali, R.; Vieira, W.; Yasei, P.; Yang, G.C.

1985-10-01

320

The reciprocal relationship between adiponectin and LOX-1 in the regulation of endothelial dysfunction in ApoE knockout mice  

PubMed Central

We hypothesized that the reciprocal association between adiponectin and lectin-like oxidized LDL (ox-LDL) receptor (LOX)-1 contributes to the regulation of aortic endothelial dysfunction in atherosclerosis. To test this hypothesis, endothelium-dependent (ACh) and endothelium-independent (sodium nitroprusside) vasorelaxation of isolated aortic rings from control mice, apolipoprotein E (ApoE) knockout (KO) mice, and ApoE KO mice treated with either adiponectin (15 ?g·day?1·mouse?1 sc for 8 days) or neutralizing antibody to LOX-1 (anti-LOX-1, 16 ?g/ml, 0.1 ml/mouse ip for 7 days) were examined. Although vasorelaxation to sodium nitroprusside was not different between control and ApoE KO mice, relaxation to ACh was impaired in ApoE KO mice. Adiponectin and anti-LOX-1 restored nitric oxide-mediated endothelium-dependent vasorelaxation in ApoE KO mice. Aortic ROS formation and ox-LDL uptake were increased in ApoE KO mice. Both adiponectin and anti-LOX-1 treatment reduced ROS production and aortic ox-LDL uptake. In mouse coronary artery endothelial cells, TNF-? incubation increased endothelial LOX-1 expression. Adiponectin reduced TNF-?-induced LOX-1 expression. Consistently, in ApoE KO mice, adiponectin treatment reversed elevated LOX-1 expression in aortas. Immunofluorescence staining showed that adiponectin was mainly colocalized with endothelial cells. Although adiponectin expression was lower in ApoE KO versus control mice, anti-LOX-1 increased aortic adiponectin expression, suggesting a reciprocal regulation between adiponectin and LOX-1. Moreover, both adiponectin and anti-LOX-1 reduced NF-?B expression in ApoE KO mice. Thus, adiponectin and LOX-1 may converge on NF-?B signaling to regulate their function. In conclusion, our results indicate that the reciprocal regulation between adiponectin and LOX-1 amplifies oxidative stress and ox-LDL uptake, leading to endothelial dysfunction in atherosclerosis.

Chen, Xiuping; Zhang, Hanrui; McAfee, Steve

2010-01-01

321

Adiponectin concentration in the orbital fat of patients with Graves' ophthalmopathy  

PubMed Central

Background “Graves’ ophthalmopathy” (GO), is an inflammatory disease of the orbit, with extensive adipose tissue involvement. Previous studies of orbital fat derived from such patients have demonstrated overexpression of the adiponectin gene and messenger RNA. Aim The study reported here aimed to measure the protein concentration of orbital adipose tissue adiponectin in GO patients, in comparison to healthy controls. Methods This was a prospective study. Orbital samples from ten healthy controls undergoing blepharoplasty and five patients with GO undergoing orbital fat decompression for proptosis were analyzed by enzyme-linked immunosorbent assay. Results The mean adiponectin concentration in samples from GO patients was 121.9 ± 29.5 ng/mL (mean ± standard deviation), versus 107.9 ± 26.6 ng/mL in the control group (P=0.20). Conclusion This study was unable to demonstrate a statistically significant difference in adiponectin protein concentrations between the two studied groups.

Soiberman, Uri; Levy, Ran; Leibovitch, Igal

2013-01-01

322

Population-specific coding variant underlies genome-wide association with adiponectin level  

PubMed Central

Adiponectin is a protein hormone that can affect major metabolic processes including glucose regulation and fat metabolism. Our previous genome-wide association (GWA) study of circulating plasma adiponectin levels in Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) detected a 100 kb two-SNP haplotype at KNG1–ADIPOQ associated with reduced adiponectin (frequency = 0.050, P = 1.8 × 10?25). Subsequent genotyping of CLHNS young adult offspring detected an uncommon variant [minor allele frequency (MAF) = 0.025] located ?800 kb from ADIPOQ that showed strong association with lower adiponectin levels (P = 2.7 × 10?15, n = 1695) and tagged a subset of KNG1–ADIPOQ haplotype carriers with even lower adiponectin levels. Sequencing of the ADIPOQ-coding region detected variant R221S (MAF = 0.015, P = 2.9 × 10?69), which explained 17.1% of the variance in adiponectin levels and largely accounted for the initial GWA signal in Filipinos. R221S was not present in 12 514 Europeans with previously sequenced exons. To explore the mechanism of this substitution, we re-measured adiponectin level in 20 R221S offspring carriers and 20 non-carriers using two alternative antibodies and determined that the presence of R221S resulted in artificially low quantification of adiponectin level using the original immunoassay. These data provide an example of an uncommon variant responsible for a GWA signal and demonstrate that genetic associations with phenotypes measured by antibody-based quantification methods can be affected by uncommon coding SNPs residing in the antibody target region.

Croteau-Chonka, Damien C.; Wu, Ying; Li, Yun; Fogarty, Marie P.; Lange, Leslie A.; Kuzawa, Christopher W.; McDade, Thomas W.; Borja, Judith B.; Luo, Jingchun; AbdelBaky, Omar; Combs, Terry P.; Adair, Linda S.; Lange, Ethan M.; Mohlke, Karen L.

2012-01-01

323

Population-specific coding variant underlies genome-wide association with adiponectin level.  

PubMed

Adiponectin is a protein hormone that can affect major metabolic processes including glucose regulation and fat metabolism. Our previous genome-wide association (GWA) study of circulating plasma adiponectin levels in Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) detected a 100 kb two-SNP haplotype at KNG1-ADIPOQ associated with reduced adiponectin (frequency = 0.050, P = 1.8 × 10(-25)). Subsequent genotyping of CLHNS young adult offspring detected an uncommon variant [minor allele frequency (MAF) = 0.025] located ~800 kb from ADIPOQ that showed strong association with lower adiponectin levels (P = 2.7 × 10(-15), n = 1695) and tagged a subset of KNG1-ADIPOQ haplotype carriers with even lower adiponectin levels. Sequencing of the ADIPOQ-coding region detected variant R221S (MAF = 0.015, P = 2.9 × 10(-69)), which explained 17.1% of the variance in adiponectin levels and largely accounted for the initial GWA signal in Filipinos. R221S was not present in 12 514 Europeans with previously sequenced exons. To explore the mechanism of this substitution, we re-measured adiponectin level in 20 R221S offspring carriers and 20 non-carriers using two alternative antibodies and determined that the presence of R221S resulted in artificially low quantification of adiponectin level using the original immunoassay. These data provide an example of an uncommon variant responsible for a GWA signal and demonstrate that genetic associations with phenotypes measured by antibody-based quantification methods can be affected by uncommon coding SNPs residing in the antibody target region. PMID:22010046

Croteau-Chonka, Damien C; Wu, Ying; Li, Yun; Fogarty, Marie P; Lange, Leslie A; Kuzawa, Christopher W; McDade, Thomas W; Borja, Judith B; Luo, Jingchun; AbdelBaky, Omar; Combs, Terry P; Adair, Linda S; Lange, Ethan M; Mohlke, Karen L

2011-10-18

324

Relationship of Serum Adiponectin and Leptin Concentrations with Body Fat Distribution in Humans  

Microsoft Academic Search

Objective: We investigated whether serum concentrations of adiponectin are determined by body fat distribution and compared the findings with leptin.Research Methods and Procedures: Serum concentrations of adiponectin and leptin were measured by radioimmunoassay (n = 394) and analyzed for correlation with sex, age, and body fat distribution, i.e., waist-to-hip ratio, waist and hip circumference, and subcutaneous adipose tissue area of

Harald Staiger; Otto Tschritter; Jürgen Machann; Claus Thamer; Andreas Fritsche; Elke Maerker; Fritz Schick; Hans-Ulrich Häring; Michael Stumvoll

2003-01-01

325

Insulin and Endothelin in the Acute Regulation of Adiponectin in Vivo in Humans  

Microsoft Academic Search

Objective: In vitro, insulin and endothelin (ET) both modulate adiponectin secretion from adipocyte cell lines. The current studies were performed to assess whether endogenous ET contributes to the acute action of insulin infusions on adiponectin levels in vivo in humans.Research Methods and Procedures: We studied 17 lean and 20 obese subjects (BMI 21.8 ± 2.2 and 34.0 ± 5.0 kg\\/m2,

Lori A. Brame; Robert V. Considine; Mikako Yamauchi; Alain D. Baron; Kieren J. Mather

2005-01-01

326

Relationship of serum adiponectin and resistin to glucose intolerance and fat topography in south-Asians  

PubMed Central

Objectives South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels. Methods In this cross-sectional study, 150 South-Asians (80 males, 70 females) were included, 60 had NGT (Control group, Age 51.33 ± 11.5, BMI 27 ± 2.3), 60 had IGT (Age 57.7 ± 12.5, BMI 27.2 ± 2.7), 30 had type 2 DM (Age 49.5 ± 10.9, BMI 28 ± 1.7). Measures of adiposity, adipocytokines and other metabolic parameters were determined. Parameters were measured using the following: a) Plasma glucose by glucose oxidase method b) CRP by immunoturbidimetric method (Roche/Hitachi analyser) c) insulin by Medgenix INS-ELISA immunoenzymetric assay by Biosource (Belgium) d) Leptin, Adiponectin by radioimmunoassay kits by Linco Research (St. Charles MO) e) Resistin by immunoassay kits by Phoenix Pharmaceuticals INC (530 Harbor Boulevard, Belmont CA 94002, USA). Results Adiponectin concentrations were highest in NGT, decreased in IGT and lowest in DMT2, (both p < 0.01). Leptin was significantly higher in DMT2 than IGT and NGT p = 0.02 and 0.04 respectively. There was a significant positive relationships between log adiponectin and 2-hr insulin values, p = 0.028 and history of hypertensions and a ischemic heart disease p = 0.008 with R = 0.65. There was a significant inverse correlation between log adiponectin and resistin, p < 0.01. Conclusion Resistin levels had an inverse correlation with adiponectin levels, indicating an inverse relationship between pro-inflammatory cytokines and adiponectin. Adiponectin levels were related to glucose tolerance.

Wasim, Hanif; Al-Daghri, Nasser M; Chetty, Raja; McTernan, Phillip G; Barnett, A H; Kumar, Sudhesh

2006-01-01

327

Effects of Spa therapy on serum leptin and adiponectin levels in patients with knee osteoarthritis  

Microsoft Academic Search

Adipocytokine, including leptin and adiponectin, may play an important role in the pathophysiology of osteoarthritis (OA).\\u000a Spa therapy is one of the most commonly used non-pharmacological approaches for OA, but its mechanisms of action are not completely\\u000a known. The aim of the present study was to assess whether spa therapy modified plasma levels of leptin and adiponectin in\\u000a thirty patients

Antonella Fioravanti; Luca Cantarini; Maria Romana Bacarelli; Arianna de Lalla; Linda Ceccatelli; Patrizia Blardi

2011-01-01

328

Adiponectin and Ghrelin Levels and Body Size in Normoglycemic Filipino, African-American, and White Women  

Microsoft Academic Search

Objective: Prior studies have reported ethnic differences in adiponectin and ghrelin, but few have assessed the role of body size in normoglycemic women. We compared fasting adiponectin and ghrelin concentrations in normoglycemic 40- to 80-year-old Filipino, African-American, and white women.Methods: Participants included women from the Rancho Bernardo Study (n = 143), the University of California-San Diego Filipino Women’s Health Study

Maria Rosario G. Araneta; Elizabeth Barrett-Connor

2007-01-01

329

Lifestyle plus Exercise Intervention Improves Metabolic Syndrome Markers without Change in Adiponectin in Obese Girls  

Microsoft Academic Search

Background\\/Aims: Little is known about whether lifestyle plus exercise intervention improves obesity, metabolic syndrome markers, and circulating adiponectin concentrations in obese girls. The goal of this study was to investigate the effects of a 12-week lifestyle plus exercise intervention on adiponectin and metabolic syndrome markers in Korean obese adolescents. Methods: A total of 44 obese adolescent girls (13–15 years old),

Tae-Gon Park; Hae-Ryen Hong; Jiyoung Lee; Hyun-Sik Kang

2007-01-01

330

Association of plasma adiponectin concentrations with chronic lymphocytic leukemia and myeloproliferative diseases.  

PubMed

Adiponectin, an adipocyte-secreted hormone, is an important negative regulator in the immune system and hematopoiesis. In this study, we investigated the association of adiponectin levels with chronic lymphocytic leukemia (CLL) and myeloproliferative diseases (MPDs). We measured adiponectin levels in 19 patients with CLL and 30 patients with MPD (chronic myelogenous leukemia, 15; polycythemia vera, 9; myelofibrosis, 4; essential thrombocythemia, 2). The data were (chronic myelogenous leukemia, 15; polycythemia vera, 9; myelofibrosis, 4; essential thrombocythemia, 2). The data were compared with results from a control group of healthy volunteers who were matched according to age, sex, and body mass index. The adiponectin levels in patients with CLL were lower than in the controls (4.71 +/- 1.33 microg/mL versus 16.61 +/- 3.91 microg/mL; P <.001). They were also significantly lower in patients with MPD than in the controls (8.95 +/- 1.33 microg/mL versus 16.16 +/- 4.77 microg/mL; P <.001). In addition, we compared the adiponectin levels of MPD patients who were treated with interferon (IFN) to the levels of patients who were not treated with IFN. Adipnectin levels were significantly higher in IFN-treated patients (11.03 +/- 1.39 microg/mL versus 6.87 +/- 1.79 microg/mL; P <.001). These results suggest that lymphopoiesis and myelopoiesis negatively influence adiponectin levels. Adiponectin may be related to inflammatory cytokine release. IFN therapy appears to have a positive influence on adiponectin secretion by suppressing inflammatory cytokines. Future studies are needed to prove causality and to provide insight about this hormone's mechanism of action and its potential role regarding the etiology and progression of CLL and MPD. PMID:16720558

Avcu, Ferit; Ural, A Ugur; Yilmaz, M Ilker; Bingol, Necati; Nevruz, Oral; Caglar, Kayser

2006-04-01

331

Interactions of Adiponectin and Lipopolysaccharide from Porphyromonas gingivalis on Human Oral Epithelial Cells  

Microsoft Academic Search

BackgroundPeriodontitis is an inflammatory disease caused by pathogenic microorganisms, such as Porphyromonas gingivalis, and characterized by the destruction of the periodontium. Obese individuals have an increased risk for periodontitis and show decreased serum levels of adiponectin. This in-vitro study was established to examine whether adiponectin modulates critical effects of lipopolysaccharide (LPS) from P. gingivalis on oral epithelial cells (OECs).Methodology\\/Principal FindingsThe

Dominik Kraus; Jochen Winter; Søren Jepsen; Andreas Jäger; Rainer Meyer; James Deschner

2012-01-01

332

Role of adiponectin and its receptors in cancer.  

PubMed

Adiponectin (APN), a novel hormone/cytokine derived from adipocyte tissue, is involved in various physiological functions. Genetics, nutrition, and adiposity are factors contributing to circulating plasma concentrations of APN. Clinical correlation studies have shown that lower levels of serum APN are associated with increased malignancy of various cancers, such as breast and colon cancers, suggesting that APN has a role in tumorigenesis. APN affects insulin resistance, thus further influencing cancer development. Tumor cells may express receptors for APN. Cellular signaling is the mechanism by which APN exerts its host-protective responses. These factors suggest that serum APN levels and downstream signaling targets of APN may serve as potential diagnostic markers for malignancies. Further research is necessary to clarify the exact role of APN in cancer diagnosis and therapy. PMID:23691481

Obeid, Stephanie; Hebbard, Lionel

2012-12-01

333

Role of Adiponectin and Its Receptors in Cancer  

PubMed Central

Adiponectin (APN), a novel hormone/cytokine derived from adipocyte tissue, is involved in various physiological functions. Genetics, nutrition, and adiposity are factors contributing to circulating plasma concentrations of APN. Clinical correlation studies have shown that lower levels of serum APN are associated with increased malignancy of various cancers, such as breast and colon cancers, suggesting that APN has a role in tumorigenesis. APN affects insulin resistance, thus further influencing cancer development. Tumor cells may express receptors for APN. Cellular signaling is the mechanism by which APN exerts its host-protective responses. These factors suggest that serum APN levels and downstream signaling targets of APN may serve as potential diagnostic markers for malignancies. Further research is necessary to clarify the exact role of APN in cancer diagnosis and therapy.

Obeid, Stephanie; Hebbard, Lionel

2012-01-01

334

Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet  

PubMed Central

Background Studies suggest that leucine supplementation (LS) has a therapeutic potential to prevent obesity and to promote glucose homeostasis. Furthermore, regular physical exercise is a widely accepted strategy for body weight maintenance and also for the prevention of obesity. The aim of this study was to determine the effect of chronic LS alone or combined with endurance training (ET) as potential approaches for reversing the insulin resistance and obesity induced by a high-fat diet (HFD) in rats. Methods Forty-seven rats were randomly divided into two groups. Animals were fed a control diet-low fat (n = 10) or HFD (n = 37). After 15 weeks on HFD, all rats received the control diet-low fat and were randomly divided according to treatment: reference (REF), LS, ET, and LS+ET (n = 7-8 rats per group). After 6 weeks of treatment, the animals were sacrificed and body composition, fat cell volume, and serum concentrations of total cholesterol, HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis factor-alpha (TNF-?) were analyzed. Results At the end of the sixth week of treatment, there was no significant difference in body weight between the REF, LS, ET and LS+ET groups. However, ET increased lean body mass in rats (P = 0.019). In addition, ET was more effective than LS in reducing adiposity (P = 0.019), serum insulin (P = 0.022) and TNF-? (P = 0.044). Conversely, LS increased serum adiponectin (P = 0.021) levels and reduced serum total cholesterol concentration (P = 0.042). Conclusions The results showed that LS had no beneficial effects on insulin sensitivity or adiposity in previously obese rats. On the other hand, LS was effective in increasing adiponectin levels and in reducing total cholesterol concentration.

2011-01-01

335

The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study.  

PubMed

The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin. PMID:22249107

Alvarez, Granada; Visitación Bartolomé, M; Miana, María; Jurado-López, Raquel; Martín, Ruben; Zuluaga, Pilar; Martinez-Martinez, Ernesto; Nieto, M Luisa; Alvarez-Sala, Luis A; Millán, Jesús; Lahera, Vicente; Cachofeiro, Victoria

2012-01-13

336

Rheumatoid Arthritis Impacts on the Independent Relationships between Circulating Adiponectin Concentrations and Cardiovascular Metabolic Risk  

PubMed Central

Adiponectin and leptin are likely involved in the pathophysiology of rheumatoid arthritis (RA) and therefore potential new therapeutic targets. Adiponectin inhibition could be expected to enhance cardiovascular metabolic risk. However, it is unknown whether RA changes the influence of adipokines on cardiovascular metabolic risk. We determined whether RA impacts on the independent relationships of circulating leptin and adiponectin concentrations with cardiovascular risk factors and carotid intima-media thickness (cIMT) in 277 black African subjects from a developing population; 119 had RA. RA impacted on the relationships of adiponectin concentrations with lipid concentrations and blood pressure, independent of confounders including adiposity (interaction P < 0.05). This translated into an association of adiponectin concentrations with more favorable lipid variables including HDL cholesterol (P = 0.0005), non-HDL cholesterol (P = 0.007), and triglyceride (P = 0.005) concentrations, total cholesterol-HDL cholesterol (P = 0.0002) and triglycerides-HDL cholesterol (P = 0.0003) ratios, and higher systolic (P = 0.0006), diastolic (P = 0.0004), and mean blood pressure (P = 0.0007) in RA but not non-RA subjects. Leptin was not associated with metabolic risk after adjustment for adiposity. The cIMT did not differ by RA status, and adipokine concentrations were unrelated to atherosclerosis. This study suggests that leptin and adiponectin inhibition may not alter overall cardiovascular risk and disease in RA.

Dessein, Patrick H.; Norton, Gavin R.; Badenhorst, Margaret; Woodiwiss, Angela J.; Solomon, Ahmed

2013-01-01

337

Cardiometabolic risk factors related to vitamin d and adiponectin in obese children and adolescents.  

PubMed

Obesity-related diseases are becoming the most important causes of mortality worldwide. Several studies have suggested an association between low levels of vitamin D and obesity. In addition, plasma adiponectin levels have been found to be lower in obese subjects. We evaluated the association of metabolic risk factors with both adiponectin and vitamin D levels and that between adiponectin and vitamin D levels. The study consisted of 114 obese and healthy subjects. 25-Hydroxy vitamin D [25(OH)D] levels were positively correlated with adiponectin and HDL-cholesterol (HDL-C) and inversely correlated with body mass index (BMI), LDL-cholesterol (LDL-C), total cholesterol (T-C), triglyceride (TG), fasting glucose, homeostasis model assessment of insulin resistance (HOMA index), systolic blood pressure (SBP), and diastolic blood pressure (DBP). The mean 25(OH)D levels in the obese and nonobese groups were 22.5 ± 5.7 and 32.3 ± 5.8?ng/mL, respectively (P < 0.0001). The mean adiponectin level in the obese group was lower than that in the nonobese group (P < 0.0001). Lower vitamin D and adiponectin levels were strongly associated with metabolic risk factors and obesity in Turkish children and adolescents. PMID:23983686

Kardas, Fatih; Kendirci, Mustafa; Kurtoglu, Selim

2013-07-24

338

Effect of adiponectin gene polymorphisms on waist circumference in patients with diabetes  

PubMed Central

Background Plasma levels of adiponectin which is secreted from adipose tissue are associated with various parameters of metabolic syndrome. This effect seems to be a result of interactions between genetic and environmental factors including central obesity. The present study was carried out to investigate the possibility of relation between single nucleotide polymorphisms of adiponectin gene (+45 T/G and ?11391 G/A) and waist circumferences (WC) in patients with type 2 diabetes. Methods This cross-sectional study was conducted on n = 238 diabetic patients selected as cases and n = 159 as healthy control who were recruited from Rafsanjan city in south – east of Iran. The possible association of +45 T/G and –11391 G/A adiponectin gene polymorphisms with WC according to age and sex was evaluated. Results There was no significant difference in distribution of frequencies of +45 T/G and –11391 G/A adiponectin gene polymorphisms in each group. We only found a significant association between –11391 G/A adiponectin gene polymorphism with WC in diabetic group (p = 0.021). This association was remained significant after adjustment in multivariate regression model (p = 0.019, OR: 0.244, 95%CI: 0.075-0.791) and also this effect was independent of sex and age. Conclusion We found higher abdominal obesity in GA or AA carriers of adiponectin – 11391 G/A genotype in type 2 diabetes patients independent of age and sex.

2012-01-01

339

Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice.  

PubMed

Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on regulating glucose and lipid homeostasis and insulin sensitivity. However, the mechanisms underlying the metabolic actions of FGF21 remain unknown. Here we show that the insulin-sensitizing adipokine adiponectin is a downstream effector of FGF21. Treatments with FGF21 enhanced both expression and secretion of adiponectin in adipocytes, thereby increasing serum levels of adiponectin in mice. Adiponectin knockout mice were refractory to several therapeutic benefits of FGF21, including alleviation of obesity-associated hyperglycemia, hypertriglyceridemia, insulin resistance, and hepatic steatosis. Furthermore, the effects of FGF21 on attenuation of obesity-induced impairment in insulin signaling in liver and skeletal muscle were abrogated in adiponectin knockout mice, whereas FGF21-mediated activation of ERK1/ERK2 in adipose tissues remained unaffected. Therefore, adiponectin couples FGF21 actions in local adipocytes to liver and skeletal muscle, thereby mediating the systemic effects of FGF21 on energy metabolism and insulin sensitivity. PMID:23663741

Lin, Zhuofeng; Tian, Haishan; Lam, Karen S L; Lin, Shaoqiang; Hoo, Ruby C L; Konishi, Morichika; Itoh, Nobuyuki; Wang, Yu; Bornstein, Stefan R; Xu, Aimin; Li, Xiaokun

2013-05-01

340

Effects of short-term lifestyle activity modification on adiponectin mRNA expression and plasma concentrations  

Microsoft Academic Search

Adiponectin mRNA and plasma concentrations were reduced in obesity. Exercise training may reduce the adipose tissue (AT), although it is not well known, whether exercise – induced change in AT, increases adiponectin mRNA expression and plasma concentrations or not. Therefore, the purpose of this study was to examine the effects of short-term lifestyle activity modification (LAM) on adiponectin mRNA and

Mehrzad Moghadasi; Hamid Mohebbi; Farhad Rahmani-Nia; Sadegh Hassan-Nia; Hamid Noroozi

2011-01-01

341

Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions  

Microsoft Academic Search

Adiponectin plays a central role as an antidiabetic and antiatherogenic adipokine. AdipoR1 and AdipoR2 serve as receptors for adiponectin in vitro, and their reduction in obesity seems to be correlated with reduced adiponectin sensitivity. Here we show that adenovirus-mediated expression of AdipoR1 and R2 in the liver of Lepr?\\/? mice increased AMP-activated protein kinase (AMPK) activation and peroxisome proliferator-activated receptor

Toshimasa Yamauchi; Yasunori Nio; Toshiyuki Maki; Masaki Kobayashi; Takeshi Takazawa; Masato Iwabu; Miki Okada-Iwabu; Sachiko Kawamoto; Naoto Kubota; Tetsuya Kubota; Yusuke Ito; Junji Kamon; Atsushi Tsuchida; Katsuyoshi Kumagai; Hideki Kozono; Yusuke Hada; Hitomi Ogata; Kumpei Tokuyama; Masaki Tsunoda; Tomohiro Ide; Kouji Murakami; Motoharu Awazawa; Iseki Takamoto; Philippe Froguel; Kazuo Hara; Kazuyuki Tobe; Ryozo Nagai; Kohjiro Ueki; Takashi Kadowaki

2007-01-01

342

Leptin-to-adiponectin ratio as independent predictor of insulin sensitivity during growth in overweight Hispanic youth  

Microsoft Academic Search

because leptin and adiponectin are counter-regulated in vivo and exert opposing effects on glucose metabolism, fat oxidation and insulin sensitivity, the ratio of leptin-to-adiponectin has been investigated as a potential atherogenic index, suggesting that the index is a better biomarker for atherosclerotic risk in obese type 2 diabetic patients than either leptin or adiponectin alone. However, no information is available

C. Koebnick; G. Q. Shaibi; L. A. Kelly; C. K. Roberts; C. Toledo-Corral; J. N. Davis; C. Byrd-Williams; M. J. Weigensberg; M. I. Goran

343

Blockade of the Renin-Angiotensin System Increases Plasma Adiponectin Levels in Type2 Diabetic Patients with Proteinuria  

Microsoft Academic Search

Background\\/Aims: Adiponectin seems to be an important modulator for metabolic and vascular diseases. A case study was designed to measure plasma adiponectin levels and to investigate the effects of angiotensin-converting enzyme inhibitors on adiponectin levels in type-2 diabetic patients with proteinuria. Methods: Forty-nine patients (28 males, 21 females) and 23 healthy volunteers (13 males, 10 females) were included in the

Müjdat Yenicesu; Mahmut Ilker Yilmaz; Kayser Caglar; Alper Sonmez; Tayfun Eyileten; Cengizhan Acikel; Selim Kilic; Necati Bingol; Sezin Bingol; Abdulgaffar Vural

2005-01-01

344

ChAy/Bx, a novel chimeric high-molecular-weight glutenin subunit gene apparently created by homoeologous recombination in Triticum turgidum ssp. dicoccoides.  

PubMed

High-molecular-weight glutenin subunits (HMW-GSs) are of considerable interest, because they play a crucial role in determining dough viscoelastic properties and end-use quality of wheat flour. In this paper, ChAy/Bx, a novel chimeric HMW-GS gene from Triticum turgidum ssp. dicoccoides (AABB, 2n=4x=28) accession D129, was isolated and characterized. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that the electrophoretic mobility of the glutenin subunit encoded by ChAy/Bx was slightly faster than that of 1Dy12. The complete ORF of ChAy/Bx contained 1671bp encoding a deduced polypeptide of 555 amino acid residues (or 534 amino acid residues for the mature protein), making it the smallest HMW-GS gene known from Triticum species. Sequence analysis showed that ChAy/Bx was neither a conventional x-type nor a conventional y-type subunit gene, but a novel chimeric gene. Its first 1305 nt sequence was highly homologous with the corresponding sequence of 1Ay type genes, while its final 366 nt sequence was highly homologous with the corresponding sequence of 1Bx type genes. The mature ChAy/Bx protein consisted of the N-terminus of 1Ay type subunit (the first 414 amino acid residues) and the C-terminus of 1Bx type subunit (the final 120 amino acid residues). Secondary structure prediction showed that ChAy/Bx contained some domains of 1Ay subunit and some domains of 1Bx subunit. The special structure of this HMW glutenin chimera ChAy/Bx subunit might have unique effects on the end-use quality of wheat flour. Here we propose that homoeologous recombination might be a novel pathway for allelic variation or molecular evolution of HMW-GSs. PMID:24012818

Guo, Xiao-Hui; Bi, Zhe-Guang; Wu, Bi-Hua; Wang, Zhen-Zhen; Hu, Ji-Liang; Zheng, You-Liang; Liu, Deng-Cai

2013-09-04

345

Serum adiponectin and transient elastography as non-invasive markers for postoperative biliary atresia  

PubMed Central

Background Biliary atresia (BA) is a progressive inflammatory disorder of the extrahepatic bile ducts leading to the obliteration of bile flow. The purpose of this study was to determine serum adiponectin in BA patients and to investigate the relationship of adiponectin with clinical parameters and liver stiffness scores. Methods Sixty BA patients post Kasai operation and 20 controls were enrolled. The mean age of BA patients and controls was 9.6 ± 0.7 and 10.1 ± 0.7 years, respectively. BA patients were classified into two groups according to their serum total bilirubin (TB) levels (non-jaundice, TB < 2 mg/dl vs. jaundice, TB ? 2 mg/dl) and liver stiffness (insignificant fibrosis, liver stiffness < 7 kPa vs. significant fibrosis, liver stiffness ? 7 kPa). Serum adiponectin levels were analyzed by enzyme-linked immunosorbent assay. Liver stiffness scores were examined by transient elastography (FibroScan). Results BA patients had markedly higher serum adiponectin levels (15.5 ± 1.1 vs. 11.1 ± 1.1 ?g/ml, P = 0.03) and liver stiffness than controls (30.1 ± 3.0 vs. 5.1 ± 0.5 kPa, P < 0.001). Serum adiponectin levels were significantly elevated in BA patients with jaundice compared with those without jaundice (24.4 ± 1.4 vs. 11.0 ± 0.7 ?g/ml, P < 0.001). In addition, BA patients with significant liver fibrosis had remarkably greater serum adiponectin than insignificant fibrosis counterparts (17.7 ± 1.2 vs. 9.4 ± 1.1 ?g/ml, P < 0.001). Subsequent analysis revealed that serum adiponectin was positively correlated with total bilirubin, hyaluronic acid, and liver stiffness (r = 0.58, r = 0.46, and r = 0.60, P < 0.001, respectively). Conclusions Serum adiponectin and liver stiffness values were higher in BA patients compared with normal participants. The elevated serum adiponectin levels also positively correlated with the degree of hepatic dysfunction and liver fibrosis. Accordingly, serum adiponectin and transient elastography could serve as the useful non-invasive biomarkers for monitoring the severity and progression in postoperative BA.

2011-01-01

346

TYPES AND RATES OF SEQUENCE EVOLUTION AT HMW-GLUTENIN LOCUS IN HEXAPLOID WHEAT AND ITS ANCESTRAL GENOMES  

Technology Transfer Automated Retrieval System (TEKTRAN)

The Glu-1 locus, encoding the High Molecular Weight-glutenin protein subunits, controls bread-making quality in hexaploid wheat (Triticum aestivum) and represents a recently evolved region unique to Triticeae genomes. To understand the molecular evolution of this locus region, three orthologous Glu...

347

High fat diet enhances cardiac abnormalities in SHR rats: Protective role of heme oxygenase-adiponectin axis  

PubMed Central

Background High dietary fat intake is a major risk factor for development of cardiovascular and metabolic dysfunction including obesity, cardiomyopathy and hypertension. Methods The present study was designed to examine effect of high fat (HF) diet on cardio-vascular structure and function in spontaneously hypertensive rats (SHR), fed HF diet for 15 weeks, a phenotype designed to mimic metabolic syndrome. Results Development of metabolic syndrome like phenotype was confirmed using parameters, including body weight, total cholesterol and blood pressure levels. High fat diet impaired vascular relaxation by acetylcholine and exacerbated cardiac dysfunction in SHRs as evidenced by lower left ventricular function, and higher coronary resistance (CR) as compared to controls (p < 0.05). The histological examination revealed significant myocardial and peri-vascular fibrosis in hearts from SHRs on HF diet. This cardiac dysfunction was associated with increased levels of inflammatory cytokines, COX-2, NOX-2, TxB2 expression and increase in superoxide (O2-) levels in SHR fed a HF diet (p < 0.05). HO-1 induction via cobalt-protoporphyrin (CoPP,3 mg/kg), in HF fed rats, not only improved cardiac performance parameters, but also prevented myocardial and perivascular fibrosis. These effects of CoPP were accompanied by enhanced levels of cardiac adiponectin levels, pAMPK, peNOS and iNOS expression; otherwise significantly attenuated (p < 0.05) in HF fed SHRs. Prevention of such beneficial effects of CoPP by the concurrent administration of the HO inhibitor stannic mesoporphyrin (SnMP) corroborates the role of HO system in mediating such effects. Conclusion In conclusion, this novel study demonstrates that up-regulation of HO-1 improves cardiac and vascular dysfunction by blunting oxidative stress, COX-2 levels and increasing adiponectin levels in hypertensive rats on HF diet.

2011-01-01

348

Guava leaf extracts alleviate fatty liver via expression of adiponectin receptors in SHRSP.Z-Leprfa/Izm rats  

PubMed Central

Background In recent years, the number of people with metabolic syndrome has continued to rise because of changing eating habits, and accompanying hepatic steatosis patients have also increased. This study examined the effect of guava leaf extract on liver fat accumulation using SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP/ZF), which are a metabolic syndrome model animal. Method Seven-week-old male SHRSP/ZF rats were divided into two groups, a control group and a guava leaf extract (GLE) group. We gave 2 g/kg/day GLE or water by forced administration for 6 weeks. After the experimental period, the rats were sacrificed and organ weight, hepatic lipids, serum aminotransferase and liver pathology were examined. To search for a possible mechanism, we examined the changes of key enzyme and transcriptional factors involved in hepatic fatty acid beta-oxidation. Results The triglyceride content of the liver significantly decreased in the GLE group in comparison with the control group, and decreased fat-drop formation in the liver tissue graft in the GLE group was observed. In addition, the improvement of liver organization impairments with fat accumulation restriction was suggested because blood AST and ALT in the GLE group significantly decreased. Furthermore, it was supposed that the activity of AMPK and PPAR? significantly increased in the GLE group via the increase of adiponectin receptors. These were thought to be associated with the decrease of the triglyceride content in the liver because AMPK and PPAR? in liver tissue control energy metabolism or lipid composition. On the other hand, insulin resistance was suggested to have improved by the fatty liver improvement in GLE. Conclusion Our results indicate that administration of GLE may have preventive effects of hepatic accumulation and ameliorated hepatic insulin resistance by enhancing the adiponectin beta-oxidation system. Guava leaf may be potentially useful for hepatic steatosis without the side effects of long-term treatments.

2012-01-01

349

In Vitro Polymerization of Wheat Glutenin Subunits with Inorganic Oxidizing Agents. I. Comparison of Single-Step and Stepwise Oxidations of High Molecular Weight Glutenin Subunits  

Microsoft Academic Search

Cereal Chem. 77(5):582-588 High molecular weight glutenin subunits (HMW-GS) were isolated from wheat flour and polymerized in vitro at pH 3.0 with different oxidizing agents (KBrO3, KIO3, H2O2). An oxidation protocol with single addition of oxidant (single-step oxidation) was compared with a set-up in which the oxidant was added in multiple steps (stepwise oxidation). Changes in size distribution were evaluated

Wim S. Veraverbeke; Oscar R. Larroque; Frank Békés; Jan A. Delcour

2000-01-01

350

Quantitative Determination of High Molecular Weight Glutenin Subunits of Hard Red Spring Wheat by SDS-PAGE. I. Quantitative Effects of Total Amounts on Breadmaking Quality Characteristics 1  

Microsoft Academic Search

Cereal Chem. 74(6):781-785 Thirteen hard red spring wheat genotypes in which seven genotypes had the same high molecular weight (HMW) glutenin subunits (2*, 7+9, 5+10) were compared for their physical-chemical and breadmaking prop- erties. These samples were categorized into three groups based on their dough mixing and baking performances as follows: the strong dough (SD) group (six genotypes), characterized by

Dong Yin Huang; Khalil Khan

1997-01-01

351

Synergistic and Additive Effects of Three High Molecular Weight Glutenin Subunit Loci. II. Effects on Wheat Dough Functionality and End-Use Quality  

Microsoft Academic Search

Cereal Chem. 79(2):301-307 Understanding the relationship between basic and applied rheological parameters and the contribution of wheat flour protein content and com- position in defining these parameters requires information on the roles of individual flour protein components. The high molecular weight glutenin subunit (HMW-GS) proteins are major contributors to dough strength and stability. This study focused on eight homozygous wheat

H. L. Beasley; S. Uthayakumaran; F. L. Stoddard; S. J. Partridge; L. Daqiq; P. Chong; F. Békés

2002-01-01

352

Drosophila adiponectin receptor in insulin producing cells regulates glucose and lipid metabolism by controlling insulin secretion.  

PubMed

Adipokines secreted from adipose tissue are key regulators of metabolism in animals. Adiponectin, one of the adipokines, modulates pancreatic beta cell function to maintain energy homeostasis. Recently, significant conservation between Drosophila melanogaster and mammalian metabolism has been discovered. Drosophila insulin like peptides (Dilps) regulate energy metabolism similarly to mammalian insulin. However, in Drosophila, the regulatory mechanism of insulin producing cells (IPCs) by adipokine signaling is largely unknown. Here, we describe the discovery of the Drosophila adiponectin receptor and its function in IPCs. Drosophila adiponectin receptor (dAdipoR) has high homology with the human adiponectin receptor 1. The dAdipoR antibody staining revealed that dAdipoR was expressed in IPCs of larval and adult brains. IPC- specific dAdipoR inhibition (Dilp2>dAdipoR-Ri) showed the increased sugar level in the hemolymph and the elevated triglyceride level in whole body. Dilps mRNA levels in the Dilp2>dAdipoR-Ri flies were similar with those of controls. However, in the Dilp2>dAdipoR-Ri flies, Dilp2 protein was accumulated in IPCs, the level of circulating Dilp2 was decreased, and insulin signaling was reduced in the fat body. In ex vivo fly brain culture with the human adiponectin, Dilp2 was secreted from IPCs. These results indicate that adiponectin receptor in insulin producing cells regulates insulin secretion and controls glucose and lipid metabolism in Drosophila melanogaster. This study demonstrates a new adipokine signaling in Drosophila and provides insights for the mammalian adiponectin receptor function in pancreatic beta cells, which could be useful for therapeutic application. PMID:23874700

Kwak, Su-Jin; Hong, Seung-Hyun; Bajracharya, Rijan; Yang, Se-Yeol; Lee, Kyu-Sun; Yu, Kweon

2013-07-12

353

Low Adiponectin Concentration in Pregnancy Predicts Postpartum Insulin Resistance, Beta-cell Dysfunction, and Fasting Glycaemia  

PubMed Central

Aims/Hypothesis The postpartum following gestational diabetes (GDM) is characterized by subtle metabolic defects, including beta-cell dysfunction that is believed to mediate the increased future risk of type 2 diabetes in this patient population. Recently, low circulating levels of adiponectin and increased leptin and C-reactive protein (CRP) have emerged as novel diabetic risk factors, although their relevance to GDM and subsequent diabetes has not been characterized. Thus, we sought to determine whether adiponectin, leptin and CRP in pregnancy relate to the postpartum metabolic defects linking GDM with type 2 diabetes. Methods 487 women underwent metabolic characterization, including oral glucose tolerance test (OGTT), in pregnancy and at 3-months postpartum. Based on the antepartum OGTT, there were 137 women with GDM, 91 with gestational impaired glucose tolerance, and 259 with normal glucose tolerance. Results Adiponectin levels were lowest (p<0.0001) and CRP levels highest (p=0.0008) in women with GDM. Leptin did not differ between the glucose tolerance groups (p=0.4483). Adiponectin (r=0.41,p<0.0001), leptin (r=?0.36,p<0.0001) and CRP (r=?0.30,p<0.0001) in pregnancy were all associated with postpartum insulin sensitivity (ISOGTT). Intriguingly, adiponectin was also related to postpartum beta-cell function (insulinogenic index/HOMA-IR) (r=0.16,p=0.0009). Indeed, on multiple linear regression analyses, adiponectin in pregnancy independently predicted both postpartum insulin sensitivity (t=3.97,p<0.0001) and beta-cell function (t=2.37,p=0.0181), even after adjustment for GDM. Furthermore, adiponectin emerged as a significant negative independent determinant of postpartum fasting glucose (t=?3.01,p=0.0027). Conclusions Hypoadiponectinemia in pregnancy predicts postpartum insulin resistance, beta-cell dysfunction, and fasting glycaemia, and hence may be relevant to the pathophysiology relating GDM with type 2 diabetes.

Retnakaran, R; Qi, Y; Connelly, PW; Sermer, M; Hanley, AJ; Zinman, B

2010-01-01

354

Plasma adiponectin level and sleep structures in children with Prader-Willi syndrome.  

PubMed

Adiponectin, an adipose tissue-derived hormone, has been negatively related to obstructive sleep apnea syndrome. Besides sleep apnea, children with Prader-Willi syndrome (PWS) may have excessive daytime sleepiness and rapid eye movement (REM) sleep abnormality. The aim of this study is to determine whether changes in sleep structures are related to plasma adiponectin levels in PWS. Correlations between adiponectin level and sleep variables were analyzed in 28 children with PWS and 18 controls. Overnight polysomnography was performed. The fasting plasma adiponectin levels were higher in the children with PWS than in the controls (P = 0.0006). In the PWS, Epworth sleepiness scale was significantly higher (P = 0.002); sleep latency (P = 0.003) and REM latency (P = 0.001) were significantly shortened; the apnea-hypopnea index (AHI) was significantly increased (P = 0.0001); and the duration of non-rapid eye movement (NREM) sleep stages 3 and 4 was decreased (P = 0.005). Multiple regression analysis revealed correlations between the adiponectin level and the total sleep time (beta = 0.688, P = 0.009), AHI (beta = 1.274, P = 0.010), REM latency (beta = -0.637, P = 0.021) and the percentage of NREM sleep (beta = -7.648, P = 0.002) in PWS. In children with PWS, higher plasma adiponectin levels were independently associated with several sleep variables, which was not observed in the control group. These results suggest a potential influence of elevated adiponectin level on the sleep structures in PWS. PMID:19912511

Joo, Eun Yeon; Hong, Seung Bong; Sohn, Young Bae; Kwak, Min Jung; Kim, Su Jin; Choi, Young Ok; Kim, Seon Woo; Paik, Kyung-Hoon; Jin, Dong-Kyu

2009-11-11

355

Down-regulation of adiponectin in patients with familial Mediterranean fever during attack-free period.  

PubMed

To evaluate the circulating levels of adipokines (leptin and adiponectin) and ghrelin in patients with familial Mediterranean fever (FMF) and also to assess the relationships between these molecules and disease-related parameters. Forty-eight FMF patients in attack-free period (31 men, [M], 17 women, [F], mean age 35.8 ± 8.6 years, and a mean body mass index [BMI] of 24.7 ± 3.1) and 40 age-, sex-, and BMI-matched healthy controls (24 M, 16 F, mean age 35.5 ± 8.5 years, and a mean BMI of 24.5 ± 2.8) were included in the study. Patients and controls with a history of any other chronic diseases and obese or underweight subjects were excluded. High-sensitive C-reactive protein (hs-CRP), leptin, adiponectin, and total ghrelin concentrations were studied. Age, sex, BMI, waist circumference, and smoking status were similar between FMF patients and controls (P > 0.05). Adipose tissue-derived molecules including leptin, and adiponectin were lower than healthy controls but only adiponectin levels reached the statistically significance (16.7 ± 8.9 ng/ml vs. 27.7 ± 15.9 ng/ml, P < 0.001) and leptin concentrations just missed significance (25.2 ± 16.2 ng/ml vs. 34.9 ± 27.2 ng/ml, P = 0.051). Ghrelin concentrations were not different between the groups. Adiponectin levels were significantly and negatively correlated with hs-CRP (P < 0.05, r = -0.24). The results of this study suggest that low-grade chronic inflammation during attack-free period in FMF patients may suppress adiponectin production or low levels of adiponectin might contribute to subclinical inflammation in these patients. PMID:21877244

Gerdan, Vedat; Sari, Ismail; Kozac?, Didem; Önen, Fatos; Yüksel, Feride; Soysal, Ozgül; Solmaz, Dilek; Günay, Necati; Akkoc, Nurullah; Akar, Servet

2011-08-30

356

Serum Adiponectin and Type 2 Diabetes: A 6-Year Follow-Up Cohort Study  

PubMed Central

Background Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women. Methods A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used. Results Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders. Conclusion A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.

Ahn, Chul Woo; Park, Jong Suk; Park, Chang Gyu; Kim, Hyon-Suk; Lee, Sang-Hak; Park, Sungha; Lee, Myoungsook; Lee, Chang Beom; Park, Hye Soon; Kimm, Heejin; Choi, Sung Hee; Sung, Jidong; Oh, Seungjoon; Joung, Hyojee; Kim, Sung Rae; Youn, Ho-Joong; Kim, Sun Mi; Lee, Hong Soo; Mok, Yejin; Choi, Eunmi; Yun, Young Duk; Baek, Soo-Jin; Jo, Jaeseong; Huh, Kap Bum

2013-01-01

357

Obesity, adiponectin and inflammation as predictors of new-onset diabetes mellitus after kidney transplantation.  

PubMed

The high incidence of new-onset diabetes mellitus after transplantation (NODAT) suggests the need to find new factors to explain the pathogenesis. Our objectives were (1) to confirm that low levels of pre-transplant adiponectin are an independent risk factor for the development of NODAT in a larger transplanted population; (2) to analyze whether adiponectin is a better predictor of NODAT than other inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and pregnancy-associated plasma protein A (PAPP-A)) and (3) to assess the relationship between obesity, inflammatory markers and NODAT. One hundred ninety-nine non-diabetic patients (128 men; age: 53 +/- 11 years; body mass index (BMI) 24.98 +/- 3.76 kg/m2) were included. Pre-transplant plasma glucose, insulin, adiponectin, CRP, TNF-alpha, IL-6 and PAPP-A were measured. Forty-five patients developed NODAT. Patients with NODAT had a greater BMI (p = 0.005). Adiponectin was lower (p < 0.001) and CRP higher (p = 0.032) in patients with NODAT. Multivariate logistic regression and Cox analysis showed that the calcineurin inhibitor used, pre-transplant BMI and adiponectin were predictors of NODAT. ROC analysis showed that an adiponectin concentration of 11.4 microg/mL had a significant negative prediction for NODAT risk (sensitivity: 81% and specificity: 70%). Of the inflammatory markers studied, adiponectin proved to be an independent predictor of NODAT. PMID:17229078

Bayés, B; Granada, M L; Pastor, M C; Lauzurica, R; Salinas, I; Sanmartí, A; Espinal, A; Serra, A; Navarro, M; Bonal, J; Romero, R

2007-01-04

358

Oligomeric adiponectin forms and their complexes in the blood of healthy donors and patients with type 2 diabetes mellitus.  

PubMed

Adiponectin (Adn) is a protein that circulates in the blood in several oligomeric forms, namely low-, medium-, and high-molecular-weight forms. Adn may serve as a risk factor for type 2 diabetes mellitus (T2DM). The aims of this work were (1) to produce monoclonal antibodies (MAbs) specific to different Adn oligomeric forms, (2) to design immunoassays suitable for measuring the Adn forms present in human blood, and (3) to investigate the changes in Adn forms that occur in patients with T2DM. Gel filtration, fluoroimmunoassays, and Western blotting were utilized as major techniques in this study. MAbs recognizing various oligomeric forms of Adn were obtained. Complexes between Adn and complement component C1q and between the low molecular weight form of Adn and albumin were described in human blood. A decrease in the total Adn and Adn-albumin complex levels in the blood of patients with T2DM and no difference in the levels of the Adn-C1q complex in comparison with healthy volunteers were demonstrated. An Adn94-Adn63 fluoroimmunoassay was selected as the technique that most accurately measured the mass ratio of Adn oligomers in blood samples, and an Adn214-Adn27 assay that measured the low-molecular-weight form of Adn only. PMID:23537302

Kogan, Alexander E; Filatov, Vladimir L; Kolosova, Olga V; Katrukha, Ivan A; Mironova, Ekaterina V; Zhuravleva, Natalya S; Nagibin, Oleg A; Kara, Andrei N; Bereznikova, Anastasiya V; Katrukha, Alexey G

2013-01-01

359

Genetic variation in the adiponectin receptor 2 (ADIPOR2) gene is associated with coronary artery disease and increased ADIPOR2 expression in peripheral monocytes  

Microsoft Academic Search

BACKGROUND: Adiponectin is an adipose tissue secreted protein known for its insulin sensitising and anti-atherogenic actions. To this date two adiponectin receptors have been discovered, adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). The aim of this study was to investigate the association of ADIPOR2 gene variations with coronary artery disease (CAD). METHODS: Eight common single nucleotide polymorphisms (SNPs)

Iosif Halvatsiotis; Panayoula C Tsiotra; Ignatios Ikonomidis; Anastasios Kollias; Panagiota Mitrou; Eirini Maratou; Eleni Boutati; John Lekakis; George Dimitriadis; Theofanis Economopoulos; Dimitrios T Kremastinos; Sotirios A Raptis

2010-01-01

360

Adiponectin receptor genes: mutation screening in syndromes of insulin resistance and association studies for type 2 diabetes and metabolic traits in UK populations  

Microsoft Academic Search

Aims\\/hypothesis  Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. Several reports suggest that genetic\\u000a variants in the adiponectin gene are associated with circulating levels of adiponectin, insulin sensitivity and type 2 diabetes\\u000a risk. Recently two receptors for adiponectin have been cloned. Genetic studies have yielded conflicting results on the role\\u000a of these genes and type 2 diabetes predisposition. In this

S. C. Collins; J. Luan; A. J. Thompson; A. Daly; R. K. Semple; S. O’Rahilly; N. J. Wareham; I. Barroso

2007-01-01

361

Regulation of adiponectin gene expression in adipose tissue by thyroid hormones.  

PubMed

Available experimental data suggest that adiponectin and thyroid hormones have biological interaction in vivo. However, the effects of thyroid hormones on adipose adiponectin gene expression in thyroid dysfunction are unclear. We induced hyper- (HYPER) and hypothyroidism (HYPO) by daily administration of a 12 mg/l of levothyroxine and 250 mg/l of methimazole in drinking water of rats, respectively, for 42 days. The white adipose tissues and serum sample were taken on days 15, 28, 42 and also 2 weeks after treatment cessation. Analysis of adiponectin gene expression was performed by real-time PCR and 2(-??ct) method. The levels of adipose tissue adiponectin mRNA in the HYPO rats were decreased during the 6-week treatment when compared to control rats (<0.05) and were increased significantly 2 weeks after HYPO cessation (P?adiponectin gene expression occurred in parallel with a decrease in T3, T4, fT3 and fT4 concentrations (P?adiponectin gene expression was increased in HYPER rats during the 6-week treatment in parallel with an increase the thyroid hormones concentrations (P?Adiponectin gene expression levels showed significant negative correlations with concentrations of LDL (HYPO; r?=?-0.806, P?=?0.001 and HYPER; r?=?-0.749, P?=?0.002), triglyceride (HYPO; r?=?-0.825, P?=?0.001 and HYPER; r?=?-0.824, P?=?0.001) and significant positive correlations with concentrations of glucose (HYPO; r?=?0.674, P?=?0.004 and HYPER; r?=?0.866, P?=?0.001) and HDL (HYPO; r?=?0.755, P?=?0.001 and HYPER; r?=?0.839, P?=?0.001). The current study provides evidence that adiponectin gene expression in adipose tissue is regulated by thyroid hormones at the translation level and that lipid and carbohydrate disturbances in a patient with thyroid dysfunction may be, in part, due to adiponectin gene expression changes. PMID:22127636

Seifi, Samira; Tabandeh, Mohammad Reza; Nazifi, Saed; Saeb, Mehdi; Shirian, Sadegh; Sarkoohi, Parisa

2011-11-30

362

Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages  

Microsoft Academic Search

These results suggest that adiponectin predominantly inhibits proliferation of my- elomonocytic lineage cells. At least one mechanism of the growth inhibition is induction of apoptosis because treat- ment of acute myelomonocytic leukemia lines with adiponectin induced the appear- ance of subdiploid peaks and oligonucleo- somal DNA fragmentation. Aside from inhibiting growth of myelomonocytic pro- genitors, adiponectin suppressed mature macrophage functions.

Takafumi Yokota; Kenji Oritani; Isao Takahashi; Jun Ishikawa; Akifumi Matsuyama; Noriyuki Ouchi; Shinji Kihara; Tohru Funahashi; Andrea J. Tenner; Yoshiaki Tomiyama; Yuji Matsuzawa

2000-01-01

363

Regulation of adiponectin secretion by soy isoflavones has implication for endocrine function of the testis.  

PubMed

Testicular Leydig cells are the predominant source of the male sex steroid hormone testosterone (T), which is required to maintain male fertility. There is now growing evidence that environmental stressors, including chemicals present in food, air and water, may affect energy balance. A relationship between energy balance and reproductive capacity has been proposed for a long time. In the present study, developmental exposures of male rats to soy isoflavones in the maternal diet from gestational day 12 to day 21 post-partum enhanced adiponectin expression in adipose tissue and increased serum adiponectin concentrations in adulthood. However, exposure to soy isoflavones caused a decrease in T production and expression of adiponectin and its receptor (adipoR2) in Leydig cells. In separate experiments, incubation of Leydig cells with recombinant adiponectin in the absence of isoflavones caused a decrease in T biosynthesis associated with diminished expression of the cholesterol transporter steroidogenic acute regulatory protein (StAR). Thus, chemical-induced alterations in serum adiponectin concentrations have implication for steroid hormone secretion. The results also imply that changes in adipose tissue metabolism occasioned by exposure to dietary estrogens, and perhaps other estrogenic agents, possibly contribute to deficiencies in reproductive capacity attributed to these compounds. PMID:22155228

Pfaehler, Andrew; Nanjappa, Manjunatha K; Coleman, Elaine S; Mansour, Mahmoud; Wanders, Desiree; Plaisance, Eric P; Judd, Robert L; Akingbemi, Benson T

2011-12-03

364

Vanadyl acetylacetonate upregulates PPAR? and adiponectin expression in differentiated rat adipocytes.  

PubMed

Vanadium compounds are promising agents in the therapeutic treatment of diabetes mellitus, but their mechanism of action has not been fully elucidated. The current work investigated the effects of vanadyl acetylacetonate, VO(acac)2, on peroxisome-proliferator-activated receptor ? (PPAR?) and adiponectin, which are important targets of antidiabetic drugs. The experimental results revealed that vanadyl complexes increased the expression and multimerization of adiponectin in differentiated rat adipocytes. VO(acac)2 caused activation of p38 mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) and elevation of PPAR? levels. The specific inhibitors SB203580 (p38 MAPK inhibitor) and T0070907 (PPAR? inhibitor) decreased the expression of adiponectin; however, compound C (AMPK inhibitor) did not significantly reduce the expression of adiponectin. In addition, vanadyl complexes induced protein-protein interaction between PPAR? and a vanadium-binding chaperone, heat shock protein 60 kDa. Overall, our results suggest that vanadyl complexes may upregulate PPAR? by suppressing PPAR? degradation, and thus stimulate adiponectin expression and multimerization. The present work has provided new insights into the mechanism of the antidiabetic actions of vanadium compounds. PMID:23737070

Wu, Yaling; Huang, Meiling; Zhao, Pan; Yang, Xiaoda

2013-06-05

365

Subetta Treatment Increases Adiponectin Secretion by Mature Human Adipocytes In Vitro  

PubMed Central

Purpose. To investigate the mechanism of action in peripheral tissues of novel complex drug containing release-active dilutions of antibodies to the beta subunit of the insulin receptor and antibodies to endothelial nitric oxide synthase (Subetta), which has shown efficacy in animal models of diabetes. Methods. Human mature adipocytes were incubated either with Subetta, with one of negative controls (placebo or vehicle), with one of nonspecific controls (release-active dilutions of antibodies to cannabinoid receptor type I or release-active dilutions of rabbit nonimmune serum), or with dimethyl sulfoxide (DMSO) at 37°C in a humidified incubator at 5% CO2 for three days. Rosiglitazone was used as reference drug. Secretion of adiponectin was measured by quantitative enzyme-linked immunosorbent assay (ELISA). Results. Only Subetta significantly stimulates adiponectin production by mature human adipocytes. Nonspecific controls did not significantly affect adiponectin secretion, resulting in adiponectin levels comparable to background values of the negative controls and DMSO. Conclusion. Increasing adiponectin production in absence of insulin by Subetta probably via modulating effect on the beta subunit of the insulin receptor might serve as one of the mechanisms of the antidiabetic effect of this drug. These in vitro results give first insight on possible mechanism of action of Subetta and serve as a background for further studies.

Nicoll, Jim; Gorbunov, Evgeniy A.; Tarasov, Sergey A.; Epstein, Oleg I.

2013-01-01

366

Bisphenol A: Perinatal exposure and body weight  

PubMed Central

Bisphenol A (BPA) is a component of polycarbonate and other plastics including resins that line food and beverage containers. BPA is known to leach from products in contact with food and drink, and is therefore thought to be routinely ingested. In a recent cross sectional study, BPA was detected in urine samples from 92.6% of the US population examined. The potential for BPA to influence body weight is suggested by in vitro studies demonstrating effects of BPA on adipocyte differentiation, lipid accumulation, glucose transport and adiponectin secretion. Data from in vivo studies have revealed dose-dependent and sex dependent effects on body weight in rodents exposed perinatally to BPA. The mechanisms through which perinatal BPA exposure acts to exert persistent effects on body weight and adiposity remain to be determined. Possible targets of BPA action are discussed.

Rubin, Beverly S.; Soto, Ana M.

2010-01-01

367

Prospective investigation of metabolic characteristics in relation to weight gain in older adults: the Hoorn Study.  

PubMed

The objective of this investigation was to determine the relation between baseline glucose, insulin, adiponectin, and leptin levels and subsequent 6-year weight and waist change in older men and women without diabetes in a prospective cohort study. Participants were 1,198 Dutch men and women without diabetes who were aged 50-77 years when baseline metabolic and anthropometric measurements were evaluated (1989-1991). Approximately 6 years later, body weight and waist circumference were re-measured at a follow-up examination (1996-1998). Metabolic variables (fasting plasma glucose, 2-h postchallenge plasma glucose, homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and leptin) were evaluated as predictors of changes in weight and waist circumference. Postchallenge plasma glucose (mmol/l) significantly predicted less gain in both weight and waist circumference (beta = -0.28 kg, s.e. = 0.11; beta = -0.31 cm, s.e. = 0.14, respectively) during follow-up. Leptin (microg/l) significantly predicted greater increases in weight (beta = 0.29 kg, s.e. = 0.07) and waist (beta = 0.16 cm, s.e. = 0.08) among men and in waist among women (beta = 0.06 cm, s.e. = 0.02). Fasting plasma glucose (mmol/l) predicted an increase in waist among women (beta = 1.59 cm, s.e. = 0.63), but not in men (beta = -0.74 cm, s.e. = 0.55). Adiponectin and insulin did not predict weight or waist change. The authors conclude that lower postchallenge plasma glucose and higher fasting leptin levels significantly predicted long-term increases in weight and waist circumference. In contrast, measures of insulin resistance and adiponectin were not associated with weight change in this cohort of older persons without diabetes. PMID:19197256

Wedick, Nicole M; Snijder, Marieke B; Dekker, Jacqueline M; Heine, Robert J; Stehouwer, Coen D A; Nijpels, Giel; van Dam, Rob M

2009-02-05