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1

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. PMID:23497474

2013-01-01

2

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. PMID:22431719

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

2012-01-01

3

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

4

Urinary excretion of high molecular weight adiponectin is an independent predictor of decline of renal function in type 2 diabetes.  

PubMed

Adiponectin and urinary adiponectin excretions have been ascribed a function in glomerular physiology and seem to indicate vascular disease in diabetes. The aim of this study was to compare the urinary excretion of albumin and adiponectin as predictors for decline of renal function in patients with type 2 diabetes and early kidney disease. Over 141 patients were screened for renal function (estimated GFR, ml/min*1.73 m(2)), albumin excretion rate (AER, mg/24 h), total as well as high molecular weight (HMW) urinary adiponectin excretion (ng/mol u-creatinine). AER and adiponectin excretion were studied as predictors of renal function after 1 year. After 1 year, 36 patients were in the upper quartile of eGFR decline and defined as progressors (delta eGFR = - 12.3 ± 6.3) while the remaining 105 patients were defined as non-progressors (delta eGFR = 1.4 ± 6.0). At baseline, HMW-adiponectin excretion was positively correlated with HbA1c (p < 0.001) and negatively with eGFR (p < 0.001), but not with AER (p = 0.14). Progressors showed increased urinary HMW-adiponectin at baseline (158[IQR41/479] vs. 65[24/168] ng/mol; p < 0.01), while total adiponectin (182[101/1534] vs. 345[118/1361] ng/mol) and AER (48[23/109] vs. 46[25/108] mg/24 h) excretion showed no differences between the groups. Multivariate logistic regression showed that HMW-adiponectin excretion was an independent predictor of renal progression in all patients (OR 1.86 [95 % CI 1.34-2.59]; p < 0.01), especially in those (n = 45) with normal AER at baseline (OR 2.16 [95 % CI 1.1-4.56]; p < 0.05). Urinary HMW-adiponectin but not AER improved the prediction of progressors in ROC analysis (AUC 0.72 [95 % CI 0.63-0.81] vs. 0.80 [95 % CI 0.71-0.90], p < 0.05). In conclusion, urinary HMW-adiponectin excretion may identify diabetes patients at increased risk for progression of kidney disease. PMID:24366425

Kopf, Stefan; Oikonomou, Dimitrios; von Eynatten, Maximilian; Kieser, Meinhard; Zdunek, Dietmar; Hess, Gregor; Morcos, Michael; Forsblom, Carol; Bierhaus, Angelika; Groop, Per-Henrik; Nawroth, Peter P; Humpert, Per M

2014-01-01

5

Independent associations of total and high molecular weight adiponectin with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with rheumatoid arthritis: a cross-sectional study  

PubMed Central

Introduction Whether adiponectin levels associate with atherogenesis in RA is uncertain. We examined the independent relationships of total and high molecular weight (HMW) adiponectin concentrations with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with RA. Methods We determined total and HMW adiponectin concentrations and those of endothelial activation molecules including soluble E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), in 210 (119 black and 91 white) RA patients. Associations were determined in potential confounder and mediator adjusted mixed regression models. Results Total and HMW adiponectin concentrations related similarly to metabolic risk factors and endothelial activation. In all patients, total and HMW adiponectin concentrations associated paradoxically with high systolic, diastolic and mean blood pressure (partial R = 0.155 to 0.241, P ?0.03). Ethnic origin did not impact on these relationships (interaction P ?0.09). Total and HMW adiponectin concentrations associated with those of glucose in white and black patients respectively (partial R = -0.304, P = 0.006 and -0.246, P = 0.01). In black but not white participants, total and HMW adiponectin concentrations also related favorably to lipid profiles (partial R = 0.292 to 0.360, P ?0.003 for HDL cholesterol concentrations, -0.269 to -0.299, P ?0.006 for triglyceride concentrations and -0.302 to -0.390, P ?0.002 for total-HDL cholesterol ratio) and the number of metabolic risk factors (partial R = -0.210 to -0.238, P ?0.03). In white but not black patients, total and HMW adiponectin concentrations associated paradoxically with overall endothelial activation as estimated by a standard z-score of endothelial activation molecule concentrations (partial R = 0.262, P = 0.01 and 0.252, P = 0.02); in the respective models, the extent of effect of total and HMW adiponectin concentrations on endothelial activation was larger in white compared to black participants (standardized ? (SE) = 0.260 (0.107) versus -0.106 (0.107), P = 0.01 and 0.260 (0.120) versus -0.100 (0.111), P = 0.02). The HMW-total adiponectin ratio related inconsistently to metabolic risk factors and not to endothelial activation. Conclusion In this study, total and HMW adiponectin concentrations associated with increased blood pressure parameters, and in white patients additionally with endothelial activation. The potential mechanism(s) underlying these paradoxical relationships between adiponectin concentrations and cardiovascular risk in RA merit further investigation. PMID:24286214

2013-01-01

6

Unique Profile of Chicken Adiponectin, a Predominantly Heavy Molecular Weight Multimer,  

E-print Network

. Immunoprecipitation and elution under neutral pH preserved the HMW adiponectin multimer, whereasbriefexposuretoacidicp, treatment of diabetic human subjects with insulin-sensitizing thiazolidinedione drugs increased the blood in humans. The objectives of the present study were to characterize adiponectin protein and quantify plasma

Ramachandran, Ramesh

7

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. PMID:21122061

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

2010-01-01

8

Adiponectin self-regulates its expression and multimerization in adipose tissue: an autocrine/paracrine mechanism?  

PubMed

Adiponectin, a 30-kDa peptide hormone discovered in the mid 1990s, is secreted abundantly and exclusively by adipose tissue. Adiponectin exists in three major forms: a low molecular weight (LMW) trimer, a medium molecular weight (MMW) hexamer, and a high molecular weight (HMW) 18-36 oligomer. The HMW oligomer has the most potent insulin-sensitizing activity therefore impaired adiponectin multimerization may lead to impaired glycemic control. Decreased ratio of HMW/total adiponectin has been observed in patients with obesity, type-2 diabetes mellitus, cardiovascular diseases and insulin resistance-related metabolic syndrome. Previous studies have indicated that berberine or aminoimidazole carboxamide ribonucleotide (AICAR)-induced activation of AMP-activated protein kinase (AMPK) suppresses the expression of adiponectin but promotes adiponectin multimerization in adipocytes. Since adiponectin activates AMPK through adiponectin receptors (AdipoRs) in the membranes of adipocytes, we speculate that adiponectin self-regulates its expression and multimerization in adipose tissue. The hypothesis suggests a potential drug target for treating insulin resistance and provides new interpretation of several clinical observations. In addition, we propose a rapid method for one-step detection of the distribution of adiponectin oligomers in approximately 30 min, based on the open sandwich immunoassay and fluorescence resonance energy transfer technology. With the development of this new method, the ratio of HMW/total adiponectin may be applied in clinical diagnosis as a novel biomarker for insulin resistance and metabolic disorders. PMID:22014406

Lin, Huan; Li, Zhen

2012-01-01

9

Extracellular conversion of adiponectin hexamers into trimers  

PubMed Central

Adiponectin is an adipocyte-secreted hormone that exists as trimers, hexamers and larger species collectively referred to as HMW (high-molecular-weight) adiponectin. Whether hexamers or HMW adiponectin serve as precursors for trimers outside the circulation is currently unknown. Here, we demonstrate that adiponectin trimers can be generated from larger oligomers secreted from primary rat adipose cells or differentiated 3T3-L1 adipocytes. Purified hexameric, but not HMW, adiponectin converted into trimers in conditioned media separated from 3T3-L1 adipocytes or, more efficiently, when enclosed in the dialysis membrane in the presence of adipocytes. Several lines of evidence indicate that the conversion is mediated by an extracellular redox system. First, N-terminal epitope-tagged hexamers converted into trimers without proteolytic removal of the tag. Secondly, appearance of trimers was associated with conversion of disulfide-bonded dimers into monomers. Thirdly, thiol-reactive agents inhibited conversion into trimers. Consistent with a redox-based mechanism, purified hexamers reductively converted into trimers in defined glutathione redox buffer with reduction potential typically found in the extracellular environment while the HMW adiponectin remained stable. In addition, conversion of hexamers into trimers was enhanced by NADPH, but not by NADP+. Collectively, these data strongly suggest the presence of an extracellular redox system capable of converting adiponectin oligomers. PMID:22973892

Kim, Jeong-a; Nuñez, Martha; Briggs, David B.; Laskowski, Bethany L.; Chhun, Jimmy J.; Eleid, Joseph K.; Quon, Michael J.; Tsao, Tsu-Shuen

2012-01-01

10

Plasma adiponectin complexes have distinct biochemical characteristics.  

PubMed

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. PMID:18202126

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

2008-05-01

11

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. PMID:24052897

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

2013-01-01

12

Adiponectin Changes in Relation to the Macronutrient Composition of a Weight-Loss Diet  

Microsoft Academic Search

Adiponectin is an adipose-derived protein with beneficial metabolic effects. Low adiponectin is associated with obesity and related diseases. Significant weight loss increases adiponectin, reducing disease risk. This study compared the effects of two weight-loss diets with different macronutrient compositions on adiponectin. Eighty-one obese women in two cohorts were randomized to a low-fat (LF) or a low-carbohydrate (LC) diet. All subjects

Suzanne S. Summer; Bonnie J. Brehm; Stephen C. Benoit; David A. D'Alessio

2011-01-01

13

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. PMID:22916229

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

2012-01-01

14

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

15

Promotion of adiponectin multimerization by emodin: a novel AMPK activator with PPAR?-agonist activity.  

PubMed

Adiponectin is an important insulin-sensitizing adipokine with multiple beneficial effects on obesity-associated medical complications. It is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). Each oligomeric form of adiponectin exerts non-overlapping biological functions, with the HMW oligomer possessing the most potent insulin-sensitizing activity. In this study, we reported that emodin, a natural product and active ingredient of various Chinese herbs, activates AMPK in both 3T3-L1 adipocytes and 293T cells. Activation of AMPK by emodin promotes the assembly of HMW adiponectin and increases the ratio of HMW adiponectin to total adiponectin in 3T1-L1 adipocytes. Emodin might activate AMPK by an indirect mechanism similar to berberine. We also found that emodin activates PPAR? and promotes differentiation and adiponectin expression during differentiation of 3T3-L1 preadipocytes. Therefore, emodin is a novel AMPK activator with PPAR?-agonist activity. Our results demonstrate that the effects of emodin on adiponectin expression and multimerization are the ultimate effects resulting from both AMPK activation and PPAR? activation. The dual-activity makes emodin or the derivatives potential drug candidates for the treatment of type 2 diabetes and other obesity-related metabolic diseases. PMID:22730200

Chen, Zhifen; Zhang, Lu; Yi, Junyang; Yang, Zhuanbo; Zhang, Zhijie; Li, Zhen

2012-11-01

16

Phase variation and host immunity against high molecular weight (HMW) adhesins shape population dynamics of nontypeable Haemophilus influenzae within human hosts.  

PubMed

Nontypeable Haemophilus influenzae (NTHi) is a bacterium that resides within the human pharynx. Because NTHi is human-restricted, its long-term survival is dependent upon its ability to successfully colonize new hosts. Adherence to host epithelium, mediated by bacterial adhesins, is one of the first steps in NTHi colonization. NTHi express several adhesins, including the high molecular weight (HMW) adhesins that mediate attachment to the respiratory epithelium where they interact with the host immune system to elicit a strong humoral response. hmwA, which encodes the HMW adhesin, undergoes phase variation mediated by 7-base pair tandem repeats located within its promoter region. Repeat number affects both hmwA transcription and HMW-adhesin production such that as the number of repeats increases, adhesin production decreases. Cells expressing large amounts of HMW adhesins may be critical for the establishment and maintenance of NTHi colonization, but they might also incur greater fitness costs when faced with an adhesin-specific antibody-mediated immune response. We hypothesized that the occurrence of large deletion events within the hmwA repeat region allows NTHi cells to maintain adherence in the presence of antibody-mediated immunity. To study this, we developed a mathematical model, incorporating hmwA phase variation and antibody-mediated immunity, to explore the trade-off between bacterial adherence and immune evasion. The model predicts that antibody levels and avidity, catastrophic loss rates, and population carrying capacity all significantly affected numbers of adherent NTHi cells within a host. These results suggest that the occurrence of large, yet rare, deletion events allows for stable maintenance of a small population of adherent cells in spite of HMW adhesin specific antibody-mediated immunity. These adherent subpopulations may be important for sustaining colonization and/or maintaining transmission. PMID:24747580

Davis, Gregg S; Marino, Simeone; Marrs, Carl F; Gilsdorf, Janet R; Dawid, Suzanne; Kirschner, Denise E

2014-08-21

17

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. PMID:24065958

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

2013-01-01

18

THE ASSOCIATION OF SNP276G>T AT ADIPONECTIN GENE WITH CIRCULATING ADIPONECTIN AND INSULIN RESISTANCE IN RESPONSE TO MILD WEIGHT LOSS  

Technology Transfer Automated Retrieval System (TEKTRAN)

The purpose of this study was to determine whether common single nucleotide polymorphisms (SNPs) at the adiponectin (ADIPOQ) locus influence changes in circulating adiponectin and the features of insulin resistance in response to a weight loss intervention. 294 nondiabetic/overweight-obese Koreans ...

19

Essential roles of insulin, AMPK signaling and lysyl and prolyl hydroxylases in the biosynthesis and multimerization of adiponectin.  

PubMed

Post-translational modifications (PTMs) of the adiponectin molecule are essential for its full bioactivity, and defects in PTMs leading to its defective production and multimerization have been linked to the mechanisms of insulin resistance, obesity, and type-2 diabetes. Here we observed that, in differentiated 3T3-L1 adipocytes, decreased insulin signaling caused by blocking of insulin receptors (InsR) with an anti-InsR blocking antibody, increased rates of adiponectin secretion, whereas concomitant elevations in insulin levels counteracted this effect. Adenosine monophosphate-activated protein kinase (AMPK) signaling regulated adiponectin production by modulating the expression of adiponectin receptors, the secretion of adiponectin, and eventually the expression of adiponectin itself. We found that lysyl hydroxylases (LHs) and prolyl hydroxylases (PHs) were expressed in white-adipose tissue of ob/ob mice, wherein LH3 levels were increased compared with controls. In differentiated 3T3-L1 adipocytes, both non-specific inhibition of LHs and PHs by dipyridyl, and specific inhibition of LHs by minoxidil and of P4H with ethyl-3,4-dihydroxybenzoate, caused significant suppression of adiponectin production, more particularly of the higher-order isoforms. Transient gene knock-down of LH3 (Plod3) caused a suppressive effect, especially on the high molecular-weight (HMW) isoforms. These data indicate that PHs and LHs are both required for physiological adiponectin production and in particular are essential for the formation/secretion of the HMW isoforms. PMID:25240468

Zhang, Lin; Li, Ming-Ming; Corcoran, Marie; Zhang, Shaoping; Cooper, Garth J S

2015-01-01

20

Obesity and sex influence insulin resistance and total and multimer adiponectin levels in adult neutered domestic shorthair client-owned cats.  

PubMed

In this study, we estimated insulin sensitivity and determined plasma concentrations of total-, low-molecular-weight (LMW), and high-molecular-weight (HMW) adiponectin and leptin in 72 domestic shorthair, neutered, client-owned cats. Glucose tolerance was assessed with an intravenous glucose tolerance test and body fat percentage (BF%) was measured with dual-energy x-ray absorptiometry. Total adiponectin was measured with 2 different ELISAs. Low-molecular-weight and HMW adiponectin plasma concentrations were determined by Western blot analysis after sucrose-gradient velocity centrifugation, and the adiponectin multimer ratio [SA = HMW/(HMW + LMW)] was calculated. Differences in glucose tolerance, leptin, total adiponectin, and multimer ratio among lean (BF% <35; n = 26), overweight (35 45; n = 18) cats as well as between male (n = 34) and female (n = 38) neutered cats were evaluated by linear regression and 2-way ANOVA. Sex and age were included as covariates for analysis of BF%, whereas BF%, fat mass, and lean body mass were covariates for analysis of sex differences. Increased BF% was negatively correlated with multimer ratio (SA, r = -45; P < 0.002), whereas no differences were found in total adiponectin concentrations among BF% groups (P > 0.01). Male cats had indices of decreased insulin tolerance and significantly lower total adiponectin concentrations than did female cats (mean ± SEM, 3.7 ± 0.4 vs 5.4 ± 0.5 ?g/mL; P < 0.02). Altered SAs could contribute to an obesity-associated decreasing glucose tolerance in cats, and low total adiponectin concentrations may relate to increased risk of diabetes mellitus in neutered male cats. PMID:24373250

Bjornvad, C R; Rand, J S; Tan, H Y; Jensen, K S; Rose, F J; Armstrong, P J; Whitehead, J P

2014-04-01

21

Adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer  

Microsoft Academic Search

The aim of the present study was to examine the relationship between adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer (NSCLC). Measurement of anthropometry, acute phase proteins, interleukin-6, leptin (total and free) and adiponectin were carried out on healthy subjects (n=13) and non-small cell lung cancer patients with weight loss (n=20). The groups were

Nigel B Jamieson; Duncan J. F Brown; A Michael Wallace; Donald C McMillan

2004-01-01

22

Abdominal obesity and serum adiponectin complexes among population-based elementary school children in Japan: a cross-sectional study  

PubMed Central

Background There are a limited number of studies regarding the association between abdominal obesity and serum adiponectin complexes (high, medium, and low molecular weight adiponectins) among population-based elementary school children, especially in Japan, where blood collection is not usually performed during annual health examinations of school children. The aim of the present study was to investigate the relationship between abdominal obesity and serum adiponectin complexes among population-based elementary school children in Japan. Methods Subjects were all the fourth-grade school children (9 or 10 years of age) in the town of Ina during 2005–2008 (N?=?1675). The height, weight, percent body fat, and waist circumference (WC) of each subject were measured. Blood samples were drawn from subjects to measure adiponectin isoform values. Childhood abdominal obesity was defined as “a waist-to-height ratio greater than or equal to 0.5” or “a WC greater than or equal to 75 cm”. The Wilcoxon rank-sum test and the logistic regression model were used to analyze the association between abdominal obesity and each adiponectin isoform value. Results Data from 1654 subjects (846 boys and 808 girls) were analyzed. Adiponectin complexes were lower in the abdominal obesity group than in the non-abdominal obesity group regardless of sex. Abdominal obesity significantly increased the odds ratio (OR) for each adiponectin isoform level less than or equal to the median value in boys; the OR (95% confidence interval [CI]) was 2.50 (1.59-3.92) for high molecular weight adiponectin (HMW-adn), 2.47 (1.57-3.88) for medium molecular weight adiponectin (MMW-adn), and 1.75 (1.13-2.70) for low molecular weight adiponectin (LMW-adn). In girls, the OR (95% CI) was 1.95 (1.18-3.21) for HMW-adn, 1.40 (0.86-2.28) for MMW-adn, and 1.06 (0.65-1.70) for LMW-adn. Conclusions Abdominal obesity was associated with lower adiponectin complexes and the influence of abdominal obesity varied by adiponectin isoform. Furthermore, the impact of abdominal obesity was larger in boys than in girls. The present study results suggest that prevention of abdominal obesity could contribute to the prevention of lower adiponectin levels, especially in boys. PMID:24670108

2014-01-01

23

Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels  

PubMed Central

Background Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes, and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. Methods Overweight/obese postmenopausal women (n=439) were randomized as follows: 1) a reduced calorie, weight loss diet (diet; N=118); 2) moderate-to-vigorous intensity aerobic exercise (exercise; N=117); 3) a combination of a reduced calorie, weight loss diet and moderate-to-vigorous intensity aerobic exercise (diet+exercise; N=117); or 4) control (N=87). The reduced calorie diet had a 10% weight loss goal. The exercise intervention consisted of 45 minutes of moderate-to-vigorous aerobic activity 5 days/week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay. Results Adiponectin increased by 9.5 % in the diet group and 6.6 % in the diet+exercise group (both p?0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet+exercise, ?40.1%, p<0.0001; diet, ?27.1%, p<0.0001; exercise, ?12.7%, p=0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, p-trend=0.0002; diet+exercise, p-trend=0.0005) and directly associated with leptin (diet, p-trend<0.0001; diet+exercise, p-trend<0.0001). Conclusion Weight loss through diet or diet+exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet+exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin. PMID:23432360

Abbenhardt, Clare; McTiernan, Anne; Alfano, Catherine M.; Wener, Mark H.; Campbell, Kristin L.; Duggan, Catherine; Foster-Schubert, Karen E.; Kong, Angela; Toriola, Adetunji T; Potter, John D.; Mason, Caitlin; Xiao, Liren; Blackburn, George L.; Bain, Carolyn; Ulrich, Cornelia M.

2013-01-01

24

Ictal Adiponectin Levels in Episodic Migraineurs: A Randomized Pilot Trial  

PubMed Central

Objective To assess ictal adiponectin (ADP) levels before and after acute abortive treatment in women episodic migraineurs. Methods Peripheral blood specimens were collected from women episodic migraineurs before and after acute abortive treatment with sumatriptan/naproxen sodium (suma/nap) versus placebo. Univariate and multivariate models were utilized to examine the relationship between serum total-ADP (T-ADP), ADP oligomers (high molecular weight [HMW], middle molecular weight [MMW], and low molecular weight [LMW]-ADP) and ADP ratio levels and pain severity. Paired-t tests and random intercept longitudinal models were utilized to assess the mean changes in T-ADP, ADP oligomers and ratios over time in treatment responders and non-responders. Results Twenty participants (11 responders, 9 non-responders) have been studied to date. In all participants, increases in the HMW:LMW adiponectin ratio were associated with an increase in pain severity. For every 1 point increase in the HMW:LMW ratio, pain severity increased by 0.22 (CI: 0.07, 0.37; p=0.004). In contrast, for every 0.25 µg/mL increase in LMW-ADP, pain severity decreased by 0.20 (CI: -0.41, -0.002; p=0.047). In treatment responders, T-ADP levels were reduced at 30 min (12.52 ± 3.4; p=0.03), 60 min (12.32 ± 3.2; p=0.017) and 120 min (12.65 ± 3.2; p=0.016) after treatment as compared to onset (13.48 ± 3.8). Additionally, in responders, the HMW:LMW ratio level was greater at pain onset (3.70 ±1.9 µg/mL) as compared to non-responders (2.29 ± 0.71 µg/mL), p=0.050. Responders also showed a decrease in the HMW:LMW ratio at 60 min (2.37 ± 1.1; p=0.002) and 120 min (2.76 ± 1.4; p=0.02) after treatment as compared to onset (3.70 ± 1.9). These changes in responders remained significant after adjusting for covariates, including measured BMI (m-BMI). Although non-responders showed no significant changes in unadjusted T-ADP or ADP oligomer or ratio levels, the HMW:LMW ratio was increased in non-responders after adjustments, (p=0.025). Conclusion In this pilot study of women episodic migraineurs, the HMW:LMW adiponectin ratio level was associated with migraine severity and predictive of acute treatment response. ADP and the HMW:LMW ratio of adiponectin represent potential novel biomarkers and drug targets for episodic migraine. PMID:23489216

Peterlin, B. Lee; Tietjen, Gretchen E.; Gower, Barbara A.; Ward, Thomas N.; Tepper, Stewart J.; White, Linda W.; Dash, Paul D.; Hammond, Edward R.; Haythornthwaite, Jennifer A.

2013-01-01

25

Weight loss larger than 10% is needed for general improvement of levels of circulating adiponectin and markers of inflammation in obese subjects: a 3-year weight loss study  

Microsoft Academic Search

Objective: To investigate the effects of: I) short- (8 weeks), II) long-term (3 years) weight loss, and III) the degree of weight loss on circulating levels of adiponectin, high sensitive-C reactive protein (hs-CRP), and fibrinogen in obese subjects. Moreover, to evaluate the effect of the lipase inhibitor, orlistat, on these parameters. Design: Weight loss induced in 93 obese subjects (mean

Erik L Madsen; Aila Rissanen; Jens M Bruun; Kristin Skogstrand; Serena Tonstad; David M Hougaard; Bjørn Richelsen

2008-01-01

26

Resistin and Adiponectin Expression in Visceral Fat of Obese Rats: Effect of Weight Loss  

Microsoft Academic Search

Objective: Obesity-related insulin resistance is closely associated with visceral fat accumulation. Several adipocyte-secreted molecules have been implicated in the development of type 2 diabetes, among them, the recently discovered adiponectin and resistin proteins. Some of these adipocytokines are also present in the immune system, thus suggesting an intriguing functional connection.Research Methods and Procedures: We determined adiponectin and resistin expressions in

Gabriella Milan; Marnie Granzotto; Alessandro Scarda; Alessandra Calcagno; Claudio Pagano; Giovanni Federspil; Roberto Vettor

2002-01-01

27

Identification of unprecedented anticancer properties of high molecular weight biomacromolecular complex containing bovine lactoferrin (HMW-bLf).  

PubMed

With the successful clinical trials, multifunctional glycoprotein bovine lactoferrin is gaining attention as a safe nutraceutical and biologic drug targeting cancer, chronic-inflammatory, viral and microbial diseases. Interestingly, recent findings that human lactoferrin oligomerizes under simulated physiological conditions signify the possible role of oligomerization in the multifunctional activities of lactoferrin molecule during infections and in disease targeting signaling pathways. Here we report the purification and physicochemical characterization of high molecular weight biomacromolecular complex containing bovine lactoferrin (?250 kDa), from bovine colostrum, a naturally enriched source of lactoferrin. It showed structural similarities to native monomeric iron free (Apo) lactoferrin (?78-80 kDa), retained anti-bovine lactoferrin antibody specific binding and displayed potential receptor binding properties when tested for cellular internalization. It further displayed higher thermal stability and better resistance to gut enzyme digestion than native bLf monomer. High molecular weight bovine lactoferrin was functionally bioactive and inhibited significantly the cell proliferation (p<0.01) of human breast and colon carcinoma derived cells. It induced significantly higher cancer cell death (apoptosis) and cytotoxicity in a dose-dependent manner in cancer cells than the normal intestinal cells. Upon cellular internalization, it led to the up-regulation of caspase-3 expression and degradation of actin. In order to identify the cutting edge future potential of this bio-macromolecule in medicine over the monomer, its in-depth structural and functional properties need to be investigated further. PMID:25222273

Ebrahim, Fawzi; Shankaranarayanan, Jayanth Suryanarayanan; Kanwar, Jagat R; Gurudevan, Sneha; Krishnan, Uma Maheswari; Kanwar, Rupinder K

2014-01-01

28

A Review of Weight Loss Following Roux-en-Y Gastric Bypass vs Restrictive Bariatric Surgery: Impact on Adiponectin and Insulin  

Microsoft Academic Search

Background  Bariatric surgery is a common procedure often used to ameliorate comorbidities associated with obesity, including type 2 diabetes.\\u000a Substantial weight loss leads to alterations in inflammation and insulin sensitivity as well as numerous metabolic and physiologic\\u000a pathways. Several inflammatory markers have been evaluated, yet adiponectin, an anti-inflammatory adipokine, has not been\\u000a fully investigated. Adiponectin may play a key role as

Katrina L. Butner; Sharon M. Nickols-Richardson; Susan F. Clark; Warren K. Ramp; William G. Herbert

2010-01-01

29

Adiponectin Isoforms Differentially Affect Gene Expression and the Lipidome of Primary Human Hepatocytes  

PubMed Central

Adiponectin (APN) exerts multiple beneficial effects in obesity and protects from liver injury. Different APN isoforms circulate in serum, and here, the effect of low molecular weight (LMW) and higher molecular weight (HMW) APN on primary human hepatocytes (PHH) has been analyzed. APN is not detected in hepatocyte lysates; levels are strongly increased by HMW-APN, but not by LMW-APN, suggesting the distinct uptake/degradation of APN isoforms by PHH. Several genes with a role in fibrosis, glucose and lipid metabolism known to be regulated by HMW-APN are not affected by the LMW-isoform. Follistatin is reduced by HMW-APN and induced by LMW-APN in supernatants of PHH. Fibroblast growth factor 21 is repressed by both isoforms. Cellular triglycerides and cholesterol levels are not reduced by APN. Total phospholipids, including plasmalogens and sphingomyelins, are not changed upon APN incubation, while distinct species are either induced or repressed. Unexpectedly, total ceramide is increased by LMW-APN. Current data show that APN isoforms differentially affect hepatocyte gene expression, but do not grossly alter the hepatocyte lipidome. PMID:24957032

Wanninger, Josef; Liebisch, Gerhard; Eisinger, Kristina; Neumeier, Markus; Aslanidis, Charalampos; Voggenreiter, Lisa; Pohl, Rebekka; Weiss, Thomas S.; Krautbauer, Sabrina; Buechler, Christa

2014-01-01

30

The Effects of 6 Isocaloric Meals on Body Weight, Lipid Profiles, Leptin, and Adiponectin in Overweight Subjects (BMI > 25)  

PubMed Central

Background: It seems that meal frequency is negatively related to body weight, but the relationship between meal frequency and weight loss is not clearly known yet. Objectives: The present study aimed to investigate whether 6 isocaloric meals affected body weight, lipid profiles, leptin, and adiponectin in overweight subjects. Methods: The present randomized controlled trial was conducted on 90 overweight subjects in 3 months. The subjects were randomly divided into two groups. The control group continued their normal diet, while the intervention group was required to follow a 6 isocaloric meal diet instead of their previous meal pattern (3 meals and 2 snacks). The planned reduced calorie diets for both groups were identical, except for meal pattern. Blood samples were analyzed prior to and at the end of the study for total cholesterol, triglyceride, HDL-C, LDL-C, leptin, and adiponectinn concentrations. Paired t-test was used for comparison of the measurements before and after the study in each group. Besides, independent t-test was used for comparison of the measurements between the groups. P value less than 0.05 was considered as statistically significant. Results: The mean age of the participants was 36.38 ± 9.7 in the intervention group and 37.6 ± 10.9 in the control group. In comparison to the control group, the intervention group showed a significant decrease in total cholesterol (P < 0.001), LDL-C (P < 0.001), BMI (P < 0.001), triglyceride (P < 0.001), and leptin (P = 0.002) and a significant increase in HDL (P < 0.001) and adiponectin (P = 0.031). Conclusions: The 6 isocaloric meal pattern led to a reduction in BMI, lipid profiles (total cholesterol, LDL-C, triglyceride), and leptin concentrations and an increase in HDL and adiponectin compared to the normal diet. PMID:24936481

Hatami Zargaran, Zeynab; Salehi, Moosa; Heydari, Seyed Taghi; Babajafari, Siavash

2014-01-01

31

Characterization of two HMW glutenin subunit genes from Taenitherum Nevski.  

PubMed

The compositions of high molecular weight (HMW) glutenin subunits from three species of Taenitherum Nevski (TaTa, 2n = 2x = 14), Ta. caput-medusae, Ta. crinitum and Ta. asperum, were investigated by SDS-PAGE analysis. The electrophoresis mobility of the x-type HMW glutenin subunits were slower or equal to that of wheat HMW glutenin subunit Dx2, and the electrophoresis mobility of the y-type subunits were faster than that of wheat HMW glutenin subunit Dy12. Two HMW glutenin genes, designated as Tax and Tay, were isolated from Ta. crinitum, and their complete nucleotide coding sequences were determined. Sequencing and multiple sequences alignment suggested that the HMW glutenin subunits derived from Ta. crinitum had the similar structures to the HMW glutenin subunits from wheat and related species with a signal peptide, and N- and C-conservative domains flanking by a repetitive domain consisted of the repeated short peptide motifs. However, the encoding sequences of Tax and Tay had some novel modification compared with the HMW glutenin genes reported so far: (1) A short peptide with the consensus sequences of KGGSFYP, which was observed in the N-terminal of all known HMW glutenin genes, was absent in Tax; (2) There is a specified short peptide tandem of tripeptide, hexapeptide and nonapeptide and three tandem of tripeptide in the repetitive domain of Tax; (3) The amino acid residues number is 105 (an extra Q presented) but not 104 in the N-terminal of Tay, which was similar to most of y-type HMW glutenin genes from Elytrigia elongata and Crithopsis delileana. Phylogenetic analysis indicated that Tax subunit was mostly related to Ax1, Cx, Ux and Dx5, and Tay was more related to Ay, Cy and Ry. PMID:16850230

Yan, Ze-Hong; Wei, Yu-Ming; Wang, Ji-Rui; Liu, Deng-Cai; Dai, Shou-Fen; Zheng, You-Liang

2006-05-01

32

A common variant in the adiponectin gene on weight loss and body composition under sibutramine therapy in obesity  

PubMed Central

In this study, we aimed to explore whether a common single nucleotide polymorphism (SNP), rs266729 (?11,377C > G), in the adiponectin C1Q and collagen domain containing (ADIPOQ) gene could influence weight reduction and fat change under sibutramine therapy in an obese population. There were 131 obese Taiwanese patients, including 44 in the placebo group and 87 in the sibutramine (10 mg daily) group. We assessed the measures of weight loss and body fat reduction at the end of the 12-week treatment period by analysis of covariance (ANCOVA) models using gender, baseline weight, and baseline percent body fat as covariates. By comparing the placebo and sibutramine groups with ANCOVA, our data revealed a strong effect of sibutramine on percent body fat loss (1.9 ± 0.3 vs 4.6 ± 0.5%; P < 0.001) and on weight reduction (2.8 ± 2.0 vs 7.9 ± 1.6 kg; P < 0.001) for subjects with the CC genotype. On the contrary, sibutramine had no significant effect on percent body fat loss or on weight loss in the GG and GC individuals. The results suggest that the SNP rs266729 of the ADIPOQ gene may contribute to weight reduction and fat loss in response to sibutramine therapy in Taiwanese obese patients. PMID:22291493

Hsiao, Tun-Jen; Wu, Lawrence Shih-Hsin; Huang, Shih-Yi; Lin, Eugene

2010-01-01

33

Characterization of adiponectin concentrations and molecular weight forms in serum, seminal plasma, and ovarian follicular fluid from cattle.  

PubMed

Adiponectin (AdipoQ), an adipocyte-derived hormone, is one of the most abundant adipokines in the blood circulation. Adiponectin has various metabolic functions, such as improving insulin sensitivity in humans and rodents. The role of AdipoQ in reproduction is not yet fully understood, but the expression of AdipoQ in reproductive tissues has been observed in various animals and humans, including chicken testis, bovine ovary, and human placenta. The objective of this study was to characterize AdipoQ in the bovine body fluids related to reproduction. Therefore, we evaluated the seminal plasma (SP) from breeding bulls (n = 29) and follicular fluid (FF) from heifers (n = 14), and we also collected blood samples from these animals. In addition, blood samples from other bulls (n = 30) and heifers (n = 14) were assayed for AdipoQ. The concentrations were assessed using a bovine-specific ELISA, and the molecular weight (MW) pattern of the AdipoQ protein was estimated by the Western blot analysis. The SP AdipoQ concentrations were approximately 180-fold lower compared with that in the serum concentrations. Furthermore, the AdipoQ concentrations in the serum and SP were positively correlated. The MW patterns of AdipoQ in the serum and SP were different such that the high MW form of AdipoQ was more abundant in the SP than serum. The AdipoQ concentrations in the serum and SP also increased with age: old bulls (>6 years) had higher AdipoQ concentrations in the serum and SP than bulls aged 24 months or lesser (P < 0.05). In the FF, the AdipoQ concentrations were 1.6-fold lower than those in the corresponding serum samples, and the concentrations in the serum and FF were not correlated (P > 0.1). In the FF, only the middle MW forms of AdipoQ were detectable by Western blotting. The MW pattern in the serum did not differ between the sexes. Our data provide both the AdipoQ concentration and the MW patterns for bovine body fluids related to reproduction. PMID:25468552

Heinz, Johanna F L; Singh, Shiva P; Janowitz, Ulrich; Hoelker, Michael; Tesfaye, Dawit; Schellander, Karl; Sauerwein, Helga

2015-02-01

34

Total adiponectin, but not inflammatory markers C-reactive protein, tumor necrosis factor-?, interluekin-6 and monocyte chemoattractant protein-1, correlates with increasing glucose intolerance in pregnant Chinese–Americans  

PubMed Central

Background Elevated insulin, C-reactive protein (CRP), tumor necrosis factor (TNF)-?, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels and decreased high molecular weight adiponectin (HMW-APN) levels have been reported in Caucasians with gestational diabetes mellitus (GDM). No similar studies have been performed in Chinese women. Methods Serum samples were obtained 1?h after a 50-g glucose challenge test (1HGCT) from Chinese–American women at 24–28 gestational weeks and total adiponectin (T-APN), HMW-APN, CRP, TNF-?, IL-6, and MCP-1 concentrations were measured. Correlation coefficients for glucose (1HGCT), HbA1c, insulin, and body mass index (BMI) were calculated against T-APN, HMW-APN, CRP, TNF-?, IL-6, and MCP-1. Significant P-values were determined using Bonferroni adjustments. Results Women with GDM had higher insulin and 1HGCT and lower T-APN. In addition, T-APN was lower in non-GDM subjects who had 1HGCT ?135?mg/dL with no abnormal or one abnormal glucose value on the 3-h oral glucose tolerance test. There were no significant differences in HMW-APN and inflammatory marker levels between non-GDM and GDM groups. There were negative correlations between T-APN and 1HGCT, insulin, BMI, and HbA1c, as well as between HMW-APN and 1HGCT, insulin, and BMI. No significant correlations were observed between 1HGCT, HbA1c, insulin, or BMI and CRP, TNF-?, IL-6, or MCP-1. Conclusions T-APN is reduced in Chinese women with GDM and those without GDM but with evidence of glucose intolerance. Unlike results reported for Caucasians, Chinese–American women with GDM do not exhibit elevated levels of CRP, TNF-?, IL-6, or MCP-1, possibly because Chinese women are relatively leaner compared with Caucasians. PMID:24330072

Kim, So-Young; Sy, Vanessa; Araki, Takako; Babushkin, Nicole; Huang, Diana; Tan, Doris; Liao, Emilia; Liu, George; Wan, Stephen; Poretsky, Leonid; Seto-Young, Donna

2014-01-01

35

Differential transendothelial transport of adiponectin complexes  

PubMed Central

Background Adiponectin’s effects on systemic physiology and cell-specific responses are well-defined, but little is known about how this insulin-sensitizing and anti-inflammatory adipokine reaches its target cells. All molecules face active and passive transport limitations, but adiponectin is particularly noteworthy due to the diverse size range and high molecular weights of its oligomers. Additionally, its metabolic target organs possess a range of endothelial permeability. Methods Full-length recombinant murine adiponectin was produced and oligomer fractions isolated by gel filtration. Adiponectin complex sizes were measured by dynamic light scattering to determine Stokes radii. Transendothelial transport of purified oligomers was quantitatively assessed under a number of different conditions in vitro using murine endothelial cells and in vivo using several mouse models of altered endothelial function. Results Adiponectin oligomers exhibit large transport radii that limit transendothelial transport. Oligomerization is a significant determinant of flux across endothelial monolayers in vitro; low molecular weight adiponectin is preferentially transported. In vivo sampled sera from the heart, liver, and tail vein demonstrated significantly different complex distribution of lower molecular weight oligomers. Pharmacological interventions, such as PPAR? agonist treatment, differentially affect adiponectin plasma clearance and tissue uptake. Exercise induces enhanced adiponectin uptake to oxidative skeletal muscles, wherein adiponectin potently lowers ceramide levels. In total, endothelial barriers control adiponectin transport in a cell- and tissue-specific manner. Conclusions Adiponectin oligomer efficacy in a given tissue may therefore be endothelial transport mediated. Targeting endothelial dysfunction in the metabolic syndrome through exercise and pharmaceuticals may afford an effective approach to increasing adiponectin’s beneficial effects. PMID:24552349

2014-01-01

36

Prevalence, distribution, and sequence diversity of hmwA among commensal and otitis media non-typeable Haemophilus influenzae.  

PubMed

Nontypeable Haemophilus influenzae (NTHi) are Gram-negative coccobacilli that colonize the human pharynx, their only known natural reservoir. Adherence to the host epithelium facilitates NTHi colonization and marks one of the first steps in NTHi pathogenesis. Epithelial cell attachment is mediated, in part, by a pair of high molecular weight (HMW) adhesins that are highly immunogenic, antigenically diverse, and display a wide range of amino acid diversity both within and between isolates. In this study, the prevalence of hmwA, which encodes the HMW adhesin, was determined for a collection of 170 NTHi isolates recovered from the middle ears of children with otitis media (OM isolates) or throats or nasopharynges of healthy children (commensal isolates) from Finland, Israel, and the U.S. Overall, hmwA was detected in 61% of NTHi isolates and was significantly more prevalent (P=0.004) among OM isolates than among commensal isolates; the prevalence ratio comparing hmwA prevalence among ear isolates with that of commensal isolates was 1.47 (95% CI (1.12, 1.92)). Ninety-five percent (98/103) of the hmwA-positive NTHi isolates possessed two hmw loci. To advance our understanding of hmwA binding sequence diversity, we determined the DNA sequence of the hmwA binding region of 33 isolates from this collection. The average amino acid identity across all hmwA sequences was 62%. Phylogenetic analyses of the hmwA binding revealed four distinct sequence clusters, and the majority of hmwA sequences (83%) belonged to one of two dominant sequence clusters. hmwA sequences did not cluster by chromosomal location, geographic region, or disease status. PMID:25290952

Davis, Gregg S; Patel, May; Hammond, James; Zhang, Lixin; Dawid, Suzanne; Marrs, Carl F; Gilsdorf, Janet R

2014-12-01

37

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

38

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

PubMed Central

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

39

Comparative measurement of ghrelin, leptin, adiponectin, EGF and IGF-1 in breast milk of mothers with overweight/obese and normal-weight infants.  

PubMed

Background/Objectives:Obese infants are more susceptible to develop adulthood obesity and its related comorbidities. Previous studies have shown the presence of hormones and growth factors in maternal breast milk that may influence infant adiposity. The aim of this study was to investigate differences in concentrations of three hormones and two growth factors in the breast milk of mothers with obese and non-obese infants.Subjects/Methods:In this cross-sectional study, 40 mothers with overweight or obese infants (weight for length percentile >97) and 40 age-matched mothers with normal-weight infant (-10<weight for length percentile<85) who were between 2 and 5 months of age were enrolled. Anthropometric indices of infants and mothers were measured by routine methods. Breast milk concentrations of ghrelin and adiponectin, leptin, epithelial growth factor (EGF) and insulin-like growth factor-1 (IGF-1) were measured using enzyme-linked immunosorbent assay methods.Results:The mean breast milk concentration of ghrelin was higher in mothers with normal-weight infants, 137.50?pg/ml, than in mothers with obese infants, 132.00?pg/ml (P=0.001). This was also true regarding the concentration of EGF in mothers with (0/04?ng/ml) and without (0/038?ng/ml) normal-weight infants (P=0.01). No significant differences were observed in concentrations of leptin, adiponectin and IGF-1 between two groups (P>0.05). There was also a significant positive correlation between EGF and ghrelin in both groups.Conclusions:This study revealed that there was a correlation between ghrelin and EGF level in breast milk of mothers with obese and non-obese infants, suggesting a possible regulatory effect of these two hormones on weight in infants.European Journal of Clinical Nutrition advance online publication, 5 November 2014; doi:10.1038/ejcn.2014.205. PMID:25351650

Khodabakhshi, A; Ghayour-Mobarhan, M; Rooki, H; Vakili, R; Hashemy, S-I; Mirhafez, S R; Shakeri, M-T; Kashanifar, R; Pourbafarani, R; Mirzaei, H; Dahri, M; Mazidi, M; Ferns, G; Safarian, M

2014-11-01

40

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. PMID:23169576

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

2012-01-01

41

Multiplex PCR identification of wheat HMW glutenin subunit genes by allele-specific markers  

Microsoft Academic Search

Wheat bread-making quality is closely correlated with composition and quantity of gluten proteins, in particular with high-molecular weight (HMW) glutenin subunits encoded by the Glu-1 genes. A multiplex polymerase chain reaction (PCR) method was developed to identify the allele composition of HMW glutenin com- plex Glu-1 loci (Glu-A1, Glu-B1 and Glu-D1) in common wheat genotypes. The study of multiplex PCR

Marcin MOCZULSKI; P. SALMANOWICZ

42

Fat-cell mass, serum leptin and adiponectin changes during weight gain and loss in yellow-bellied marmots ( Marmota flaviventris )  

Microsoft Academic Search

Leptin and adiponectin are proteins produced and secreted from white adipose tissue and are important regulators of energy balance and insulin sensitivity. Seasonal changes in leptin and adiponectin have not been investigated in mammalian hibernators in relationship to changes in fat cell and fat mass. We sought to determine the relationship between serum leptin and adiponectin levels with seasonal changes

Gregory L. Florant; Heather Porst; Aubrey Peiffer; Susan F. Hudachek; Chris Pittman; Scott A. Summers; Michael W. Rajala; Philipp E. Scherer

2004-01-01

43

Adiponectin in Anorexia Nervosa and Bulimia Nervosa  

Microsoft Academic Search

To study the role of adiponectin, a novel adipocyte-specific secreted protein, on the pathophysiology of eating disorders, circulating levels of fasting adiponectin, leptin, insulin, and glucose were measured in 31 female patients with anorexia nervosa (AN) and in 11 with bulimia nervosa. Hormone levels were compared with 16 age-matched, normal body weight con- trols, six healthy constitutionally thin subjects, and

TETSUYA TAGAMI; NORIKO SATOH; TAKESHI USUI; KAZUNORI YAMADA; AKIRA SHIMATSU; HIDESHI KUZUYA

44

Analysis of HMW glutenin subunits and their coding sequences in two diploid Aegilops species.  

PubMed

Considerable progress has been made in understanding the structure, function and genetic regulation of high-molecular-weight (HMW) glutenin subunits in hexaploid wheat. In contrast, less is known about these types of proteins in wheat related species. In this paper, we report the analysis of HMW glutenin subunits and their coding sequences in two diploid Aegilops species, Aegilops umbellulata (UU) and Aegilops caudata (CC). SDS-PAGE analysis demonstrated that, for each of the four Ae. umbellulata accessions, there were two HMW glutenin subunits (designated here as 1Ux and 1Uy) with electrophoretic mobilities comparable to those of the x- and y-type subunits encoded by the Glu-D1 locus, respectively. In our previous study involving multiple accessions of Ae. caudata, two HMW glutenin subunits (designated as 1Cx and 1Cy) with electrophoretic mobilities similar to those of the subunits controlled by the Glu-D1 locus were also detected. These results indicate that the U genome of Ae. umbellulata and the C genome of Ae. caudata encode HMW glutenin subunits that may be structurally similar to those specified by the D genome. The complete open reading frames (ORFs) coding for x- and y-type HMW glutenin subunits in the two diploid species were cloned and sequenced. Analysis of deduced amino acid sequences revealed that the primary structures of the x- and y-type HMW glutenin subunits of the two Aegilops species were similar to those of previously published HMW glutenin subunits. Bacterial expression of modified ORFs, in which the coding sequence for the signal peptide was removed, gave rise to proteins with electrophoretic mobilities identical to those of HMW glutenin subunits extracted from seeds, indicating that upon seed maturation the signal peptide is removed from the HMW glutenin subunit in the two species. Phylogenetic analysis showed that 1Ux and 1Cx subunits were most closely related to the 1Dx type subunit encoded by the Glu-D1 locus. The 1Uy subunit possessed a higher level of homology to the 1Dy-type subunit compared with the 1Cy subunit. In conclusion, our study suggests that the Glu-U1 locus of Ae. umbellulata and the Glu-C1 locus of Ae. caudata specify the expression of HMW glutenin subunits in a manner similar to the Glu-D1 locus. Consequently, HMW glutenin subunits from the two diploid species may have potential value in improving the processing properties of hexaploid wheat varieties. PMID:12750780

Liu, Z; Yan, Z; Wan, Y; Liu, K; Zheng, Y; Wang, D

2003-05-01

45

Characterization of HMW prolamines and their coding sequences from Crithopsis delileana.  

PubMed

The high-molecular-weight (HMW) prolamines subunits and their coding sequences from wheat-related diploid species Crithopsis delileana were investigated. Only one HMW prolamine subunit with the similar electrophoresis mobility to the y-type HMW glutenin subunit of hexaploid wheat was observed in two accessions of C. delileana by SDS-PAGE analyses of the total storage protein fractions. It was confirmed by sequencing and expression analysis that this prolamine subunit was an x-type subunit. The amino acid sequence of this subunit had the similar typical structure to those of x-type HMW glutenin genes previously described in wheat. An in-frame stop codon was found in the coding sequences of y-type prolamine subunits. It was found by specifically extraction of HMW prolamines and sequence analysis that the coding regions of Ky prolamine subunit gene is very likely to be not expressed as a full-length protein. Phylogenetic analysis indicated that the Kx subunit could be clustered together with 1Ax1 subunit by an interior paralleled branch, and Ky subunit (inactive) was most closely related to the 1Ay subunit. The coding sequences of Kx subunit could successfully be expressed in bacterial expression system, and the expressed protein had the same electrophoresis mobility as the Kx subunit from the seed of C. delileana. It was the first time that the HMW prolamines subunits encoded by K genome of C. delileana were characterized. PMID:16970613

Guo, Zhi-Fu; Yan, Ze-Hong; Wang, Ji-Rui; Wei, Yu-Ming; Zheng, You-Liang

2005-02-01

46

No evidence for a role of the peroxisome proliferator-activated receptor gamma (PPARG) and adiponectin (ADIPOQ) genes in antipsychotic-induced weight gain.  

PubMed

Antipsychotics frequently cause changes in glucose metabolism followed by development of weight gain and/or diabetes. Recent findings from our group indicated an influence of glucose-related genes on this serious side effect. With this study, we aimed to extend previous research and performed a comprehensive study on the peroxisome proliferator-activated receptor gamma (PPARG) and the adiponectin (ADIPOQ) genes. In 216 schizophrenic patients receiving antipsychotics for up to 14 weeks, we investigated single-nucleotide polymorphisms in or near PPARG (N=24) and ADIPOQ (N=18). Statistical analysis was done using ANCOVA in SPSS. Haplotype analysis was performed in UNPHASED 3.1.4 and Haploview 4.2. None of the PPARG or ADIPOQ variants showed significant association with antipsychotic-induced weight gain in our combined sample or in a refined subsample of patients of European ancestry treated with clozapine or olanzapine after correction for multiple testing. Similarly, no haplotype association could withstand multiple test correction. Although we could not find a significant influence of ADIPOQ and PPARG on antipsychotic-induced weight gain, our comprehensive examination of these two genes contributes to understanding the biology of this serious side effect. More research on glucose metabolism genes is warranted to elucidate their role in metabolic changes during antipsychotic treatment. PMID:24953421

Brandl, Eva J; Tiwari, Arun K; Zai, Clement C; Chowdhury, Nabilah I; Lieberman, Jeffrey A; Meltzer, Herbert Y; Kennedy, James L; Müller, Daniel J

2014-10-30

47

The nucleotide sequence of a HMW glutenin subunit gene located on chromosome 1A of wheat (Triticum aestivum L.).  

PubMed Central

A cloned 8.2 kb EcoRI fragment has been isolated from a genomic library of DNA derived from Triticum aestivum L. cv. Cheyenne. This fragment contains sequences related to the high molecular weight (HMW) subunits of glutenin, proteins considered to be important in determining the elastic properties of gluten. The cloned HMW subunit gene appears to be derived from chromosome 1A. The nucleotide sequence of this gene has provided new information on the structure and evolution of the HMW subunits. However, hybrid-selection translation experiments suggest that this gene is silent. Images PMID:2997729

Forde, J; Malpica, J M; Halford, N G; Shewry, P R; Anderson, O D; Greene, F C; Miflin, B J

1985-01-01

48

Isolation and Quantitation of Adiponectin Higher Order Complexes  

PubMed Central

Adiponectin is a circulating bioactive hormone secreted by adipocytes as oligomers ranging in size from 90 kDa trimers and 180 kDa hexamers to larger high molecular weight oligomers that may reach 18- or 36-mers in size. While total circulating adiponectin levels correlate well with metabolic health, it is the relative distribution of adiponectin complexes that is most clinically relevant to glucose sensitivity and inflammation. High molecular weight adiponectin best mirrors insulin sensitivity, while trimeric adiponectin dominates with insulin resistance and adipose tissue inflammation. Experimental animal and in vitro models have also linked the relative fraction of high molecular weight adiponectin to its positive effects. Quantitating adiponectin size distribution thus provides a window into metabolic health and can serve as a surrogate marker for adipose tissue fitness. Here, we present a detailed protocol for isolating and quantitating adiponectin complexes in serum or plasma that has been extensively utilized for both human clinical samples and numerous animal models under various experimental conditions. Examples are presented of different adiponectin distributions and tips are provided for optimization using available equipment. Comparison of this rigorous approach to other available methods is also discussed. In total, this summary is a blueprint for the expanded quantitation and study of adiponectin complexes. PMID:24480350

Rutkowski, Joseph M.; Scherer, Philipp E.

2014-01-01

49

Characterizing HMW-GS alleles of decaploid Agropyron elongatum in relation to evolution and wheat breeding  

PubMed Central

Bread wheat quality is mainly correlated with high molecular weight glutenin subunits (HMW-GS) of endosperm. The number of HMW-GS alleles with good processing quality is limited in bread wheat cultivars, while there are plenty of HMW-GS alleles in wheat-related grasses to exploit. We report here on the cloning and characterization of HMW-GS alleles from the decaploid Agropyron elongatum. Eleven novel HMW-GS alleles were cloned from the grass. Of them, five are x-type and six y-type glutenin subunit genes. Three alleles Aex4, Aey7, and Aey9 showed high similarity with another three alleles from the diploid Lophopyrum elongatum, which provided direct evidence for the Ee genome origination of A. elongatum. It was noted that C-terminal regions of three alleles of the y-type genes Aey8, Aey9, and Aey10 showed more similarity with x-type genes than with other y-type genes. This demonstrates that there is a kind of intermediate state that appeared in the divergence between x- and y-type genes in the HMW-GS evolution. One x-type subunit, Aex4, with an additional cysteine residue, was speculated to be correlated with the good processing quality of wheat introgression lines. Aey4 was deduced to be a chimeric gene from the recombination between another two genes. How the HMW-GS genes of A. elongatum may contribute to the improvement of wheat processing quality are discussed. PMID:17992503

Liu, Shuwei; Gao, Xin

2007-01-01

50

Characterizing HMW-GS alleles of decaploid Agropyron elongatum in relation to evolution and wheat breeding.  

PubMed

Bread wheat quality is mainly correlated with high molecular weight glutenin subunits (HMW-GS) of endosperm. The number of HMW-GS alleles with good processing quality is limited in bread wheat cultivars, while there are plenty of HMW-GS alleles in wheat-related grasses to exploit. We report here on the cloning and characterization of HMW-GS alleles from the decaploid Agropyron elongatum. Eleven novel HMW-GS alleles were cloned from the grass. Of them, five are x-type and six y-type glutenin subunit genes. Three alleles Aex4, Aey7, and Aey9 showed high similarity with another three alleles from the diploid Lophopyrum elongatum, which provided direct evidence for the Ee genome origination of A. elongatum. It was noted that C-terminal regions of three alleles of the y-type genes Aey8, Aey9, and Aey10 showed more similarity with x-type genes than with other y-type genes. This demonstrates that there is a kind of intermediate state that appeared in the divergence between x- and y-type genes in the HMW-GS evolution. One x-type subunit, Aex4, with an additional cysteine residue, was speculated to be correlated with the good processing quality of wheat introgression lines. Aey4 was deduced to be a chimeric gene from the recombination between another two genes. How the HMW-GS genes of A. elongatum may contribute to the improvement of wheat processing quality are discussed. PMID:17992503

Liu, Shuwei; Gao, Xin; Xia, Guangmin

2008-02-01

51

[Sequencing and expression analysis of a novel HMW-glutenin gene Kx from Crithopsis delileana].  

PubMed

Using SDS-PAGE analysis, the High-molecular-weight (HMW) glutenin subunits of two Crithopsis delileana accessions were detected. It was found that the two accessions had the same HMW glutenin subunits. Only one HMW glutenin subunit with the similar electrophoresis mobility to the y-type HMW glutenin subunit of hexaploid wheat was observed in C. delileana. However, It was indicated that this glutenin subunit was an x-type glutenin subunit Kx by gene sequence analysis. The full coding region of Kx gene is 2052bp and could encodes a mature protein with 661 amino acid residues. The Kx gene could be expressed in the bacterial expression system, and the expressed protein had the same electrophoresis mobility as that in the seed of C. delileana. The primary structure of Kx subunit was very similar to the x-type HMW glutenin subunits encoded by the A, B and D genomes of wheat, the C and U genomes of Aegilops, and the R genome of Secale cereale. In the phylogenetic analysis, Kx subunit was clustered together with Ax1 subunit by an interior parallelled branch. In conclsion, Kx gene is a novel x type glutenin subunit gene from C. delileana. PMID:16108359

Guo, Zhi-Fu; Yan, Ze-Hong; Wei, Yu-Ming; Zheng, You-Liang

2005-05-01

52

Adiposity distribution influences circulating adiponectin levels.  

PubMed

Thirty percent of obese individuals are metabolically healthy and were noted to have increased peripheral obesity. Adipose tissue is the primary source of adiponectin, an adipokine with insulin-sensitizing and anti-inflammatory properties. Lower adiponectin levels are observed in individuals with obesity and those at risk for cardiovascular disease. Conversely, higher levels are noted in some obese individuals who are metabolically healthy. Our objective was to determine whether abdominal adiposity distribution, rather than body mass index (BMI) status, influences plasma adiponectin level. A total of 424 subjects (female, 255) of Northern European ancestry were recruited from "Take Off Pounds Sensibly" weight loss club members. Demographics, anthropometrics, and dual-emission x-ray absorptiometry of the whole body, and computed tomography scan of the abdomen were performed to obtain total body fat content and to quantify subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), respectively. Laboratory measurements included fasting plasma glucose, insulin, lipid panel, and adiponectin. Age- and gender-adjusted correlation analyses showed that adiponectin levels were negatively correlated with BMI, waist circumference, triglycerides, total fat mass, and VAT. A positive correlation was noted with high-density lipoprotein cholesterol and fat-free mass (P < 0.05). SAT-to-VAT ratios were also significantly associated with adiponectin (r = 0.13, P = 0.001). Further, the best positive predictors for plasma adiponectin were found to be SAT-to-VAT ratios and gender by regression analyses (P < 0.01). Abdominal adiposity distribution is an important predictor of plasma adiponectin and obese individuals with higher SAT-to-VAT ratios may have higher adiponectin levels. PMID:24811003

Guenther, Mitchell; James, Roland; Marks, Jacqueline; Zhao, Shi; Szabo, Aniko; Kidambi, Srividya

2014-10-01

53

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 ...

54

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. PMID:22547160

Dalamaga, Maria; Diakopoulos, Kalliope N.

2012-01-01

55

Fat-cell mass, serum leptin and adiponectin changes during weight gain and loss in yellow-bellied marmots (Marmota flaviventris).  

PubMed

Leptin and adiponectin are proteins produced and secreted from white adipose tissue and are important regulators of energy balance and insulin sensitivity. Seasonal changes in leptin and adiponectin have not been investigated in mammalian hibernators in relationship to changes in fat cell and fat mass. We sought to determine the relationship between serum leptin and adiponectin levels with seasonal changes in lipid mass. We collected serum and tissue samples from marmots (Marmota flaviventris) in different seasons while measuring changes in fat mass, including fat-cell size. We found that leptin is positively associated with increasing fat mass and fat-cell size, while adiponectin is negatively associated with increasing lipid mass. These findings are consistent with the putative roles of these adipokines: leptin increases with fat mass and is involved in enhancing lipid oxidation while adiponectin appears to be higher in summer when hepatic insulin sensitivity should be maintained since the animals are eating. Our data suggest that during autumn/winter animals have switched from a lipogenic condition to a lipolytic state, which may include leptin resistance. PMID:15517283

Florant, Gregory L; Porst, Heather; Peiffer, Aubrey; Hudachek, Susan F; Pittman, Chris; Summers, Scott A; Rajala, Michael W; Scherer, Philipp E

2004-11-01

56

Adiponectin and breast cancer  

Microsoft Academic Search

Adiponectin, an adipose tissue-derived hormone, has been studied intensively for the past decade because of its anti-inflammatory,\\u000a anti-atherogenic, and anti-diabetic properties. Recent advances suggest that adiponectin also plays an important role in the\\u000a development and progression of various cancers, especially obesity-related cancers. In this review, the authors focus on the\\u000a potential role of adiponectin in breast cancer, an obesity- and

Xiuping Chen; Yitao Wang

57

Antibodies to the HMW1/HMW2 and Hia Adhesins of Nontypeable Haemophilus influenzae Mediate Broad-Based Opsonophagocytic Killing of Homologous and Heterologous Strains  

PubMed Central

The HMW1/HMW2 and Hia proteins are highly immunogenic surface adhesins of nontypeable Haemophilus influenzae (NTHi). Approximately 75% of NTHi strains express HMW1/HMW2 adhesins, and most of the remaining 25% express an Hia adhesin. Our objective in this study was to assess the ability of antisera raised against purified HMW1/HMW2 proteins or recombinant Hia proteins to mediate opsonophagocytic killing of a large panel of unrelated NTHi strains. Native HMW1/HMW2 proteins were purified from three HMW1/HMW2-expressing NTHi strains. Recombinant fusion proteins expressing surface-exposed segments of either of two prototype Hia proteins were purified from Escherichia coli transformants. Immune sera raised in guinea pigs were assessed for their ability to mediate killing of NTHi in an opsonophagocytic assay with the HL-60 phagocytic cell line. The three HMW1/HMW2 antisera mediated killing of 22 of 65, 43 of 65, and 28 of 65 unrelated HMW1/HMW2-expressing NTHi strains, respectively. As a group, the three sera mediated killing of 48 of 65 HMW1/HMW2-expressing strains. The two Hia immune sera mediated killing of 12 of 24 and 13 of 24 unrelated Hia-expressing NTHi strains, respectively. Together, they mediated killing of 15 of 24 Hia-expressing strains. Neither the HMW1/HMW2 nor the Hia antisera mediated killing of NTHi expressing the alternative adhesin type. Antibodies directed against native HMW1/HMW2 proteins and recombinant Hia proteins are capable of mediating broad-based opsonophagocytic killing of homologous and heterologous NTHi strains. A vaccine formulated with a limited number of HMW1/HMW2 and Hia proteins might provide protection against disease caused by most NTHi strains. PMID:24574538

Winter, Linda E.

2014-01-01

58

Antibodies to the HMW1/HMW2 and Hia adhesins of nontypeable haemophilus influenzae mediate broad-based opsonophagocytic killing of homologous and heterologous strains.  

PubMed

The HMW1/HMW2 and Hia proteins are highly immunogenic surface adhesins of nontypeable Haemophilus influenzae (NTHi). Approximately 75% of NTHi strains express HMW1/HMW2 adhesins, and most of the remaining 25% express an Hia adhesin. Our objective in this study was to assess the ability of antisera raised against purified HMW1/HMW2 proteins or recombinant Hia proteins to mediate opsonophagocytic killing of a large panel of unrelated NTHi strains. Native HMW1/HMW2 proteins were purified from three HMW1/HMW2-expressing NTHi strains. Recombinant fusion proteins expressing surface-exposed segments of either of two prototype Hia proteins were purified from Escherichia coli transformants. Immune sera raised in guinea pigs were assessed for their ability to mediate killing of NTHi in an opsonophagocytic assay with the HL-60 phagocytic cell line. The three HMW1/HMW2 antisera mediated killing of 22 of 65, 43 of 65, and 28 of 65 unrelated HMW1/HMW2-expressing NTHi strains, respectively. As a group, the three sera mediated killing of 48 of 65 HMW1/HMW2-expressing strains. The two Hia immune sera mediated killing of 12 of 24 and 13 of 24 unrelated Hia-expressing NTHi strains, respectively. Together, they mediated killing of 15 of 24 Hia-expressing strains. Neither the HMW1/HMW2 nor the Hia antisera mediated killing of NTHi expressing the alternative adhesin type. Antibodies directed against native HMW1/HMW2 proteins and recombinant Hia proteins are capable of mediating broad-based opsonophagocytic killing of homologous and heterologous NTHi strains. A vaccine formulated with a limited number of HMW1/HMW2 and Hia proteins might provide protection against disease caused by most NTHi strains. PMID:24574538

Winter, Linda E; Barenkamp, Stephen J

2014-05-01

59

Characterization of a novel type of HMW subunit of glutenin from Australopyrum retrofractum.  

PubMed

The Triticeae species Australopyrum retrofractum (genome WW) produces a single high molecular weight glutenin subunit (HMW-GS) in its endosperm. However, degenerate PCR amplification of its genome DNA revealed the presence of two related HMW-GS sequences, each consisting of an open reading frame. One of these (Glu-W1-2) has not previously been reported. Here, we sequenced Glu-W1-2 and showed that it encodes the same type of HMW-GS as Glu-W1-1, although its overall product length was much shorter, because the number of certain repetitive motifs was lower in its central region. Both A. retrofractum HMW-GSs have a unique repetitive motif, which differentiates them from other known x- and y-type subunits present in Triticeae species. We suggest that A. retrofractum must have diverged from the main Triticeae lineage prior to the Glu-1 duplication event which led to the evolution of the x- and y-type genes. PMID:22115575

Li, Fei; Jiang, Xilong; Wei, Yanfeng; Xia, Guangmin; Liu, Shuwei

2012-01-15

60

The wheat D-genome HMW-glutenin locus: BAC sequencing, gene distribution, and retrotransposon clusters.  

PubMed

A bacterial-artificial-chromosome (BAC) clone from the genome of Triticum tauschii, the D-genome ancestor of hexaploid bread wheat, was sequenced and the presence of the two paralogous x- and y-type high-molecular-weight (HMW) glutenin genes of the Glu-D1 locus was confirmed. These two genes occur in the same orientation, are 51,893 bp apart, and the separating DNA includes a 31,000-bp cluster of retrotransposons. A second retrotransposon cluster of 32,000 bp follows the x-type HMW-glutenin gene region. Each HMW-glutenin gene is found within a region of mainly unique DNA sequence which includes multiple additional genes including an active endosperm globulin gene not previously reported in the Triticeae family, a leucine-rich-repeat (LRR) type gene truncated at the 5' end of the BAC, a kinase gene of unknown activity, remnants of a paralogous second globulin gene, and genes similar to two hypothetical rice genes. The newly identified globulin genes are assigned to a locus designated Glo-2. Comparison to available orthologous regions of the wheat A and B genomes show rapid sequence divergences flanking the HMW-glutenin genes, and the absence of two hypothetical and unknown genes found 5' to the B-genome x-type ortholog. The region surrounding the Glu-D1 locus is similar to other reported Triticeae BAC sequences; i.e. small gene islands separated by retrotransposon clusters. PMID:12590343

Anderson, O D; Rausch, C; Moullet, O; Lagudah, E S

2003-03-01

61

Novel variants of HMW glutenin subunits from Aegilops section Sitopsis species in relation to evolution and wheat breeding  

PubMed Central

Background High molecular weight glutenin subunits (HMW-GSs), encoded by the genes at Glu-1 loci in wheat and its related species, are significant in the determination of grain processing quality. However, the diversity and variations of HMW-GSs are relatively low in bread wheat. More interests are now focused on wheat wild relatives in Triticeae. The genus Aegilops represents an important germplasm for novel HWM-GSs and other useful genes for wheat genetic improvement. Results Six novel Glu-1 alleles and HMW-GSs were identified and characterized from three species of Aegilops section Sitopsis (S genome). Both open reading frames (ORFs) and promoter regions of these Glu-1 alleles were sequenced and characterized. The ORFs of Sitopsis Glu-1 genes are approximately 2.9?kb and 2.3?kb for x-type and y-type subunits, respectively. Although the primary structures of Sitopsis HMW-GSs are similar to those of previously reported ones, all six x-type or y-type subunits have the large fragment insertions. Our comparative analyses of the deduced amino acid sequences verified that Aegilops section Sitopsis species encode novel HMW-GSs with their molecular weights larger than almost all other known HMW-GSs. The Glu-1 promoter sequences share the high homology among S genome. Our phylogenetic analyses by both network and NJ tree indicated that there is a close phylogenetic evolutionary relationship of x-type and y-type subunit between S and D genome. Conclusions The large molecular weight of HMW-GSs from S genome is a unique feature identified in this study. Such large subunits are resulted from the duplications of repetitive domains in Sitopsis HMW-GSs. The unequal crossover events are the most likely mechanism of variations in glutenin subunits. The S genome-encoded subunits, 1Dx2.2 and 1Dx2.2* have independent origins, although they share similar evolutionary mechanism. As HMW-GSs play a key role in wheat baking quality, these large Sitopsis glutenin subunits can be used as special genetic resources for wheat quality improvement. PMID:22646663

2012-01-01

62

Adiponectin resistance and pro-inflammatory changes in the visceral adipose tissue induced by fructose consumption via ketohexokinase-dependent pathway.  

PubMed

An epidemic of obesity and type 2 diabetes is linked with the increase in consumption of fructose-containing sugars, such as sucrose and high fructose corn syrup (HFCS). In mammalian cells, fructose is metabolized predominantly via phosphorylation to fructose-1 phosphate by ketohexokinase (KHK) or by alternative pathways. Here we demonstrate that KHK-dependent pathway mediates insulin resistance and inflammatory changes in the visceral fat in response to high fructose.We used mice (males, C57BL/6 background) including littermate wild type control and mice lacking both isoforms of KHK (KHK-null).Fructose diet induced metabolic syndrome including visceral obesity, insulin resistance, proinflammatory changes in the visceral fat (production of proinflammatory adipokines and macrophage infiltration), the endoplasmic reticulum (ER) stress signaling, and decrease of the high molecular weight (HMW) adiponectin followed by decrease in the downstream signaling. KHK-KO mice consuming the same high fructose diet remained lean, with normal insulin sensitivity and healthy visceral adipose tissue with normal adiponectin function not distinguishable from the control by any of the tested parameters.This study demonstrates that blocking KHK and redirecting fructose metabolism to alternative pathways is an effective way to prevent visceral obesity and insulin resistance induced by high fructose, a widespread component of Western diets. PMID:25187370

Marek, George; Pannu, Varinderpal; Shanmugham, Prashanth; Pancione, Brianna; Mascia, Dominic; Crosson, Sean; Ishimoto, Takuji; Sautin, Yuri Y

2014-09-01

63

Generation of novel high quality HMW-GS genes in two introgression lines of Triticum aestivum/Agropyron elongatum  

PubMed Central

Background High molecular weight glutenin subunits (HMW-GS) have been proved to be mostly correlated with the processing quality of common wheat (Triticum aestivum). But wheat cultivars have limited number of high quality HMW-GS. However, novel HMW-GS were found to be present in many wheat asymmetric somatic hybrid introgression lines of common wheat/Agropyron elongatum. Results To exploit how these new subunits were generated, we isolated HMW-GS genes from two sib hybrid lines (II-12 and 11-4-6) and compared them with those from their parents. The result shows that two genes of hybrid (H11-3-3 and H11-4-3) are directly introgressed from the donor parent Agropyron elongatum; one hybrid gene (H1Dx5) comes from point mutation of a parental wheat gene (1Dx2.1); two other hybrid genes (H1By8 and H1By16) are likely resulting from unequal crossover or slippage of a parental wheat gene (1By9.1); and the sixth novel hybrid gene (H1Dy12) may come from recombination between two parental genes. Conclusion Therefore, we demonstrate that novel HMW-GS genes can be rapidly created through asymmetric somatic hybridization in a manner similar with the evolution mechanism of these genes supposed before. We also described gene shuffling as a new mechanism of novel HMW-GS gene formation in hybrids. The results suggest that asymmetric somatic hybridization is an important approach for widening HMW-GS genebank of wheat quality improvement. PMID:17502002

Liu, Shuwei; Zhao, Shuangyi; Chen, Fanguo; Xia, Guangmin

2007-01-01

64

Molecular characterisation and evolution of HMW glutenin subunit genes in Brachypodium distachyon L.  

PubMed

Brachypodium distachyon, a small wild grass within the Pooideae family, is a new model organism for exploring the functional genomics of cereal crops. It was shown to have close relationships to wheat, barley and rice. Here, we describe the molecular characterisation and evolutionary relationships of high molecular weight glutenin subunits (HMW-GS) genes from B. distachyon. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), high performance capillary electrophoresis (HPCE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses demonstrated that there was no HMW-GS expression in the Brachypodium grains due to the silencing of their encoding genes. Through allele-specific polymerase chain reaction (AS-PCR) amplification and cloning, a total of 13 HMW-GS encoding genes from diploid, tetraploid and hexaploid Brachypodium species were obtained, and all of them had typical structural features of y-type HMW-GS genes from common wheat and related species, particularly more similar to the 1Dy12 gene. However, the presence of an in-frame premature stop codon (TAG) at position 1521 in the coding region resulted in the conversion of all the genes to pseudogenes. Further, quantitative real-time PCR (qRT-PCR) analysis revealed that HMW-GS genes in B. distachyon displayed a similar trend, but with a low transcriptional expression profile during grain development due to the occurrence of the stop codon. Phylogenetic analysis showed that the highly conserved Glu-1-2 loci were presented in B. distachyon, which displayed close phylogenetic evolutionary relationships with Triticum and related species. PMID:24306693

Subburaj, Saminathan; Chen, Guanxing; Han, Caixia; Lv, Dongwen; Li, Xiaohui; Zeller, Friedrich J; Hsam, Sai L K; Yan, Yueming

2014-02-01

65

Cloning, expression and functional analysis of HMW glutenin subunit 1By8 gene from Italy pasta wheat ( Triticum turgidum L. ssp. durum)  

Microsoft Academic Search

Cloning and functional analysis of high molecular weight wheat glutenin subunit (HMW-GS) 1By8 from Italy durum cultivar Simeto was carried out in this study. All HMW-GS from Simeto were separated and characterized by appropriate electrophoresis methods, reversed-phased high performance liquid chromatography (RP-HPLC) and mass spectrometry (MS). The complete gene encoding 1By8 subunit was amplified by allele-specific PCR primers, including an

Y. M. Yan; Y. Jiang; X. L. An; Y. H. Pei; X. H. Li; Y. Z. Zhang; A. L. Wang; Z. Heb; X. Xia; F. Bekes; W. Ma

2009-01-01

66

High frequency of HMW-GS sequence variation through somatic hybridization between Agropyron elongatum and common wheat.  

PubMed

A symmetric somatic hybridization was performed to combine the protoplasts of tall wheatgrass (Agropyron elongatum) and bread wheat (Triticum aestivum). Fertile regenerants were obtained which were morphologically similar to tall wheatgrass, but which contained some introgression segments from wheat. An SDS-PAGE analysis showed that a number of non-parental high-molecular weight glutenin subunits (HMW-GS) were present in the symmetric somatic hybridization derivatives. These sequences were amplified, cloned and sequenced, to deliver 14 distinct HMW-GS coding sequences, eight of which were of the y-type (Hy1-Hy8) and six x-type (Hx1-Hx6). Five of the cloned HMW-GS sequences were successfully expressed in E. coli. The analysis of their deduced peptide sequences showed that they all possessed the typical HMW-GS primary structure. Sequence alignments indicated that Hx5 and Hy1 were probably derived from the tall wheatgrass genes Aex5 and Aey6, while Hy2, Hy3, Hx1 and Hy6 may have resulted from slippage in the replication of a related biparental gene. We found that both symmetric and asymmetric somatic hybridization could promote the emergence of novel alleles. We discussed the origination of allelic variation of HMW-GS genes in somatic hybridization, which might be the result from the response to genomic shock triggered by the merger and interaction of biparent genomes. PMID:19902245

Gao, Xin; Liu, Shu Wei; Sun, Qun; Xia, Guang Min

2010-01-01

67

Adiponectin and resistin in the neonatal rat  

Microsoft Academic Search

Hypoxia is a common neonatal stress that induces insulin resistance and a decrease in body weight gain. Dexamethasone is often\\u000a used to treat neonatal cardiopulmonary disease, and also leads to insulin resistance and a decrease in body weight gain. The\\u000a current study addressed the hypothesis that serum concentrations of the adipokines adiponectin and\\/or resistin are altered\\u000a during hypoxia and\\/or dexamethasone

Hershel Raff; Eric D. Bruder

2006-01-01

68

Effects of interventions on adiponectin and adiponectin receptors  

PubMed Central

Adiponectin secreted from adipose tissue binds to two distinct adiponectin receptors (AdipoR1 and AdipoR2) identified and exerts its anti-diabetic effects in insulin-sensitive organs including liver, skeletal muscle and adipose tissue as well as amelioration of vascular dysfunction in the various vasculatures. A number of experimental and clinical observations have demonstrated that circulating levels of adiponectin are markedly reduced in obesity, type 2 diabetes, hypertension, and coronary artery disease. Therapeutic interventions which can improve the action of adiponectin including elevation of circulating adiponectin concentration or up-regulation and/or activation of its receptors, could provide better understanding of strategies to ameliorate metabolic disorders and vascular disease. The focus of the present review is to summarize accumulating evidence showing the role of interventions such as pharmacological agents, exercise, and calorie restriction in the expression of adiponectin and adiponectin receptors. PMID:24877039

Lee, Sewon; Kwak, Hyo-Bum

2014-01-01

69

Identification of chromosome arms influencing expression of the HMW glutenins in wheat.  

PubMed

The high-molecular-weight (HMW) glutenin genes, located on the group 1L chromosome arms, are a major determinant for baking quality in wheat ( Triticum aestivum L.). In addition, the HMW glutenin genes provide a valuable model system for studying the evolution and regulation of orthologous and paralogous genes in polyploid species. The goal of this study was to identify loci that modify the expression of the HMW glutenins, and to map them to specific chromosome arms. Comparisons were made between endosperms with zero versus three (or three versus six) doses for each of the 42 chromosome arms of wheat. SDS-PAGE and scanning densitometry were used to quantify the protein expression levels of the four HMW glutenin genes in cv. Chinese Spring, for each of the dosage comparisons. Fifteen chromosome arms were found to have significant effects on Glu-B1-1, excluding the structural gene dosage effect: eight positive effects on 1AL, 2AS, 2BL, 2DS, 5DS, 6AL, 6DL, and 7AL and seven negative effects on 1BS, 1DS, 1DL, 4DL, 6BS, 6DS, and 7AS. Nineteen chromosome arms had significant effects on Glu-B1-2, excluding the structural gene dosage effect: eight positive effects on 1AL, 2AS, 2BS, 3AL, 4BL, 6DS, 7BL and 7DS and 11 negative effects on 1AS, 1BS, 1DS, 1DL, 2AL, 2BL, 3DS, 4BS, 4DL, 5BL, and 6BS. Twenty chromosome arms had significant effects on Glu-D1-1, excluding the structural gene dosage effect: 11 positive effects on 1AL, 1BL, 2BS, 2DS, 5BS, 5DS, 6AL, 6DS, 6DL, 7AL, and 7BL and nine negative effects on 1AS, 1BS, 1DS, 2BL, 4DL, 5BL, 5DL, 6BL, and 7DS. Twenty-five chromosome arms had significant effects on Glu-D1-2, excluding the structural gene dosage effect: 17 positive effects on 1BL, 2AS, 2BS, 2DS, 2DL, 3AS, 3AL, 3BS, 5AS, 5BS, 5DL, 6AL, 6DL, 7AL, 7BS, 7BL, and 7DL and eight negative effects on 1DS, 4DL, 5AL, 5BL, 6BS, 6BL, 6DS and 7DS. Of the 164 gene-chromosome arm tests performed, about 52% (85/164) showed no significant effects, and 48% (79/164) showed significant effects, excluding the structural gene dosage effects. Of the significant effects, 56% (44/79) were positive effects, and 44% (35/79) were negative effects. Comparisons of dosage effects on orthologous loci (both x-type or both y-type HMW glutenins) showed that orthologous HMW glutenin genes are largely influenced by the same regulatory systems. Less correlation was found for comparisons between paralogous genes, although considerable conservation was observed at this level as well. These observations suggest that after polyploidization, many of the duplicated orthologous regulatory loci were inactivated by mutation, thus consolidating control over the HMW glutenin genes. Possible candidates for orthologous regulatory genes were identified in maize and barley. This study represents the first comprehensive search of the wheat genome for regulators of the HMW glutenins. PMID:12582846

Wanous, M K; Munkvold, J D; Kruse, J D; Brachman, E E; Klawiter, M A; Fuehrer, K J

2003-01-01

70

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. PMID:22815927

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

71

Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): Evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation  

PubMed Central

Exposure to bisphenol A (BPA) is implicated in many aspects of metabolic disease in humans and experimental animals. We fed pregnant CD-1 mice BPA at doses ranging from 5 to 50,000 ?g/kg/day, spanning 10-fold below the reference dose to 10-fold above the currently predicted no adverse effect level (NOAEL). At BPA doses below the NOAEL that resulted in average unconjugated BPA between 2 and 200pg/ml in fetal serum (AUC0–24h),we observed significant effects in adult male offspring: an age-related change in food intake, an increase in body weight and liver weight, abdominal adipocyte mass, number and volume, and in serum leptin and insulin, but a decrease in serum adiponectin and in glucose tolerance. For most of these outcomes non-monotonic dose–response relationships were observed; the highest BPA dose did not produce a significant effect for any outcome. A 0.1-?g/kg/day dose of DES resulted in some but not all low-dose BPA outcomes. PMID:23892310

Angle, Brittany M.; Do, Rylee Phuong; Ponzi, Davide; Stahlhut, Richard W.; Drury, Bertram E.; Nagel, Susan C.; Welshons, Wade V.; Besch-Williford, Cynthia L; Palanza, Paola; Parmigiani, Stefano; vom Saal, Frederick S.; Taylor, Julia A.

2013-01-01

72

Adiponectin effects on the kidney.  

PubMed

Adiponectin is a 30-kDa polypeptide secreted primarily by adipose tissue and plays a key role in kidney disease. In obesity, reduced adiponectin levels are associated with insulin resistance, cardiovascular disease and obesity related kidney disease. The latter includes microalbuminuria, glomerulomegaly, overt proteinuria and focal segmental glomerulosclerosis. Adiponectin levels in type 2 diabetics also negatively correlate with early features of nephropathy. However, in patients with established chronic kidney disease, adiponectin levels are elevated and positively predict progression of disease. The mechanism of action of adiponectin in the kidney appears to be related to AMPK activation and NADPH oxidase. Further studies are needed to elucidate this pathway and investigate the role of potential targets of adiponectin-AMPK-Nox pathway for CKD as obesity-related CKD is increasing worldwide. PMID:24417947

Sweiss, Natalie; Sharma, Kumar

2014-01-01

73

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

74

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 PMID:2681271

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

1989-01-01

75

GLP-1 and Adiponectin: Effect of Weight Loss After Dietary Restriction and Gastric Bypass in Morbidly Obese Patients with Normal and Abnormal Glucose Metabolism  

Microsoft Academic Search

Background  It has been proposed that there is improvement in glucose and insulin metabolism after weight loss in patients who underwent\\u000a diet restriction and bariatric surgery.\\u000a \\u000a \\u000a \\u000a Methods  Eleven normal glucose tolerant (NGT) morbidly obese patients [body mass index (BMI), 46.1?±?2.27 g\\/m2] and eight abnormal glucose metabolism (AGM) obese patients (BMI, 51.20 kg\\/m2) were submitted to diet-restriction and bariatric surgery. Prospective study on weight loss

Camila Puzzi de Carvalho; Daniela Miguel Marin; Aglécio Luiz de Souza; José Carlos Pareja; Elintom Adami Chaim; Silvia de Barros Mazon; Conceição Aparecida da Silva; Bruno Geloneze; Elza Muscelli; Sarah Monte Alegre

2009-01-01

76

ASSOCIATION BETWEEN ADIPONECTIN, INSULIN RESISTANCE, AND ENDOMETRIAL CANCER  

Technology Transfer Automated Retrieval System (TEKTRAN)

BACKGROUND: Obesity is a well-known risk factor for the development of endometrial cancer; however, weight alone does not account for all cases. The authors hypothesized that insulin resistance also contributes to an increased risk for endometrial cancer. Adiponectin is a protein secreted by adipose...

77

Characterization of HMW-GS and evaluation of their diversity in morphologically elite synthetic hexaploid wheats  

PubMed Central

High molecular weight glutenin subunit composition and variation in 95 Elite-1 synthetic hexaploid (SH) wheats (Triticum turgidum/Aegilops tauschii; 2n = 6× = 42; AABBDD) were determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis method (SDS-PAGE). Twenty two different alleles at Glu-1 loci in SHs were observed. Forty four different patterns of HMW-GS in synthetics were found. This higher HMW glutenin composition was due to higher proportion of D-genome encoded subunits in these SHs. 8% urea/SDS-PAGE better discriminated subunit 2* than 12% gels. However 12% urea/SDS-PAGE allowed differentiated mobility of Glu-Dt1 subunits. Genetic variability at Glu-Dt1 locus was greater than Glu-A1 and Glu-B1 loci. The relative high frequency of superior alleles, Glu-B1b and Glu-Dt1d indicated the superior bread making quality attributes embedded in these synthetic hexaploid wheats. Of the 95 Elite-1 SHs 27.1% possessed superior alleles at Glu-A1 and 51% had superior alleles at Glu-B1 locus. At Glu-Dt1 frequency of inferior allele 1Dx2 + 1Dy12 was very low (5.26%) and nine different rare alleles along with the higher frequency (22.1%) of D-genome encoded subunit, 1Dx5 + 1Dy10, were observed. These superior alleles shall form the priority selective sieve for their usage in wheat improvement efforts. PMID:23341752

Rasheed, Awais; Safdar, Tania; Gul-Kazi, Alvina; Mahmood, Tariq; Akram, Zahid; Mujeeb-Kazi, Abdul

2012-01-01

78

A high-fat maternal diet decreases adiponectin receptor-1 expression in offspring.  

PubMed

Abstract In early life, over-nutrition may increase the risk of insulin resistance in the adult stage. Adiponectin and its receptor may play a key role in this process. This study aimed to identify the effect of a high-fat (HF) maternal diet on metabolic parameters and muscle adiponectin signaling in young adult offspring. We found that offspring born to dams fed HF chow (HF; 31% of calories from fat) had elevated body and adipose tissue weight and higher serum glucose levels after glucose challenge at three weeks (W3) and eight weeks (W8) of age. Offspring exposed to a HF diet also had higher serum adiponectin levels at W3 compared to controls. However, adiponectin levels were significantly decreased compared to controls by W8. Adiponectin receptor 1?mRNA expression in skeletal muscle was decreased in the HF group at W3 and W8, and there was no difference between the two groups in adiponectin receptor 2 expression. Furthermore, glucose transporter 4?mRNA and protein expression was decreased in the skeletal muscle of the HF group at W3 and W8. Our results suggest that a HF maternal diet decreases adiponectin receptor 1 expression in the offspring, which could contribute to reduced sensitivity to adiponectin and to adverse nutritional programing outcomes. PMID:24724805

Hou, Miao; Chu, Zhenyu; Liu, Ting; Lv, Haitao; Sun, Ling; Wang, Bo; Huang, Jie; Yan, Wenhua

2015-01-01

79

ADIPONECTIN SIGNALING IN THE LIVER  

PubMed Central

High glucose production contributes to fed and fasted hyperglycemia in Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). The breakdown of the adiponectin signaling pathway in T1D and the reduction of circulating adiponectin in T2D contribute to this abnormal increase in glucose production. Sufficient amounts of insulin could compensate for the loss of adiponectin signaling in T1D and T2D and reduce hyperglycemia. However, the combination of low adiponectin signaling and high insulin resembles an insulin resistance state associated with cardiovascular disease and decreased life expectancy. Future development of medications that correct the deficiency of adiponectin signaling in the liver could restore the metabolic balance in T1D and T2D and reduce the need for insulin. This article reviews the adiponectin signaling pathway in the liver through T-cadherin, AdipoR1, AdipoR2, AMPK, ceramidase activity, APPL1 and the recently discovered Suppressor Of Glucose from Autophagy (SOGA). PMID:24297186

Combs, Terry P.; Marliss, Errol B.

2014-01-01

80

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. PMID:19196487

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

2009-01-01

81

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. PMID:14638776

Winter, Linda E.; Barenkamp, Stephen J.

2003-01-01

82

Genomic regions influencing gene expression of the HMW glutenins in wheat  

Microsoft Academic Search

Bread wheat (Triticum aestivum L.) produces glutenin storage proteins in the endosperm. The HMW glutenins confer distinct viscoelastic properties to bread\\u000a dough. The genetics of HMW glutenin proteins have been extensively studied, and information has accumulated about individual\\u000a subunits, chromosomal locations and DNA sequences, but little is known about the regulators of the HMW glutenins. This investigation\\u000a addressed the question

Eric W. Storlie; Robert J. Ihry; Leslie M. Baehr; Karissa A. Tieszen; Jonathan H. Engbers; Jordan M. Anderson-Daniels; Elizabeth M. Davis; Anne G. Gilbertson; Niels R. Harden; Kristina A. Harris; Amanda J. Johnson; Amy M. Kerkvleit; Matthew M. Moldan; Megan E. Bell; Michael K. Wanous

2009-01-01

83

Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease?  

PubMed Central

Adiponectin is the most abundant peptide secreted by adipocytes, being a key component in the interrelationship between adiposity, insulin resistance and inflammation. Central obesity accompanied by insulin resistance is a key factor in the development of metabolic syndrome (MS) and future macrovascular complications. Moreover, the remarkable correlation between coronary artery disease (CAD) and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes mellitus (T2DM) may share a common biological background. We summarize here the current knowledge about the influence of adiponectin on insulin sensitivity and endothelial function, discussing its forthcoming prospects and potential role as a therapeutic target for MS, T2DM, and cardiovascular disease. Adiponectin is present in the circulation as a dimer, trimer or protein complex of high molecular weight hexamers, >400 kDa. AdipoR1 and AdipoR2 are its major receptors in vivo mediating the metabolic actions. Adiponectin stimulates phosphorylation and AMP (adenosin mono phosphate) kinase activation, exerting direct effects on vascular endothelium, diminishing the inflammatory response to mechanical injury and enhancing endothelium protection in cases of apolipoprotein E deficiency. Hypoadiponectinemia is consistently associated with obesity, MS, atherosclerosis, CAD, T2DM. Lifestyle correction helps to favorably modify plasma adiponectin levels. Low adiponectinemia in obese patients is raised via continued weight loss programs in both diabetic and nondiabetic individuals and is also accompanied by reductions in pro-inflammatory factors. Diet modifications, like intake of fish, omega-3 supplementation, adherence to a Mediterranean dietary pattern and coffee consumption also increase adiponectin levels. Antidiabetic and cardiovascular pharmacological agents, like glitazones, glimepiride, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are also able to improve adiponectin concentration. Fibric acid derivatives, like bezafibrate and fenofibrate, have been reported to enhance adiponectin levels as well. T-cadherin, a membrane-associated adiponectin-binding protein lacking intracellular domain seems to be a main mediator of the antiatherogenic adiponectin actions. The finding of novel pharmacologic agents proficient to improve adiponectin plasma levels should be target of exhaustive research. Interesting future approaches could be the development of adiponectin-targeted drugs chemically designed to induce the activaton of its receptors and/or postreceptor signaling pathways, or the development of specific adiponectin agonists. PMID:24957699

2014-01-01

84

Molecular cloning and comparative analysis of a y-type inactive HMW glutenin subunit gene from cultivated emmer wheat (Triticum dicoccum L.).  

PubMed

Cultivated emmer (Triticum dicoccum, 2n = 4x = 28, AABB) is closely related to bread wheat and possesses extensive allelic variations in high molecular weight glutenin subunit (HMW-GS) composition. These alleles may be an important genetic resource for wheat quality improvement. To isolate and clone HMW-GS genes from cultivated emmer, two pairs of allele-specific (AS) PCR primers were designed to amplify the coding sequence of y-type HMW-GS genes and their upstream sequences, respectively. The results showed that single bands of strong amplification were obtained through AS-PCR of genomic DNA from emmer. After cloning and sequencing the complete sequence of coding and 5'-flanking regions of a y-type subunit gene at Glu-A1 locus was obtained. Nucleotide and deduced amino acid sequences analysis showed that this gene possessed a similar structure as the previously reported Ay gene from common wheat, and is hence designated as Ay1d. The distinct feature of the Ay1d gene is that its coding region contains four stop codons and its upstream region has a 85-bp deletion in the same position of the Ay gene, which are probably responsible for the silencing of y-type subunit genes at Glu-A1 locus. Phylogenetic analysis of HMW glutenin subunit genes from different Triticum species and genomes were also carried out. PMID:15383071

Sun, Minmin; Yan, Yueming; Jiang, Yi; Xiao, Yinghua; Hu, Yingkao; Cai, Minhua; Li, Yaxuan; Hsam, Sai L K; Zeller, Friedrich J

2004-01-01

85

Multifaceted roles of Adiponectin in cancer  

PubMed Central

Obesity is linked to increased cancer risk. Pathological expansion of adipose tissue impacts adipocyte function and secretion of hormonal factors regulating tissue homeostasis and metabolism. Adiponectin is an adipocytesecreted, circulating hormone with pleiotropic functions in lipid and glucose metabolism, and beneficial roles in cardiovascular functions and inflammation. In obesity, decreased Adiponectin plasma levels correlate with tumor development and progression. The association of Adiponectin with potential tumor-limiting functions has raised significant interest in exploring this adipokine as a target for cancer-diagnostic and therapeutic applications. Recent studies, however, also implicate Adiponectin in supporting malignancy. This review highlights the evidence that links Adiponectin signaling to either cancer-protective or cancer-supporting functions. In this context, we discuss Adiponectin interactions with its receptors and associated signaling pathways. Despite significant advances in understanding Adiponectin functions and signaling mechanisms, its role in cancer remains multifaceted and subject to controversy. PMID:24417946

Hebbard, Lionel; Ranscht, Barbara

2014-01-01

86

Differential Effects of Leptin and Adiponectin in Endothelial Angiogenesis  

PubMed Central

Obesity is a major health burden with an increased risk of cardiovascular morbidity and mortality. Endothelial dysfunction is pivotal to the development of cardiovascular disease (CVD). In relation to this, adipose tissue secreted factors termed “adipokines” have been reported to modulate endothelial dysfunction. In this review, we focus on two of the most abundant circulating adipokines, that is, leptin and adiponectin, in the development of endothelial dysfunction. Leptin has been documented to influence a multitude of organ systems, that is, central nervous system (appetite regulation, satiety factor) and cardiovascular system (endothelial dysfunction leading to atherosclerosis). Adiponectin, circulating at a much higher concentration, exists in different molecular weight forms, essentially made up of the collagenous fraction and a globular domain, the latter being investigated minimally for its involvement in proinflammatory processes including activation of NF-?? and endothelial adhesion molecules. The opposing actions of the two forms of adiponectin in endothelial cells have been recently demonstrated. Additionally, a local and systemic change to multimeric forms of adiponectin has gained importance. Thus detailed investigations on the potential interplay between these adipokines would likely result in better understanding of the missing links connecting CVD, adipokines, and obesity. PMID:25650072

Adya, Raghu; Tan, Bee K.; Randeva, Harpal S.

2015-01-01

87

Effects of sugar-sweetened beverages on plasma acylation stimulating protein, leptin, and adiponectin: Relationships with metabolic outcomes  

Technology Transfer Automated Retrieval System (TEKTRAN)

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 over...

88

Homoeologous recombination within bread wheat to develop novel combinations of HMW-GS genes: transfer of the Glu-A1 locus to chromosome 1D  

Microsoft Academic Search

In an attempt to improve the bread-making quality within hexaploid wheat by elaborating novel high-molecular weight glutenin\\u000a subunits (HMW-GS) combinations useful in wheat-breeding programmes, a 1A chromosome fragment carrying the Glu-A1 locus encoding the subunit Ax2*, was translocated to the long arm of chromosome 1D. The partially isohomoeoallelic line,\\u000a designated RR239, had a meiotic behaviour as regular as cv. Courtot.

Jérôme Dumur; Gérard Branlard; Anne-Marie Tanguy; Mireille Dardevet; Olivier Coriton; Virginie Huteau; Jocelyne Lemoine; Joseph Jahier

2009-01-01

89

Molecular cloning, heterologous expression, and phylogenetic analysis of a novel y-type HMW glutenin subunit gene from the G genome of Triticum timopheevi.  

PubMed

A novel y-type high molecular weight (HMW) glutenin subunit gene from the G genome of Triticum timopheevi (2n=4x=28, AAGG) was isolated and characterized. Genomic DNA from accession CWI17006 was amplified and a 2200 bp fragment was obtained. Sequence analysis revealed a complete open reading frame including N- and C-terminal ends and a central repetitive domain encoding 565 amino acid residues. The molecular weight of the deduced subunit was 77,031, close to that of the x-type glutenin subunits. Its mature protein structure, however, demonstrated that it was a typical y-type HMW subunit. To our knowledge, this is the largest y-type subunit gene among Triticum genomes. The molecular structure and phylogenetic analysis assigned it to the G genome and it is the first characterized y-type HMW glutenin subunit gene from T. timopheevi. Comparative analysis and secondary structure prediction showed that the subunit possessed some unique characters, especially 2 large insertions of 45 (6 hexapeptides and a nonapeptide) and 12 (2 hexapeptides) amino acid residues that mainly contributed to its higher molecular weight and allowed more coils to be formed in its tertiary structure. Additionally, more alpha-helixes in the repeat domain of the subunit were found when compared with 3 other y-type subunits. We speculate that these structural characteristics improve the formation of gluten polymer. The novel subunit, expressed as a fusion protein in E. coli, moved more slowly in SDS-PAGE than the subunit Bx7, so it was designated Gy7*. As indicated in previous studies, increased size and more numerous coils and alpha-helixes of the repetitive domain might enhance the functional properties of HMW glutenins. Consequently, the novel Gy7* gene could have greater potential for improving wheat quality. PMID:18059540

Li, Xiaohui; Zhang, Yanzhen; Gao, Liyan; Wang, Aili; Ji, Kangmin; He, Zhonghu; Appels, Rudi; Ma, Wujun; Yan, Yueming

2007-12-01

90

Two quality-associated HMW glutenin subunits in a somatic hybrid line between Triticum aestivum and Agropyron elongatum  

PubMed Central

High-molecular-weight glutenin subunits (HMW-GSs) from hybrid line II-12 between wheat (Triticum aestivum L.) and Agropyron elongatum (Host) Nivski were characterized with SDS-PAGE. Out of these HMW-GSs, two subunits, h1Bx and h1By, had mobilities similar to the subunits 1Bx13 and 1By16 from common wheat 4072, which was used as control. Polyclonal antibodies (pAbs) of h1Bx and h1By were prepared, and Western blotting showed that the pAbs had strong affinities for h1Bx and h1By, separately. The specificity of h1Bx-pAb was further checked; it preferentially recognized subunits h1Bx and 1Bx13. HMW-GS gene coding sequences were amplified by genomic polymerase chain reaction from hybrid II-12. Two of the five amplicons, marked II2a and II31b, were sequenced. Their coding sequences are clustered to Glu-1Bx7 and Glu-1By9 of common wheat. Three discrepant regions in deduced amino acid sequences of II2a and 31b repeated one time more than Glu-1Bx7 and Glu-1By9. N-terminal sequences of h1Bx and h1By were determined, which were identical to the published sequences of 1Bx13 and 1By16 and in agreement with that deduced from II2a and II31b, respectively. These results indicated that the two novel genes separated from the hybrid wheat derived from the allelic variation of 1Bx7 and 1By9 of the parent wheat. There is an additional cysteine residue positioned at 271st amino acid of the mature peptide of II2a, which may be related to the high quality of the flour. PMID:15551037

Feng, Deshun; Zhao, Shuangyi; Chen, Fanguo

2004-01-01

91

Adiponectin in renal disease: Relationship to phenotype and genetic variation in the gene encoding adiponectin  

Microsoft Academic Search

Adiponectin in renal disease: Relationship to phenotype and genetic variation in the gene encoding adiponectin.BackgroundThe prevalence of cardiovascular disease (CVD) and inflammation is high in patients with end-stage renal disease (ESRD). Adiponectin 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.MethodsIn a cohort of

PETER STENVINKEL; ALICIA MARCHLEWSKA; ROBERTO PECOITS-FILHO; OLOF HEIMBÜRGER; ZHENGZHONG ZHANG; CATHERINE HOFF; CLIFF HOLMES; JONAS AXELSSON; SIVONNE ARVIDSSON; MARTIN SCHALLING; PETER BARANY; BENGT LINDHOLM; LOUISE NORDFORS

2004-01-01

92

Effect of ovariectomy on serum adiponectin levels and visceral fat in rats.  

PubMed

This study was aimed to examine the effect of ovariectomy on visceral fat, serum adiponectin levels and lipid profile. Forty-five female Sprague Dawley rats were divided into three groups (n=15 each): ovariectomized group (OVX), ovariectomized plus estrogen-treated group (OVX+E2), and sham-operated group (SHAM). Body weight, abdominal adipose tissues, serum adiponectin and lipid profile were measured and compared among the groups after three-month feeding post-surgery. Significant increases in body weight and visceral fat were found in ovariectomized rats when compared with sham-operated ones and significant increases were also observed in serum adiponectin, triglyceride and very low density lipoprotein cholesterol levels in ovariectomized rats. Body weight, visceral fat and serum adiponectin levels were profoundly reduced in OVX+E2 group as compared with OVX group. It was concluded that ovarian hormone deficiency induced by ovariectomy leads to significant increases in body weight and visceral fat, along with increased serum adiponectin, triglyceride and very low density lipoprotein cholesterol levels in rats. Attenuation in these changes can be achieved by estrogen supplementation. PMID:25480577

Camara, Ce; Zhou, Lin-Yuan; Ma, Yan; Zhu, Lin; Yu, Dong; Zhao, Yao-Wu; Yang, Nian-Hong

2014-12-01

93

Adiponectin Actions in the Cardiovascular System  

PubMed Central

Obesity is strongly associated with the pathogenesis of type 2 diabetes, hypertension, and cardiovascular disease. Levels of the hormone adiponectin are downregulated in obese individuals, and several experimental studies show that adiponectin protects against the development of various obesity-related metabolic and cardiovascular diseases. Adiponectin exhibits favorable effects on atherogenesis, endothelial function, and vascular remodeling by modulation of signaling cascades in cells of the vasculature. More recent findings have shown that adiponectin directly affects signaling in cardiac cells and is beneficial in the setting of pathological cardiac remodeling and acute cardiac injury. Several of these effects of adiponectin have been attributed to the activation of the 5’ AMP-activated protein kinase signaling cascade and other signaling proteins. This review will discuss epidemiological and experimental studies that have elucidated the role of adiponectin in a variety of cardiovascular diseases. PMID:17140553

Hopkins, Teresa A.; Ouchi, Noriyuki; Shibata, Rei; Walsh, Kenneth

2007-01-01

94

Adiponectin Gene Is Expressed in Multiple Tissues in the Chicken: Food Deprivation Influences Adiponectin  

E-print Network

mammalian species. Deletion of the adiponectin gene induces insulin resistance in mice fed with high-fat/high-sugar lipid oxidation (13, 14). Overfeeding and obesity decreases blood adiponectin concentrations, whereas obese mice (16). In addition, adiponectin acts in the brain to bring about increased energy expenditure

Ramachandran, Ramesh

95

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

96

Adipocyte iron regulates adiponectin and insulin sensitivity  

PubMed Central

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.

2012-01-01

97

Adiponectin and visfatin may serve as diagnosis markers for metabolic syndrome in Uygur population  

PubMed Central

Objectives: This study is to determine if two adipocytokines, adiponectin and visfatin, can be used as diagnosis markers for metabolic syndrome (MS) in Uygur population. Methods: Sixty-two MS patients and 41 control individuals with normal body weights were enrolled in this study. Abdominal subcutaneous and omental adipose tissues were collected for determination of biochemical indices. The adipokines serum levels were determined by enzyme-linked immunosorbent assay (ELISA). Blood were collected from the MS patients and the control individuals and extracted proteins and RNAs subjected to western blot analysis and real-time PCR to determine adiponectin and visfatin expression, respectively. Results: ELISA indicated that the serum adiponectin in the MS group was decreased (0.59 ± 0.21 versus 0.49 ± 0.18) in comparison with the control group (P < 0.05). But the serum visfatin in the MS group were increased (1.07 ± 0.41 versus 1.25 ± 0.32) when compared with the control group (P < 0.05). The western blot revealed decreased adiponectin and increased visfatin expression in the MS patients when compared with the normal controls. Further real-time RT-PCR analysis showed that the adiponectin and visfatin expression are altered via a transcriptional mechanism. Conclusions: Adiponectin and visfatin might be used as diagnosis markers of MS in Uygur population. PMID:25550948

Chang, Xi; Jiao, Yi; Lu, Jianfei; Wang, Yanjiao; Abudureyimu, Kelim; Zhang, Cheng; Nuermaimaiti, Nuerbiye; Gong, Xian; Aisa, Yiliyasi; Guan, Yaqun

2014-01-01

98

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. PMID:23418545

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

99

Identification and molecular characterisation of HMW glutenin subunit 1By16* in wild emmer.  

PubMed

In this study, a novel y-type high molecular weight glutenin subunit (HMW-GS) in wild emmer wheat Triticum turgidum L. var. dicoccoides (Körn.) accession KU1952 was identified by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), capillary electrophoresis (CE) and matrix-assisted laser desorption ionisation/time-of-flight/mass spectrometry (MALDI-TOF-MS). Its electrophoretic mobility and molecular weight were similar to those of 1By16 and was designated as 1By16*. The complete coding sequence of the 1By16* gene isolated by allelic-specific polymerase chain reaction (AS-PCR) consists of 2,157 bp, encoding 729 amino acid residues. The real presence and authenticity of the 1By16* gene in KU1952 were further confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), heterologous expression and Western blotting. The molecular structure as well as phylogenetic analysis revealed that 1By16* had 21 single-nucleotide polymorphism (SNP) variations and possessed greater similarity with superior quality subunits 1By15 and 1By16 of common wheat. Secondary structure prediction displayed higher ?-helix and ?-strand contents in the 1By16* subunit, which could form a superior gluten structure and, consequently, might have positive effects on dough quality. Our results suggest that 1By16* is expected to be a new potential gene for wheat quality improvement. PMID:22644727

Jin, M; Xie, Z-Z; Ge, P; Li, J; Jiang, S-S; Subburaj, S; Li, X-H; Zeller, F-J; Hsam, S-L-K; Yan, Y-M

2012-08-01

100

Adiponectin Abates Atherosclerosis by Reducing Oxidative Stress  

PubMed Central

Background We investigated whether the anti-atherosclerosis of adiponectin (APN) relates to the reduction of oxidative stress. We observed the overexpression of adiponectin gene with different titers on atherosclerosis (AS) models of high-fat apolipoprotein E-deficient (ApoE?/?) mice. Material/Methods We divided 48 male ApoE?/? mice into 4 groups: control group, high-fat diet group, low adiponectin group, and high adiponectin group. The low and high adiponectin group mice were treated with recombinant adenovirus expressing mice adiponectin (Ad-APN) with low-dose adiponectin 1.0×108 p.f.u. and high-dose adiponectin 5.0×108 p.f.u. via the tail every 2 weeks and given a high-fat diet for the last 8 weeks. On the 14th day after injection, blood samples were obtained from the vena cava. Results Along with increased serum adiponectin, serum superoxide dismutase (SOD) activity increased (P<0.05) and concentration of malondialdehyde (MDA) was decreased (P<0.05). Levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were decreased, especially TC and LDL-C (P<0.05). A real-time fluorescent quantitative polymerase chain reaction test was used to analyze levels of mRNA expression for endothelial nitric oxide synthase (eNOS) and adiponectin in the aorta. Along with increased adiponectin, the mRNA expression of eNOS in the aorta was increased significantly (P<0.05). The lesion formation in the aortic sinus was inhibited by 25% and 31% in the low-APN group and high-APN group, respectively (P<0.05). Along with the increase of adiponectin doses, the damage of atherosclerosis gradually eased. However, the differences between the low-APN group and high-APN group had no statistical significance. Conclusions Adiponectin may protect the aorta from atherosclerosis injury by reducing oxidative stress, reducing lesion formation size in the aortic root and reducing TC, TG, and LDL-C in serum. The molecular mechanism may involve preservation of SOD, reducing MDA in serum, and increasing eNOS and adiponectin mRNA expression in the aorta. PMID:25275545

Wang, Xuemei; Pu, Hongwei; Ma, Chuang; Jiang, Tao; Wei, Qin; Duan, Mingjun; Zhang, Chun; Shou, Xi; Su, Lipin; Zhang, Jianlong; Yang, Yining

2014-01-01

101

Interactions between adiponectin, visfatin, and omentin in subcutaneous and visceral adipose tissues and serum, and correlations with clinical and peripheral metabolic factors.  

PubMed

Adiponectin, visfatin, and omentin are adipokines involved in insulin sensitivity. This study aimed to determine interactions between these adipokines in subcutaneous and visceral fat and in serum, and their associations with clinical factors. Adiponectin was present at the highest levels in subcutaneous and visceral fat and serum. Subcutaneous adiponectin showed positive correlations with serum adiponectin and the quantitative insulin sensitivity check index (QUICKI). Serum adiponectin correlated positively with QUICKI and serum omentin-1 but negatively with body weight, BMI, and homeostasis model assessment of insulin resistance (HOMA-IR). Subcutaneous omentin correlated positively with QUICKI but negatively with waist and hip circumferences. Serum omentin-1 correlated positively with QUICKI but negatively with body weight, BMI, waist and hip circumferences, weight gain, and HOMA-IR. Serum visfatin correlated positively with serum omentin-1 and negatively with weight gain. Serum peptide YY (PYY) levels were correlated positively with subcutaneous visfatin but negatively with visceral visfatin. Positive correlations were observed between subcutaneous expression of adiponectin, visfatin, and omentin and visceral expression of these genes. Multiple linear regression analysis showed that serum adiponectin was associated with BMI and QUICKI. Serum omentin-1 could be predicted from BMI, QUICKI, and weight gain. Weight gain, serum adiponectin, omentin-1, and DBP could be used to predict serum visfatin. In conclusion, adiponectin and omentin from subcutaneous fat displayed correlations with decreased obesity and increased insulin sensitivity while visfatin showed an association with serum PYY and weight gain. The expressions of these adipokines were correlated within each type of fat but not between different fat depots. PMID:25453978

Sitticharoon, Chantacha; Nway, Nay Chi; Chatree, Saimai; Churintaraphan, Malika; Boonpuan, Peerada; Maikaew, Pailin

2014-12-01

102

Long-term globular adiponectin administration improves adipose tissue dysmetabolism in high-fat diet-fed Wistar rats.  

PubMed

Adiponectin administration to obese or type 2 diabetic patients is still far off, due to its expensive costs and absence of studies demonstrating the effectiveness of its chronic administration. We performed long-term globular adiponectin administration, testing its usefulness in improving adipose tissue metabolism. Adiponectin (98??g/day) was administered through a subcutaneous minipump with continued release (28 days) to Wistar rats fed a high-fat diet. Adiponectin decreased body weight and adipocyte size, while decreasing circulating leptin levels. More, adiponectin was able to increase IkappaBalpha and PPARgamma levels and to prevent high-fat diet-induced impairment of insulin signalling, especially in epididymal adipose tissue. This resulted in improved glucose profile. High-fat diet caused an impairment of lipolysis in epididymal adipose tissue, which was partially restored by adiponectin treatment. Long-term globular adiponectin administration was able to improve pathways of insulin signalling and lipid storage in adipose tissue of high-fat diet-fed rats, contributing to a better metabolic profile. PMID:25142333

Matafome, P; Rodrigues, T; Pereira, A; Letra, L; Azevedo, H; Paixão, A; Silvério, M; Almeida, A; Sena, C; Seiça, R

2014-10-01

103

Low Serum Adiponectin Levels in Children and Adolescents with Diabetic Retinopathy  

PubMed Central

Objective: The aim of this study was to elucidate the role of adiponectin, leptin, TNF-? and IL-6 on the early detection of the microvascular complications of type I diabetes. Materials and Methods: A total of 88 children were included in the study. There were 60 type I diabetic patients and 28 healthy control children. Results: The gender, age, weight, height, BMI and puberty status characteristics were similar in the patient and control groups (p>0.05). The serum leptin, TNF-? and IL-6 levels were similar between the patient and control groups (p>0.05) and the only difference was in the serum adiponectin level which was higher in the patient group (p:0.042). We also found no association between the adiponectin, leptin, TNF-? and IL-6 levels and diabetes duration (p>0.05). Leptin was high in the pubertal period (p:0.016), while adiponectin TNF-? and IL-6 levels were similar in the prepubertal and pubertal periods (p>0.05). The serum leptin level was high in microalbuminuria patients (p<0.041). The serum adiponectin, TNF-?, and IL-6 levels were not different in patients with and without microalbuminuria (p>0.05). The serum adiponectin level was lower in diabetic retinopathy patients (p:0.003), while the serum leptin level was higher (p:0.003). The TNF-? and IL-6 levels were similar in patients with and without retinopathy (p>0.05). Conclusion: We found increased serum adinopectin levels in children and adolescents with type I diabetes mellitus and low levels in diabetic retinopathy patients. Patients with low serum adiponectin levels and high leptin levels should be more closely monitored for chronic complication development and better metabolic control should be aimed for.

Tasci, Eser; Ozbek, Mehmet Nuri; Onenli-Mungan, Neslihan; Temiz, Fatih; Topaloglu, Ali Kemal; Yuksel, Bilgin

2011-01-01

104

Leptin, Ghrelin, and Adiponectin Evaluation in Transsexual Subjects During Hormonal Treatments  

Microsoft Academic Search

Gender differences in leptin, ghrelin, and adiponectin levels have been described in a normal population. This is important for understanding differences between males and females in the regulation of food intake, weight gain, body fat distribution, and cardiovascular risk. It is unclear how endogenous and exogenous sex hormones may regulate circulating levels of these factors. Transsexuals during hormonal treatment may

EUGENIA RESMINI; GABRIELLA ANDRAGHETTI; ALBERTO REBORA; RENZO CORDERA; LARA VERA; MASSIMO GIUSTI; FRANCESCO MINUTO; DIEGO FERONE

2008-01-01

105

Citrus auraptene acts as an agonist for PPARs and enhances adiponectin production and MCP-1 reduction in 3T3-L1 adipocytes  

SciTech Connect

Citrus fruit compounds have many health-enhancing effects. In this study, using a luciferase ligand assay system, we showed that citrus auraptene activates peroxisome proliferator-activated receptor (PPAR)-{alpha} and PPAR{gamma}. Auraptene induced up-regulation of adiponectin expression and increased the ratio of the amount of high-molecular-weight multimers of adiponectin to the total adiponectin. In contrast, auraptene suppressed monocyte chemoattractant protein (MCP)-1 expression in 3T3-L1 adipocytes. Experiments using PPAR{gamma} antagonist demonstrated that these effects on regulation of adiponectin and MCP-1 expression were caused by PPAR{gamma} activations. The results indicate that auraptene activates PPAR{gamma} in adipocytes to control adipocytekines such as adiponectin and MCP-1 and suggest that the consumption of citrus fruits, which contain auraptene can lead to a partial prevention of lipid and glucose metabolism abnormalities.

Kuroyanagi, Kayo; Kang, Min-Sook; Goto, Tsuyoshi; Hirai, Shizuka; Ohyama, Kana; Kusudo, Tatsuya [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Yu, Rina [Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749 (Korea, Republic of); Yano, Masamichi [Department of Citriculture, National Institute of Fruit Tree Science, Ministry of Agriculture, Forestry and Fisheries, Shimizu, Shizuoka 424-0292 (Japan); Sasaki, Takao [ARKRAY Inc., Kyoto 601-8045 (Japan); Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Kawada, Teruo [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)], E-mail: fat@kais.kyoto-u.ac.jp

2008-02-01

106

Adiponectin induces a20 expression in adipose tissue to confer metabolic benefit.  

PubMed

Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. We detail that mice lacking Reverb? exhibit enhanced fat storage without the predicted increased WAT inflammation or loss of insulin sensitivity. In contrast to most animal models of obesity and obese human patients, Reverb?(-/-) mice exhibit elevated serum adiponectin levels and increased adiponectin secretion from WAT explants in vitro, highlighting a potential anti-inflammatory role of this adipokine in hypertrophic WAT. Indeed, adiponectin was found to suppress primary macrophage responses to lipopolysaccharide and proinflammatory fatty acids, and this suppression depended on glycogen synthase kinase 3? activation and induction of A20. Attenuated inflammatory responses in Reverb?(-/-) WAT depots were associated with tonic elevation of A20 protein and ex vivo shown to depend on A20. We also demonstrate that adipose A20 expression in obese human subjects exhibits a negative correlation with measures of insulin sensitivity. Furthermore, bariatric surgery-induced weight loss was accompanied by enhanced WAT A20 expression, which is positively correlated with increased serum adiponectin and improved metabolic and inflammatory markers, including C-reactive protein. The findings identify A20 as a mediator of adiponectin anti-inflammatory action in WAT and a potential target for mitigating obesity-related pathology. PMID:25190567

Hand, Laura E; Usan, Paola; Cooper, Garth J S; Xu, Lance Y; Ammori, Basil; Cunningham, Peter S; Aghamohammadzadeh, Reza; Soran, Handrean; Greenstein, Adam; Loudon, Andrew S I; Bechtold, David A; Ray, David W

2015-01-01

107

Obesity indices and metabolic markers are related to hs-CRP and adiponectin levels in overweight and obese females.  

PubMed

Obese subjects had increased serum high sensitivity C-reactive protein (hs-CRP), decreased adiponectin levels, and impaired microvascular endothelial function compared to lean subjects. We investigated the relationships of serum hs-CRP, adiponectin and microvascular endothelial function with obesity indices and metabolic markers in overweight and obese female subjects. Anthropometric profile, body fat composition, biochemical analysis, serum hs-CRP and adiponectin levels, and microvascular endothelial function were measured in 91 female subjects. Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Mean age and body mass index (BMI) of subjects were 34.88 (7.87) years and 32.93 (4.82) kg/m(2). hs-CRP levels were positively correlated with weight, BMI, waist circumference, hip circumference, body fat and visceral fat. Adiponectin levels were positively correlated with insulin sensitivity index (HOMA-%S), and inversely correlated with waist hip ratio, triglyceride, fasting insulin and insulin resistance index (HOMA-IR). No relationship was seen between microvascular endothelial function and obesity indices, and metabolic markers. In overweight and obese female subjects, hs-CRP levels were correlated with obesity indices while adiponectin levels were inversely correlated with obesity indices and metabolic markers. No significant relationship was seen between microvascular endothelial function with obesity indices and metabolic markers including hs-CRP and adiponectin in female overweight and obese subjects. PMID:24306161

Sanip, Zulkefli; Ariffin, Farah Diana; Al-Tahami, Belqes Abdullah Mohammed; Sulaiman, Wan Azman Wan; Rasool, Aida Hanum Ghulam

2013-01-01

108

Effects of Pravastatin on Obesity, Diabetes, and Adiponectin in Diet-induced Obese Mice  

Microsoft Academic Search

Objective:The aim of this study was to investigate the in vivo effects of pravastatin on the development of obesity and diabetes in diet-induced obese (DIO) mice.Methods and Procedures:We examined food intake, body-weight changes, visceral white adipose tissue (WAT) adiponectin and resistin levels, and energy metabolism.Results:Treatment with 100 mg\\/kg\\/day pravastatin for 28 days decreased diet-induced weight gain and visceral adiposity. In

Kana Araki; Takayuki Masaki; Isao Katsuragi; Tetsuya Kakuma; Hironobu Yoshimatsu

2008-01-01

109

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

110

Identification of a novel distal enhancer in human adiponectin gene  

Microsoft Academic Search

Adiponectin is exclusively expressed in adipose tissue and secreted from adipocytes, and shows anti-diabetic and anti- atherogenic properties. However, the precise transcriptional mechanism of adiponectin remains elusive. In this study, the 5 0 flanking promoter region of human adiponectin gene was analyzed using UCSC genome browser, and a 10 390-bp fragment, containing an evolutionally conserved region among species, was investigated.

Katsumori Segawa; Morihiro Matsuda; Atsunori Fukuhara; Kentaro Morita; Yosuke Okuno; Ryutaro Komuro; Iichiro Shimomura

2009-01-01

111

Adiponectin and depression: A meta-analysis  

PubMed Central

Adiponectin has been indicated to be linked with depression. In the present study, a meta-analysis was performed to evaluate the association between adiponectin levels and depression. Six studies with a total of 4,220 subjects were selected for inclusion in the analysis. The references were retrieved via PubMed, Cochrane Central Register of Controlled Trials and Embase, and the following Chinese databases: The China National Knowledge Infrastructure, China Biology Medicine disc, VIP Database for Chinese Technical Periodicals and Wan Fang Data. The analyses were performed using Review Manager 5.2 software. The standardized mean difference (SMD) with 95% confidence intervals (CIs) was assessed following pooling the collected data for analysis. A significant association was detected between adiponectin levels and depression in European populations. In the European group of patients with depression, improvements were observed in adiponectin levels (SMD, ?5.00 µg/ml, 95% CI, ?7.13 to ?2.88). The current meta-analysis indicates that patients with patients had a lower adiponectin level when compared to healthy patients in European groups. PMID:25469244

HU, YAOZHI; DONG, XIAOMENG; CHEN, JINBO

2015-01-01

112

Adiponectin and depression: A meta-analysis.  

PubMed

Adiponectin has been indicated to be linked with depression. In the present study, a meta-analysis was performed to evaluate the association between adiponectin levels and depression. Six studies with a total of 4,220 subjects were selected for inclusion in the analysis. The references were retrieved via PubMed, Cochrane Central Register of Controlled Trials and Embase, and the following Chinese databases: The China National Knowledge Infrastructure, China Biology Medicine disc, VIP Database for Chinese Technical Periodicals and Wan Fang Data. The analyses were performed using Review Manager 5.2 software. The standardized mean difference (SMD) with 95% confidence intervals (CIs) was assessed following pooling the collected data for analysis. A significant association was detected between adiponectin levels and depression in European populations. In the European group of patients with depression, improvements were observed in adiponectin levels (SMD, -5.00 µg/ml, 95% CI, -7.13 to -2.88). The current meta-analysis indicates that patients with patients had a lower adiponectin level when compared to healthy patients in European groups. PMID:25469244

Hu, Yaozhi; Dong, Xiaomeng; Chen, Jinbo

2015-01-01

113

A hypothesis: Edaravone exert cardioprotection partly via modulation of adiponectin.  

PubMed

Edaravone has been recognized as a potential protective agent for cardiovascular diseases. It is well known that edaravone can attenuate oxidative stress and inhibit the production of proinflammatory cytokines such as TNF-?. However, the mechanisms behind the cardioprotection of edaravone are still incompletely understood yet. As a primary adipose-derived protein, adiponectin exhibits protective properties on the heart and blood vessels. Accumulative studies have shown that there exists a reciprocal relationship between adiponectin and TNF-?, i.e., adiponectin negatively regulates TNF-? expression, whereas adiponectin expression is inhibited by TNF-?. So we hypothesize that edaravone plays a role in cardioprotection partly through modulation of adiponectin level by suppression of TNF-?. PMID:22571939

Pei, Haifeng; Jia, Min; Sun, Lu; Zheng, Xiaohui; Zhou, Haiyan

2012-08-01

114

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

2013-01-01

115

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. PMID:24167625

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

2013-01-01

116

Adiponectin gene variant interacts with fish oil supplementation to influence serum adiponectin in older individuals.  

PubMed

Marine n3 polyunsaturated fatty acids (PUFAs) activate the transcription factor peroxisome proliferator-activated receptor (PPAR?), which modulates the expression of adiponectin. We investigated the interaction of dietary n3 PUFAs with adiponectin gene (ADIPOQ) single nucleotide polymorphism (SNP) genotypes as a determinant of serum adiponectin concentration. The Modulation of Atherosclerosis Risk by Increasing Doses of n3 Fatty Acids study is a parallel design, double-blind, controlled trial. Serum adiponectin was measured in 142 healthy men and 225 women aged 45-70 y randomized to treatment with doses of 0.45, 0.9, and 1.8 g/d 20:5n3 and 22:6n3 (1.51:1), or placebo for 12 mo. The 310 participants who completed the study were genotyped for 5 SNPs at the ADIPOQ locus: -11391 G/A (rs17300539), -11377 C/G (rs266729), -10066 G/A (rs182052), +45 T/G (rs2241766), and +276 G/T (rs1501299). The -11391 A-allele was associated with a higher serum adiponectin concentration at baseline (n = 290; P < 0.001). The interaction between treatment and age as a determinant of adiponectin was significant in participants aged >58 y after the highest dose (n = 92; P = 0.020). The interaction between +45 T/G and treatment and age was a nominally significant determinant of serum adiponectin after adjustment for BMI, gender, and ethnicity (P = 0.029). Individuals homozygous for the +45 T-allele aged >58 y had a 22% increase in serum adiponectin concentration compared with baseline after the highest dose (P-treatment effect = 0.008). If substantiated in a larger sample, a diet high in n3 PUFAs may be recommended for older individuals, especially those of the +45 TT genotype who have reported increased risk of hypoadiponectinemia, type 2 diabetes, and obesity. PMID:23658423

Alsaleh, Aseel; Crepostnaia, Daria; Maniou, Zoitsa; Lewis, Fiona J; Hall, Wendy L; Sanders, Thomas A B; O'Dell, Sandra D

2013-07-01

117

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. PMID:19581422

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

118

Adiponectin Ameliorates Experimental Periodontitis in Diet-Induced Obesity Mice  

PubMed Central

Adiponectin is an adipokine that sensitizes the body to insulin. Low levels of adiponectin have been reported in obesity, diabetes and periodontitis. In this study we established experimental periodontitis in male adiponectin knockout and diet-induced obesity mice, a model of obesity and type 2 diabetes, and aimed at evaluating the therapeutic potential of adiponectin. We found that systemic adiponectin infusion reduced alveolar bone loss, osteoclast activity and infiltration of inflammatory cells in both periodontitis mouse models. Furthermore, adiponectin treatment decreased the levels of pro-inflammatory cytokines in white adipose tissue of diet-induced obesity mice with experimental periodontitis. Our in vitro studies also revealed that forkhead box O1, a key transcriptional regulator of energy metabolism, played an important role in the direct signaling of adiponectin in osteoclasts. Thus, adiponectin increased forkhead box O1 mRNA expression and its nuclear protein level in osteoclast-precursor cells undergoing differentiation. Inhibition of c-Jun N-terminal kinase signaling decreased nuclear protein levels of forkhead box O1. Furthermore, over-expression of forkhead box O1 inhibited osteoclastogenesis and led to decreased nuclear levels of nuclear factor of activated T cells c1. Taken together, this study suggests that systemic adiponectin application may constitute a potential intervention therapy to ameliorate type 2 diabetes-associated periodontitis. It also proposes that adiponectin inhibition of osteoclastogenesis involves forkhead box O1. PMID:24836538

Zhang, Lan; Meng, Shu; Tu, Qisheng; Yu, Liming; Tang, Yin; Dard, Michel M.; Kim, Sung-Hoon; Valverde, Paloma; Zhou, Xuedong; Chen, Jake

2014-01-01

119

Adiponectin Effect on The Viability of Human Endometrial Stromal Cells and mRNA Expression of Adiponectin Receptors  

PubMed Central

Background: Adiponectin is one of the most important adipokines secreted from fatty tissue that has a direct inhibitory effect on the development of cancer cells. Adiponectin plays an important role in human reproduction system and fertility of women. Adiponectin concentration decreases in women with endometriosis and endometrial cancer. The aim of the present study was to investigate the effect of adiponectin on human endometrial stromal cell (HESC) viability as well as mRNA expression of Adipo R1 and Adipo R2 receptors. Materials and Methods: In this experimental study, eight endometrial biopsies were taken and stromal cells were separated by enzymatic digestion and cell filtrations. Stromal cells of each biopsy were divided into four groups: control, 10, 100, and 200 ng/ml adiponectin concentrations. The effect of adiponectin on viability of the normal HESCs was studied by trypan blue staining and the relative expression levels of Adipo R1 and R2 were analyzed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Data were analyzed by one way ANOVA and unpaired student’s t test and p<0.05 was considered significant. Results: Adiponectin decreased viability of normal human endometrial stromal cells in a dose and time dependent manner. Expression of Adipo R1 and Adipo R2 receptors did not change in the presence of adiponectin. Conclusion: Adiponectin can directly influence the viability of HESCs and decrease their viability, but it didn’t change expression of adiponectin receptors. PMID:24520463

Bohlouli, Somayeh; Khazaei, Mozafar; Teshfam, Masoud; Hassanpour, Hosein

2013-01-01

120

Effect of Ethnicity, Dietary Intake and Physical Activity on Plasma Adiponectin Concentrations Among Malaysian Patients with Type 2 Diabetes Mellitus  

PubMed Central

Background The Malaysian Health and morbidity Survey (2006) reported the highest prevalence of type 2 diabetes mellitus (T2DM) among the Indian population compared to the Malay and Chinese populations. Many studies have supported the important role of adiponectin in insulin-sensitizing, which is associated with T2DM. These studies have raised a research question whether the variation in prevalence is related to the adiponectin concentrations or the lifestyle factors. Objectives The purpose of this study is to determine whether the adiponectin concentrations differ between the Malay, Chinese and the Indian populations with T2DM. It is to investigate the association of adiponectin concentrations with ethnicity, dietary intake and physical activity too. Materials and Methods In this cross-sectional study, a total of 210 T2DM patients with mean (SD) age of 56.73 (10.23) years were recruited from Penang, Malaysia. Data on demographic background, medical history, anthropometry (weight, height, visceral fat, percentage of body fat and waist circumference), dietary intake (3 days 24 hours diet recall) and physical activity (International Physical Activity Questionnaire) were obtained accordingly. Plasma adiponectin and routine laboratory tests (fasting blood sugar, HbA1c, total cholesterol, LDL, HDL and triglyceride) were performed according to standard procedure. Results After adjustment for physical activity and dietary intakes, the Indian population had significantly lower adiponectin concentrations (P = 0.003) when compared with the Malay and the Chinese populations, The Indian population also had significantly higher value of HbA1c (P = 0.017) and significantly lower HDL (P = 0.013). Plasma adiponectin concentrations was significantly associated with ethnicity (P = 0.011), dietary carbohydrate (P = 0.003) and physical activity total MET score (P = 0.026), after medical history, age, sex, total cholesterol and visceral fat adjusted. However, dietary carbohydrate and physical activity did not show significantly difference among the various ethnic groups. Conclusions In conclusion, lower concentration of adiponectin in the Indian population when compared with the Malay and the Chinese populations is not associated with lifestyle factors. The possibility of adiponectin gene polymorphism should be discussed further. PMID:24348588

Chin, Koo Hui; Sathyasurya, Daniel Robert; Abu Saad, Hazizi; Jan Mohamed, Hamid Jan B

2013-01-01

121

The Effects of Atypical Antipsychotic Usage Duration on Serum Adiponectin Levels and Other Metabolic Parameters  

PubMed Central

Objective: Although atypical antipsychotics are well-tolerated and effective treatment options for schizophrenia, they have metabolic side effects, including weight gain and increased risk of Type II Diabetes Mellitus (DM). Adiponectin, produced exclusively in adipocytes, is the most abundant serum adipokine. Low levels of adiponectin are correlated with DM, insulin resistance and coronary heart disease. Usage of atypical antipsychotics may create a risk of metabolic syndrome. The aim of this study was to evaluate the effects of antipsychotic usage on parameters related to development of metabolic syndrome. Materials and Methods: A total of 27 patients (n=27) (13 women and 14 men) were recruited from our out-patient psychiatry clinic. All patients had been treated with atypical antipsychotics for at least 3 months and were in remission. Patients were evaluated for levels of HDL (High Density Lipoprotein), LDL (Low Density Lipoprotein), TG (Triglyceride) total cholesterol and fasting blood glucose, body weight, BMI (Body Mass Index), waist circumference and serum adiponectin levels. Results: Serum adiponectin levels were significantly lower (p:0.000) and body weights were significantly higher (p:0.003) in the patients who had been using atypical antipsychotics for longer than a year in comparison to patients who had been using atypical antipsychotics for one year or less. Conclusion: Our findings supported the hypothesis that the length of administration of atypical antipsychotics has an effect on metabolic changes. They also highlight the fact that when investigating metabolic changes generated by atypical antipsychotic effects, the length of time that the patient has been on the atypical antipsychotics should also be considered.

Oral, Elif; Gulec, Mustafa; Kurt, Nezahat; Yilmaz, Sumeyra; Aydin, Nazan; Kirpinar, Ismet

2011-01-01

122

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

123

Adiponectin Reduces Plasma Triglyceride by Increasing VLDL Triglyceride Catabolism  

PubMed Central

OBJECTIVE—Adiponectin is an adipocyte-derived hormone that plays an important role in glucose and lipid metabolism. The main aims of this study are to investigate the effects of adiponectin on VLDL triglyceride (VLDL-TG) metabolism and the underlying mechanism. RESEARCH DESIGN AND METHODS—Adenoviruses were used to generate a mouse model with elevated circulating adiponectin. HepG2 and C2C12 cells were treated with recombinant human adiponectin. RESULTS—Three days after Ad-mACRP30 adenovirus injection, plasma adiponectin protein levels were increased 12-fold. All three main multimeric adiponectin molecules were proportionally elevated. Fasting plasma TG levels were significantly decreased (?40%) in the mice with elevated adiponectin in circulation, as were the plasma levels of large and medium VLDL subclasses. Although apolipoprotein B mRNA levels were robustly suppressed in the livers of adiponectin-overexpressing mice and in cultured HepG2 cells treated with recombinant human adiponectin, hepatic VLDL-TG secretion rates were not altered by elevated plasma adiponectin. However, Ad-mACRP30–treated mice exhibited a significant increase of postheparin plasma lipoprotein lipase (LPL) activity compared with mice that received control viral vector. Skeletal muscle LPL activity and mRNA levels of LPL and VLDL receptor (VLDLr) were also increased in Ad-mACRP30–treated mice. Recombinant human adiponectin treatment increased LPL and VLDLr mRNA levels in differentiated C1C12 myotubes. CONCLUSIONS—These results suggest that adiponectin decreases plasma TG levels by increasing skeletal muscle LPL and VLDLr expression and consequently VLDL-TG catabolism. PMID:18375436

Qiao, Liping; Zou, Chenhui; van der Westhuyzen, Deneys R.; Shao, Jianhua

2008-01-01

124

Adiponectin as a potential biomarker of vascular disease  

PubMed Central

The increasing prevalence of diabetes and its complications heralds an alarming situation worldwide. Obesity-associated changes in circulating adiponectin concentrations have the capacity to predict insulin sensitivity and are a link between obesity and a number of vascular diseases. One obvious consequence of obesity is a decrease in circulating levels of adiponectin, which are associated with cardiovascular disorders and associated vascular comorbidities. Human and animal studies have demonstrated decreased adiponectin to be an independent risk factor for cardiovascular disease. However, in animal studies, increased circulating adiponectin alleviates obesity-induced endothelial dysfunction and hypertension, and also prevents atherosclerosis, myocardial infarction, and diabetic cardiac tissue disorders. Further, metabolism of a number of foods and medications are affected by induction of adiponectin. Adiponectin has beneficial effects on cardiovascular cells via its antidiabetic, anti-inflammatory, antioxidant, antiapoptotic, antiatherogenic, vasodilatory, and antithrombotic activity, and consequently has a favorable effect on cardiac and vascular health. Understanding the molecular mechanisms underlying the regulation of adiponectin secretion and signaling is critical for designing new therapeutic strategies. This review summarizes the recent evidence for the physiological role and clinical significance of adiponectin in vascular health, identification of the receptor and post-receptor signaling events related to the protective effects of the adiponectin system on vascular compartments, and its potential use as a target for therapeutic intervention in vascular disease. PMID:25653535

Ebrahimi-Mamaeghani, Mehrangiz; Mohammadi, Somayeh; Arefhosseini, Seyed Rafie; Fallah, Parviz; Bazi, Zahra

2015-01-01

125

Isolation and characterization of five novel high molecular weight subunit of glutenin genes from Triticum timopheevi and Aegilops cylindrica.  

PubMed

Analysis by SDS-PAGE of total protein fractions from single seeds of Aegilops cylindrica (genomes C and D) and Triticum timopheevi (genomes A and G) showed the presence of three bands corresponding to high molecular weight subunits of glutenin (HMW subunits) in the former and two major bands and a minor band corresponding to HMW subunits in the latter. Three Ae. cylindrica and two T. timopheevi HMW subunit gene sequences, each comprising the entire coding region, were amplified by polymerase chain reaction (PCR) and their complete nucleotide sequences determined. A combination of N-terminal amino acid sequencing of the proteins identified by SDS-PAGE and alignments of the derived amino acid sequences of the proteins encoded by the PCR products identified the Ae. cylindrica HMW subunits as 1Cx, 1Cy and 1Dy, and the T. timopheevi HMW subunits as 1Gx, 1Ax and 1Ay. It was not clear whether or not a 1Gy HMW subunit was present in T. timopheevi. The PCR products from Ae. cyclindrica were derived from 1Cy and 1Dy genes and a silent 1Dx gene containing an in-frame internal stop codon, while those from T. timopheevi were derived from 1Ax and 1Ay genes. The 1Cx, 1Gx and 1Gy sequences were not amplified successfully. The proteins encoded by the five novel genes had similar structures to previously characterized HMW subunits of bread wheat ( Triticum aestivum). Differences and similarities in sequence and structure, and in the distribution of cysteine residues (relevant to the ability of HMW subunits to form high M(r) polymers) distinguished the HMW subunits of x- and y-type and of each genome rather than those of the different species. There was no evidence of a change in HMW subunit expression or structure resulting from selective breeding of bread wheat. The novel 1Ax, 1Ay, 1Cy and 1Dy HMW subunits were expressed in Escherichia coli, and the expressed proteins were shown to have very similar mobilities to the endogenous HMW subunits on SDS-PAGE. The truncated 1Dx gene from Ae. cylindrica failed to express in E. coli, and no HMW subunit-related protein of the size predicted for the truncated 1Dx subunit could be identified by immunodetection in seed extracts. PMID:12582643

Wan, Y.; Wang, D.; Shewry, R.; Halford, G.

2002-04-01

126

Expression of the high molecular weight melanoma-associated antigen by pericytes during angiogenesis in tumors and in healing wounds.  

PubMed Central

In the course of immunohistochemical characterization of murine monoclonal antibodies recognizing the human high molecular weight-melanoma associated antigen (HMW-MAA), a striking reactivity with blood vessels in the tumor stroma was noted. Immunocytochemical analysis by light and electronmicroscopy of a panel of tissues and cell lines showed that the staining of microvessels by anti-HMW-MAA monoclonal antibodies was restricted to pericytes. Correspondingly, anti-HMW-MAA monoclonal antibodies were found to react with cultured pericytes from human brain, but not with endothelial cells in serologic assays, and to immunoprecipitate from biosynthetically labeled pericytes an antigen with the characteristic structural profile of HMW-MAA. At the subcellular level, the expression of HMW-MAA in cultured pericytes was mainly restricted to microspikes that are localized in clusters on the cellular membrane. Staining by anti-HMW-MAA monoclonal antibodies of pericytes was not only found in the tumor stroma, but also in other lesions associated with angiogenesis, such as granulation tissue of wound healing and synovitis. In these lesions, microvascular staining for another marker of pericytes, ie, alpha-smooth muscle actin, also was observed. These results suggest that, in conditions associated with vascular proliferation, 1) pericytes acquire HMW-MAA and 2) the number of pericytes may be increased as compared with normal tissues. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 PMID:1694058

Schlingemann, R. O.; Rietveld, F. J.; de Waal, R. M.; Ferrone, S.; Ruiter, D. J.

1990-01-01

127

Identification and characterization of high-molecular-weight secalins from triticale seeds by capillary zone electrophoresis.  

PubMed

A rapid and reliable method for separation and characterization of the variability of high-molecular-weight secalin subunits (HMW-SS) in hexaploid triticale (x Triticosecale Wittmack) by CZE has been developed. In this method, a mixture of two poly(ethylene oxide) polymers differing in molecular weight and a high concentration of ACN in isoelectric buffer was applied as the running electrolyte. For dynamic coating of the capillary inner wall, a low-concentration mixture of poly(vinylpyrrolidone) and hydroxypropylmethylcellulose was employed. Wide allelic variations in rye HMW-SS composition, including some novel x- and y-type HMW-SS, were detected by CZE. The CZE electropherograms of HMW-SS showed two groups of peaks in accordance with y- and x-type subunits, with migration times of 8.0-8.8 and 11.0-13.3 min, respectively. HMW-SS differed in migration times from the simultaneously resolved HMW glutenin subunits, but frequently had very similar electrophoretic mobilities during separation by SDS-PAGE. Each of the two rye subunits 2r and 6.5r detected by SDS-PAGE represents in fact two subunits (5.1r or 5.2r, and 6.4r or 6.5r, respectively). After analyzing 106 European triticale cultivars, 12 HMW-SS were identified (six x-type and six y-type). They form six allelic variants of these subunits. The simultaneous separation and identification of triticale HMW glutenin and secalin subunits by CZE is an efficient alternative to SDS-PAGE and should facilitate breeding of valuable cultivars. PMID:20593398

Salmanowicz, Boleslaw P

2010-07-01

128

Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia.  

PubMed

Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment. PMID:25284335

Klemettilä, J-P; Kampman, O; Seppälä, N; Viikki, M; Hämäläinen, M; Moilanen, E; Mononen, N; Lehtimäki, T; Leinonen, E

2015-02-01

129

Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance  

PubMed Central

The antidiabetic and antiatherosclerotic effects of adiponectin make it a desirable drug target for the treatment of metabolic and cardiovascular diseases. However, the adiponectin-based drug development approach turns out to be difficult due to extremely high serum levels of this adipokine. On the other hand, a significant correlation between adiponectin multimerization and its insulin-sensitizing effects has been demonstrated, suggesting a promising alternative therapeutic strategy. Here we show that transgenic mice overexpressing disulfide bond A oxidoreductase-like protein in fat (fDsbA-L) exhibited increased levels of total and the high-molecular-weight form of adiponectin compared with wild-type (WT) littermates. The fDsbA-L mice also displayed resistance to diet-induced obesity, insulin resistance, and hepatic steatosis compared with WT control mice. The protective effects of DsbA-L overexpression on diet-induced insulin resistance, but not increased body weight and fat cell size, were significantly decreased in adiponectin-deficient fDsbA-L mice (fDsbA-L/Ad?/?). In addition, the fDsbA-L/Ad?/? mice displayed greater activity and energy expenditure compared with adiponectin knockout mice under a high-fat diet. Taken together, our results demonstrate that DsbA-L protects mice from diet-induced obesity and insulin resistance through adiponectin-dependent and independent mechanisms. In addition, upregulation of DsbA-L could be an effective therapeutic approach for the treatment of obesity and its associated metabolic disorders. PMID:22807031

Liu, Meilian; Xiang, Ruihua; Wilk, Sarah Ann; Zhang, Ning; Sloane, Lauren B.; Azarnoush, Kian; Zhou, Lijun; Chen, Hongzhi; Xiang, Guangda; Walter, Christi A.; Austad, Steven N.; Musi, Nicolas; DeFronzo, Ralph A.; Asmis, Reto; Scherer, Philipp E.; Dong, Lily Q.; Liu, Feng

2012-01-01

130

The role of adiponectin in endothelial dysfunction and hypertension.  

PubMed

It has been two decades since the discovery of adiponectin, and today its role in insulin resistance, inflammation, and atherosclerosis are areas of major interest. Production of adiponectin is reduced in all inflammatory processes and states of insulin resistance such as obesity, type 2 diabetes mellitus, and coronary artery disease. Adiponectin regulates carbohydrate metabolism, and may also regulate vascular homeostasis by affecting important signaling pathways in endothelial cells and modulating inflammatory responses in the subendothelial space. Clinical studies have demonstrated a relationship between serum adiponectin concentrations and the activity of the renin-angiotensin-aldosterone system (RAAS), causing changes in blood pressure. Antihypertensive therapy with angiotensin II receptor blockers (ARBs) has been demonstrated to increase adiponectin levels in 3-6 months. Adiponectin has also been shown to play a role in cardiac injury in modulation of pro-survival reactions, cardiac energy metabolism, and inhibition of hypertrophic remodeling. The effects of adiponectin on the cardiovascular system are believed to be partially mediated by the activation of 5' adenosine monophosphate-activated protein kinase (AMPK) and cyclooxygenase-2 (COX-2) pathways, reducing endothelial cell apoptosis, promoting nitric oxide production, decreasing tumor necrosis factor-alpha (TNF-?) activity, and preventing atherosclerotic proliferation and smooth muscle cell migration. Further evaluation of biologically active forms of adiponectin and its receptor should help to clarify how obesity affects the cardiovascular system. PMID:24924994

Rojas, Edward; Rodríguez-Molina, Daloha; Bolli, Peter; Israili, Zafar H; Faría, Judith; Fidilio, Enzamaría; Bermúdez, Valmore; Velasco, Manuel

2014-08-01

131

Linkage analysis of circulating levels of adiponectin in Hispanic children  

Technology Transfer Automated Retrieval System (TEKTRAN)

Adiponectin is produced exclusively by adipose tissue and is inversely associated with insulin resistance and pro-inflammatory conditions. The aim of this study was to conduct a genome scan of circulating levels of adiponectin in Hispanic children. The present study included extended families with ...

132

Adiponectin as a protective factor in hepatic steatosis  

Microsoft Academic Search

Abstract Abstract Abstract Abstract AIM: Obesity and insulin resistance (IR) are closely related to hepatic steatosis (HS), and adiponectin is a hepatic insulin sensitizer that has important effects in liver function. This study aims at investigating the relationship between serum adiponectin concentration and the presence of HS. METHODS: We carried out a cross-sectional study in a check-up unit of a

Nahum Méndez-Sánchez; Norberto C. Chávez-Tapia; Antonio R. Villa; Karla Sánchez-Lara; Daniel Zamora-Valdés; Martha H. Ramos; Misael Uribe

2005-01-01

133

Plasma Adiponectin Levels and Metabolic Factors in Nondiabetic Adolescents  

Microsoft Academic Search

Objectives: The relationship of plasma adiponectin levels with various anthropometric and metabolic factors has been surveyed extensively in adults. However, how plasma adiponectin levels are related to various anthropometric indices and cardiovascular risk factors in adolescents is not as vigorously studied. In this study, we investigated this among healthy nondiabetic adolescents.Research Methods and Procedures: Two hundred thirty nondiabetic subjects (125

Kuo-Chin Huang; Bee-Horng Lue; Ruoh-Fang Yen; Christopher G. Shen; Shiuh-Rong Ho; Tong-Yuan Tai; Wei-Shiung Yang

2004-01-01

134

Adiponectin is partially associated with exosomes in mouse serum.  

PubMed

Exosomes are membrane vesicles 30-120 nm in diameter that are released by many cell types and carry a cargo of proteins, lipids, mRNA, and microRNA. Cultured adipocytes reportedly release exosomes that may play a role in cell-to-cell communication during the development of metabolic diseases. However, the characteristics and function of exosomes released from adipocytes in vivo remain to be elucidated. Clearly, adipocyte-derived exosomes could exist in the circulation and may be associated with adipocyte-specific proteins such as adipocytokines. We isolated exosomes from serum of mice by differential centrifugation and analyzed adiponectin, leptin, and resistin in the exosome fraction. Western blotting detected adiponectin but no leptin and only trace amounts of resistin in the exosome fraction. The adiponectin signal in the exosome fraction was decreased by proteinase K treatment and completely quenched by a combination of proteinase K and Triton X-100. Quantitative ELISA showed that the exosome fraction contains considerable amounts of adiponectin, but not leptin or resistin. The concentration of adiponectin in the serum and the ratio of adiponectin to total protein in the exosome fraction were lower in obese mice than in lean mice. These results suggest that a portion of adiponectin exists as a transmembrane protein in the exosomes in mouse serum. We propose adiponectin as a marker of exosomes released from adipocytes in vivo. PMID:24792183

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

2014-06-01

135

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...

136

Recovery of an HMWP/hmwBP (pUL48/pUL47) Complex from Virions of Human Cytomegalovirus: Subunit Interactions, Oligomer Composition, and Deubiquitylase Activity  

PubMed Central

ABSTRACT We report that the human cytomegalovirus (HCMV) high-molecular-weight tegument protein (HMWP, pUL48; 253 kDa) and the HMWP-binding protein (hmwBP, pUL47; 110 kDa) can be recovered as a complex from virions disrupted by treatment with 50 mM Tris (pH 7.5), 0.5 M NaCl, 0.5% NP-40, and 10 mM dithiothreitol [DTT]. The subunit ratio of the complex approximates 1:1, with a shape and structure consistent with an elongated heterodimer. The HMWP/hmwBP complex was corroborated by reciprocal coimmunoprecipitation experiments using antipeptide antibodies and lysates from both infected cells and disrupted virus particles. An interaction of the amino end of pUL48 (amino acids [aa] 322 to 754) with the carboxyl end of pUL47 (aa 693 to 982) was identified by fragment coimmunoprecipitation experiments, and a head-to-tail self-interaction of hmwBP was also observed. The deubiquitylating activity of pUL48 is retained in the isolated complex, which cleaves K11, K48, and K63 ubiquitin isopeptide linkages. IMPORTANCE Human cytomegalovirus (HCMV, or human herpesvirus 5 [HHV-5]) is a large DNA-containing virus that belongs to the betaherpesvirus subfamily and is a clinically important pathogen. Defining the constituent elements of its mature form, their organization within the particle, and the assembly process by which it is produced are fundamental to understanding the mechanisms of herpesvirus infection and developing drugs and vaccines against them. In this study, we report isolating a complex of two large proteins encoded by HCMV open reading frames (ORFs) UL47 and UL48 and identifying the binding domains responsible for their interaction with each other and of pUL47 with itself. Our calculations indicate that the complex is a rod-shaped heterodimer. Additionally, we determined that the ubiquitin-specific protease activity of the ORF UL48 protein was functional in the complex, cleaving K11-, K48-, and K63-linked ubiquitin dimers. This information builds on and extends our understanding of the HCMV tegument protein network that is required to interface the HCMV envelope and capsid. PMID:24829352

Tullman, Jennifer A.; Harmon, Mary-Elizabeth; Delannoy, Michael

2014-01-01

137

Virus-induced gene-silencing in wheat spikes and grains and its application in functional analysis of HMW-GS-encoding genes  

PubMed Central

Background The Barley stripe mosaic virus (BSMV)-based vector has been developed and used for gene silencing in barley and wheat seedlings to assess gene functions in pathogen- or insect-resistance, but conditions for gene silencing in spikes and grains have not been evaluated. In this study, we explored the feasibility of using BSMV for gene silencing in wheat spikes or grains. Results Apparent photobleaching on the spikes infected with BSMV:PDS at heading stage was observed after13 days post inoculation (dpi), and persisted until 30dpi, while the spikes inoculated with BSMV:00 remained green during the same period. Grains of BSMV:PDS infected spikes also exhibited photobleaching. Molecular analysis indicated that photobleached spikes or grains resulted from the reduction of endogenous PDS transcript abundances, suggesting that BSMV:PDS was able to induce PDS silencing in wheat spikes and grains. Inoculation onto wheat spikes from heading to flowering stage was optimal for efficient silencing of PDS in wheat spikes. Furthermore, we used the BSMV-based system to reduce the transcript level of 1Bx14, a gene encoding for High-molecular-weight glutenin subunit 1Bx14 (HMW-GS 1Bx14), by 97?% in the grains of the BSMV:1Bx14 infected spikes at 15dpi, compared with that in BSMV:00 infected spikes, and the reduction persisted until at least 25 dpi. The amount of the HMW-GS 1Bx14 was also detectably decreased. The percentage of glutenin macropolymeric proteins in total proteins was significantly reduced in the grains of 1Bx14-silenced plants as compared with that in the grains of BSMV:00 infected control plants, indicating that HMW-GS 1Bx14 is one of major components participating in the formation of glutenin macropolymers in wheat grains. Conclusion This is one of the first reports of successful application of BSMV-based virus-induced-gene-silencing (VIGS) for gene knockdown in wheat spikes and grains and its application in functional analysis of the 1Bx14 gene. The established BSMV-VIGS system will be very useful in future research on functional analysis of genes contributing to grain quality and the metabolic networks in developing seeds of wheat. PMID:22882902

2012-01-01

138

Cold Exposure Suppresses Serum Adiponectin Levels through Sympathetic Nerve Activation in Mice  

Microsoft Academic Search

Objective: Several lines of evidence suggest important roles for adiponectin in glucose and lipid metabolism and atherosclerosis. However, the mechanisms regulating serum adiponectin levels and adiponectin production are still not completely understood. Our aim was to determine whether adiponectin synthesis is physiologically regulated by the sympathetic nervous system (SNS).Research Methods and Procedures: Mice were exposed to cold (4 °C) for

Junta Imai; Hideki Katagiri; Tetsuya Yamada; Yasushi Ishigaki; Takehide Ogihara; Kenji Uno; Yutaka Hasegawa; Junhong Gao; Hisamitsu Ishihara; Hironobu Sasano; Yoshitomo Oka

2006-01-01

139

Adiponectin signals through Adiponectin Receptor 1 to reverse imatinib resistance in K562 human chronic myeloid leukemia cells.  

PubMed

Adiponectin, a member of adipokines, is a functional ligand for Adiponectin Receptor-1 (AdipoR1) and Adiponectin Receptor-2 (AdipoR2), and has been found to be linked to the risk of CML. Imatinib has undoubtedly revolutionised the management and outcome of chronic myeloid leukemia (CML), however imatinib resistance has been recognized as a major problem in CML therapy. In this study, we first established imatinib-resistant K562 CML cells, and then evaluated the effect of Adiponectin in reversing imatinib resistance. The data presented here demonstrated that Adiponectin was able to reverse K562 resistance to imatinib in vitro and in vivo. Additional data with molecular approaches suggested that the reversion of Adiponectin in imatinib resistance signals through AdipoR1 but not AdipoR2 to downregulate Bcr-Abl expression and effect in imatinib-resistant K562 CML cells. Taken together, our data showed that Adiponectin can reverse imatinib resistance in CML, and to a certain extent elucidate the mechanism of Adiponectin reversing imatinib resistance that may provide a new and promising approach in imatinib resistance management in CML therapy. PMID:25475722

Wu, Shenghao; Zheng, Cuiping; Chen, Songyan; Lin, Bijing; Chen, Yuemiao; Zhou, Wenjin; Li, Zhenyu

2015-01-01

140

Characterization of y-type high-molecular-weight glutenins in tetraploid species of Leymus.  

PubMed

Three y-type high-molecular-weight (HMW) glutenin gene open reading frames (ORFs), Chiy1, Chiy2, and Racy, were isolated and characterized from Leymus chinensis PI499516 and Leymus racemosus ssp. racemosus W623305. They shared an extra glutamine in the N-terminal and LAAQLPAMCRL peptides in the C-terminal with x-type HMW glutenins but had different N-terminal lengths. Like other y-type HMW glutenins, Chiy2 and Racy had 104 (or 105) amino acid (aa) residues at the N-terminal and started with EGEASR, whereas Chiy1 had 99 aa in this domain and started with QLQCER because of the deletion of EGEASR. Five other y-type glutenins, including those from Elymus ciliaris, Pseudoroegneria libanotica, and Leymus mollis, were similar to Chiy1. The ORF of Chiy2 was probably not expressed. The ORFs of both Chiy1 and Racy were expressed in bacteria. The maximum likelihood phylogenic tree based on the signal peptide and N-terminal and C-terminal aa residues revealed two clades of y-type HMW glutenins in Triticeae; the first contained Ay, By, Cy, Dy, Eey, Gy, Ky, Ry, Tay, and Uy, while the second clade contained the remaining y types, including those from Leymus. Within the second clade, HMW glutenins lacking the EGEASR peptide formed a subclade. These y-type HMW glutenins in Leymus could not be targeted to the Xm or Ns genome. PMID:24068388

Sun, Yanqi; Pu, Zongjun; Dai, Shoufen; Pu, Xiaoxue; Liu, Dengcai; Wu, Bihua; Lan, Xiujin; Wei, Yuming; Zheng, Youliang; Yan, Zehong

2014-02-01

141

Identification and Characterization of High-Molecular-Weight Glutenin Subunits from Agropyron intermedium  

PubMed Central

High-molecular-weight glutenin subunit (HMW-GS) is a primary determinant of processing quality of wheat. Considerable progress has been made in understanding the structure, function and genetic regulation of HMW-GS in wheat and some of its related species, but less is known about their orthologs in Agropyron intermedium, a useful related species for wheat improvement. Here seven HMW-GSs in Ag. intermedium were identified using SDS-PAGE and Western blotting experiments. Subsequently, the seven genes (Glu-1Aix1?4 and Glu-1Aiy1?3) encoding the seven HMW-GSs were isolated using PCR technique with degenerate primers, and confirmed by bacterial expression and Western blotting. Sequence analysis indicated that the seven Ag. intermedium HMW-GSs shared high similarity in primary structure to those of wheat, but four of the seven subunits were unusually small compared to the representatives of HMW-GS from wheat and two of them possessed extra cysteine residues. The alignment and clustering analysis of deduced amino acid sequences revealed that 1Aix1 and 1Aiy1 subunits had special molecular structure, belonging to the hybrid type compounding between typical x- and y-type subunit. The xy-type subunit 1Aix1 is composed of the N-terminal of x-type and C-terminal of y-type, whereas yx-type subunit 1Aiy1 comprises the N-terminal of y-type and C-terminal of x-type. This result strongly supported the hypothesis of unequal crossover mechanism that might generate the novel coding sequence for the hybrid type of HMW-GSs. In addition to the aforementioned, the other novel characteristics of the seven subunits were also discussed. Finally, phylogenetic analysis based on HMW-GS genes was carried out and provided new insights into the evolutionary biology of Ag. intermedium. PMID:24503781

Cao, Shuanghe; Li, Zhixin; Gong, Caiyan; Xu, Hong; Yang, Ran; Hao, Shanting; Wang, Xianping; Wang, Daowen; Zhang, Xiangqi

2014-01-01

142

An approach for isolating high-molecular-weight glutenin subunit genes using monoclonal antibodies.  

PubMed

High-molecular-weight glutenin subunits (HMW-GSs) play an important role in the breadmaking quality of wheat flour. In China, cultivars such as Triticum aestivum 'Xiaoyan No. 6' carrying the 1Bx14 and 1By15 glutenin subunits usually have attributes that result in high-quality bread and noodles. HMW-GS 1Bx14 and 1By15 were isolated by preparative sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and used as an antigen to immunize BALB/c mice. A resulting monoclonal antibody belonging to the IgG1 subclass was shown to bind to all HMW-GSs of Triticum aestivum cultivars, but did not bind to other storage proteins of wheat seeds in a Western blot analysis. After screening a complementary DNA expression library from immature seeds of 'Xiaoyan No. 6' using the monoclonal antibody, the HMW-GS 1By15 gene was isolated and fully sequenced. The deduced amino acid sequence showed an extra stretch of 15 amino acid repeats consisting of a hexapeptide and a nonapeptide in the repetitive domain of this y-type HMW subunit. Bacterial expression of a modified 1By15 gene, in which the coding sequence for the signal peptide was removed and a BamHI site eliminated, gave rise to a protein with mobility identical to that of HMW-GSs extracted from seeds of 'Xiaoyan No. 6' via SDS-PAGE. This approach for isolating genes using specific monoclonal antibody against HMW-GS genes is a good alternative to the extensively used polymerase chain reaction (PCR) technology based on sequence homology of HMW-GSs in wheat and its relatives. PMID:16498468

Wang, H Q; Zhang, X Y

2006-02-01

143

Identification and characterization of high-molecular-weight glutenin subunits from Agropyron intermedium.  

PubMed

High-molecular-weight glutenin subunit (HMW-GS) is a primary determinant of processing quality of wheat. Considerable progress has been made in understanding the structure, function and genetic regulation of HMW-GS in wheat and some of its related species, but less is known about their orthologs in Agropyron intermedium, a useful related species for wheat improvement. Here seven HMW-GSs in Ag. intermedium were identified using SDS-PAGE and Western blotting experiments. Subsequently, the seven genes (Glu-1Aix1 ? 4 and Glu-1Aiy1 ? 3) encoding the seven HMW-GSs were isolated using PCR technique with degenerate primers, and confirmed by bacterial expression and Western blotting. Sequence analysis indicated that the seven Ag. intermedium HMW-GSs shared high similarity in primary structure to those of wheat, but four of the seven subunits were unusually small compared to the representatives of HMW-GS from wheat and two of them possessed extra cysteine residues. The alignment and clustering analysis of deduced amino acid sequences revealed that 1Aix1 and 1Aiy1 subunits had special molecular structure, belonging to the hybrid type compounding between typical x- and y-type subunit. The xy-type subunit 1Aix1 is composed of the N-terminal of x-type and C-terminal of y-type, whereas yx-type subunit 1Aiy1 comprises the N-terminal of y-type and C-terminal of x-type. This result strongly supported the hypothesis of unequal crossover mechanism that might generate the novel coding sequence for the hybrid type of HMW-GSs. In addition to the aforementioned, the other novel characteristics of the seven subunits were also discussed. Finally, phylogenetic analysis based on HMW-GS genes was carried out and provided new insights into the evolutionary biology of Ag. intermedium. PMID:24503781

Cao, Shuanghe; Li, Zhixin; Gong, Caiyan; Xu, Hong; Yang, Ran; Hao, Shanting; Wang, Xianping; Wang, Daowen; Zhang, Xiangqi

2014-01-01

144

A pilot three-month sitagliptin treatment increases serum adiponectin level in Japanese patients with type 2 diabetes mellitus- a randomized controlled trial START-J study  

PubMed Central

Background The dipeptidyl-peptidase-IV (DPP-4) inhibitors, including sitagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM). Adiponectin, an adipocyte-derived circulating protein, has anti-atherosclerotic and anti-diabetic properties and is effectively elevated in bloodstream by thiazolidinediones, an insulin sensitizer. However, the effect of sitagliptin treatment on serum adiponectin level in T2DM has not fully elucidated in Japanese T2DM patients. The aim of the present study was to examine the effect of sitagliptin treatment on serum adiponectin levels in T2DM subjects. Methods Twenty-six consecutive Japanese T2DM outpatients were recruited between April 2011 and March 2013, and randomized into the control (conventional treatment, n?=?10) group and sitagliptin treatment group (n?=?16). Serum adiponectin was measured by enzyme-linked immunosorbent assay. Results Indices of glycemic control, such as hemoglobin A1c, glycated albumin, and 1.5-anhydro-D-glucitol, were significantly improved after the three-month treatment in both the control and sitagliptin groups. Serum adiponectin level was significantly increased in sitagliptin group from 6.7?±?0.8 to 7.4?±?1.0 ?g/mL without change of body mass index (p?=?0.034), while serum adiponectin level was not altered in the control group (p?=?0.601). Conclusion In Japanese T2DM patients, serum adiponectin level was elevated by three-month treatment with sitagliptin without change of body weight. Trial registration UMIN000004721 PMID:24884787

2014-01-01

145

Adiponectin Levels Are Reduced While Markers of Systemic Inflammation and Aortic Remodelling Are Increased in Intrauterine Growth Restricted Mother-Child Couple  

PubMed Central

Aim of the Study. To investigate the relationships between the adipocytokine levels, markers of inflammation, and vascular remodelling in pregnancies complicated by intrauterine growth restriction (IUGR). Materials and Methods. This was a retrospective study. One hundred and forty pregnant patients were enrolled. Adiponectin, leptin, tumor necrosis factor ? (TNF?), interleukin-6 (IL-6), and C reactive protein (CRP) were assessed in IUGR, small for gestational age (SGA), and appropriate for gestational age (AGA) mother-child couples at delivery. IUGR and SGA fetuses were defined as fetuses whose estimated fetal weight (EFW) was below 10th percentile for gestational age with and without umbilical artery (UA) Doppler abnormalities, respectively. Fetal aorta intima media thickness (aIMT) was evaluated by ultrasound in the same fetal groups. Data were analyzed by R (version 2.15.2). Results. There were 37 IUGR mother-child couples, 33 SGA, and 70 AGA. Leptin, TNF?, IL-6, and CRP serum levels were higher in IUGR pregnant patients (P < 0.05). Adiponectin levels were significantly reduced in IUGR fetuses compared to SGA and AGA, while leptin, TNF?, and IL-6 levels were higher in IUGR group (P ? 0.05). Fetal aIMT was significantly higher in IUGR (P < 0.05) and in this group there was a negative correlation between aIMT and adiponectin/leptin ratio (A/L ratio) (P < 0.05) and between adiponectin and IL-6 levels (P < 0.05). Conclusions. In conclusion, compared to SGA and AGA, IUGR fetuses had reduced circulating levels of adiponectin and elevated measures of aIMT and several inflammatory markers. Moreover, adiponectin levels were negatively correlated with aIMT in IUGR fetuses suggesting a possible causal link between reduced adiponectin and vessel remodelling. PMID:25045669

Visentin, Silvia; Lapolla, Annunziata; Londero, Ambrogio Pietro; Cosma, Chiara; Dalfrà, Mariagrazia; Camerin, Martina; Faggian, Diego; Plebani, Mario; Cosmi, Erich

2014-01-01

146

Implications of adiponectin in linking metabolism to testicular function.  

PubMed

Obesity is a major health problem, contributing to the development of various diseases with aging. In humans, obesity has been associated with reduced testosterone production and subfertility. Adipose tissue is an important source of hormones having influences on both metabolism and reproduction. Among them, the production and secretion of adiponectin is inversely correlated to the severity of obesity. The purpose of this review of literature is to present the current state of knowledge on adiponectin research to determine whether this hormone affects reproduction in men. Surprisingly, evidences show negative influences of adiponectin on GnRH secretion from the hypothalamus, LH and FSH secretion from the pituitary and testosterone at the testicular level. Thus far, the involvement of adiponectin in the influence of metabolism on reproduction in men is limited. However, adiponectin and its receptors are expressed by different cell types of the male gonad, including Leydig cells, spermatozoa, and epididymis. In addition, actions of adiponectin at the testicular level have been shown to promote spermatogenesis and sperm maturation. Therefore, autocrine/paracrine actions of adiponectin in the testis may contribute to support male reproductive function. PMID:24287788

Martin, Luc J

2014-05-01

147

Epidemiologic Evidence on Serum Adiponectin Level and Lipid Profile  

PubMed Central

The concentration of adiponectin, a hormone which is secreted from adipose tissue, is inversely correlated with body fat mass. This hormone has anti inflammatory and anti atherogenic properties. Its concentration reduces in metabolic syndrome and cardiovascular diseases. This study reviews the evidence on the relationship between serum adiponectin concentration and lipid profile. In this study former clinical trials, cross sectional and prospective studies have been reviewed. The PubMed search engine has been used to find related research for the topic by considering dyslipidemia, total cholesterol (TC), high and low density protein (HDL and LDL), triglyceride (TG), lipid profile (LP) and adiponectin as the key words. Finally, 25 articles were recruited to review in the present article. Serum adiponectin level was positively correlated with plasma HDL cholestrol concentrations. There was a significant inverse relationship between plasma triglyceride and serum adiponectin. An inverse correlation between very low density lipoprotein (VLDL) and LDL levels and adiponectin was reported from the studies. So, Adiponectin has an important role in the metabolism of lipid profile including HDLc. PMID:23543874

Izadi, Vajihe; Farabad, Elaheh; Azadbakht, Leila

2013-01-01

148

Molecular Mechanisms of HMW Glutenin Subunits from 1Sl Genome of Aegilops longissima Positively Affecting Wheat Breadmaking Quality  

PubMed Central

A wheat cultivar “Chinese Spring” chromosome substitution line CS-1Sl(1B), in which the 1B chromosome was substituted by 1Sl from Aegilops longissima, was developed and found to possess superior dough and breadmaking quality. The molecular mechanism of its super quality conformation is studied in the aspects of high molecular glutenin genes, protein accumulation patterns, glutenin polymeric proteins, protein bodies, starch granules, and protein disulfide isomerase (PDI) and PDI-like protein expressions. Results showed that the introduced HMW-GS 1Sl×2.3* and 1Sly16* in the substitution line possesses long repetitive domain, making both be larger than any known x- and y-type subunits from B genome. The introduced subunit genes were also found to have a higher level of mRNA expressions during grain development, resulting in more HMW-GS accumulation in the mature grains. A higher abundance of PDI and PDI-like proteins was observed which possess a known function of assisting disulfide bond formation. Larger HMW-GS deposited in protein bodies were also found in the substitution line. The CS substitution line is expected to be highly valuable in wheat quality improvement since the novel HMW-GS are located on chromosome 1Sl, making it possible to combine with the known superior D×5+Dy10 subunits encoded by Glu-D1 for developing high quality bread wheat. PMID:23593125

Li, Ning; Li, Xiaohui; Ma, Wujun; Weißgerber, H.; Zeller, Friedrich; Hsam, Sai; Yan, Yueming

2013-01-01

149

Molecular mechanisms of HMW glutenin subunits from 1S(l) genome of Aegilops longissima positively affecting wheat breadmaking quality.  

PubMed

A wheat cultivar "Chinese Spring" chromosome substitution line CS-1S(l)(1B), in which the 1B chromosome was substituted by 1S(l) from Aegilops longissima, was developed and found to possess superior dough and breadmaking quality. The molecular mechanism of its super quality conformation is studied in the aspects of high molecular glutenin genes, protein accumulation patterns, glutenin polymeric proteins, protein bodies, starch granules, and protein disulfide isomerase (PDI) and PDI-like protein expressions. Results showed that the introduced HMW-GS 1S(l)×2.3* and 1S(l)y16* in the substitution line possesses long repetitive domain, making both be larger than any known x- and y-type subunits from B genome. The introduced subunit genes were also found to have a higher level of mRNA expressions during grain development, resulting in more HMW-GS accumulation in the mature grains. A higher abundance of PDI and PDI-like proteins was observed which possess a known function of assisting disulfide bond formation. Larger HMW-GS deposited in protein bodies were also found in the substitution line. The CS substitution line is expected to be highly valuable in wheat quality improvement since the novel HMW-GS are located on chromosome 1S(l), making it possible to combine with the known superior D×5+Dy10 subunits encoded by Glu-D1 for developing high quality bread wheat. PMID:23593125

Wang, Shunli; Yu, Zitong; Cao, Min; Shen, Xixi; Li, Ning; Li, Xiaohui; Ma, Wujun; Weißgerber, H; Zeller, Friedrich; Hsam, Sai; Yan, Yueming

2013-01-01

150

Effects of angiotensin converting enzyme inhibition on adiponectin levels and lipid profile in the ovariectomized-aged rats  

PubMed Central

Objective: To investigate the relationship between angiotensin converting enzyme (ACE) and adiponectin and lipid profile in the ovariectomized-aged rats. Materials and Methods: Wistar albino rats were first divided into two groups; control (C) and ovariectomized (OVX). Bilateral ovariectomy were carried out on rats (n = 30) except control group (n = 10). After 6 weeks from ovariectomy, ovariectomized rats were subdivided into three groups; one group received no treatment (OVX), two groups received low dose (OVX + Cap5; 5 mg/kg/day) and high dose (OVX + Cap20; 20 mg/kg/day) captopril (Cap). Body weights were monitored weekly. Adiponectin, triglyceride, cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol (VLDL-C) levels were measured at the end of the 6 weeks. Results: In the OVX group, body weights increased (P < 0.001). In the OVX + Cap20 group, body weights significantly decreased compared with the OVX group during weeks 5 and 6 (P < 0.05). While adiponectin levels increased in the OVX + Cap5 group (P = 0.014), triglyceride and cholesterol levels decreased in the OVX + Cap20 group (P = 0.016 and P < 0.001, respectively) compared to the OVX group. HDL-C and VLDL-C levels decreased only in OVX + Cap20 group (P < 0.005). Conclusions: ACE inhibitors may be decreasing the ovariectomy-induced weight gain by increasing adiponectin levels, and by affecting lipid profiles. The adipose tissue renin-angiotensin system (RAS) may be playing an important role in the development of adiposity. PMID:24554906

Dost, Turhan; Kafkas, Samet; Gokalp, Filiz; Karul, Aslihan; Birincioglu, Mustafa

2014-01-01

151

Role of adiponectin in the metabolic effects of cannabinoid type 1 receptor blockade in mice with diet-induced obesity.  

PubMed

The adipocyte-derived hormone adiponectin promotes fatty acid oxidation and improves insulin sensitivity and thus plays a key role in the regulation of lipid and glucose metabolism and energy homeostasis. Chronic cannabinoid type 1 (CB1) receptor blockade also increases lipid oxidation and improves insulin sensitivity in obese individuals or animals, resulting in reduced cardiometabolic risk. Chronic CB1 blockade reverses the obesity-related decline in serum adiponectin levels, which has been proposed to account for the metabolic effects of CB1 antagonists. Here, we investigated the metabolic actions of the CB1 inverse agonist rimonabant in high-fat diet (HFD)-induced obese adiponectin knockout (Adipo(-/-)) mice and their wild-type littermate controls (Adipo(+/+)). HFD-induced obesity and its hormonal/metabolic consequences were indistinguishable in the two strains. Daily treatment of obese mice with rimonabant for 7 days resulted in significant and comparable reductions in body weight, serum leptin, free fatty acid, cholesterol, and triglyceride levels in the two strains. Rimonabant treatment improved glucose homeostasis and insulin sensitivity to the same extent in Adipo(+/+) and Adipo(-/-) mice, whereas it reversed the HFD-induced hepatic steatosis, fibrosis, and hepatocellular damage only in the former. The adiponectin-dependent, antisteatotic effect of rimonabant was mediated by reduced uptake and increased ?-oxidation of fatty acids in the liver. We conclude that reversal of the HFD-induced hepatic steatosis and fibrosis by chronic CB1 blockade, but not the parallel reduction in adiposity and improved glycemic control, is mediated by adiponectin. PMID:24381003

Tam, Joseph; Godlewski, Grzegorz; Earley, Brian J; Zhou, Liang; Jourdan, Tony; Szanda, Gergö; Cinar, Resat; Kunos, George

2014-02-15

152

Globular adiponectin but not full-length adiponectin induces increased procoagulability in human endothelial cells  

Microsoft Academic Search

Adiponectin (APN), a recently discovered adipocytokine, is present in human serum in a full length (fAPN) and a globular form (gAPN). gAPN is a proteolytic cleavage product of fAPN and seems to show independent biological activities compared to the properties of fAPN. The influence of gAPN and fAPN on procoagulability of cells is still unknown. This study examined the effect

Peter Bobbert; Silvio Antoniak; Heinz-Peter Schultheiss; Ursula Rauch

2008-01-01

153

SNPs in the adiponectin receptor 2 gene and their associations with chicken performance traits.  

PubMed

The adiponectin receptor 2 (ADIPOR2) is a receptor for both globular and full-length adiponectin. In the current study, two genetic variations in ADIPOR2 gene were identified in an F2 resource population of Gushi chicken and Anka broiler. Association analysis between the two SNPs and chicken performance traits were determined using the linear mixed model. The data revealed that the g.34490C > T mutation in intron 3 was significantly associated with liver weight and globulin, the g.35363T > C polymorphism in exon 5 was significantly associated with body weights at 6, 10, and 12 weeks of age. Both polymorphisms have no significant effects on serum glucose and fat-related traits. The g.34490C > T mutation might play an important role in regulating liver weight. The g.35363T > C polymorphism does contribute in a significant manner to growth traits at the medium and later development stage but it is uncertain whether it could be a molecular marker for liver disease. PMID:25153449

Wang, Lele; Tian, Yadong; Mei, Xingxing; Han, Ruili; Li, Guoxi; Kang, Xiangtao

2015-01-01

154

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...

155

Analysis of membrane-enriched and high molecular weight proteins in Leishmania infantum promastigotes and axenic amastigotes.  

PubMed

Membrane and high molecular weight (HMW) proteins tend to be underrepresented in proteome analyses. Here, we optimized a protocol designed for the extraction and purification of membranes from the protozoan parasite Leishmania using a combination of serial centrifugation and free-flow zone electrophoresis (ZE-FFE). We also enriched for Leishmania HMW proteins from total extracts using the Gelfree 8100 fractionation system. This allowed the study of expression of both membrane-enriched and HMW proteins in Leishmania infantum promastigotes and amastigotes. We identified 194 proteins with at least one transmembrane domain (TMD) and 171 HMW proteins (?100 kDa) in the invertebrate promastigote stage and 66 proteins with at least one TMD and 154 HMW proteins in the mammalian amastigote stage. Several of the proteins identified in one of the stages are part of pathways consistent with the known biology of the parasite, with many proteins involved in lipid synthesis, numerous dynein heavy chains, and some surface antigen proteins 2 detected in the promastigote stage. Notably, some proteins involved in transport and proteolysis were detected either in promastigote or amastigote. The present study is using improved proteomic methods for studying membrane-enriched and HMW proteins helping to achieve a better understanding of the parasite life cycle. PMID:22716046

Brotherton, Marie-Christine; Racine, Gina; Ouameur, Amin Ahmed; Leprohon, Philippe; Papadopoulou, Barbara; Ouellette, Marc

2012-08-01

156

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. PMID:24130737

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

2013-01-01

157

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. PMID:24167669

Ma, Yu; Liu, Zhiwei; Zhang, Yan

2013-01-01

158

IGFBP-3, hypoxia and TNF-{alpha} inhibit adiponectin transcription  

SciTech Connect

The thiazolidinedione rosiglitazone, an agonist ligand for the nuclear receptor PPAR-{gamma}, improves insulin sensitivity in part by stimulating transcription of the insulin-sensitizing adipokine adiponectin. It activates PPAR-{gamma}-RXR-{alpha} heterodimers bound to PPAR-{gamma} response elements in the adiponectin promoter. Rosiglitazone-stimulated adiponectin protein synthesis in 3T3-L1 mouse adipocytes has been shown to be inhibited by IGFBP-3, which can be induced by hypoxia and the proinflammatory cytokine, TNF-{alpha}, two inhibitors of adiponectin transcription. The present study demonstrates that IGFBP-3, the hypoxia-mimetic agent cobalt chloride, and TNF-{alpha} inhibit rosiglitazone-induced adiponectin transcription in mouse embryo fibroblasts that stably express PPAR-{gamma}2. Native IGFBP-3 can bind RXR-{alpha} and inhibited rosiglitazone stimulated promoter activity, whereas an IGFBP-3 mutant that does not bind RXR-{alpha} did not. These results suggest that IGFBP-3 may mediate the inhibition of adiponectin transcription by hypoxia and TNF-{alpha}, and that IGFBP-3 binding to RXR-{alpha} may be required for the observed inhibition.

Zappala, Giovanna, E-mail: zappalag@mail.nih.gov [Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States)] [Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States); Rechler, Matthew M. [Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States) [Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States); Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States)

2009-05-15

159

Adiponectin: Probe of the molecular paradigm associating diabetes and obesity  

PubMed Central

Type 2 diabetes is an emerging health challenge all over the world as a result of urbanization, high prevalence of obesity, sedentary lifestyle and other stress related factors compounded with the genetic prevalence. The health consequences and economic burden of the obesity and related diabetes mellitus epidemic are enormous. Different signaling molecules secreted by adipocytes have been implicated in the development of obesity and associated insulin resistance in type 2 diabetes. Human adiponectin, a 244-amino acid collagen-like protein is solely secreted by adipocytes and acts as a hormone with anti-inflammatory and insulin-sensitizing properties. Adiponectin secretion, in contrast to secretion of other adipokines, is paradoxically decreased in obesity which may be attributable to inhibition of adiponectin gene transcription. There are several mechanisms through which adiponectin may decrease the risk of type 2 diabetes, including suppression of hepatic gluconeogenesis, stimulation of fatty acid oxidation in the liver, stimulation of fatty acid oxidation and glucose uptake in skeletal muscle, and stimulation of insulin secretion. To date, no systematic review has been conducted that evaluate the potential importance of adiponectin metabolism in insulin resistance. In this review attempt has been made to explore the relevance of adiponectin metabolism for the development of diabetes mellitus. This article also identifies this novel target for prospective therapeutic research aiming successful management of diabetes mellitus. PMID:25685286

Ghoshal, Kakali; Bhattacharyya, Maitree

2015-01-01

160

Modulation of adiponectin as a potential therapeutic strategy.  

PubMed

Adiponectin is produced predominantly by adipocytes and plays an important role in metabolic and cardiovascular homeostasis through its insulin-sensitizing actions and anti-inflammatory and anti-atherogenic properties. Recently, it has been observed that lower levels of adiponectin can substantially increase the risk of developing type 2 diabetes, metabolic syndrome, atherosclerosis, and cardiovascular disease in patients who are obese. Circulating adiponectin levels are inversely related to the inflammatory process, oxidative stress, and metabolic dysregulation. Intensive lifestyle modifications and pharmacologic agents, including peroxisome proliferator-activated receptor-? or ? agonists, some statins, renin-angiotensin-aldosterone system blockers, some calcium channel blockers, mineralocorticoid receptor blockers, new ?-blockers, and several natural compounds can increase adiponectin levels and suppress or prevent disease initiation or progression, respectively, in cardiovascular and metabolic disorders. Therefore, it is important for investigators to have a thorough understanding of the interventions that can modulate adiponectin. Such knowledge may lead to new therapeutic approaches for diseases such as type 2 diabetes, metabolic syndrome, cardiovascular disease, and obesity. This review focuses on recent updates regarding therapeutic interventions that might modulate adiponectin. PMID:24603219

Lim, Soo; Quon, Michael J; Koh, Kwang Kon

2014-04-01

161

Adiponectin as a biomarker of osteoporosis in postmenopausal women: controversies.  

PubMed

The literature reports indicating a link between plasma levels of adiponectin and body fat, bone mineral density, sex hormones, and peri- and postmenopausal changes, draw attention to the possible use of adiponectin as an indicator of osteoporotic changes, suggesting that adiponectin may also modulate bone metabolism. In this study, we attempted to analyze the available in vitro and in vivo results which could verify this hypothesis. Although several studies have shown that adiponectin has an adverse effect on bone mass, mainly by intensifying resorption, this peptide has also been demonstrated to increase the proliferation and differentiation of osteoblasts, inhibit the activity of osteoclasts, and reduce bone resorption. There are still many ambiguities; for example, it can be assumed that concentrations of adiponectin in plasma do not satisfactorily reflect its production by adipose tissue, as well as conflicting in vitro and in vivo results. It seems that the potential benefit in the treatment of patients with osteoporosis associated with the pharmacological regulation of adiponectin is controversial. PMID:24591772

Lubkowska, Anna; Dobek, Aleksandra; Mieszkowski, Jan; Garczynski, Wojciech; Chlubek, Dariusz

2014-01-01

162

Adiponectin: Probe of the molecular paradigm associating diabetes and obesity.  

PubMed

Type 2 diabetes is an emerging health challenge all over the world as a result of urbanization, high prevalence of obesity, sedentary lifestyle and other stress related factors compounded with the genetic prevalence. The health consequences and economic burden of the obesity and related diabetes mellitus epidemic are enormous. Different signaling molecules secreted by adipocytes have been implicated in the development of obesity and associated insulin resistance in type 2 diabetes. Human adiponectin, a 244-amino acid collagen-like protein is solely secreted by adipocytes and acts as a hormone with anti-inflammatory and insulin-sensitizing properties. Adiponectin secretion, in contrast to secretion of other adipokines, is paradoxically decreased in obesity which may be attributable to inhibition of adiponectin gene transcription. There are several mechanisms through which adiponectin may decrease the risk of type 2 diabetes, including suppression of hepatic gluconeogenesis, stimulation of fatty acid oxidation in the liver, stimulation of fatty acid oxidation and glucose uptake in skeletal muscle, and stimulation of insulin secretion. To date, no systematic review has been conducted that evaluate the potential importance of adiponectin metabolism in insulin resistance. In this review attempt has been made to explore the relevance of adiponectin metabolism for the development of diabetes mellitus. This article also identifies this novel target for prospective therapeutic research aiming successful management of diabetes mellitus. PMID:25685286

Ghoshal, Kakali; Bhattacharyya, Maitree

2015-02-15

163

Mechanisms of assembly of wheat high molecular weight glutenins inferred from expression of wild-type and mutant subunits in transgenic tobacco.  

PubMed

Following sequestration into the endoplasmic reticulum, wheat high molecular weight glutenin subunits (HMW-GS) assemble into polymers through intermolecular disulfide bond formation. These polymers, which also include low molecular weight glutenin subunits (LMW-GS), have a broad distribution of molecular mass reaching up to several million daltons. To study the mechanism of assembly of the HMW-GS, we have expressed x- and y-type HMW-GS in transgenic tobacco plants. Both types, when expressed individually or in combination, were incorporated into polymers. Partial reduction of polymers formed by different subunits resulted in different patterns of release of homodimers, heterodimers, and monomers. This suggested different arrangements of intermolecular disulfide bonds or different peptide conformations in the vicinity of the disulfide bonds linking x-x, y-y, and x-y type HMW-GS. A mutant of the x-type subunit, lacking a conserved cysteine in the C-terminal domain, assembled into oligomers linked by intermolecular disulfide bonds, but not into large polymers. This mutant was deposited, however, in dense protein bodies, similar to those formed by the native HMW-GS, suggesting that polymer formation and packaging into protein bodies may be the result of different types of interactions. Pulse-chase labeling of proteins in wheat endosperm showed that the assembly of the HMW-GS into insoluble polymers occurs by a slow process which apparently continues after the initiation of protein body formation. PMID:8132629

Shani, N; Rosenberg, N; Kasarda, D D; Galili, G

1994-03-25

164

Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype  

PubMed Central

Adiponectin is a cardioprotective adipokine derived predominantly from visceral fat. We recently demonstrated that exogenous adiponectin induces vascular smooth muscle cell (VSMC) differentiation via repression of mTORC1 and FoxO4. Here we report for the first time that VSMC express and secrete adiponectin, which acts in an autocrine and paracrine manner to regulate VSMC contractile phenotype. Adiponectin was found to be expressed in human coronary artery and mouse aortic VSMC. Importantly, siRNA knock-down of endogenous adiponectin in VSMC significantly reduced the expression of VSMC contractile proteins. Contractile protein deficiency was also observed in primary VSMC isolated from Adiponectin-/- mice. This deficiency could be rescued by culturing Adiponectin-/- VSMC in conditioned media from wild type (WT) VSMC. Moreover, the paracrine effect of VSMC-derived adiponectin was confirmed as adiponectin neutralizing antibody blocked the rescue. Overexpressed adiponectin also exerted paracrine effects on neighboring untransfected VSMC, which was also blocked by adiponectin neutralizing antibody. Interestingly, adiponectin expression was inducible by the PPAR? agonist rosiglitazone. Our data support an important role for VSMC-derived adiponectin in maintaining VSMC contractile phenotype, contributing to critical cardioprotective functions in the vascular wall. PMID:21952104

Ding, Min; Carrao, Ana Catarina; Wagner, Robert J.; Xie, Yi; Jin, Yu; Rzucidlo, Eva M.; Yu, Jun; Li, Wei; Tellides, George; Hwa, John; Aprahamian, Tamar R.; Martin, Kathleen A.

2011-01-01

165

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

2010-11-01

166

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

E-print Network

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. ...

Liu, Qingqing

167

Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells  

SciTech Connect

It is well established that obesity is a risk factor for breast cancer and that blood levels of adiponectin, a hormone mainly secreted by white adipocytes, are inversely correlated with the body fat mass. As adiponectin elicits anti-proliferative effects in some cell types, we tested the hypothesis that adiponectin could influence human breast cancer MCF-7 cell growth. Here we show that MCF-7 cells express adiponectin receptors and respond to human recombinant adiponectin by reducing their growth, AMPkinase activation, and p42/p44 MAPkinase inactivation. Further, we demonstrate that the anti-proliferative effect of adiponectin involves activation of cell apoptosis and inhibition of cell cycle. These findings suggest that adiponectin could act in vivo as a paracrine/endocrine growth inhibitor towards mammary epithelial cells. Moreover, adipose adiponectin production being strongly reduced in obesity, this study may help to explain why obesity is a risk factor of developing breast cancers.

Dieudonne, Marie-Noelle [Service de Biochimie et Biologie Moleculaire, UPRES-EA 2493, Faculte de Medecine Paris-Ile de France Ouest, Universite Versailles-St Quentin, Centre Hospitalier de Poissy, 78303 Poissy Cedex (France); Bussiere, Marianne [Service de Biochimie et Biologie Moleculaire, UPRES-EA 2493, Faculte de Medecine Paris-Ile de France Ouest, Universite Versailles-St Quentin, Centre Hospitalier de Poissy, 78303 Poissy Cedex (France); Dos Santos, Esther [Service de Biochimie et Biologie Moleculaire, UPRES-EA 2493, Faculte de Medecine Paris-Ile de France Ouest, Universite Versailles-St Quentin, Centre Hospitalier de Poissy, 78303 Poissy Cedex (France); Leneveu, Marie-Christine [Service de Biochimie et Biologie Moleculaire, UPRES-EA 2493, Faculte de Medecine Paris-Ile de France Ouest, Universite Versailles-St Quentin, Centre Hospitalier de Poissy, 78303 Poissy Cedex (France); Giudicelli, Yves [Service de Biochimie et Biologie Moleculaire, UPRES-EA 2493, Faculte de Medecine Paris-Ile de France Ouest, Universite Versailles-St Quentin, Centre Hospitalier de Poissy, 78303 Poissy Cedex (France)]. E-mail: biochip@wanadoo.fr; Pecquery, Rene [Service de Biochimie et Biologie Moleculaire, UPRES-EA 2493, Faculte de Medecine Paris-Ile de France Ouest, Universite Versailles-St Quentin, Centre Hospitalier de Poissy, 78303 Poissy Cedex (France)

2006-06-23

168

ATOMIC FORCE MICROSCOPY OF A HYBRID HIGH-MOLECULAR-WEIGHT GLUTENIN SUBUNIT FROM A TRANSGENIC HEXAPLOID WHEAT  

Technology Transfer Automated Retrieval System (TEKTRAN)

The high-molecular-weight glutenin subunits (HMW-GS) of wheat gluten in their native form are incorporated into an intermolecularly disulfide-linked, polymeric system that gives rise to the elasticity of wheat flour doughs. These protein subunits range in molecular weight from about ''K-90K and are...

169

The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity  

Microsoft Academic Search

Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and

T. Yamauchi; J. Kamon; H. Waki; Y. Terauchi; N. Kubota; K. Hara; Y. Mori; T. Ide; K. Murakami; N. Tsuboyama-Kasaoka; O. Ezaki; Y. Akanuma; O. Gavrilova; C. Vinson; M. L. Reitman; H. Kagechika; K. Shudo; M. Yoda; Y. Nakano; K. Tobe; R. Nagai; S. Kimura; M. Tomita; P. Froguel; T. Kadowaki

2001-01-01

170

Paradoxical Decrease of an Adipose-Specific Protein, Adiponectin, in Obesity  

Microsoft Academic Search

We isolated the human adipose-specific and most abundant gene transcript, apM1 (Maeda, K., et al.,Biochem. Biophys. Res. Commun.221, 286–289, 1996). The apM1 gene product was a kind of soluble matrix protein, which we named adiponectin. To quantitate the plasma adiponectin concentration, we have produced monoclonal and polyclonal antibodies for human adiponectin and developed an enzyme-linked immunosorbent assay (ELISA) system. Adiponectin

Yukio Arita; Shinji Kihara; Noriyuki Ouchi; Masahiko Takahashi; Kazuhisa Maeda; Jun-ichiro Miyagawa; Kikuko Hotta; Iichiro Shimomura; Tadashi Nakamura; Koji Miyaoka; Hiroshi Kuriyama; Makoto Nishida; Shizuya Yamashita; Kosaku Okubo; Kenji Matsubara; Masahiro Muraguchi; Yasuichi Ohmoto; Tohru Funahashi; Yuji Matsuzawa

1999-01-01

171

LDL but not HDL increases adiponectin release of primary human adipocytes.  

PubMed

Adipocytes in obesity have inappropriately low cholesterol while adiponectin release is reduced. Cholesterol shortage may contribute to low adiponectin and 3T3-L1 cells treated with lovastatin have diminished adiponectin in cell supernatants. LDL and HDL deliver cholesterol to adipocytes. LDL but not HDL increases adiponectin in cell supernatants of primary human adipocytes. The effect of LDL is not blocked by receptor associated protein suggesting that members of the LDL-receptor family are not involved. To evaluate whether these in vitro observations translate into changes in systemic adiponectin, adiponectin was measured in serum of three patients before, immediately after and 3d after LDL-apheresis. Whereas circulating lipoproteins are reduced immediately after apheresis adiponectin is not changed. Therefore, acute lowering of lipoproteins does not affect systemic adiponectin also excluding that plenty of adiponectin is bound to lipoprotein particles. Accordingly, levels of adiponectin in purified lipoproteins are quite low. Familial hypobetalipoproteinemia (FHBL) is a rare disorder associated with low plasma LDL. Serum adiponectin is, however, similar compared to healthy controls. Thus, neither LDL nor HDL directly contributes to circulating adiponectin concentrations. PMID:24158017

Krautbauer, Sabrina; Neumeier, Markus; Eisinger, Kristina; Hader, Yvonne; Dada, Ashraf; Schmitz, Gerd; Aslanidis, Charalampos; Buechler, Christa

2013-12-01

172

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

2013-05-01

173

Increased serum concentrations of adiponectin in canine hypothyroidism.  

PubMed

Serum concentrations of adiponectin were compared between sex-matched hypothyroid (n?=?18) and euthyroid (n?=?18) client-owned dogs with comparable ages and body condition scores (BCS). Concentrations of adiponectin (mean; 95% confidence interval) were significantly (P?adiponectin were significantly negatively associated with concentrations of total thyroxine (P?<0.05) and positively correlated with concentrations of cholesterol (r?=?0.6, P?<0.01) in hypothyroid dogs. In conclusion, this study demonstrated increased serum concentrations of adiponectin in dogs with hypothyroidism. Suggestive of the presence of resistance to adiponectin that could have contributed to development of hyperlipidemia and insulin resistance in these dogs or alternatively, could be a consequence of these metabolic alterations. PMID:25555336

Mazaki-Tovi, Michal; Abood, Sarah K; Kol, Amir; Farkas, Amnon; Schenck, Patricia A

2015-02-01

174

Improved isolation protocol to detect high molecular weight polysaccharide structures of Campylobacter jejuni.  

PubMed

Simple detection of high molecular weight, LPS-like structures of Campylobacter jejuni is still an unsolved problem. A phenol-free extraction method for the detection of HMW polysaccharide was developed without the need for Western blot. This method provides a reliable technique for large-scale screening and comparative characterization study of different isolates. PMID:25229649

Kovács, Judit K; Fels?, Péter; Em?dy, Levente; Schneider, György; Kocsis, Béla

2014-12-01

175

Development of second generation peptides modulating cellular adiponectin receptor responses  

PubMed Central

The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM—low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10–1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions. PMID:25368867

Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim D.; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John D.; Surmacz, Eva; Lovas, Sandor

2014-01-01

176

Adipokines (adiponectin and plasminogen activator inhhibitor-1) in metabolic syndrome  

PubMed Central

Background: The clustering of cardiovascular risk factors is termed the metabolic syndrome (MS), which strongly predicts the risk of diabetes and cardiovascular disease (CVD). Adipokines may contribute to the development of obesity and insulin resistance and may be a causal link between MS, diabetes and CVD. Hence, we studied the adipokines – adiponectin and plasminogen activator inhibitor-1 (PAI-1) – in subjects with MS. Materials and Methods: We studied 50 subjects with MS diagnosed by International Diabetes Federation (IDF) criteria and 24 healthy age- and sex-matched controls. Clinical evaluation included anthropometry, body fat analysis by bioimpedance, highly sensitive C-reactive protein, insulin, adiponectin, and PAI-1 measurement. Results: Subjects with MS had lower adiponectin (4.01 ± 2.24 vs. 8.7 ± 1.77 ?g/ml; P < 0.0001) and higher PAI-1 (53.85 ± 16.45 vs. 17.35 ± 4.45 ng/ml; P < 0.0001) levels than controls. Both were related with the number of metabolic abnormalities. Adiponectin was negatively and PAI-1 was positively associated with body mass index, waist hip ratio (WHR), body fat mass, percent body fat, and all the parameters of MS, except HDL where the pattern reversed. WHR and triglycerides were independent predictors of adipokines in multiple regression analysis. Receiver operating characteristic curve analysis showed that adiponectin (6.7 ?g/ml) and PAI-1 (25.0 ng/ml) levels predicted the MS with high sensitivity, specificity and accuracy in Indian population. Conclusions: Subjects with MS have lower adiponectin and higher PAI-1 levels compared to healthy controls. Lifestyle measures have been shown to improve the various components of MS, and hence there is an urgent need for public health measures to prevent the ongoing epidemic of diabetes and CVD. PMID:22276262

Garg, M. K.; Dutta, M. K.; Mahalle, Namita

2012-01-01

177

Large-scale expression and purification of high-molecular-weight glutenin subunits.  

PubMed

The high-molecular-weight glutenin subunits (HMW-GSs) are considered to be one of the most important components of wheat gluten, contributing to the unique viscoelastic properties of wheat dough. The HMW-GSs are highly homologous in sequence and structure and a mixture of subunits is usually present in wheat flours. Consequently, it is difficult to purify these proteins separately in appreciable amounts. Expression in heterologous systems provides a clear opportunity to produce large amounts of single HMW-GS proteins, amounts (up to 100 mg) which are required for in vitro analysis of these proteins. However, since the first expression studies of HMW-GSs, over 10 years ago, this technology has not been widely utilized. Previous studies have been analytical or small scale (5-100 ml) and in most cases only partial purity was obtained. In the present paper, we describe in detail the expression of the HMW-GSs Glu1-Dx2, Dx5, Dy10, and Dy12 for the first time on a large scale, producing up to 100 mg of target protein from a 2-liter bacterial culture, using a Biostat fermenter. Our results include optimization of expression conditions to increase yield and stability of proteins. Results also include localization, differences between x- and y-type expression and small-scale versus large-scale expression. We also developed a large-scale purification procedure. The bacterially expressed proteins have the same molecular weight on SDS-PAGE and the same retention times on RP-HPLC as their native counterparts extracted from flour. Functionality tests, on the bacterially produced proteins, have shown a clear correlation with the equivalent native proteins from flour. These results provide a clear opportunity to produce protein in amounts necessary for more detailed studies of the structure and function of the HMW-GSs and glutenin polymers on dough development and quality. PMID:12071704

Dowd, Caitriona; Bekes, Ferenc

2002-06-01

178

Expression of brain adiponectin in a murine model of transient cerebral ischemia  

PubMed Central

Objective: Adiponectin is a hormone that is mainly secreted by fat cells. Adiponectin has anti-inflammatory and anti-atherosclerotic effects, and a protective effect against ischemic brain injury, but the level of expression of adiponectin in brain tissue is unknown. In the current study, a mouse model of transient cerebral ischemia was used to determine the level of expression of adiponectin in ischemic brain tissue. Methods: Sixty CD-1 mice underwent transient middle cerebral artery occlusion. The level of expression of adiponectin in mouse brain tissues 1 hour, 4 hours, 1 day, 3 days, and 7 days, after cerebral ischemia/reperfusion injury were determined using a real-time quantitative polymerase chain reaction, Western blot, and immunohistochemistry. Results: The level of expression of adiponectin in mouse ischemic brain tissues increased after cerebral ischemia/reperfusion injury and was higher in the central area of ischemia than in the peripheral area. The level of expression of adiponectin occurred only in vascular endothelial cells. There was no significant change in the level of expression of adiponectin mRNA in brain tissue pre- and post-ischemia/reperfusion injury. Conclusion: After cerebral ischemia/reperfusion injury, adiponectin accumulated in the vascular endothelial cells of ischemic brain tissues, and non-endogenous adiponectin was generated. Circulating adiponectin accumulated in ischemic brain tissues through its role in adhering to damaged vascular endothelial cells.

Shen, Lin-Hui; Miao, Jie; Zhao, Ya-Jie; Zhao, Yong-Ju; Liang, Wei

2014-01-01

179

Modulation of ovarian steroidogenesis by adiponectin during delayed embryonic development of Cynopterus sphinx.  

PubMed

The aim of present study was to evaluate role of adiponectin in ovarian steroidogenesis during delayed embryonic development of Cynopterus sphinx. This study showed significantly low circulating adiponectin level and a decline in expression of adiponectin receptor 1 (AdipoR1) in the ovary during the period of delayed embryonic development as compared with the normal development. The adiponectin treatment in vivo during the period of delayed development caused significantly increased in circulating progesterone and estradiol levels together with increased expression of AdipoR1 in the ovary. The in vitro study confirmed the stimulatory effect of adiponectin on progesterone synthesis. Both in vivo and in vitro studies showed that the effects of adiponectin on ovarian steroidogenesis were mediated through increased expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein and 3?-hydroxyl steroid dehydrogenase enzyme. The adiponectin treatment may also promote progesterone synthesis by modulating ovarian angiogenesis, cell survival and rate of apoptosis. PMID:24787661

Anuradha; Krishna, Amitabh

2014-09-01

180

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. PMID:20561616

Michalakis, Konstantinos G.; Segars, James H.

2011-01-01

181

High-power DPSS Laser hosted on a HMW-THS  

NASA Astrophysics Data System (ADS)

The Hollow Metallic Winglets / HMW-THS, a turbo engine optimised for cooling electronics, handles large flows of energy, gas and air. Its heat exchanging shell, of huge area, tops the pressurised Can; the bottom fits a window. The hosted machine is built around a large inner gas distributor which integrates the main athermal structures. Considering the power levels, the ducting ease of both outer air-flows is as important and cuts noise. Two banks of hybrid mounted Laser Diodes / LDs, side or end feed each lasing Z-slab, thin and exposed to the cooling gas, which flows fast on both sides. The least path to reach the cooling gas minimises dT; to further reduce the thermal lensing effects, the local cooling can be tailored / spoiled to copy the heating density. The simplest optical etc layout is preferable but the current schemes and materials seem suitable; if required, the slab ends etc can be Brewster cut etc. The pumping section can sport a MOPA configuration to eases this function exploiting coherence. The inner pressure can be relevat but affects mildly only the outer window. Compactness and more degrees of symmetry lead to a natural athermal behaviour; the inner structure includes gas ducts dedicated to equalize its temperature. The neuter, clean He sports a top C P and flows easily; speed and pressure increase the heat removal rate and reduce dT; the fast cycle can be important. H II would spoil the HT / HR coatings and the electronics and generates water. Note that He was used to cool the largest AC generators. To improve the heat removal from hot spots or weak elements, a Thermo Electric cooler can yield local, sub-ambient temperature flows. A cycle including dedicated turbo stages, intercoolers and gas expansion suits larger critical sections.

Checchetti, Maurizio

2007-02-01

182

Leptin, adiponectin, and ghrelin dysregulation in chronic kidney disease.  

PubMed

In the past 10 years, 3 new metabolic compounds, leptin, adiponectin, and ghrelin, involved in energy metabolism, body composition, and appetite regulation, have been discovered. We have assessed their characteristics in 46 patients with stage 3 to 4 chronic kidney disease to evaluate the role of decreased renal function in the abnormal handling reported in more severe end-stage renal disease patients. In addition to the usual correlations with body mass index and body fat mass, the results show unexpected positive correlations between leptin and insulin, leptin and adiponectin, a weak inverse relationship between adiponectin and glomerular filtration rate, and no influence of C-reactive protein on either leptin or adiponectin in these noninflamed patients. Serum ghrelin was inversely correlated with body mass index and with glomerular filtration rate as measured by inulin clearance. Thus, ghrelin and leptin, 2 antagonist signals for energy balance, both seem to increase when glomerular filtration rate is reduced, potentially neutralizing their respective biologic effects in severe renal insufficiency. PMID:15648019

Guebre-Egziabher, Fitsum; Bernhard, Jacques; Geelen, Ghislaine; Malvoisin, Etienne; Hadj-Aissa, Aoumeur; Fouque, Denis

2005-01-01

183

Edinburgh Research Explorer Proangiogenic contribution of adiponectin toward mammary  

E-print Network

constituents of the mammary gland. They are essential for mammary tumor growth and survival. Metabolically, oneEdinburgh Research Explorer Proangiogenic contribution of adiponectin toward mammary tumor growth toward mammary tumor growth in vivo' Clinical Cancer Research, vol 15, no. 10, pp. 3265-76., 10

Millar, Andrew J.

184

Relation of Adiponectin to Glucose Tolerance Status, Adiposity, and Cardiovascular Risk Factor Load  

PubMed Central

Objective. Adiponectin has anti-atherogenic and anti-inflammatory properties. We investigated the influence of adiponectin on glucose tolerance status, adiposity and cardiovascular risk factors (CVRFs). Design and Patients. Study consisted of 107 subjects: 55 with normal glucose tolerance (NGT) and 52 with impaired glucose regulation (IGR) who were divided into two groups: 24 subjects with impaired fasting glucose (IFG Group) and 28 patients with type 2 diabetes mellitus (DM Group). In additional analysis, study participants were divided into two groups, according to CVRFs: low and high risk. Measurements: Patients were evaluated for glucose, HbA1C, insulin, lipids, CRP, HOMA-IR and adiponectin. Measurements. Patients were evaluated for glucose, HbA1C, insulin, lipids, CRP, HOMA-IR and adiponectin. Results. Adiponectin was significantly higher in NGT group than in IFG (P = 0.003) and DM (P = 0.01) groups. Adiponectin was significantly, positively associated with HDL and inversely associated with glucose, HbA1c, ALT, AST, TG, HOMA-IR. Patients with higher CVRFs load have lesser adiponectin compared to patients with low cardiovascular risk P < 0.0001). Adiponectin was inversely associated with the number of risk factors (r = ?0.430, P = 0.0001). Conclusions. Circulating adiponectin was significantly lower in subjects with different degree of IGR compared to subjects with normal glucose homeostasis. Adiponectin was significantly lower in high risk group than low risk group and decreased concurrently with increased number of CVRFs. PMID:22253614

Wolfson, N.; Gavish, D.; Matas, Z.; Boaz, M.; Shargorodsky, M.

2012-01-01

185

The Relationships of Adiponectin with Insulin and Lipids Are Strengthened with Increasing Adiposity  

PubMed Central

Context Adipose tissue inflammation has been implicated in the pathogenesis of obesity related co-morbidities. Adiponectin, an anti-inflammatory protein, improves insulin sensitivity and lipid levels systemically. Because adiponectin is secreted by adipocytes, it may also act locally to counteract insulin resistance and dyslipidemia worsened by inflammation. Objective To determine whether associations between adiponectin and insulin sensitivity and lipids are stronger with increasing adiposity. Design A cross-sectional study of participants in the “The Princeton School District Study.” Setting Princeton City schools (Cincinnati, OH, 2001–2002 school year). Participants 1196 non-Hispanic white and black students in grades 5–12. Main Outcome Measure The relationships between adiponectin and high-density lipoprotein cholesterol (HDL), triglycerides, and insulin. To test our hypothesis we: 1) compared correlation and regression coefficients of lean and non-lean individuals and 2) incorporated an adiponectin by adiposity interaction in regression models. Results For HDL and triglycerides, the relationship with adiponectin, while present among lean adolescents, strengthened with increasing adiposity. However, with insulin, a relationship with adiponectin was only present among non-lean adolescents. Conclusions These analyses suggest that adiponectin’s relationship with insulin and lipids strengthens with increasing adiposity, such that heavier adolescents have a greater benefit from high levels of adiponectin than their lean counterparts. PMID:15870125

Martin, Lisa J.; Woo, Jessica G.; Daniels, Stephen R.; Goodman, Elizabeth; Dolan, Lawrence M.

2015-01-01

186

Adiponectin Induces Pro-inflammatory Programs in Human Macrophages and CD4+ T Cells  

PubMed Central

Abundant experimental and clinical data support a modulatory role for adiponectin in inflammation, dysmetabolism, and disease. Because the activation of cells involved in innate and adaptive immunity contributes to the pathogenesis of diseases such as atherosclerosis and obesity, this study investigated the role of adiponectin in human macrophage polarization and T cell differentiation. Examination of the adiponectin-induced transcriptome in primary human macrophages revealed that adiponectin promotes neither classical (M1) nor alternative (M2) macrophage activation but elicits a pro-inflammatory response that resembles M1 more closely than M2. Addition of adiponectin to polyclonally activated CD4+ T lymphocytes did not affect cell proliferation but induced mRNA expression and protein secretion of interferon (IFN)-? and interleukin (IL)-6. Adiponectin treatment of CD4+ T cells increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and signal transducer and activation of transcription (STAT) 4 and augmented T-bet expression. Inhibition of p38 with SB203580 abrogated adiponectin-induced IFN-? production, indicating that adiponectin enhances TH1 differentiation through the activation of the p38-STAT4-T-bet axis. Collectively, our results demonstrate that adiponectin can induce pro-inflammatory functions in isolated macrophages and T cells, concurring with previous observations that adiponectin induces a limited program of inflammatory activation that likely desensitizes these cells to further pro-inflammatory stimuli. PMID:22948153

Cheng, Xiang; Folco, Eduardo J.; Shimizu, Koichi; Libby, Peter

2012-01-01

187

Yin-Yang Regulation of Adiponectin Signaling by APPL Isoforms in Muscle Cells*  

PubMed Central

APPL1 is a newly identified adiponectin receptor-binding protein that positively mediates adiponectin signaling in cells. Here we report that APPL2, an isoform of APPL1 that forms a dimer with APPL1, can interacts with both AdipoR1 and AdipoR2 and acts as a negative regulator of adiponectin signaling in muscle cells. Overexpression of APPL2 inhibits the interaction between APPL1 and AdipoR1, leading to down-regulation of adiponectin signaling in C2C12 myotubes. In contrast, suppressing APPL2 expression by RNAi significantly enhances adiponectin-stimulated glucose uptake and fatty acid oxidation. In addition to targeting directly to and competing with APPL1 in binding with the adiponectin receptors, APPL2 also suppresses adiponectin and insulin signaling by sequestrating APPL1 from these two pathways. In addition to adiponectin, metformin also induces APPL1-APPL2 dissociation. Taken together, our results reveal that APPL isoforms function as an integrated Yin-Yang regulator of adiponectin signaling and mediate the cross-talk between adiponectin and insulin signaling pathways in muscle cells. PMID:19661063

Wang, Changhua; Xin, Xiaoban; Xiang, Ruihua; Ramos, Fresnida J.; Liu, Meilian; Lee, Hak Joo; Chen, Hongzhi; Mao, Xuming; Kikani, Chintan K.; Liu, Feng; Dong, Lily Q.

2009-01-01

188

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

2013-03-22

189

Smoking Habits and Neuropeptides: Adiponectin, Brain-derived Neurotrophic Factor, and Leptin Levels  

PubMed Central

This study aimed to identify changes in the level of neuropeptides among current smokers, former smokers, and individuals who had never smoked, and how smoking habits affect obesity and metabolic syndrome (MetS). Neuropeptide levels, anthropometric parameters, and metabolic syndrome diagnostic indices were determined among male workers; 117 of these had never smoked, whereas 58 and 198 were former and current smokers, respectively. The total sample comprised 373 male workers. The results obtained from anthropometric measurements showed that current smokers attained significantly lower body weight, body mass index, waist circumference, and abdominal fat thickness values than former smokers and those who had never smoked. Current smokers’ eating habits proved worse than those of non-smokers and individuals who had never smoked. The level of brain-derived neurotrophic factor (BDNF) in the neuropeptides in the case of former smokers was 23.6 ± 9.2 pg/ml, higher than that of current smokers (20.4 ± 6.1) and individuals who had never smoked (22.4 ± 5.8) (F = 6.520, p = 0.002). The level of adiponectin among former smokers was somewhat lower than that of current smokers, whereas leptin levels were higher among former smokers than current smokers; these results were not statistically significant. A relationship was found between adiponectin and triglyceride among non-smokers (odds ratio = 0.660, ? value = ?0.416, p < 0.01) and smokers (odds ratio = 0.827, ? value = ?0.190, p < 0.05). Further, waist circumference among non-smokers (odds ratio = 1.622, ? value = 0.483, p < 0.001) and smokers (odds ratio = 1.895, ? value = 0.639, p < 0.001) was associated with leptin. It was concluded that cigarette smoking leads to an imbalance of energy expenditure and appetite by changing the concentration of neuropeptides such as adiponectin, BDNF, leptin, and hsCRP, and influences food intake, body weight, the body mass index, blood pressure, and abdominal fat, which are risk factors for MetS and cardiovascular disease. PMID:25071918

Won, Yong Lim; Ko, Kyung Sun; Roh, Ji won

2014-01-01

190

Identification and characterization of high-molecular-weight glutenin genes in Polish triticale cultivars by PCR-based DNA markers  

Microsoft Academic Search

Molecular markers were used to identify the allele\\/gene composition of complex lociGlu-A1 andGlu-B1 of high-molecular-weight (HMW) glutenin subunits in triticale cultivars. Forty-six Polish cultivars of both winter and spring\\u000a triticale were analysed with 7 PCR-based markers. Amplified DNA fragments of HMW gluteninGlu-1 genes were separated by agarose slab-gel electrophoresis. Differences between all 3 alleles at the locusGlu-A1 [Glu-A1a (encoding Ax1),1b

Boles?aw P. Salmanowicz; Monika Dylewicz

2007-01-01

191

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

PubMed

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. PMID:22289908

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

2012-03-15

192

Effect of high molecular weight glutenin subunit composition in common wheat on dough properties and steamed bread quality  

Technology Transfer Automated Retrieval System (TEKTRAN)

Steamed bread is a popular staple in Asia with different flour quality requirements from pan bread. Little is known about how glutenin characteristics affect steamed bread quality. This work investigated how deletions of high molecular weight glutenin subunits (HMW-GS) influence gluten properties an...

193

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. PMID:23430039

Finelli, Carmine; Tarantino, Giovanni

2013-01-01

194

Visceral and Subcutaneous Adiposity and Adiponectin in Middle-aged Japanese Men: The ERA JUMP Study  

PubMed Central

Adiponectin is reduced in obesity, and has been suggested to play an important role in modulation of atherosclerosis. We studied the relationship between visceral (VAT) and subcutaneous (SAT) adipose tissue and serum adiponectin concentrations in Japanese men. Participants were 304 randomly selected community-based Japanese men aged 40 to 49 without a prior history of cardiovascular disease. Participants were grouped according to tertiles of serum adiponectin. In multiple linear regression analysis including age, pack years of smoking, and alcohol intake as covariates, log-transformed adiponectin was inversely associated with both VAT and SAT when these two obesity measures were included separately in the models. However, log-transformed adiponectin was inversely associated with VAT (standardized ? estimate= ?0.465, P< 0.0001) and positively associated with SAT (standardized ? estimate = 0.166, P=0.03), when these were included concomitantly in the model. In conclusion, VAT and SAT had differential associations with serum adiponectin concentrations. PMID:19584883

Nakamura, Yasuyuki; Sekikawa, Akira; Kadowaki, Takashi; Kadota, Aya; Kadowaki, Sayaka; Maegawa, Hiroshi; Kita, Yoshikuni; Evans, Rhobert W; Edmundowicz, Daniel; Curb, J David; Ueshima, Hirotsugu

2010-01-01

195

Ultrastructural Localization of Adiponectin protein in Vasculature of Normal and Atherosclerotic mice  

PubMed Central

Adiponectin, adipose-specific secretory protein, abundantly circulates in bloodstream and its concentration is around 1000-fold higher than that of other cytokines and hormones. Hypoadiponectinemia is a risk factor for atherosclerosis. There is little or no information on ultrastructural localization of adiponectin in the vasculature. Herein we investigated the localization of vascular adiponectin in the aorta using the immunoelectron microscopic technique. In wild-type (WT) mice, adiponectin was mainly detected on the luminal surface membrane of endothelial cells (ECs) and also found intracellularly in the endocytic vesicles of ECs. In the atherosclerotic lesions of apolipoprotein E-knockout (ApoE-KO) mice, adiponectin was detected in ECs, on the cell surface membrane of synthetic smooth muscle cells, and on the surface of monocytes adherent to ECs. Changes in adiponectin localization within the wall of the aorta may provide novel insight into the pathogenesis of atherosclerosis. PMID:24809933

Mori, Takuya; Koyama, Yoshihisa; Maeda, Norikazu; Nakamura, Yukiko; Fujishima, Yuya; Matsuda, Keisuke; Funahashi, Tohru; Shimada, Shoichi; Shimomura, Iichiro

2014-01-01

196

High-fat diet exacerbates renal dysfunction in SHR: reversal by induction of HO-1-adiponectin axis.  

PubMed

High-dietary fat intake is a major risk factor for development of metabolic and cardiovascular-renal dysfunction including obesity, coronary artery disease, hypertension, and chronic renal failure. We examined the effect of a high-fat diet on renal function and morphology in spontaneously hypertensive rats (SHR), a phenotype designed to mimic metabolic syndrome. High-fat diet induced increase (P < 0.05) in blood pressure, body weight, and renal lipid deposition in these rats. This increase in body weight was accompanied by elevations (P < 0.05) of blood glucose and low-density lipoprotein (LDL) levels, a decrease (P < 0.05) in adiponectin and increases (P < 0.05) in plasma monocyte chemotactic protein-1 (MCP-1) along with renal macrophage infiltration. These pathophysiological perturbations were attenuated (P < 0.05) by heme oxygenase-1 (HO-1) induction by treatment with cobalt protoporphyrin (CoPP). Further effects of CoPP included increased (P < 0.05) renal expression of adiponectin along with enhancement (P < 0.05) of pAKT, pAMPK, and p-eNOS in SHRs fed a high-fat diet. Prevention of such beneficial effects of CoPP by the concurrent administration of the heme-HO inhibitor stannous mesoporphyrin (SnMP) corroborates the role of HO system in mediating such effects. Taken together, our results demonstrate that high-fat diet induces a metabolic syndrome-like phenotype in hypertensive rats, which is amenable to rescue by increases in HO-1- and adiponectin-dependent pathways. PMID:22193921

Cao, Jian; Inoue, Kazuyoshi; Sodhi, Komal; Puri, Nitin; Peterson, Stephen J; Rezzani, Rita; Abraham, Nader G

2012-05-01

197

Isotopic analysis of bulk, LMW, and HMW DON d15N indicates recycled nitrogen release from marine DON  

NASA Astrophysics Data System (ADS)

Nitrogen (N) concentration and stable isotope ratio (d15N) measurements were made on bulk and size fractionated surface ocean dissolved organic nitrogen (DON) samples collected in the oligotrophic North Atlantic and Pacific Oceans. The bulk DON concentration in the upper 100 m is similar between the North Atlantic and North Pacific, between 4.5 and 5.0 uM, but the average d15N of bulk DON is significantly different, 3.9 per mil vs. air in the North Atlantic and 4.7 per mil in the North Pacific. The d15N of both bulk and HMW DON from the western tropical North Atlantic are similar to previous measurements, ~4.0 to 4.5 per mil. We report the first measurements of LMW DON d15N, which is consistently lower than HMW DON d15N. Neither the concentration nor d15N of bulk or size-fractionated DON varied with in situ N2 fixation rate, although significant variation in bulk and LMW DON d15N was observed between January and July of the same year in the western tropical North Atlantic. We propose a conceptual model to explain 1) the elevated d15N of bulk DON relative to other surface ocean N pools and fluxes, 2) the elevation of HMW DON d15N relative to LMW DON d15N, and 3) the inter-basin difference in the d15N of bulk DON. In this model, DON is produced from suspended particulate organic nitrogen (PON) without isotope fractionation because the conversion from PON to DON largely does not involve N-bearing bonds. In contrast, deamination and amide hydrolysis, with N isotope effects of 3 to 10 per mil, are major mechanisms by which DON is converted to ammonia and/or to other simple N compounds (e.g., amino acids). Thus these N-specific DON loss reactions result in an elevated d15N of residual DON relative to the parent DON and therefore also to the PON source. Moreover, the ammonium and simple organic N compounds released by microbial DON degradation are efficiently reassimilated back into the PON pool, as an integral part of the regenerated N cycle that further lowers the d15N of suspended PON relative to subsurface nitrate. Based on a d15N budget for the subtropical North Atlantic euphotic zone, we propose that this recycled N release via DON degradation (and not zooplankton ammonium excretion or N2 fixation) is the dominant mechanism lowering the d15N of PON relative to subsurface nitrate in the low-latitude ocean. DON degradation may also explain why the d15N of HMW DON is elevated relative to LMW DON: LMW DON may be produced by the isotope fractionating reactions responsible for degrading DON in general. Alternatively, LMW and HMW DON may have distinct sources. Finally, in this explanation, the difference in the d15N of DON between the North Atlantic and North Pacific primarily reflects the inter-basin difference in the d15N of subsurface nitrate fueling productivity in the euphotic zone.

Knapp, A. N.; Sigman, D. M.; Lipschultz, F.; Kustka, A.; Capone, D. G.

2010-12-01

198

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

199

Effect of monomeric adiponectin on cardiac function and perfusion in anesthetized pig.  

PubMed

Adiponectin, the most abundant adipokine released by adipose tissue, appears to play an important role in the regulation of vascular endothelial and cardiac function. To date, however, the physiological effects of human monomeric adiponectin on the coronary vasculature and myocardial systo-diastolic function, as well as on parasympathetic/sympathetic involvement and nitric oxide (NO) release, have not yet been investigated. Thus, we planned to determine the primary in vivo effects of human monomeric adiponectin on coronary blood flow and cardiac contractility/relaxation and the related role of autonomic nervous system, adiponectin receptors, and NO. In 30 anesthetized pigs, human monomeric adiponectin was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure, and the effects on coronary blood flow, left ventricular systo-diastolic function, myocardial oxygen metabolism, and NO release were examined. The mechanisms of the observed hemodynamic responses were also analyzed by repeating the highest dose of human monomeric adiponectin infusion after autonomic nervous system and NO blockade, and after specific adiponectin 1 receptor antagonist administration. Intracoronary human monomeric adiponectin caused dose-related increases of coronary blood flow and cardiac function. Those effects were accompanied by increased coronary NO release and coronary adiponectin levels. Moreover, the vascular effects of the peptide were prevented by blockade of ?2-adrenoceptors and NO synthase, whereas all effects of human monomeric adiponectin were prevented by adiponectin 1 receptor inhibitor. In conclusion, human monomeric adiponectin primarily increased coronary blood flow and cardiac systo-diastolic function through the involvement of specific receptors, ?2-adrenoceptors, and NO release. PMID:24860147

Grossini, Elena; Prodam, Flavia; Walker, Gillian Elisabeth; Sigaudo, Lorenzo; Farruggio, Serena; Bellofatto, Kevin; Marotta, Patrizia; Molinari, Claudio; Mary, David; Bona, Gianni; Vacca, Giovanni

2014-07-01

200

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. PMID:20219117

2010-01-01

201

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. PMID:23691032

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

2013-01-01

202

Leptin, adiponectin and serotonin levels in lean and obese dogs  

PubMed Central

Background Serotonin (5-hydroytryptamine or 5HT) is associated with numerous behavioral and psychological factors and is a biochemical marker of mood. 5HT is involved in the hypothalamic regulation of energy consumption. 5HT controls appetite in the central nerve system (CNS) and stimulates intestinal mobility. There are few studies looking at the role of 5HT and the relationship between peripheral circulating serotonin and obesity. The aim of this study was to find any differences in leptin, adiponectin, and 5HT between lean and obese dogs and to identify correlations among these factors. Results Leptin, triglyceride (TG) and cholesterol levels were higher in the obese group (all p < 0.01). Adiponectin and 5HT levels were higher in the lean group compared to the obese group (p < 0.01). Leptin (r = 0.628, p < 0.01), TG (r = 0.491, p < 0.01) and cholesterol (r = 0.419, p < 0.01) were positively correlated with body condition score (BCS), and adiponectin (r = -0.446, p < 0.01) and 5HT (r = -0.490, p < 0.01) were negatively correlated with BCS. Leptin was negatively correlated with adiponectin (r = -0.294, p < 0.01) and 5HT (r = -0.343, p < 0.01). 5HT was negatively correlated with leptin (r = -0.343, p < 0.01), TG (r = -0.268, p < 0.05) and cholesterol (r = -0.357, p < 0.05). Conclusions 5HT is an important appetite control neurotransmitter, but there are limited studies for 5HT levels related to obesity in dogs. To the best of our knowledge, this is the first study to evaluate peripheral 5HT levels in obese dogs. From this research, we can assume that 5HT may be correlated with canine obesity. Further studies will be needed to further elucidate the role of low serum 5HT levels in canine obesity. PMID:24886049

2014-01-01

203

Alterations of adiponectin in the course of inflammation and severe sepsis.  

PubMed

The adipocyte-specific protein adiponectin reveals anti-inflammatory, antioxidant, antiatherosclerotic and vasoprotective effects. This study aims to investigate adiponectin expression in cultured human adipocytes within an inflammatory model and in patients with severe sepsis and evaluates treatment effects of drotrecogin ? (activated) (DAA). In an in vitro inflammatory model of adipocyte cell culture, the effect of DAA on adiponectin mRNA expression was evaluated. Synthesis of mRNA was measured by quantitative polymerase chain reaction. Supernatants of these adipocytes and serum levels of adiponectin were measured in blood of 104 patients by enzyme-linked immunosorbent assay on days 1, 3, and 5 of severe sepsis. Twenty-six patients were treated with DAA (DAA), 78 patients without DAA (DAA). Stimulation of human adipocytes with tumor necrosis factor ? over 6 and 24 h resulted in a significant decrease in adiponectin mRNA transcripts. After 24 h of incubation, adiponectin mRNA expression was significantly upregulated according to applied dosages of DAA at 50 ng/mL and 5 ?g/mL (P < 0.05). Accordingly, adiponectin levels of supernatants of adipocyte culture increased after 24 h (P < 0.05). DAA patients revealed significantly higher adiponectin serum levels compared with healthy controls (P < 0.1) and DAA patients (P < 0.05) at days 1 and 3. On day 5 after 96-h infusion of DAA (24 ?g/kg per hour), adiponectin levels significantly increased in DAA patients and equalized toward DAA patients (P > 0.1). Adiponectin might be involved in the pathogenesis of the systemic inflammatory response during sepsis. Administration of DAA upregulates adiponectin expression under circumstances of systemic inflammation. PMID:22744305

Behnes, Michael; Brueckmann, Martina; Lang, Siegfried; Putensen, Christian; Saur, Joachim; Borggrefe, Martin; Hoffmann, Ursula

2012-08-01

204

Urinary adiponectin concentration is positively associated with micro- and macro-vascular complications  

PubMed Central

Background A relationship between plasma adiponectin level and a number of metabolic conditions, including insulin resistance, obesity, and type 2 diabetes, has been reported. This study aimed to assess whether urinary adiponectin concentration is correlated with vascular complications. Methods The study comprised 708 subjects who enrolled in the Seoul Metro City Diabetes Prevention Program and were carefully monitored from September 2008 to December 2008. Levels of urinary adiponectin were measured using an enzyme linked immunosorbent assay (ELISA) kit (AdipoGen, Korea). Urinary albumin excretion was assessed by the ratio of urinary albumin to creatinine (A/C ratio). Participants were divided into three groups based on tertiles of urinary adiponectin concentration, and we investigated whether urinary adiponectin levels are associated with microalbuminuria and pulse wave velocity. Results Urinary adiponectin concentrations were significantly higher in subjects with microalbuminuria than subjects with normoalbuminuria (P?adiponectin concentration was positively correlated with age, fasting plasma glucose level, HbA1C level, triglyceride level, HOMA-IR, systolic/diastolic blood pressure, and urinary A/C ratio (all P?adiponectin concentration had an increased likelihood of microalbuminuria than those in the lowest tertile (Odds ratio (OR), 6.437; 95% confidence interval (CI), 4.202 to 9.862; P?adiponectin concentration to be a significant determinant of mean brachial-ankle pulse wave velocity (baPWV). Conclusions An increased urinary adiponectin concentration is significantly associated with microalbuminuria and increased mean baPWV. These results suggest that urinary adiponectin may play an important role as a biomarker for vascular dysfunction. PMID:24073643

2013-01-01

205

Adiponectin and adiponectin receptors in the mouse preimplantation embryo and uterus  

PubMed Central

BACKGROUND Adiponectin (Adipoq), a protein secreted by adipocytes in inverse proportion to the adipose mass present, modulates energy homeostasis and increases insulin sensitivity. Tissue Adipoq signaling decreases in settings of maternal diabetes, polycystic ovary syndrome (PCOS) and endometriosis, conditions which are associated with reproductive difficulty. Our objective was to define the expression and hormonal regulation of Adipoq and its receptors in the mouse preimplantation embryo and uterus. METHODS AND RESULTS By real-time quantitative PCR, mRNA transcripts for Adipoq, AdipoR1, AdipoR2, Ppara, Ppard, FATP1 (SLC27A1) and acyl CoA oxidase (Acox1) were identified in mouse 2-cell and 8-cell embryos, while blastocyst stage embryos and trophoblast stem (TS) cells expressed mRNA for all genes except Adipoq. Protein expression of Adipoq, AdipoR1, AdipoR2, the insulin sensitive transporters GLUT8 (Slc2A8), GLUT12 (Slc2A12) and p-PRKAA1 was identified by immunofluorescence staining in all stages of preimplantation embryos including the blastocyst. In situ hybridization demonstrated the presence of Adipoq, AdipoR1 and AdipoR2 mRNA in the mouse decidual cells of the implantation site and in artificially decidualized cells, and the expression of these proteins was confirmed by western blotting. Flow cytometry confirmed cell surface expression of AdipoR1 and AdipoR2 in TS cells and decidual cells. CONCLUSIONS These results suggest for the first time that Adipoq signaling may play an important role in preimplantation embryo development and uterine receptivity by autocrine and paracrine methods in the mouse. Implantation failures and pregnancy loss, specifically those experienced in women with maternal metabolic conditions such as diabetes, obesity and PCOS, may be the result of aberrant Adipoq and AdipoR1 and AdipoR2 expression and suboptimal decidualization in the uterus. PMID:21106494

Kim, S.T.; Marquard, K.; Stephens, S.; Louden, E.; Allsworth, J.; Moley, K.H.

2011-01-01

206

A recombinant protein of two high molecular weight glutenins alters gluten polymer formation in transgenic wheat.  

PubMed

Wheat high molecular weight glutenin subunits (HMW-GS) are the most important determinants of its superiority for making leavened bread. Following synthesis, these proteins are sequestered into the endoplasmic reticulum and assemble into extremely large elastic polymers, linked by noncovalent and intermolecular disulfide bonds. To study the structural requirements for the assembly of HMW-GS, we have expressed in transgenic wheat a recombinant protein between two cognate x- and y-type subunits. In contrast to the natural polymerized x- and y-type HMW-GS, a significant amount of the recombinant subunit remained monomeric. Nonreducing SDS-polyacrylamide gel electrophoresis, coupled with limited proteolysis, showed that the monomeric form of the recombinant subunit contained an unusual intramolecular disulfide bond, linking an N-terminal cysteine to the single C-terminal cysteine residue. In addition, sucrose gradient analysis revealed that this intramolecular disulfide bond impeded the ability of the recombinant subunit to assemble into polymers. Despite of its altered assembly, a notable amount of the overexpressed recombinant subunit was also present in glutenin polymers. Moreover, its presence significantly altered the subunit composition of the polymer. Our results show that it is possible to modify gluten assembly and properties by expressing recombinant HMW-GS in transgenic wheat, and have a major implication for the improvement of wheat bread-making quality. PMID:9182582

Shimoni, Y; Blechl, A E; Anderson, O D; Galili, G

1997-06-13

207

Adiponectin exerts antiproliferative effect on human placenta via modulation of the JNK/c-Jun pathway  

PubMed Central

To determine the effects of adiponectin on human placenta during gestational diabetes mellitus (GDM) and on high glucose (HG)-induced BeWo cell proliferation. We examined the expression levels of adiponectin in control and GDM placenta using quantitative real-time PCR, Western blot, and immunohistochemistry (IHC). Cell proliferation and viability were assessed using a colorimetric assay (cell counting kit-8), PCNA immunocytochemical staining, and Western blot analysis of cyclin D1. Transfection of siRNA against c-jun was performed using Lipofectamine 2000. Cell cycle analysis was performed using propidium iodide staining and flow cytometry. Results show a decreased expression of adiponectin and an increased degree of trophoblast cell proliferation in GDM placenta compared to the normal placenta. Similarly, HG can promote BeWo cell proliferation that is associated with adiponectin down-regulation. This proliferation could be depressed by addition of exogenous adiponectin, i.e. adiponectin exerts antiproliferative effects on HG-induced trophoblast cells. Adiponectin suppresses the HG-induced BeWo cell proliferation by inhibiting the activation of JNK/c-jun. In conclusion, adiponectin inhibits HG-induced proliferation of BeWo cells through down-regulation of JNK/c-jun phosphorylation. PMID:25031708

Chen, Haitian; Chen, Hanqing; Wu, Yanxin; Liu, Bin; Li, Zhuyu; Wang, Zilian

2014-01-01

208

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:...

209

Effects of adiponectin on ovarian folliculogenesis and steroidogenesis in the vespertilionid bat, Scotophilus heathi.  

PubMed

The bat Scotophilus heathi undergo anovulation, known as delayed ovulation, coinciding with the period of seasonal adiposity due to fat accumulation. Because adiponectin is a well known fat cell product, it might be responsible for adiposity related anovulation in S. heathi. The aim of this study was thus to evaluate the effects of adiponectin treatment on ovarian activity in S. heathi. The bat during the period of delayed ovulation was treated with adiponectin (25 ?g/day) for 12 days. Changes taken place in the ovarian activity of the treated bat was compared with the control bat and results obtained are presented here. Adiponectin treatment significantly decreased body mass by depleting adipose tissue. It acts directly upon the ovary and promotes antral follicular development by stimulating cell proliferation and modulating ovarian steroidogenesis. The bat treated with adiponectin showed significant decrease in circulating androstenedione (A4) and estradiol (E2) levels, but increase in circulating progesterone (P4) level. The inhibitory effect of adiponectin on androgen synthesis may be due to decreased thecal-interstitial cells differentiation in stroma by suppressing adiponectin receptor type 1 (AdipoR1), luteinizing hormone (LH) and insulin receptors in the ovary of S. heathi. The study provides evidences suggesting that the adiponectin treatment suppresses adiposity and restores normal ovarian activity. PMID:22796157

Singh, Ajit; Krishna, Amitabh

2012-09-15

210

Serum Adiponectin Level and Different Kinds of Cancer: A Review of Recent Evidence  

PubMed Central

Background. Adiponectin, an adipokine secreted from adipose tissue, has antiobesity, anti-insulin resistance, and anticancer roles. The present study aimed to review the epidemiologic evidence about the association between adiponectin and cancers. Method. We searched in PubMed from 2002 to October 2011 by using the following key words: cancer, malignancy, cell proliferation, and adiponectin. Finally, 45 articles were recruited to review in the present paper. Findings. Several findings suggested inverse association between concentration of hormone and breast cancer risk. Low levels of adiponectin increase the risk of endometrial cancer in women. Adiponectin levels were significantly associated with prostate cancer in men. It seems that there is an inverse relationship between levels of adiponectin or its gene and colorectal cancer. Significant association between hormone and pancreatic cancer was found. Conclusion. Several findings suggested the negative correlation between adiponectin and risk of cancers. This relationship was more elucidated by the correlation between the hormone with obesity and insulin resistance. Suppression of growth and proliferation of cancer cells by adiponectin were explained via several mechanisms. PMID:23213569

Izadi, Vajihe; Farabad, Elaheh; Azadbakht, Leila

2012-01-01

211

Decrease in Serum Adiponectin Level Due to Obesity and Visceral Fat Accumulation in Children  

Microsoft Academic Search

Objective: To determine whether serum adiponectin is decreased in obesity and is restored toward normal level after treatment in children.Research Methods and Procedures: Subjects were 53 Japanese obese children, 33 boys and 20 girls (6 to 14 years old), and 30 age-matched nonobese controls for measuring adiponectin (16 boys and 14 girls). Blood was drawn after an overnight fast, and

Kohtaro Asayama; Hidemasa Hayashibe; Kazushige Dobashi; Norihiko Uchida; Takaya Nakane; Kohji Kodera; Akira Shirahata; Matsuo Taniyama

2003-01-01

212

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

213

Up- and down-regulation of adiponectin expression and multimerization: Mechanisms and therapeutic implication  

PubMed Central

Adiponectin has been receiving a great deal of attention due to its potential therapeutic use for metabolic and cardiovascular disorders. Adiponectin expression levels and multimerization are down-regulated in obesity and up-regulated by insulin sensitizers such as thiazolidinediones (TZDs), metformin, sulfonylurea and resveratrol (RSV). The precise mechanisms underlying adiponectin up- and down-regulation remain largely unknown, but recent studies indicate that the cellular and plasma levels of adiponectin could be regulated at both transcriptional and post-transcriptional levels. At the post-translational level, TZDs and resveratrol promote adiponectin levels and multimerization via up-regulation of disulfidebond-A oxidoreductase-like protein (DsbA-L). Adiponectin levels are also stimulated by FOXO1 and AMP-activated protein kinase (AMPK), and are suppressed by PKA or silencing mediator of retinoid andthyroid hormone receptors (SMRT). Since multimerization is important not only for adiponectin function but also for stability, increasing adiponectin multimerization has become a promising drug target for the treatment of metabolic diseases and other related disorders. PMID:22342903

Liu, Meilian; Liu, Feng

2012-01-01

214

A Pilot Study of the Association of Low Plasma Adiponectin and Barrett's Esophagus  

Microsoft Academic Search

BACKGROUND AND AIMS:Gastroesophageal reflux disease (GERD) and obesity are associated with esophageal adenocarcinoma (EAC). We hypothesized that the obesity–EAC relation is mediated by factors secreted from adipocytes. Adiponectin is a peptide secreted by adipocytes, and its plasma levels are inversely associated with obesity. We aimed to estimate the effect of circulating adiponectin on the risk of Barrett's esophagus (BE), an

Joel H. Rubenstein; Anne Dahlkemper; John Y. Kao; Min Zhang; Hal Morgenstern; Laurence McMahon; John M. Inadomi

2008-01-01

215

Cancer Immunotherapy Targeting the High Molecular Weight Melanoma-Associated Antigen Protein Results in a Broad Antitumor Response and Reduction of Pericytes in the Tumor Vasculature  

Microsoft Academic Search

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

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

216

Effect of the Molecular Weight on the Physicochemical Properties of Poly(lactic acid) Nanoparticles and on the Amount of Ovalbumin Adsorption  

Microsoft Academic Search

were obtained by direct polycondensation from D,L lactic acid and used to prepare nanoparticles by solvent displacement method. The effect of the molecular weight on the physicochemical properties of the polymers, on the nanoparticles dispersions and the amount of ovalbumin (OVA) adsorption was studied. The PLA HMW and PLA LMW were characterized by Fourier transformed infrared spectroscopy (FTIR), thermogravimetrical analysis

Juliana Palacio; Víctor H. Orozco; Betty L. López

2011-01-01

217

An asparagines residue at the N-terminus affects the maturation process of low molecular weight glutenin subunits of wheat endosperm  

Technology Transfer Automated Retrieval System (TEKTRAN)

Wheat (Triticum spp.) glutenin polymers are of two main types, high- (HMW-GS) and low- (LMW-GS) molecular weight subunits. The most common are the latter, based on the first amino acid of the mature sequence, are known as LMW-m and LMW-s types. They differ as a result of three extra amino acids (MET...

218

MOLAR FRACTIONS OF HIGH MOLECULAR WEIGHT GLUTENINS SUBUNITS ARE STABLE WHEN WHEAT IS GROWN UNDER VARIOUS MINERAL NUTRITION AND TEMPERATURE REGIMENS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Molar ratios of the high molecular weight glutenin subunits (HMW-GS) were determined for flour from bread wheat (Triticum aestivum L. cv Butte86) produced under 13 different combinations of temperature, water and mineral nutrition. Despite great differences in duration of grain fill, total protein ...

219

TRANSGENIC WHEATS WITH ELEVATED LEVELS OF DX5 AND/OR DY10 HIGH-MOLECULAR-WEIGHT GLUTENIN SUBUNITS YIELD DOUGHS WITH INCREASED MIXING STRENGTH AND TOLERANCE  

Technology Transfer Automated Retrieval System (TEKTRAN)

In order to test the effects of independently increasing the in vivo levels of high-molecular-weight glutenin subunits (HMW-GS) Dx5 and Dy10 on wheat flour properties, we increased the copy numbers of their corresponding genes by genetic transformation. Thirteen transformants with increases in one o...

220

New insights into anticarcinogenic properties of adiponectin: a potential therapeutic approach in breast cancer?  

PubMed

Obesity is a recognized breast cancer risk factor in postmenopausal women. A recent hypothesis suggests a major role for adipose tissue in carcinogenesis. During many years, the adipose tissue was only considered as a fat storage of energy. This tissue is now described as an endocrine organ secreting a large range of molecules called adipokines. Among these adipokines, adiponectin may play a major role in breast cancer. Plasma adiponectin levels were found to be decreased in cases of breast cancer and in obese patients. Adiponectin may act directly on breast cancer cells by inhibiting proliferation and angiogenesis or by stimulating apoptosis. Increasing adiponectin levels may be of major importance in the prevention and/or the treatment of breast cancer. This therapeutic approach may be of particular significance for obese patients. The beneficial effects of adiponectin and its possible therapeutic applications will be discussed in this review. PMID:23017724

Delort, Laetitia; Jardé, Thierry; Dubois, Virginie; Vasson, Marie-Paule; Caldefie-Chézet, Florence

2012-01-01

221

Adiponectin Regulates Vascular Endothelial Growth Factor-C Expression in Macrophages via Syk-ERK Pathway  

PubMed Central

Adiponectin is exclusively expressed in adipose tissues and exhibits protective effects against cardiovascular and metabolic diseases. It enhances AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor ? (PPAR?) signaling in the liver and skeletal muscles, however, its signaling pathways in macrophages remain to be elucidated. Here, we show that adiponectin upregulated the expression of vascular endothelial growth factor (VEGF)-C, and induced phosphorylation of extracellular signal-regulated kinase (ERK) in macrophages. Inhibition of Syk abrogated adiponectin-induced VEGF-C expression and ERK phosphorylation. Furthermore, inhibition of ERK blocked the induction of VEGF-C gene. Inhibition of Syk, but not that of ERK, abrogated adiponectin-induced expression of cyclooxygenase (COX)-2, tissue inhibitor of metalloproteinase (TIMP)-1, and interleukin (IL)-6. These results indicate that adiponectin regulates VEGF-C expression via Syk-ERK pathway in macrophages. PMID:23424645

Hu, Di; Fukuhara, Atsunori; Miyata, Yugo; Yokoyama, Chieko; Otsuki, Michio; Kihara, Shinji; Shimomura, Iichiro

2013-01-01

222

Adiponectin protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity.  

PubMed

1-Methyl-4-phenylpyridinium ion (MPP+), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome characterized by elevation of intracellular reactive oxygen species level and apoptotic death. Adiponectin, secreted from adipose tissue, mediates systemic insulin sensitivity with liver and muscle as target organs. Adiponectin can also suppress superoxide generation in endothelial cells. In the present study, we investigated the protective effects of adiponectin on MPP+-induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as the underlying mechanism. Our results suggest that the protective effects of adiponectin on MPP+-induced apoptosis may be ascribed to its anti-oxidative properties, anti-apoptotic activity via inducing expression of SOD and catalase, and regulation of Bcl-2 and Bax expression. These data indicated that adiponectin might provide a useful therapeutic strategy for the treatment of progressive neurodegenerative diseases such as Parkinson's disease. PMID:16554029

Jung, Tae Woo; Lee, Ji Young; Shim, Wan Sub; Kang, Eun Seok; Kim, Jong Sun; Ahn, Chul Woo; Lee, Hyun Chul; Cha, Bong Soo

2006-05-01

223

Adiponectin protects human neuroblastoma SH-SY5Y cells against acetaldehyde-induced cytotoxicity.  

PubMed

Acetaldehyde, an inhibitor of mitochondrial function, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of the intracellular reactive oxygen species (ROS) level and apoptosis. Adiponectin, secreted from adipose tissue, mediates systemic insulin sensitivity with liver and muscle as target organs. In this study, we investigated the protective effects of adiponectin on acetaldehyde-induced apoptosis in human neuroblastoma SH-SY5Y cells and attempted to examine its mechanism. Acetaldehyde-induced apoptosis was moderately reversed by adiponectin treatment. Our results suggest that the protective effects of adiponectin on acetaldehyde-induced apoptosis may be ascribed to ability to induce the expression of anti-oxidant enzymes and to regulate Bcl-2 and Bax expression. These data indicate that adiponectin may provide a useful therapeutic strategy for the prevention of progressive neurodegenerative disease such as Parkinson's disease. PMID:16814256

Jung, Tae Woo; Lee, Ji Young; Shim, Wan Sub; Kang, Eun Seok; Kim, Jong Sun; Ahn, Chul Woo; Lee, Hyun Chul; Cha, Bong Soo

2006-08-28

224

Detection of high molecular weight organic tracers in vegetation smoke samples by high-temperature gas chromatography-mass spectrometry  

SciTech Connect

High-temperature high-resolution gas chromatography (HTGC) is an established technique for the separation of complex mixtures of high molecular weight (HMW) compounds which do not elute when analyzed on conventional GC columns. The combination of this technique with mass spectrometry is not so common and application to aerosols is novel. The HTGC and HTGC-MS analyses of smoke samples taken by particle filtration from combustion of different species of plants provided the characterization of various classes of HMW compounds reported to occur for the first time in emissions from biomass burning. Among these components are a series of wax esters with up to 58 carbon numbers, aliphatic hydrocarbons, triglycerides, long chain methyl ketones, alkanols and a series of triterpenyl fatty acid esters which have been characterized as novel natural products. Long chain fatty acids with more than 32 carbon numbers are not present in the smoke samples analyzed. The HMW compounds in smoke samples from the burning of plants from Amazonia indicate the input of directly volatilized natural products in the original plants during their combustion. However, the major organic compounds extracted from smoke consist of a series of lower molecular weight polar components, which are not natural products but the result of the thermal breakdown of cellulose and lignin. In contrast, the HMW natural products may be suitable tracers for specific sources of vegetation combustion because they are emitted as particles without thermal alternation in the smoke and can thus be related directly to the original plant material.

Elias, V.O.; Simoneit, B.R.T. (Oregon State Univ., Corvallis, OR (United States)); Pereira, A.S.; Cardoso, J.N. (Univ. Federal do Rio de Janeiro (Brazil)); Cabral, J.A. (Inst. de Pesquisas da Amazonia, Amazonas (Brazil))

1999-07-15

225

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

2012-03-01

226

MicroRNA-378 Regulates Adiponectin Expression in Adipose Tissue: A New Plausible Mechanism  

PubMed Central

Aims Mechanisms regulating adiponectin expression have not been fully clarified. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are involved in biological processes, including obesity and insulin resistance. We evaluated whether the miRNA-378 pathway is involved in regulating adiponectin expression. Methods and Results First, we determined a putative target site for miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene by in silico analysis. The levels of adiponectin mRNA and protein were decreased in 3T3-L1 cells overexpressing the mimic of miRNA-378. Luminescence activity in HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence was inhibited by overexpressing the mimic of miRNA-378, and the decrease was reversed by adding the inhibitor of miRNA-378. Moreover, we confirmed the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3?-UTR binding site. Addition of tumor necrosis factor-? (TNF?) led a upregulation of miR-378 and downregulation of adiponectin at mRNA and protein levels in 3T3-L1 cells. Level of miR-378 was higher and mRNA level of adiponectin was lower in diabetic ob/ob mice than those of normal C57BL/6 mice and levels of miR378 and adiponectin were negatively well correlated (r?=??0.624, p?=?0.004). Conclusions We found that levels of miRNA-378 could modulate adiponectin expression via the 3'UTR sequence-binding site. Our findings warrant further investigations into the role of miRNAs in regulating the adiponectin expression. PMID:25379946

Ishida, Masayoshi; Shimabukuro, Michio; Yagi, Shusuke; Nishimoto, Sachiko; Kozuka, Chisayo; Fukuda, Daiju; Soeki, Takeshi; Masuzaki, Hiroaki; Tsutsui, Masato; Sata, Masataka

2014-01-01

227

Adiponectin induces apoptosis in hepatocellular carcinoma through differential modulation of thioredoxin proteins.  

PubMed

Adiponectin blocks hepatocellular carcinoma (HCC) progression by inducing cell apoptosis through the modulation of C-Jun N-terminal kinase and mammalian target of rapamycin. However, the precise upstream signaling pathways or molecules remain elusive. In the present study, we analyzed the role of antioxidant protein thioredoxin (Trx) in adiponectin-induced apoptosis in HCC. Adiponectin treatment decreased the viabilities of both HepG2 and Huh7 HCC cells accompanied by increased accumulation of intracellular reactive oxygen species, as evidenced by 2',7'-dichlorodihydrofluorescein diacetate staining. Pretreatment of these cells with the deoxidant N-acetylcysteine blocked the inhibitory effect of adiponectin. Levels of Trx2 protein in both HCC cells were significantly decreased, and the level of Trx1 was significantly inhibited in Huh7 cells while unchanged in HepG2 cells. However, the redox state of Trx1 was altered from reduced to the oxidized form following adiponectin treatment in HepG2 cells. Overexpression of both Trx proteins rescued adiponectin-induced cell apoptosis, whereas mutated Trx proteins were less effective. Further analysis suggested that both ASK1 and JNK signaling are involved in this process. Trx1 and Trx2 proteins also manifested protective effects on HCC cells in response to adiponectin treatment in a xenograft tumor model. Furthermore, high levels of Trx proteins and low adiponectin expression levels were found in primary human HCC samples compared with paracancerous tissues. These results suggest that Trx proteins play important roles in mediating adiponectin-induced HCC cell apoptosis, thus providing new insights into the pathogenesis of HCC and identifying adiponectin and Trx proteins as potential combinational therapeutic targets for the treatment of HCC. PMID:25514170

Xing, Su-Qian; Zhang, Chen-Guang; Yuan, Ji-Fang; Yang, Hui-Min; Zhao, Shu-Dong; Zhang, Hong

2015-01-15

228

A novel high molecular weight glutenin subunit from Australopyrum retrofractum.  

PubMed

We describe the sequence of a gene encoding a high molecular weight glutenin subunit (HMW-GS) expressed in the endosperm of the wheat relative Australopyrum retrofractum. Although the subunit has a similar primary structure to that HMW-GS genes present in other Triticeae species, its N-terminal domain is shorter, its central repetitive domain includes a unique dodecameric motif, and its C-terminal domain contain an extra cysteine residue. A phylogenetic analysis showed that the Glu-W1 gene is neither a true x- nor a true y-type subunit, although it is more closely related to the y-type genes present in the K and E genomes than to any other published HMW-GS gene. All these results indicated that this novel subunit may undergo a special evolutionary process different from other Triticeae species. A flour supplementation experiment showed that the Glu-W1 subunit has a negative effect on dough quality, which might be the result of interaction between the two closely placed cysteine residues in the C-terminal region. PMID:20058039

Liu, Shuwei; Zhao, Feng; Gao, Xin; Chen, Fanguo; Xia, Guangmin

2010-07-01

229

Comparison of serum maternal adiponectin concentrations in women with isolated intrauterine growth retardation and intrauterine growth retardation concomitant with pre-eclampsia  

PubMed Central

Objective The aim of this study was to compare serum maternal adiponectin concentrations in pregnant women with isolated intrauterine growth retardation (IUGR) and in pregnant women with IUGR concomitant with pre-eclampsia (IUGRcwPE). Material and Methods Thirty patients with isolated IUGR (group 1), 20 patients with IUGRcwPE (group 2), and 30 healthy controls (group 3) between age 18–40 were included into the study. Venous blood samples of those patients were obtained in the starving state. Adiponectin concentrations were measured by enzyme-linked immunosorbent assay in serum obtained after centrifugation. To find the differences between the groups, student t-test and one-way ANOVA statistical methods were used. Results There were no differences between the groups in terms of age, body mass index, gestational age, and parity (p>0.05). The values of amniotic fluid index (p<0.001) and weight gained during pregnancy (p=0.017) were significantly different when compared among the three groups. The mean concentrations of adiponectin were 94.041 pg/mL in the IUGR group, 55.717 pg/mL in the IUGRcwPE group, and 51.831 pg/mL in the control group. Both of the differences between the IUGR and IUGRcwPE groups (p value; <0.05) and IUGR and control groups were statistically significant (p value; <0.001). However, there were no significant differences between the IUGRcwPE group and control group (p>0.05). Conclusion We found that IUGR increased maternal serum adiponectin concentrations; however, this rise does not occur in pregnant women with IUGRcwPE. PMID:25317046

Büke, Bar??; Topçu, Hasan Onur; Engin-Üstün, Yaprak; Dan??man, Nuri

2014-01-01

230

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

231

The relationship between serum adiponectin and inflammatory cytokines in obese Korean juveniles  

PubMed Central

Purpose Obesity is related to systemic inflammatory processes causing cardiovascular complications. Intercellular adhesion molecule-1 (ICAM-1), CD40 ligand (CD40L), P-selectin are newly described mediators of inflammation and have a significant effect in atherosclerosis. Adiponectin has shown anti-inflammatory effects in adults. The aim of this study was to evaluate the relationship between adiponectin and inflammatory mediators in children and adolescents. Methods Fifty children or adolescents, twenty two with a body mass index (BMI) over 95th percentile, and twenty eight with a BMI below 75th percentile were included in the study. Serum soluble ICAM-1 (sICAM-1), P-selectin, CD40L, lipid profiles, aspartate aminotransferase, alanine aminotransferase, glucose and insulin were measured to evaluate associations with adiponectin. Comparison of these variables was performed between the obese and the nonobese group. Results We found a adiponectin to be significant lower and sICAM-1 significant higher in the obese group compared to the nonobese group, but there were no significant differences in P-selectin and soluble CD40L. Adiponectin was negatively associated with ICAM-1 and P-selectin in the obese group. Conclusion Negative associations of adiponectin with ICAM-1 and P-selectin in obese children and adolescents suggest that serum adiponectin level may represent the inflammatory status. PMID:25653687

Byun, Sung Hwan; Kwon, Eun Byul

2014-01-01

232

Effects of Fenofibrate on Adiponectin Expression in Retinas of Streptozotocin-Induced Diabetic Rats  

PubMed Central

Adiponectin has been associated with increased risks of microvascular complications in diabetes; however, its role in the development of diabetic retinopathy (DR) is unknown. Fenofibrate is a lipid-lowering agent that has been shown to be capable of preventing DR progression. We investigated the expression of adiponectin and its receptors in DR and evaluated the effects of fenofibrate on their expression. The mRNA and protein levels of adiponectin and its receptors were elevated in retinas of streptozotocin-induced diabetic rats and were suppressed following fenofibrate treatment. Immunofluorescence staining demonstrated that adiponectin and adipoR1 were expressed in cells located within blood vessels, the retinal ganglion, and the inner nuclear layer. AdipoR1 was strongly expressed whereas adipoR2 was only weekly expressed in vascular endothelial cells. The in vitro experiments showed that adiponectin expression was induced by high glucose concentrations in RGC-5 and RAW264.7 cells and was suppressed following fenofibrate treatment. AdipoR1 and adipoR2 levels in RGC-5 cells were elevated in high glucose concentrations and suppressed by fenofibrate. Our results demonstrated that adiponectin may be a proinflammatory mediator in diabetic retinas and fenofibrate appears to modulate the expression of adiponectin and its receptors in diabetic retinas, effectively reducing DR progression.

Hsu, Ying-Jung; Wang, Lu-Chun; Yang, Wei-Shiung; Yang, Chung-May; Yang, Chang-Hao

2014-01-01

233

The Association of Adiponectin with Computed Tomography Phenotypes in Chronic Obstructive Pulmonary Disease  

PubMed Central

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder associated with systemic manifestations that contribute to its morbidity and mortality. Recent work suggests that biomarker signatures in the blood may be useful in evaluating COPD phenotypes and may provide insight into the pathophysiology of systemic manifestations. Adiponectin, primarily produced by fat cells, has been implicated in the pathophysiology of emphysema. Objectives: To investigate the association of adiponectin with clinical and radiologic COPD phenotypes. Methods: Adiponectin levels were determined in 633 individuals, including 432 individuals with COPD from a cohort of former or current smokers enrolled in the COPDGene study. Univariate and multiple regression analysis were used to examine the association of adiponectin with clinical and physiologic data together with quantitative high-resolution computed tomography parameters. Measurements and Main Results: Multiple regression analysis confirmed that higher plasma adiponectin levels were independently associated with emphysema, decreasing body mass index, female sex, older age, and lower percentage change in prebronchodilator/post-bronchodilator FEV1. Conclusions: The association between plasma adiponectin and computed tomography–assessed emphysema suggests a contribution of adiponectin to the development of emphysema and highlights a role for metabolic derangements in the pathophysiology of emphysema. PMID:23777323

Carolan, Brendan J.; Kim, Yu-il; Williams, André A.; Kechris, Katerina; Lutz, Sharon; Reisdorph, Nichole

2013-01-01

234

Nicotinic Acid Increases Adiponectin Secretion from Differentiated Bovine Preadipocytes through G-Protein Coupled Receptor Signaling.  

PubMed

The transition period in dairy cows (3 weeks prepartum until 3 weeks postpartum) is associated with substantial mobilization of energy stores, which is often associated with metabolic diseases. Nicotinic acid (NA) is an antilipolytic and lipid-lowering compound used to treat dyslipidaemia in humans, and it also reduces non-esterified fatty acids in cattle. In mice the G-protein coupled receptor 109A (GPR109A) ligand NA positively affects the secretion of adiponectin, an important modulator of glucose and fat metabolism. In cattle, the corresponding data linking NA to adiponectin are missing. Our objective was to examine the effects of NA on adiponectin and AMPK protein abundance and the expression of mRNAs of related genes such as chemerin, an adipokine that enhances adiponectin secretion in vitro. Differentiated bovine adipocytes were incubated with pertussis toxin (PTX) to verify the involvement of GPR signaling, and treated with 10 or 15 µM NA for 12 or 24 h. NA increased adiponectin concentrations (p ? 0.001) and the mRNA abundances of GPR109A (p ? 0.05) and chemerin (p ? 0.01). Pre-incubation with PTX reduced the adiponectin response to NA (p ? 0.001). The NA-stimulated secretion of adiponectin and the mRNA expression of chemerin in the bovine adipocytes were suggestive of GPR signaling-dependent improved insulin sensitivity and/or adipocyte metabolism in dairy cows. PMID:25411802

Kopp, Christina; Hosseini, Afshin; Singh, Shiva P; Regenhard, Petra; Khalilvandi-Behroozyar, Hamed; Sauerwein, Helga; Mielenz, Manfred

2014-01-01

235

Adiponectin Enhances Intercellular Adhesion Molecule-1 Expression and Promotes Monocyte Adhesion in Human Synovial Fibroblasts  

PubMed Central

Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and is involved in energy homeostasis. Adiponectin expression is significantly high in the synovial fluid of patients with osteoarthritis (OA). Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that mediates monocyte adhesion and infiltration during OA pathogenesis. Adiponectin-induced expression of ICAM-1 in human OA synovial fibroblasts (OASFs) was examined by using qPCR, flow cytometry and western blotting. The intracellular signaling pathways were investigated by pretreated with inhibitors or transfection with siRNA. The monocyte THP-1 cell line was used for an adhesion assay with OASFs. Stimulation of OASFs with adiponectin induced ICAM-1 expression. Pretreatment with AMP-activated protein kinase (AMPK) inhibitors (AraA and compound C) or transfection with siRNA against AMPK?1 and two AMPK upstream activator- liver kinase B1 (LKB1) and calmodulin-dependent protein kinase II (CaMKII) diminished the adiponectin-induced ICAM-1 expression. Stimulation of OASFs with adiponectin increased phosphorylation of LKB1, CaMKII, AMPK, and c-Jun, resulting in c-Jun binding to AP-1 element of ICAM-1 promoter. In addition, adiponectin-induced activation of the LKB1/CaMKII, AMPK, and AP-1 pathway increased the adhesion of monocytes to the OASF monolayer. Our results suggest that adiponectin increases ICAM-1 expression in human OASFs via the LKB1/CaMKII, AMPK, c-Jun, and AP-1 signaling pathway. Adiponectin-induced ICAM-1 expression promoted the adhesion of monocytes to human OASFs. These findings may provide a better understanding of the pathogenesis of OA and can utilize this knowledge to design a new therapeutic strategy. PMID:24667577

Chen, Hsien-Te; Tsou, Hsi-Kai; Chen, Jui-Chieh; Shih, James Meng-Kun; Chen, Yen-Jen; Tang, Chih-Hsin

2014-01-01

236

Circulating adiponectin levels in Indian patients with psoriasis and its relation to metabolic syndrome  

PubMed Central

Background: Adiponectin is a cytokine mainly secreted from the adipose tissue, which has insulin-sensitizing effects, antiatherosclerotic actions, and antiinflammatory properties. There are a few studies that have demonstrated that adiponectin is reduced in patients with psoriasis suggesting that this adipocytokine may have a role in the pathogenesis of psoriasis. There have been no studies so far on adiponectin in relation to psoriasis and metabolic syndrome (MetS). Objectives: This study was performed to analyze serum adiponectin and insulin levels in psoriasis patients with and without MetS and in controls with and without MetS. Materials and Methods: We performed a case control study on 60 psoriasis patients, 29 with MetS and 31 without MetS and 40 controls, 20 with and 20 without MetS, matched for age, sex, and body mass index (BMI). Fasting serum insulin and adiponectin levels were measured in all groups. Results: The overall serum adiponectin levels were significantly reduced in psoriasis patients when compared with controls (P = 0.000). A significant reduction was also observed in psoriasis patients with MetS than those without MetS in the same group (P = 0.000). Similar decrease was observed between those with MetS in the psoriasis and control groups (P = 0.001). The lowest mean value of serum adiponectin (6387.9 ng/ml) was observed in psoriasis with MetS group and highest value (12146.3 ng/ml) in controls without MetS. Conclusion: Adiponectin levels are decreased in psoriasis patients irrespective of MetS thus indicating a role in its pathogenesis. This study prompts future trials on drugs increasing adiponectin levels in patients with psoriasis. PMID:24741515

Madanagobalane, Shraddha; Sandhya, Venkatswami; Anandan, Sankarasubramanian; Seshadri, Krishna G.

2014-01-01

237

Adiponectin links adipose tissue function and monocyte inflammatory responses during bovine metabolic stress.  

PubMed

The periparturient period of dairy cows is characterized by intense lipid mobilization from adipose tissue leading to increased plasma concentrations of nonesterified fatty acids (NEFA). High NEFA are a predisposing factor for inflammatory based diseases. A major component of these diseases is uncontrolled macrophage/monocyte inflammatory responses. Changes in the endocrine activity of adipose tissue during the periparturient period could impact macrophage function by modifying the secretion of adipokines including adiponectin. Currently, the effects of adiponectin on monocyte activation in dairy cattle are unknown. In humans and rodents, this adipokine regulates monocyte phenotype and alterations in its plasma levels are linked with the development of inflammatory diseases. The objectives of this study were to establish associations between plasma adiponectin expression dynamics and different markers of lipid mobilization during the periparturient period of dairy cows and to characterize the effects of adiponectin on the inflammatory response of bovine monocytes. Plasma adiponectin, NEFA, BHB, albumin, and subcutaneous and retroperitoneal fat depots depth were measured during the periparturient period of dairy cows. In vitro, bovine monocytes were cultured with adiponectin to assess changes in pro-inflammatory responses following LPS stimulation. Results from this study demonstrate that alterations in plasma adiponectin levels in periparturient cattle are inversely correlated with the concentrations of plasma NEFA, an important marker of lipid mobilization. Furthermore, adiponectin exposure significantly decreased monocyte expression of TNF? after LPS stimulation thus markedly reducing their inflammatory response. Reduced plasma adiponectin during the periparturient period could predispose dairy cows to the development of uncontrolled monocyte inflammatory responses. PMID:24296305

Kabara, Ed; Sordillo, Lorraine M; Holcombe, Sue; Contreras, G Andres

2014-01-01

238

Adiponectin Receptor Signaling on Dendritic Cells Blunts Antitumor Immunity  

PubMed Central

Immune escape is a fundamental trait of cancer. Dendritic cells (DC) that interact with T cells represent a crucial site for the development of tolerance to tumor antigens, but there remains incomplete knowledge about how DC-tolerizing signals evolve during tumorigenesis. In this study, we show that DCs isolated from patients with metastatic or locally advanced breast cancer express high levels of the adiponectin receptors AdipoR1 and AdipoR2, which are sufficient to blunt antitumor immunity. Mechanistic investigations of ligand–receptor interactions on DCs revealed novel signaling pathways for each receptor. AdipoR1 stimulated IL10 production by activating the AMPK and MAPKp38 pathways, whereas AdipoR2 modified inflammatory processes by activating the COX-2 and PPAR? pathways. Stimulation of these pathways was sufficient to block activation of NF-?B in DC, thereby attenuating their ability to stimulate antigen-specific T-cell responses. Together, our findings reveal novel insights into how DC-tolerizing signals evolve in cancer to promote immune escape. Furthermore, by defining a critical role for adiponectin signaling in this process, our work suggests new and broadly applicable strategies for immunometabolic therapy in patients with cancer. PMID:25261236

Tan, Peng H.; Tyrrell, Helen E.J.; Gao, Liquan; Xu, Danmei; Quan, Jianchao; Gill, Dipender; Rai, Lena; Ding, Yunchuan; Plant, Gareth; Chen, Yuan; Xue, John Z.; Handa, Ashok I.; Greenall, Michael J.; Walsh, Kenneth; Xue, Shao-An

2015-01-01

239

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

240

Marker-Assisted Selection for Recognizing Wheat Mutant Genotypes Carrying HMW Glutenin Alleles Related to Baking Quality  

PubMed Central

Allelic diversity of HMW glutenin loci in several studies revealed that allelic combinations affect dough quality. Dx5 + Dy10 subunits are related to good baking quality and Dx2 + Dy12 are related to undesirable baking quality. One of the most regular methods to evaluate the baking quality is SDS-PAGE which is used to improve baking quality labs. Marker-assisted selection is the method which can recognize the alleles related to baking quality and this method is based on polymerase chain reaction. 10 pairs of specific primers related to Dx2, Dx2.1, Dx5, Dy10, and Dy12 subunits were used for recognizing baking quality of some wheat varieties and some mutant genotypes. Only 5 pairs of them could show the specific bands. All subunits were recognized by the primers except Dx2.1. Some of the primers were extracted from previous studies and the others were designed based on D genome subunits of wheat. SDS-PAGE method accomplished having confidence in these marker's results. To realize the effect of mutation, seed storage proteins were measured. It showed that mutation had effect on the amount of seed storage protein on the mutant seeds (which showed polymorphism). PMID:24883389

Zamani, Mohammad Javad; Bihamta, Mohammad Reza; Naserian Khiabani, Behnam; Tahernezhad, Zahra; Hallajian, Mohammad Taher; Shamsi, Marzieh Varasteh

2014-01-01

241

Association of adiponectin gene polymorphism 45TG with gestational diabetes mellitus diagnosed on the new IADPSG criteria, plasma adiponectin levels and adverse pregnancy outcomes.  

PubMed

The aim of this study was to identify the association of adiponectin gene single nucleotide polymorphism (SNP) 45TG with gestational diabetes mellitus (GDM) diagnosed on the new International Diabetes in Pregnancy Consensus Group (IADPSG) criteria, plasma adiponectin levels and adverse pregnancy outcomes in Han women of Nantong area in China. This cross-sectional study included 128 pregnant women with GDM (GDM group) and 140 pregnant women with normal glucose tolerance (NGT group) according to oral glucose tolerance test results based on the new IADPSG criteria. The GDM pregnant women were treated by diet control or diet control and insulin injection. All pregnant women attended antenatal cares and were recorded until delivery. Adiponectin gene was amplified through PCR, and SNP was detected using restriction enzyme SmaI. Plasma adiponectin levels were measured by ELISA. The G allele and TG+GG genotype were significantly more frequent than the T allele in the GDM group than in the NGT group (p < 0.05). Plasma adiponectin concentrations of TG+GG genotype carriers were significantly lower than those of TT genotype in both groups (p < 0.01). After adjustment for confounding factors, plasma adiponectin level remained significantly lower in pregnant women with TG+GG genotype than those with TT genotype (p < 0.05). Compared with the NGT group, the GDM group with glycemic control still had significantly higher incidences of macrosomia, neonatal hypoglycemia and asphyxia (p < 0.05). Further analysis revealed that the incidences of macrosomia and neonatal hypoglycemia were significantly higher in pregnant women with TG+GG genotype than those with TT genotype after adjustment for potential confounders in affecting pregnancy outcomes (p < 0.05). Even though pregnant women are diagnosed as GDM according to the new IADPSG criteria, the adiponectin SNP45 may be closely correlated with the prevalence of GDM in Han women of Nantong area in China, and the allele +45G in adiponectin gene might be associated with reduced plasma adiponectin levels and adverse pregnancy outcomes. PMID:24664457

Han, Yun; Zheng, Yan-Li; Fan, Yu-Ping; Liu, Man-Hua; Lu, Xiao-Yan; Tao, Qian

2015-02-01

242

Adiponectin inhibits insulin function in primary trophoblasts by PPAR?-mediated ceramide synthesis.  

PubMed

Maternal adiponectin (ADN) levels are inversely correlated with birth weight, and ADN infusion in pregnant mice down-regulates placental nutrient transporters and decreases fetal growth. In contrast to the insulin-sensitizing effects in adipose tissue and muscle, ADN inhibits insulin signaling in the placenta. However, the molecular mechanisms involved are unknown. We hypothesized that ADN inhibits insulin signaling and insulin-stimulated amino acid transport in primary human trophoblasts by peroxisome proliferator-activated receptor-? (PPAR?)-mediated ceramide synthesis. Primary human term trophoblast cells were treated with ADN and/or insulin. ADN increased the phosphorylation of p38 MAPK and PPAR?. ADN inhibited insulin signaling and insulin-stimulated amino acid transport. This effect was dependent on PPAR?, because activation of PPAR? with an agonist (GW7647) inhibited insulin signaling and function, whereas PPAR?-small interfering RNA reversed the effects of ADN on the insulin response. ADN increased ceramide synthase expression and stimulated ceramide production. C2-ceramide inhibited insulin signaling and function, whereas inhibition of ceramide synthase (with Fumonisin B1) reversed the effects of ADN on insulin signaling and amino acid transport. These findings are consistent with the model that maternal ADN limits fetal growth mediated by activation of placental PPAR? and ceramide synthesis, which inhibits placental insulin signaling and amino acid transport, resulting in reduced fetal nutrient availability. PMID:24606127

Aye, Irving L M H; Gao, Xiaoli; Weintraub, Susan T; Jansson, Thomas; Powell, Theresa L

2014-04-01

243

Adiponectin as an independent predictor of left ventricular hypertrophy in nondiabetic patients with hypertension.  

PubMed

We evaluated novel and traditional biomarkers as well as hemodynamic parameters associated with the development of left ventricular hypertrophy (LVH) in nondiabetic patients with hypertension. Nondiabetic patients with hypertension (n = 86) were evaluated for lipids, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), adiponectin, aldosterone, renin, matrix metalloproteinase 2, and endothelin. Arterial elasticity was evaluated using pulse wave contour. The LVH parameters were assessed echographically. Adiponectin was significantly and inversely associated with left ventricular mass (LVM; P = .032). The aldosterone-renin ratio (ARR) was significantly, positively associated with LVM (P = .031). Fasting insulin as well as HOMA-IR was significantly, positively associated with LVM (P = .036 and P = .025, respectively). In multiple linear regression analysis, adiponectin and ARR remained a significant predictor of LVM. The present study found that adiponectin and ARR are important independent determinants of LVH in nondiabetic patients with hypertension. PMID:24576986

Peer, Maya; Mashavi, Margarita; Matas, Zipora; Harpaz, David; Shargorodsky, Marina

2015-03-01

244

Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications.  

PubMed

Leptin and adiponectin represent two newly discovered adipose tissue derived hormones with important roles in energy homeostasis and insulin resistance. Their interrelations with the manifestations of the HIV associated metabolic syndrome and specific somatomorphic changes i.e. fat redistribution is reviewed. A synopsis of published studies is presented and the potential role of leptin and adiponectin is discussed. We have described an association of the HIV metabolic syndrome with a state of reduced insulin sensitivity due to adiponectin deficiency. The metabolic syndrome is also accompanied by leptin deficiency in lipoatrophic subjects and possibly by a leptin resistance state in lipohypertrophic patients. Adiponectin and / or leptin therapy in a manner similar to other leptin deficiency states may assist in the future management of such patients. PMID:17183414

Tsiodras, Sotirios; Mantzoros, Christos

2006-01-01

245

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

246

Adiponectin-deficient mice are protected against tobacco-induced inflammation and increased emphysema  

PubMed Central

Adiponectin is a cytokine with both proinflammatory and anti-inflammatory properties that is expressed in epithelial cells in the airway in chronic obstructive pulmonary disease-emphysema (COPD-E). To determine whether adiponectin modulates levels of lung inflammation in tobacco smoke-induced COPD-E, we used a mouse model of COPD-E in which either adiponectin-deficient or wild-type (WT) mice were exposed to tobacco smoke for 6 mo. Outcomes associated with tobacco smoke-induced COPD-E were quantitated including lung inflammation [bronchoalveolar lavage (BAL) and total and differential cell count], lung mediators of inflammation (cytokines and chemokines), air space enlargement (i.e., linear intercept), and lung function (tissue elastance) in the different groups of mice. Whereas exposure of WT mice to tobacco smoke for 6 mo induced significant lung inflammation (increased total BAL cells, neutrophils, and macrophages), adiponectin-deficient mice had minimal BAL inflammation when exposed to tobacco smoke for 6 mo. In addition, whereas chronic tobacco-exposed WT mice had significantly increased levels of lung mediators of inflammation [i.e., TNF-?, keratinocyte-derived chemokine (KC), and adiponectin] as well as significantly increased air space enlargement (increased linear intercept) and decreased tissue elastance, exposure of adiponectin-deficient mice to chronic tobacco smoke resulted in no further increase in lung mediators, air space enlargement, or tissue elastance. In vitro studies demonstrated that BAL macrophages derived from adiponectin-deficient mice incubated in media containing tobacco smoke expressed minimal TNF-? or KC compared with BAL macrophages from WT mice. These studies suggest that adiponectin plays an important proinflammatory role in tobacco smoke-induced COPD-E. PMID:20935231

Miller, Marina; Pham, Alexa; Cho, Jae Youn; Rosenthal, Peter

2010-01-01

247

Adiponectin as a novel determinant of bone mineral density and visceral fat  

Microsoft Academic Search

Growing evidence suggests that positive associations between fat mass (FM) and bone mineral density (BMD) are mediated by not only biomechanical but also biochemical factors. Adiponectin is a novel adipocyte-derived hormone that regulates energy homeostasis and has anti-inflammatory and anti-atherogenic effects. Unlike other adipokines such as leptin, adiponectin levels decrease in obesity and type 2 diabetes. The purpose of our

L Lenchik; T. C Register; F-C Hsu; K Lohman; B. J Nicklas; B. I Freedman; C. D Langefeld; J. J Carr; D. W Bowden

2003-01-01

248

Sex-specific determinants of serum adiponectin in older adults: the role of endogenous sex hormones  

Microsoft Academic Search

Objective:To assess the sex-specific association of adiponectin with multiple factors thought to influence its levels, with a special emphasis on endogenous sex hormones.Design and methods:A cross-sectional study of determinants of serum adiponectin in 873 men and 673 postmenopausal women, ages 50–92. Factors evaluated include age, body size, fat distribution, lifestyle (exercise, smoking, alcohol intake), insulin resistance, renal function and endogenous

G A Laughlin; E Barrett-Connor; S May

2007-01-01

249

Serum levels and mesenteric fat tissue expression of adiponectin and leptin in patients with Crohn's disease  

PubMed Central

Crohn's disease (CD) is characterized by inflammation and an aetiology that is still unknown. Hypertrophy of mesenteric fat is a reflection of disease activity, as this fat covers the entire length of the affected area. Adipocytes synthesize leptin and adiponectin, adipocytokines responsible for pro- and anti-inflammatory effects. Therefore, we evaluated serum levels of adiponectin and leptin, as well as mesenteral expression of adiponectin in active CD and those in remission. Sixteen patients with ileocaecal CD followed at the Outpatient Clinic, Coloproctology Unit of University of Campinas Clinical Hospital, participated in the study. Analysis of serum adiponectin and leptin by enzyme-linked immunosorbent assay was performed in patients with active CD (ACD group), remission CD (RCD group) and in six healthy controls. Ten patients with active ileocaecal CD (FCD group) and eight patients with non-inflammatory disease selected for surgery were also studied. The specimens were snap-frozen and the expression of adiponectin was determined by immunoblot of protein extracts. Serum C-reactive protein levels were higher in the ACD group when compared to the others and no difference of body mass index was observed between the groups. Serum adiponectin was lower in the ACD group when compared to control, but no differences were seen when comparing the ACD and RCD groups. Mesenteric adiponectin expression was lower in the FCD group when compared to the FC group. Serum leptin was similar in all groups. The lower levels of serum and mesenteric adiponectin in active CD suggest a defective regulation of anti-inflammatory pathways in CD pathogenesis. PMID:23121676

Rodrigues, V S; Milanski, M; Fagundes, J J; Torsoni, A S; Ayrizono, M L S; Nunez, C E C; Dias, C B; Meirelles, L R; Dalal, S; Coy, C S R; Velloso, L A; Leal, R F

2012-01-01

250

Novel Modulator for Endothelial Adhesion Molecules Adipocyte-Derived Plasma Protein Adiponectin  

Microsoft Academic Search

Background—Among the many adipocyte-derived endocrine factors, we recently found an adipocyte-specific secretory protein, adiponectin, which was decreased in obesity. Although obesity is associated with increased cardiovascular mortality and morbidity, the molecular basis for the link between obesity and vascular disease has not been fully clarified. The present study investigated whether adiponectin could modulate endothelial function and relate to coronary disease.

Noriyuki Ouchi; Shinji Kihara; Yukio Arit; Kazuhisa Maeda; Hiroshi Kuriyama; Yoshihisa Okamoto; Kikuko Hott; Makoto Nishida; Masahiko Takahashi; Tadashi Nakamura; Shizuya Yamashita; Tohru Funahashi; Yuji Matsuzawa

251

Anthropometric, Dietary, and Hormonal Correlates of Serum Adiponectin in Asian American Women  

Microsoft Academic Search

There is increasing evidence that adiponectin has a critical role in the development of breast cancer, but factors that influence adiponectin concentrations have not been well studied. We conducted a cross-sectional study among Asian-American controls who participated in a population-based case-control study of breast cancer. Participants were interviewed in-person and donated a blood specimen. Using multivariate models, we investigated the

Anna H. Wu; Mimi C. Yu; Frank Z. Stanczyk; Chiu-Chen Tseng; Malcolm C. Pike

2011-01-01

252

Regulatory Role of Autophagy in Globular Adiponectin-Induced Apoptosis in Cancer Cells  

PubMed Central

Adiponectin, an adipokine predominantly secreted from adipose tissue, exhibits diverse biological responses, including metabolism of glucose and lipid, and apoptosis in cancer cells. Recently, adiponectin has been shown to modulate autophagy as well. While emerging evidence has demonstrated that autophagy plays a role in the modulation of proliferation and apoptosis of cancer cells, the role of autophagy in apoptosis of cancer cell caused by adiponectin has not been explored. In the present study, we demonstrated that globular adiponectin (gAcrp) induces both apoptosis and autophagy in human hepatoma cell line (HepG2 cells) and breast cancer cells (MCF-7), as evidenced by increase in caspase-3 activity, Bax, microtubule-associated protein light chain 3-II (LC3 II) protein levels, and autophagosome formation. Interestingly, gene silencing of LC3B, an autophagy marker, significantly enhanced gAcrp-induced apoptosis in both HepG2 and MCF-7 cell lines, whereas induction of autophagy by rapamycin, an mTOR inhibitor, significantly prevented gAcrp-induced apoptosis in hepatoma cells HepG2. Furthermore, modulation of autophagy produced similar effects on gAcrp-induced Bax expression in HepG2 cells. These results implicate that induction of autophagy plays a regulatory role in adiponectin-induced apoptosis of cancer cells, and thus inhibition of autophagy would be a novel promising target to enhance the efficiency of cancer cell apoptosis by adiponectin. PMID:25414767

Nepal, Saroj; Park, Pil-Hoon

2014-01-01

253

Localization of adiponectin and its receptor and its possible roles in the ovary of a vespertilionid bat, Scotophilus heathi.  

PubMed

The aim of this study was to evaluate the seasonal variation in serum adiponectin levels and ovarian expression of adiponectin and its receptor in the Scotophilus heathi bat and their relationship to the changes in the body fat mass, serum insulin and luteinizing hormone (LH) levels, and ovarian activity. A very high level of circulating adiponectin was found during recrudescence, whereas a very low level of circulating adiponectin was observed during pre-ovulatory period. The increased circulating adiponectin level coincided with fat deposition, insulin resistance and hyperinsulinemia (HI) in S. heathi. Immunocytochemical study in the ovary of bat showed localization of adiponectin mainly in thecal-interstitial cells (TICs), and adiponectin receptor 1 (AdipoR1) in the granulosa cells of growing follicles, but showed no staining in atretic follicle. Seasonal changes in ovarian adiponectin and AdipoR1 levels showed two peaks (during recrudescence and ovulatory phases) coinciding with two periods of follicular development. Adiponectin in the absence of LH, as occur during recrudescence, stimulates androstenedione (A4) synthesis in vitro by up-regulating the insulin receptor (IR). Adiponectin in presence of LH, as occur during pre-ovulatory phase, inhibits A4 synthesis in vitro by down-regulating androgen receptor (AR). Further, the in vitro study showed that adiponectin, in presence of LH, also promotes luteinizing hormone receptor (LH-R) and steroidogenic acute regulatory protein (StAR) level in the ovary, which might help in development of ovulatory follicles. In brief, adiponectin in the absence of LH induces increased A4 synthesis and consequently the condition of delayed ovulation, whereas in the presence LH suppresses both synthesis and action of A4 and thus induces preovulatory condition in the ovary of S. heathi. PMID:22342274

Singh, Ajit; Krishna, Amitabh

2012-04-01

254

Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor ?  

PubMed Central

Adiponectin is a protein hormone involved in maintaining energy homeostasis in metabolically active tissues. It enhances glucose and lipid metabolism via activation of AMP-dependent kinase (AMPK) in skeletal muscle and liver. Energy homeostasis is vital for the heart to work as a pump. In this study, we investigated whether adiponectin and its receptors are expressed in adult ventricular cardiomyocytes. We observed adiponectin transcript and protein in cultured ventricular cardiomyocytes isolated from adult rat, by quantitative real-time PCR, ELISA assays, Western blots, and immunofluorescent staining. In addition, we detected adiponectin receptor (AdipoR1 and AdipoR2) expression in the heart. AdipoR1 was expressed in rat myocardium at a level of about 50% of that in skeletal muscle; whereas adipoR2 was expressed at a similar level to that in liver. Rosiglitazone, a Peroxisome proliferator activated receptor ? (PPAR?) activator, substantially elevated expression of adiponectin in cultured cardiomyocytes and its secretion into cultured media. Rosiglitazone also increased adipoR1 and adipoR2 expression in cardiomyocytes. Treatment of recombinant globular adiponectin in cultured cardiomyocytes increased fatty acid oxidation and glucose uptake via activation of AMPK, suggesting a role for adiponectin in cardiac energy metabolism. Together, these data establish the existence of a local cardiac-specific adiponectin system that is regulated by PPAR?. Moreover, these findings indicate a role for adiponectin on normal myocardial energy homeostasis, in part, through the activation of AMPK. PMID:17532004

Ding, Guoliang; Qin, Qianhong; He, Nu; Francis-David, Sharon C.; Hou, Jie; Ricks, Ernest; Yang., Qinglin

2007-01-01

255

Effects of pioglitazone and/or simvastatin on circulating TNF? and adiponectin levels in insulin resistance.  

PubMed

The current study investigated the effects of 14-day pioglitazone (PIO) and/or simvastatin (SIM) treatments on serum adiponectin (Adp) and TNF? levels (markers of adipocyte dysfunction), as well as on metabolic perturbations that arise from prolonged (8 week) consumption of a high fructose (HFD; 60%) diet in a rat model of pre-diabetic insulin resistance. The HFD induced a deranged lipid profile that was associated with adipose tissue hypertrophy, increased ratios of visceral and epididymal fats to body weight, and fatty liver. These perturbations were associated with hypo-adiponectinemia (50.8%) and increased serum TNF? (6.5-fold) levels. Treatment with PIO ameliorated the altered blood and hepatic glucose metabolism via an Adp-dependent mechanism; PIO also mitigated the changes in blood TNF? and led to a hyperelevation of Adp levels. SIM amended hepatic and overall lipid metabolism, regulated TNF?, but failed to alter the glucose intolerance or significantly impact on the HFD-altered Adp levels. Coadministration of SIM + PIO was superior in improving overall metabolic parameters compared to each monotherapy. Cotreatment was optimal in reestablishing insulin resistance, most efficacious in improving serum lipid profiles, normalizing percentage ratios of epididymal and visceral fats to body weight, and augmenting Adp/reducing TNF? levels relative to that in the HFD group or with HFD + each drug alone. The results here show that use of either monotherapy or a combined SIM + PIO approach might, from a clinical perspective, provide an ability to delay progression to Type 2 diabetes and its associated inflammatory/cardiovascular effects. PMID:22428554

Schaalan, Mona F

2012-01-01

256

Expression of adiponectin and its receptors in the porcine hypothalamus during the oestrous cycle.  

PubMed

Adiponectin is a hormonal link between obesity and reproduction, and its actions are mediated by two types of receptors: adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). This study compares the expression levels of adiponectin and adiponectin receptor mRNAs and proteins in selected areas of the porcine hypothalamus responsible for GnRH production and secretion: the mediobasal hypothalamus (MBH), pre-optic area (POA) and stalk median eminence (SME). The tissue samples were harvested on days 2-3, 10-12, 14-16 and 17-19 of the oestrous cycle. Adiponectin mRNA expression in MBH was significantly lower on days 14-16, whereas in SME, the most pronounced gene expression was found on days 2-3 of the cycle (p < 0.05). Adiponectin protein in MBH was most abundant on days 17-19 and in POA on days 2-3 (p < 0.05). Adiponectin protein expression in SME was at similar level throughout the most of the cycle with a statistically significant drop (p < 0.05) on days 14-16. AdipoR1 gene expression in POA was potentiated on days 2-3 and 10-12 of the oestrous cycle (p < 0.05). In SME, the highest AdipoR1 mRNA expression was noted on days 2-3 (p < 0.05). The concentrations of the AdipoR1 protein in POA were similar throughout the luteal phase (days 2-14 of the cycle), and they decreased on days 17-19 (p < 0.05). In SME, AdipoR1 protein expression peak occurred on days 2-3 (p < 0.05). The expression patterns of the AdipoR2 gene in MBH, POA and SME revealed the highest mRNA levels on days 2-3 of the cycle (p < 0.05). The highest content of AdipoR2 protein in MBH was reported on days 2-3 (p < 0.05), while in POA on days 17-19 and in SME on days 10-12 and 14-16 (p < 0.05). This study demonstrated that adiponectin and adiponectin receptor mRNAs and proteins are present in the porcine hypothalamus and that their expression levels are determined by the pig's endocrine status related to the oestrous cycle. PMID:24592982

Kaminski, T; Smolinska, N; Maleszka, A; Kiezun, M; Dobrzyn, K; Czerwinska, J; Szeszko, K; Nitkiewicz, A

2014-06-01

257

Drosophila Adiponectin Receptor in Insulin Producing Cells Regulates Glucose and Lipid Metabolism by Controlling Insulin Secretion  

PubMed Central

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

2013-01-01

258

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

2013-01-01

259

No association between plasma adiponectin levels and central auditory function in adults.  

PubMed

Adiponectin might play a protective role in cardiometabolic and peripheral auditory disorders, but its role on central auditory function was still unclear. The aim of this study was to examine whether there is an association between plasma adiponectin levels and central auditory function in adults. We recruited 297 adults, with normal or symmetrical sensorineural hearing loss and normal cognitive functions. Multivariate linear regression was performed to assess the association between plasma adiponectin concentrations and pitch pattern sequence (PPS) score, which was one of central auditory tests. The results showed that there were 224 (75.4 %) women and 73 (24.6 %) men in this study. The mean age was 58.1?±?8.4 years, the mean waist circumference (WC) was 81.1?±?8.3 cm, and the mean body mass index (BMI) was 24.0?±?3.0 kg/m(2). The mean PPS score was 71.5?±?14.1 %, and plasma adiponectin concentration was 12.7?±?5.5 g/mL. After adjusting for age, gender, WC, coronary artery disease, hypertension, diabetes mellitus, chronic kidney disease, smoking and drinking, plasma adiponectin concentrations (coefficient?±?standard error, ??±?SE?=?-0.09?±?0.16, p?=?0.563) were found to have no significant associations with PPS score. When WC was excluded from these variables in the multivariate linear regression model, plasma adiponectin concentrations (??±?SE?=?-0.03?±?0.15, p?=?0.855) were still not significantly associated with PPS score. In conclusion, plasma adiponectin levels were not significantly associated with PPS score, which was one of central auditory function tests. More studies should be conducted for the underlying mechanisms of obesity-related central auditory dysfunction. PMID:25108594

Hwang, Juen-Haur; Tseng, Fen-Yu; Liu, Tien-Chen; Yang, Wei-Shiung

2015-02-01

260

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

2012-09-01

261

The i148m Pnpla3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls  

PubMed Central

Background Reduced adiponectin is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), and the I148M Patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism predisposes to NAFLD and liver damage progression in NASH and chronic hepatitis C (CHC) by still undefined mechanisms, possibly involving regulation of adipose tissue function. Aim of this study was to evaluate whether the I148M PNPLA3 polymorphism influences serum adiponectin in liver diseases and healthy controls. Methods To this end, we considered 144 consecutive Italian patients with NAFLD, 261 with CHC, 35 severely obese subjects, and 257 healthy controls with very low probability of steatosis, all with complete clinical and genetic characterization, including adiponectin (ADIPOQ) genotype. PNPLA3 rs738409 (I148M) and ADIPOQ genotypes were evaluated by Taqman assays, serum adiponectin by ELISA. Adiponectin mRNA levels were evaluated by quantitative real-time PCR in the visceral adipose tissue (VAT) of 35 obese subjects undergoing bariatric surgery. Results Adiponectin levels were independently associated with the risk of NAFLD and with the histological severity of the disease. Adiponectin levels decreased with the number of 148?M PNPLA3 alleles at risk of NASH both in patients with NAFLD (p?=?0.03), and in healthy subjects (p?=?0.04). At multivariate analysis, PNPLA3 148?M alleles were associated with low adiponectin levels (<6?mg/ml, median value) independently of NAFLD diagnosis, age, gender, BMI, and ADIPOQ genotype (OR 1.67, 95% c.i. 1.07-2.1 for each 148?M allele). The p.148?M PNPLA3 variant was associated with decreased adiponectin mRNA levels in the VAT of obese patients (p?adiponectin resistance, low adiponectin was associated with male gender and steatosis, but not with PNPLA3 and ADIPOQ genotypes and viral features. Conclusions The I148M PNPLA3 variant is associated with adiponectin levels in patients with NAFLD and in healthy subjects, but in the presence of adiponectin resistance not in CHC patients. The I148M PNPLA3 genotype may represent a genetic determinant of serum adiponectin levels. Modulation of serum adiponectin might be involved in mediating the susceptibility to steatosis, NASH, and hepatocellular carcinoma in carriers of the 148?M PNPLA3 variant without CHC, with potential therapeutic implications. PMID:22898488

2012-01-01

262

Glucose-Based Peritoneal Dialysis Solution Suppresses Adiponectin Synthesis Through Oxidative Stress in an Experimental Model of Peritoneal Dialysis  

PubMed Central

? Objective: Accumulation of visceral fat is one of the major risk factors for the development of cardiovascular disease in peritoneal dialysis (PD) patients. Adiponectin, an adipokine commonly regarded as a negative indicator of metabolic disease, is reported to be downregulated in its gene level in end-stage renal disease patients. Since excessive fat deposit is involved in increased reactive oxygen species (ROS), PD solution (PDS) may contribute to ROS production, resulting in dysregulation of adiponectin. In this study, we tested our hypothesis that oxidative stress induced by PDS may play a role in the regulation of adiponectin. ? Methods: Commercial PDS containing 3.86% glucose (20 – 30 mL) was administered to SD rats for 12 weeks with and without N-acetylcysteine (NAC; 10 mmol/L). ELISA was used to quantify adiponectin in plasma and spent dialysate. For in vitro studies, fully differentiated 3T3-L1 adipocytes and adipocytes isolated from abdominal fat were treated with a high glucose solution, PDS, and H2O2. Adiponectin levels in the conditioned media were measured by ELISA and immunoblot assays. The mRNA levels of adiponectin in mature adipocytes were examined using real-time RT-PCR. ? Results: The levels of adiponectin in plasma and spent dialysate were significantly downregulated by PDS and this effect was suppressed by NAC. In 3T3-L1 adipocytes, adiponectin secretion was inhibited by 50 mmol/L glucose, PDS diluted 2-fold, and H2O2 (200 ?mol/L). In addition, H2O2 downregulated expression of adiponectin mRNA and secretion of adiponectin oligomer complexes. ? Conclusions: Our data suggest that ROS induced by conventional glucose-based PDS may contribute to pathophysiological changes in abdominal fat and downregulate adiponectin secreted from adipocytes during long-term PD. PMID:20798331

Huh, Joo Young; Seo, Eun-Young; Lee, Hi Bahl; Ha, Hunjoo

2012-01-01

263

Is adiponectin a bystander or a mediator in heart failure? The tangled thread of a good-natured adipokine in aging and cardiovascular disease  

Microsoft Academic Search

Adiponectin is an adipose tissue-derived adipokine abundant in human plasma. Increasing evidence from experimental studies\\u000a suggests that adiponectin plays a protective role in the cardiovascular system. However, epidemiological studies revealed\\u000a that high levels of adiponectin were associated with increased mortality and severity of congestive heart failure. Furthermore,\\u000a several prospective studies indicated that high levels of adiponectin were positively correlated with

Ken Shinmura

2010-01-01

264

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

265

Plasma adiponectin is inversely associated with antenatal anxiety: Results from a Brazilian cohort.  

PubMed

Antenatal anxiety may increase the risk of undesirable birth outcomes. Studies have demonstrated an association between adiponectin and anxiety, but this issue has not been investigated during pregnancy. This study aimed to evaluate the association between plasma adiponectin, measured throughout gestation, and the occurrence of anxiety at late pregnancy (30-36th weeks). A prospective cohort was investigated in Rio de Janeiro, Brazil. Healthy pregnant women, aged 20-40 years, were evaluated between gestational weeks 5-13, 22-26 and 30-36. State anxiety was measured using a validated version of the State-Trait Anxiety Inventory, and women were categorized as high (score?50, n=30) or low anxiety (score<50, n=129). Plasma samples for all trimesters were analyzed using commercial ELISA kits to determine adiponectin concentrations (U/mL). Statistical analysis involved student's t-tests, chi-square, Pearson correlation, multiple logistic regression and linear mixed effects (LME) regression to model longitudinal trends of adiponectin, stratified for anxiety categories. Women with higher anxiety scores had lower mean concentrations of 3rd trimester adiponectin compared with those with lower scores (7.9; 95% CI: 7.0-8.9 vs. 9.9; 95% CI: 9.1-10.7). Women with 3rd trimester adiponectin values within the third tertile (10.47-26.57U/mL) were less likely to have high antenatal anxiety (adjusted OR=0.30; 95% CI: 0.09-0.98) compared with those within the first tertile (2.25-7.08U/mL). Unlike women with low levels of anxiety, those with high levels had a significant decrease of plasma adiponectin throughout pregnancy (?=-0.07; 95% CI: -0.13-[-0.01] vs. ?=-0.01; 95% CI: -0.05 to 0.03). Multiple LME model indicated higher adiponectin throughout pregnancy for women with low anxiety (?=-1.57; 95% CI: -2.78-[-0.37]). In conclusion, plasma adiponectin throughout pregnancy was inversely associated with antenatal anxiety. PMID:25305545

Rebelo, Fernanda; de Jesus Pereira Pinto, Thatiana; Franco-Sena, Ana Beatriz; Lepsch, Jaqueline; Benaim, Camila; Struchiner, Claudio José; Kac, Gilberto

2015-01-01

266

Adiponectin serum level in chronic hepatitis C infection and therapeutic profile  

PubMed Central

Hepatic steatosis is commonly seen in the patients with chronic hepatitis C virus (HCV) infection. HCV is closely associated with lipid metabolism, and viral steatosis is more common in genotype 3 infection owing to a direct cytopathic effect of HCV core protein. In non-genotype 3 infection, hepatic steatosis is considered largely to be the result of the alterations in host metabolism; metabolic steatosis is primarily linked with HCV genotype 1. Adipose tissue secretes different hormones involved in glucose and lipid metabolisms. It has been demonstrated that adipocytokines are involved in the pathogenesis of non-alcoholic fatty liver disease, as the decreased plasma adiponectin levels, a soluble matrix protein expressed by adipoctyes and hepatocyte, are associated with liver steatosis. Various studies have shown that steatosis is strongly correlated negatively with adiponectin in the patients with HCV infection. The role of adiponectin in hepatitis C virus induced steatosis is still not completely understood, but the relationship between adiponectin low levels and liver steatosis is probably due to the ability of adiponectin to protect hepatocytes from triglyceride accumulation by increasing ?-oxidation of free fatty acid and thus decreasing de novo free fatty acid production. PMID:25624996

Peta, Valentina; Torti, Carlo; Milic, Natasa; Focà, Alfredo; Abenavoli, Ludovico

2015-01-01

267

Adiponectin serum level in chronic hepatitis C infection and therapeutic profile.  

PubMed

Hepatic steatosis is commonly seen in the patients with chronic hepatitis C virus (HCV) infection. HCV is closely associated with lipid metabolism, and viral steatosis is more common in genotype 3 infection owing to a direct cytopathic effect of HCV core protein. In non-genotype 3 infection, hepatic steatosis is considered largely to be the result of the alterations in host metabolism; metabolic steatosis is primarily linked with HCV genotype 1. Adipose tissue secretes different hormones involved in glucose and lipid metabolisms. It has been demonstrated that adipocytokines are involved in the pathogenesis of non-alcoholic fatty liver disease, as the decreased plasma adiponectin levels, a soluble matrix protein expressed by adipoctyes and hepatocyte, are associated with liver steatosis. Various studies have shown that steatosis is strongly correlated negatively with adiponectin in the patients with HCV infection. The role of adiponectin in hepatitis C virus induced steatosis is still not completely understood, but the relationship between adiponectin low levels and liver steatosis is probably due to the ability of adiponectin to protect hepatocytes from triglyceride accumulation by increasing ?-oxidation of free fatty acid and thus decreasing de novo free fatty acid production. PMID:25624996

Peta, Valentina; Torti, Carlo; Milic, Natasa; Focà, Alfredo; Abenavoli, Ludovico

2015-01-27

268

Regulation of T cell-mediated hepatic inflammation by adiponectin and leptin.  

PubMed

Concanavalin A-induced hepatotoxicity was compared in lipodystrophic aP2-nSREBP-1c transgenic mice (LD mice) lacking adipose tissue, obese leptin-deficient ob/ob mice, and lean wild-type (WT) mice. Serum leptin and adiponectin were low in LD mice, whereas ob/ob mice had undetectable leptin, but high adiponectin. Protection from hepatotoxicity was observed in ob/ob, but not in LD mice, despite low cytokine levels and reduced T cell activation and hepatic natural killer T cells in both groups. Administration of adiponectin protected LD mice from hepatotoxicity without altering cytokine levels. In contrast, administration of leptin heightened disease susceptibility by restoring cytokine production. Neutralization of TNF alpha protected LD mice from liver damage. Increased in vivo susceptibility to the hepatotoxic effect of TNF alpha was observed in LD mice. In vitro, adiponectin protected primary hepatocytes from TNF alpha-induced death, whereas leptin had no protective effect. In conclusion, although leptin increases susceptibility to hepatotoxicity by regulating cytokine production and T cell activation, adiponectin protects hepatocytes from TNF alpha-induced death. PMID:15677756

Sennello, Joseph A; Fayad, Raja; Morris, Alison M; Eckel, Robert H; Asilmaz, Esra; Montez, Jason; Friedman, Jeffrey M; Dinarello, Charles A; Fantuzzi, Giamila

2005-05-01

269

Study of Leptin and Adiponectin as Disease Markers in Subjects with Obstructive Sleep Apnea  

PubMed Central

Background. Published studies showed conflicting results of the associations between adiponectin and leptin levels and obstructive sleep apnoea (OSA). In obese patients, plasma leptin is elevated and adiponectin is decreased, and we postulate that these adipokines could be potential markers of clinical and metabolic perturbations in patients with OSA. Methods. 147 patients with suspected OSA had polysomnography to determine the Respiratory Disturbance Index (RDI). We measured fasting plasma glucose (FPG), fasting serum insulin, plasma leptin, adiponectin, and full lipid profile. Patients were classified on the basis of the RDI, degree of adiposity, and insulin resistance (IR) (homeostasis model assessment of insulin resistance (HOMAIR)). Results. 28.6% of subjects had normal polysomnography, 34.8% had mild OSA, 19.6% had moderate OSA, and 17% had severe OSA. Obesity was more prevalent in subjects with moderate-severe OSA (47%). Adiponectin decreased significantly (P = 0.041) with increasing severity of OSA. Though BMI was significantly higher in subjects with severe OSA, paradoxically, leptin was lowest in those subjects independent of gender dimorphism. Conclusions. Adiponectin is an independent marker of disease severity in patients with OSA. The paradoxical decrease in circulating leptin, which suggests impaired secretion, deserves further studies as a potential marker of severe OSA. PMID:24982545

Mojiminiyi, Olusegun A.; Al Alawi, Alia; Al Rammah, Tahani; Abdella, Nabila

2014-01-01

270

The regulation of adiponectin receptors in human prostate cancer cell lines  

SciTech Connect

Obesity is a risk factor for prostate cancer, and plasma levels of the adipokine, adiponectin, are low in the former but high in the latter. Adiponectin has been shown to modulate cell proliferation and apoptosis, suggesting that adiponectin and its receptors (Adipo-R1, Adipo-R2) may provide a molecular association between obesity and prostate carcinogenesis. We show for First time, the protein distribution of Adipo-R1 and Adipo-R2 in LNCaP and PC3 cells, and in human prostate tissue. Using real-time RT-PCR we provide novel data demonstrating the differential regulation of Adipo-R1 and Adipo-R2 mRNA expression by testosterone, 5-{alpha} dihydrotestosterone, {beta}-estradiol, tumour necrosis factor-{alpha}, leptin, and adiponectin in LNCaP and PC3 cells. Our findings suggest that adiponectin and its receptors may contribute to the molecular association between obesity and prostate cancer through a complex interaction with other hormones and cytokines that also play important roles in the pathophysiology of obesity and prostate cancer.

Mistry, T. [Clinical Sciences Research Institute, University of Warwick Medical School, Gibbet Hill Road, Coventry CV4 7AL (United Kingdom); Department of Urology, University Hospital Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX (United Kingdom); Digby, J.E. [Clinical Sciences Research Institute, University of Warwick Medical School, Gibbet Hill Road, Coventry CV4 7AL (United Kingdom); Chen, J. [Clinical Sciences Research Institute, University of Warwick Medical School, Gibbet Hill Road, Coventry CV4 7AL (United Kingdom); Desai, K.M. [Department of Urology, University Hospital Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX (United Kingdom); Randeva, H.S. [Clinical Sciences Research Institute, University of Warwick Medical School, Gibbet Hill Road, Coventry CV4 7AL (United Kingdom)]. E-mail: H.Randeva@warwick.ac.uk

2006-09-29

271

Subetta treatment increases adiponectin secretion by mature human adipocytes in vitro.  

PubMed

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. PMID:23690773

Nicoll, Jim; Gorbunov, Evgeniy A; Tarasov, Sergey A; Epstein, Oleg I

2013-01-01

272

Gene–environment interaction between adiponectin gene polymorphisms and environmental factors on the risk of diabetic retinopathy  

PubMed Central

Aims/Introduction To evaluate whether the adiponectin gene is associated with diabetic retinopathy (DR) risk and interaction with environmental factors modifies the DR risk, and to investigate the relationship between serum adiponectin levels and DR. Materials and Methods Four adiponectin polymorphisms were evaluated in 372 DR cases and 145 controls. Differences in environmental factors between cases and controls were evaluated by unconditional logistic regression analysis. The model-free multifactor dimensionality reduction method and traditional multiple regression models were applied to explore interactions between the polymorphisms and environmental factors. Results Using the Bonferroni method, we found no significant associations between four adiponectin polymorphisms and DR susceptibility. Multivariate logistic regression found that physical activity played a protective role in the progress of DR, whereas family history of diabetes (odds ratio 1.75) and insulin therapy (odds ratio 1.78) were associated with an increased risk for DR. The interaction between the C-11377 G (rs266729) polymorphism and insulin therapy might be associated with DR risk. Family history of diabetes combined with insulin therapy also increased the risk of DR. No adiponectin gene polymorphisms influenced the serum adiponectin levels. Serum adiponectin levels did not differ between the DR group and non-DR group. Conclusions No significant association was identified between four adiponectin polymorphisms and DR susceptibility after stringent Bonferroni correction. The interaction between C-11377G (rs266729) polymorphism and insulin therapy, as well as the interaction between family history of diabetes and insulin therapy, might be associated with DR susceptibility.

Li, Yuan; Wu, Qun Hong; Jiao, Ming Li; Fan, Xiao Hong; Hu, Quan; Hao, Yan Hua; Liu, Ruo Hong; Zhang, Wei; Cui, Yu; Han, Li Yuan

2015-01-01

273

Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network  

Technology Transfer Automated Retrieval System (TEKTRAN)

Adiponectin is an adipose-secreted protein that has been linked to changes in insulin sensitivity, high-density lipoprotein cholesterol levels, and inflammatory patterns. Although fenofibrate therapy can raise adiponectin levels, treatment response is heterogeneous and heritable, suggesting a role f...

274

Synergistic effect of high and low molecular weight molecules in the foamability and foam stability of sparkling wines.  

PubMed

The foam of sparkling wines is a key parameter of their quality. However, the compounds that are directly involved in foam formation and stabilization are not yet completely established. In this work, seven sparkling wines were produced in Bairrada appellation (Portugal) under different conditions and their foaming properties evaluated using a Mosalux-based device. Fractionation of the sparkling wines into four independent fractions, (1) high molecular weight material, with molecular weight higher than 12 kDa (HMW), (2) hydrophilic material with molecular weigh between 1 and 12 kDa (AqIMW), (3) hydrophobic material with molecular weigh between 1 and 12 kDa (MeIMW), and (4) hydrophobic material with a molecular weight lower than 1 kDa (MeLMW), allowed the observation that the wines presenting the lower foam stability were those that presented lower amounts of the MeLMW fraction. The fraction that presented the best foam stability was HMW. When HMW is combined with MeLMW fraction, the foam stability largely increased. This increase was even larger, approaching the foam stability of the sparkling wine, when HMW was combined with the less hydrophobic subfraction of MeLMW (fraction 3). Electrospray tandem mass spectrometry (ESI-MS/MS) of fraction 3 allowed the assignment of polyethylene glycol oligomers (n = 5-11) and diethylene glycol 8-hydroxytridecanoate glyceryl acetate. To observe if these molecules occur in sparkling wine foam, the MeLMW was recovered directly from the sparkling wine foam and was also analyzed by ESI-MS/MS. The presence of monoacylglycerols of palmitic and stearic acids, as well as four glycerylethylene glycol fatty acid derivatives, was observed. These surface active compounds are preferentially partitioned by the sparkling wine foam rather than the liquid phase, allowing the inference of their role as key components in the promotion and stabilization of sparkling wine foam. PMID:21375299

Coelho, Elisabete; Reis, Ana; Domingues, M Rosário M; Rocha, Sílvia M; Coimbra, Manuel A

2011-04-13

275

Adiponectin protects against hyperoxic lung injury and vascular leak  

PubMed Central

Adiponectin (Ad), an adipokine exclusively secreted by the adipose tissue, has emerged as a paracrine metabolic regulator as well as a protectant against oxidative stress. Pharmacological approaches of protecting against clinical hyperoxic lung injury during oxygen therapy/treatment are limited. Earlier, we have reported that Ad inhibits the NADPH oxidase-catalyzed formation of superoxide from molecular oxygen in human neutrophils. Having this as the premise, we conducted studies to determine whether (i) exogenous Ad would protect against the hyperoxia-induced barrier dysfunction in the lung endothelial cells (ECs) in vitro and (ii) endogenously synthesized Ad would protect against hyperoxic lung injury in wild type (WT) and Ad-overexpressing transgenic (AdTg) mice in vivo. The results demonstrated that exogenous Ad protected against the hyperoxia-induced oxidative stress, loss of glutathione (GSH), cytoskeletal reorganization, barrier dysfunction, and leak in the lung ECs in vitro. Furthermore, the hyperoxia-induced lung injury, vascular leak, and lipid peroxidation were significantly attenuated in AdTg mice in vivo. Also, AdTg mice exhibited elevated levels of total thiols and GSH in the lungs as compared to WT mice. For the first time, our studies demonstrated that Ad protected against the hyperoxia-induced lung damage apparently through attenuation of oxidative stress and modulation of thiol-redox status. PMID:22183615

Sliman, Sean M.; Patel, Rishi B.; Cruff, Jason P.; Kotha, Sainath R.; Newland, Christie A.; Schrader, Carrie A.; Sherwani, Shariq I.; Gurney, Travis O.; Magalang, Ulysses J.; Parinandi, Narasimham L.

2014-01-01

276

Measurement and validation of the nature of salivary adiponectin.  

PubMed

Adiponectin (Ad) is an adipocyte-derived hormone that plays an essential role in regulating insulin sensitivity, inflammation, and atherogenesis. Levels of some hormones in saliva change in a fashion similar to that in plasma in response to a disease or physiological condition. Since saliva is an easy to obtain biological fluid, measurements of salivary hormonal changes are preferred in diagnoses and treatments. Therefore, it was of interest to examine the nature of salivary Ad. While there have been two publications in the literature reporting presence of Ad in human saliva, the nature of salivary Ad has not been characterized. To this end, we investigated the effect of sample dilution on the measurement of Ad in saliva. To our surprise, we observed an increase in measurable level of Ad in saliva on sample dilution. One explanation for this paradoxical observation may be the presence of inhibitor(s) of Ad/anti-Ad binding in saliva that following dilution relieves the inhibitory effect. Working with this hypothesis, we were able to demonstrate the presence of an inhibitor in saliva that co-eluted with the dimeric form of Ad and was capable of inhibiting Ad assay. The presence of such inhibitor(s) may lead to underestimation of Ad in saliva. PMID:22415037

Akuailou, Eleonore-N; Vijayagopal, Parakat; Imrhan, Victorine; Prasad, Chandan

2013-10-01

277

Biochemical and genetic characterization of a monomeric storage protein (T1) with an unusually high molecular weight in Triticum tauschii.  

PubMed

The protein named T1, present in Triticum tauschii, was previously characterized as a high-molecular-weight (HMW) glutenin subunit with a molecular size similar to that of the y-type glutenin subunit-10 of Triticum aestivum. This protein was present along with other HMW glutenin subunits named 2(t) and T2, and was considered as part of the same allele at the Glu-D (t) 1locus of T. tauschii. This paper describes a re-evaluation of this protein, involving analyses of a collection of 173 accessions of T. tauschii, by SDS-PAGE of glutenin subunits after the extraction of monomeric protein. No accessions were found containing the three HMW glutenin subunits. On the other hand, 17 lines with HMW glutenin subunits having electrophoretic mobilities similar to subunits 2(t) and T2 were identified. The absence of T1 protein in these gel patterns has shown that protein T1 is not a component of the polymeric protein. Rather, the T1 protein is an omega-gliadin with an unusually high-molecular-weight. This conclusion is based on acidic polyacrylamide gel electrophoresis (A-PAGE), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and two-dimensional gel electrophoresis (A-PAGE+ SDS-PAGE), together with analysis of its N-terminal amino-acids sequence. The inheritance of omega-gliadin T1 was studied through analyses of gliadins and HMW glutenins in 106 F(2)grains of a cross between synthetic wheat, L/18913, and the wheat cv Egret. HMW glutenin subunits and gliadins derived from T. tauschii ( Glu-D (t) 1 and Gli-D (t) 1) segregated as alleles of the Glu-D1 and Gli-D1loci of bread wheat. A new locus encoding the omega-gliadin T1 was identified and named Gli-DT1. The genetic distance between this new locus and those of endosperm proteins encoded at the 1D chromosome were calculated. The Gli-DT1 locus is located on the short arm of chromosome 1D and the map distance between this locus and the Gli-D1 and Glu-D1 loci was calculated as 13.18 cM and 40.20 cM, respectively. PMID:12582724

Gianibelli, M. C.; Lagudah, E. S.; Wrigley, C. W.; MacRitchie, F.

2002-02-01

278

Is the lack of adiponectin associated with increased ER/SR stress and inflammation in the heart?  

PubMed

Objective To study whether there is an association between adiponectin and endoplasmic reticulum/sarcoplasmic reticulum (ERSR) stress. Research design Eleven-month-old male wild-type (WT) and adiponectin knockout (ADKO) mice were placed on chow or high fat diet for 12 weeks. The changes in ER stress and inflammatory genes were determined in the epididymal adipose, as well as heart tissue of adult WT and ADKO mice. To understand the role of ER/SR stress in the regulation of adiponectin, we studied the effect of tunicamycin or palmitate on H9C2 cardiomyoblasts in culture. To demonstrate the protective role of adiponectin, we studied the effect of purified adiponectin on the regulation of ERSR stress genes and inflammation in H9C2 cardiomyoblasts. Results (1) High fat diet increased TNF? in adipose tissue of ADKO mice. (2) ERSR stress genes, HSPa5, ERN1, and GADD34, and inflammation response genes, TNF? and CD68, were increased in heart of ADKO mice. High fat diet did not further increase the effect. (3) Induction of ERSR stress by tunicamycin in H9C2 resulted in the upregulation of ERSR stress response genes along with downregulation of adiponectin, adiponectin receptors 1 and 2, and Serca2A. ER stress was accompanied by down regulation of I??? and an increase in HSPa5 proteins. (4) Adiponectin decreased ERSR stress and inflammation response genes and increased Serca2A in to H9C2 cardiomyoblasts. Conclusion The lack of adiponectin is associated with increased ER/SR stress and inflammation in the heart. Adiponectin provides a protective effect by lowering inflammation and ER/SR stress along with increasing Serca2A in H9C2 cells. PMID:24575364

Boddu, Neeraja J; Theus, Sue; Luo, Shoake; Wei, Jeanne Y; Ranganathan, Gouri

2014-01-01

279

A Low-Glycemic Load Diet Reduces Serum C-Reactive Protein and Modestly Increases Adiponectin in Overweight and Obese Adults1234  

PubMed Central

Low-glycemic load (GL) diets improve insulin resistance and glucose homeostasis in individuals with diabetes. Less is known about whether low-GL diets, independent of weight loss, improve the health profile for persons without diabetes or other preexisting conditions. We conducted a randomized, cross-over feeding study testing low- compared to High-GL diets on biomarkers of inflammation and adiposity in healthy adults. Eighty participants (n = 40 with BMI 18.5–24.9 kg/m2; n = 40 with BMI 28.0–40.0 kg/m2) completed two 28-d feeding periods in random order where one period was a high-GL diet (mean GL/d = 250) and the other a low-GL diet (mean GL/d = 125). Diets were isocaloric with identical macronutrient content (as percent energy). All food was provided and participants maintained weight and usual physical activity. Height, weight, and DXA were measured at study entry and weight assessed again thrice per week. Blood was drawn from fasting participants at the beginning and end of each feeding period and serum concentrations of high-sensitivity CRP, serum amyloid A, IL-6, leptin, and adiponectin were measured. Linear mixed models tested the intervention effect on the biomarkers; models were adjusted for baseline biomarker concentrations, diet sequence, feeding period, age, sex, and body fat mass. Among participants with high-body fat mass (>32.0% for males and >25.0% for females), the low-GL diet reduced CRP (P = 0.02) and marginally increased adiponectin (P = 0.06). In conclusion, carbohydrate quality, independent of energy, is important. Dietary patterns emphasizing low-GL foods may improve the inflammatory and adipokine profiles of overweight and obese individuals. PMID:22190020

Neuhouser, Marian L.; Schwarz, Yvonne; Wang, Chiachi; Breymeyer, Kara; Coronado, Gloria; Wang, Chin-Yun; Noar, Karen; Song, Xiaoling; Lampe, Johanna W.

2012-01-01

280

Maintenance of redox state and pancreatic beta-cell function: role of leptin and adiponectin.  

PubMed

Whereas oxidative stress is linked to cellular damage, reactive oxygen species (ROS) are also believed to be involved in the propagation of signaling pathways. Studies on the role of ROS in pancreatic beta-cell physiology, in contrast to pathophysiology, have not yet been reported. In this study we investigate the importance of maintaining cellular redox state on pancreatic beta-cell function and viability, and the effects of leptin and adiponectin on this balance. Experiments were conducted on RINm and MIN6 pancreatic beta-cells. Leptin (1-100?ng/ml) and adiponectin (1-100?nM) increased ROS accumulation, as was determined by DCFDA fluorescence. Using specific inhibitors, we found that the increase in ROS levels was mediated by NADPH oxidase (Nox), but not by AMP kinase (AMPK) or phosphatidyl inositol 3 kinase (PI3K). Leptin and adiponectin increased beta-cell number as detected by the XTT method, but did not affect apoptosis, indicating that the increased cell number results from increased proliferation. The adipokines-induced increase in viability is ROS dependent as this effect was abolished by N-acetyl-L-cysteine (NAC) or PEG-catalase. In addition, insulin secretion was found to be regulated by alterations in redox state, but not by adipokines. Finally, the effects of the various treatments on activity and mRNA expression of several antioxidant enzymes were determined. Both leptin and adiponectin reduced mRNA levels of superoxide dismutase (SOD)1. Adiponectin also decreased SOD activity and increased catalase and glutathione peroxidase (GPx) activities in the presence of H2O2. The results of this study show that leptin and adiponectin, by inducing a physiological increase in ROS levels, may be positive regulators of beta-cell mass. PMID:22253064

Chetboun, Moria; Abitbol, Guila; Rozenberg, Konstantin; Rozenfeld, Hava; Deutsch, Avigail; Sampson, Sanford R; Rosenzweig, Tovit

2012-06-01

281

Chronic administration of bovine milk-derived ?-lactalbumin improves glucose tolerance via enhancement of adiponectin in Goto-Kakizaki rats with type 2 diabetes.  

PubMed

Inflammation has been implicated in development of the insulin resistance that leads to elevated blood sugar levels associated with type 2 diabetes. It is reported that salsalate, a common non-steroidal anti-inflammatory drug, has been shown to decrease blood glucose concentration in some clinical study. Recently, we found that bovine milk-derived ?-lactalbumin had anti-in?ammatory activity caused by inhibiting cyclooxygenase-2. In this study, we investigated the effects of chronic administration of ?-lactalbumin on glucose tolerance in Goto-Kakizaki (GK) rats, a model of type 2 diabetes. After 10 weeks administration of the ?-lactalbumin (300?mg/kg, twice a day), oral glucose tolerance tests revealed significant decrements of blood glucose levels after glucose loading. However, significant differences of insulin levels were not observed among three GK rats groups after glucose loading. ?-Lactalbumin treatment enhanced high molecular weight form of adiponectin and suppressed prostaglandin E2 levels in plasma. These results suggest that ?-lactalbumin effectively decreased blood glucose levels after glucose loading in GK rat, and the decrements may be due to enhancement of adiponectin. PMID:24583859

Yamaguchi, Makoto; Takai, Shoko

2014-01-01

282

Transplantation of fetal ventral mesencephalic progenitor cells overexpressing high molecular weight fibroblast growth factor 2 isoforms in 6-hydroxydopamine lesioned rats.  

PubMed

Fibroblast growth factor-2 (FGF-2) is a potent neurotrophic factor promoting survival of dopaminergic (DA) neurons in vitro and in vivo. FGF-2 is expressed in different isoforms representing distinct translation products from a single mRNA. For this study, we focused on the high molecular weight (HMW) isoform, which, after non-viral plasmid-based overexpression in embryonic day 12 (E12) rat ventral mesencephalon (VM)-derived cells, revealed increased numbers of tyrosine hydroxylase-positive (TH(+)) cells in a 'colayer' cell culture model. To determine the therapeutic potential of VM cells producing FGF-2-HMW as their 'own' neurotrophic factor, we transplanted cell suspensions obtained from such in vitro modified and differentiated cell cultures into the 6-hydroxydopamine (6-OHDA) hemiparkinsonian rat model. Animals, having received either non-transfected cells, empty-control transfected, or FGF-2-HMW-plasmid transfected cells, were analyzed in two different transplantation paradigms each using 172,000 or 520,000 cells, respectively. The behavioral performances in the amphetamine- and apomorphine-induced rotational test as well as in the cylinder test were evaluated for up to thirteen weeks post transplantation (postTX). Finally, the integration of the grafted cells into the host striatum was analyzed by immunohistochemical measurements. Those analyses revealed improvements of behavioral deficits in all five groups receiving DA neuron grafts, except for amphetamine-induced rotation of the FGF-2-HMW small graft group. Altogether, genetic modification with the FGF-2-HMW-plasmid did not further improve functional recovery compared to the control groups and had no influence on either the number of surviving DA neurons or on the density of outgrowing TH(+) fibers. PMID:25499314

Rumpel, R; Hohmann, M; Klein, A; Wesemann, M; Baumgärtner, W; Ratzka, A; Grothe, C

2015-02-12

283

Isolation and molecular characterization of high molecular weight glutenin subunit genes 1Bx13 and 1By16 from hexaploid wheat.  

PubMed

The high molecular weight glutenin subunit (HMW-GS) pair 1Bx13 + 1By16are recognized to positively correlate with bread-making quality; however, their molecular data remain unknown. In order to reveal the mechanism by which 1By16 and 1Bx13 creates high quality, their open reading frames (ORFs) were amplified from common wheat Atlas66 and Jimai 20 using primers that were designed based on published sequences of HMW glutenin genes. The ORF of 1By16 was 2,220 bp, deduced into 738 amino acid residues with seven cysteines including 59 hexapeptides and 22 nanopeptides motifs. The ORF of 1Bx13 was 2,385 bp, deduced into 795 amino acid residues with four cysteines including 68 hexapeptides, 25 nanopeptides and six tripeptides motifs. We found that 1By16 was the largest y-type HMW glutenin gene described to date in common wheat. The 1By16 had 36 amino acid residues inserted in the central repetitive domain compared with 1By15. Expression in bacteria and western-blot tests confirmed that the sequence cloned was the ORF of HMW-GS 1By16, and that 1Bx13 was one of the largest 1Bx genes that have been described so far in common wheat, exhibiting a hexapeptide (PGQGQQ) insertion in the end of central repetitive domain compared with 1Bx7. A phylogenetic tree based on the deduced full-length amino acid sequence alignment of the published HMW-GS genes showed that the 1By16 was clustered with Glu-1B-2, and that the 1Bx13 was clustered with Glu-1B-1 alleles. PMID:18713365

Pang, Bin-Shuang; Zhang, Xue-Yong

2008-03-01

284

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 1,671 bp 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

2013-12-01

285

Actions of adiponectin on the excitability of subfornical organ neurons are altered by food deprivation.  

PubMed

Adiponectin (ADP) is a peptide produced by adipose tissue, which acts as an insulin sensitizing hormone. Recent studies have shown that adiponectin receptors (AdipoR1 and AdipoR2) are present in the CNS, and although adiponectin does appear in both circulation and the cerebrospinal fluid there is still some debate as to whether or not ADP crosses the blood brain barrier (BBB). Circumventricular organs (CVO) are CNS sites which lack normal BBB, and thus represent sites at which circulating adiponectin may act to directly influence the CNS. The subfornical organ (SFO) is a CVO that has been implicated in the regulation of energy balance as a consequence of the ability of SFO neurons to respond to a number of different circulating satiety signals including amylin, CCK, PYY and ghrelin. Our recent microarray analysis suggested the presence of adiponectin receptors in the SFO. We report here that the SFO shows a high density of mRNA for both adiponectin receptors (AdipoR1 and AdipoR2), and that ADP influences the excitability of dissociated SFO neurons. Separate subpopulations of SFO neurons were either depolarized (8.9+/-0.9 mV, 21 of 97 cells), or hyperpolarized (-8.0+/-0.5 mV, 34 of 97 cells), by bath application of 10nM ADP, effects which were concentration dependent and reversible. Our microarray analysis also suggested that 48 h of food deprivation resulted in specific increases in AdipoR2 mRNA expression (no effect on AdipoR1 mRNA), observations which we confirm here using real-time PCR techniques. The effects of food deprivation also resulted in a change in the responsiveness of SFO neurons to adiponectin with 77% (8/11) of cells tested responding to adiponectin with depolarization, while no hyperpolarizations were observed. These observations support the concept that the SFO may be a key player in sensing circulating ADP and transmitting such information to critical CNS sites involved in the regulation of energy balance. PMID:20206611

Alim, Ishraq; Fry, W Mark; Walsh, Michael H; Ferguson, Alastair V

2010-05-12

286

Antiepileptic drugs influences on body weight in people with epilepsy.  

PubMed

Data from clinical trials, retrospective and cross-sectional studies have quantified the metabolic changes associated with long-term use of antiepileptic drugs (AEDs). AEDs can be associated with weight gain or weight loss, although most are weight neutral. Weight gain is not only a cosmetic problem but also a risk for obesity-related vascular disorders. Weight loss may compromise growth in children/adolescents. This review discusses the possible contribution of peripheral and central hormones/neuropeptides (as leptin, insulin, adiponectin, neuropeptide-Y, ghrelin and galanin) and pathways that influence energy balance in the pathogenesis of weight changes with AEDs. As AEDs may influence weight, physicians have to properly select and characterize the suitable AED as an initial step or modify the existing AED if it compromises patient's health. PMID:25487080

Hamed, Sherifa Ahmed

2015-01-01

287

PCR analysis of genes encoding allelic variants of high-molecular-weight glutenin subunits at the Glu-D1 locus.  

PubMed

Genes encoding high-molecular-weight (HMW) glutenin subunits, present in bread-wheat lines and cultivars, were studied by RFLP (restriction fragment length polymorphism) and PCR (polymerase chain reaction) analyses. In particular, allelic subunits of the x-or y-type, encoded at the Glu-D1 locus present on the long arm of chromosome 1D, were investigated. The variation in size, observed in different allelic subunits, is mainly due to variation in the length of the central repetitive domain, typical of these proteins. Deletions or duplications, probably caused by unequal crossingover, have given rise to the size heterogeneity currently observed. The possibility of using the PCR technique for a detailed analysis of HMW glutenin genes in order to obtain a more accurate estimation of the molecular weight of their encoded subunits, and the detection of unexpressed genes, is also described. PMID:24185923

D'Ovidio, R; Porceddu, E; Lafiandra, D

1994-05-01

288

Orally active osteoanabolic agent GTDF binds to adiponectin receptors, with a preference for AdipoR1, induces adiponectin-associated signaling, and improves metabolic health in a rodent model of diabetes.  

PubMed

Adiponectin is an adipocytokine that signals through plasma membrane-bound adiponectin receptors 1 and 2 (AdipoR1 and -2). Plasma adiponectin depletion is associated with type 2 diabetes, obesity, and cardiovascular diseases. Adiponectin therapy, however, is yet unavailable owing to its large size, complex multimerization, and functional differences of the multimers. We report discovery and characterization of 6-C-?-D-glucopyranosyl-(2S,3S)-(+)-5,7,3',4'-tetrahydroxydihydroflavonol (GTDF) as an orally active adiponectin mimetic. GTDF interacted with both AdipoRs, with a preference for AdipoR1. It induced adiponectin-associated signaling and enhanced glucose uptake and fatty acid oxidation in vitro, which were augmented or abolished by AdipoR1 overexpression or silencing, respectively. GTDF improved metabolic health, characterized by elevated glucose clearance, ?-cell survival, reduced steatohepatitis, browning of white adipose tissue, and improved lipid profile in an AdipoR1-expressing but not an AdipoR1-depleted strain of diabetic mice. The discovery of GTDF as an adiponectin mimetic provides a promising therapeutic tool for the treatment of metabolic diseases. PMID:24848063

Singh, Abhishek Kumar; Joharapurkar, Amit Arvind; Khan, Mohd Parvez; Mishra, Jay Sharan; Singh, Nidhi; Yadav, Manisha; Hossain, Zakir; Khan, Kainat; Kumar, Sudhir; Dhanesha, Nirav Anilkumar; Mishra, Devendra Pratap; Maurya, Rakesh; Sharma, Sharad; Jain, Mukul Rameshchandra; Trivedi, Arun Kumar; Godbole, Madan Madhav; Gayen, Jiaur Rahaman; Chattopadhyay, Naibedya; Sanyal, Sabyasachi

2014-10-01

289

Novel immunomodulatory effects of adiponectin on dendritic cell functions.  

PubMed

Adiponectin (ADN) is an adipocytokine with anti-inflammatory properties. Although it has been reported that ADN can inhibit the immunostimulatory function of monocytes and macrophages, little is known of its effect on dendritic cells (DC). Recent data suggest that ADN can regulate immune responses. DCs are uniquely specialised antigen presenting cells that play a central role in the initiation of immunity and tolerance. In this study, we have investigated the immuno- modulatory effects of ADN on DC functions. We found that ADN has only moderate effect on the differentiation of murine bone marrow (BM) derived DCs but altered the phenotype of DCs. The expression of major histocompatibilty complex class II (MHCII), CD80 and CD86 on ADN conditioned DCs (ADN-DCs) was lower than that on untreated cells. The production of IL-12p40 was also suppressed in ADN-DCs. Interestingly, ADN treated DCs showed an increase in the expression of the inhibitory molecule, programmed death-1 ligand (PDL-1) compared to untreated cells. In vitro co-culture of ADN-DCs with allogeneic T cells led to a decrease in T cell proliferation and reduction of IL-2 production. Concomitant with that, a higher percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) was detected in co-cultures of T cells and ADN-DCs. Blocking PD-1/PDL-1 pathway could partially restore T cell function. These findings suggest that the immunomodulatory effect of ADN on immune responses could be at least partially be mediated by its ability to alter DC function. The PD-1/PDL-1 pathway and the enhancement of Treg expansion are implicated in the immunomodulatory mechanisms. PMID:21094289

Tsang, Julia Yuen Shan; Li, Daxu; Ho, Derek; Peng, Jiao; Xu, Aimin; Lamb, Jonathan; Chen, Yan; Tam, Paul Kwong Hang

2011-05-01

290

[Leptin and adiponectin in pathogenesis of metabolic syndrome].  

PubMed

Metabolic syndrome, hypernutrition syndrome is a phylogenetically determined sequence of symptoms having common pathogenesis. Etiologically, it is due to excessive intake of adequate food. Enterocytes and omental adipose cells form an early phylogenetically unified and paracrinically regulated community that alternately realize exo- and endotrophic biological reactions. Visceral obesity high level of non-esterified fatty acids (FA), formation of plasma FA pool and their integration into the endothelial membrane, and enlargement of enterocytes are the main cause of increased hydrodynamic pressure. Toll-like receptors perceive albumin associates containing a supraphysiological number of FA as aliens and initiate the inflammatory reaction. Lipid-overloaded cells undergo "endoplasmic stress", abnormal protein synthesis (folding), and apoptosis-like death. Visceral fat serves as phylogenetically early FA depot for the realization of biological functions of homeostasis, trophology endoecology, and adaptation; it is anatomically confined and regulated at the level of paracrine communities. The subcutaneous depot realizes the phylogenetically late locomotor function; its size is not anatomically restricted. Visceral adipose cells have no receptors for phylogenetically late insulin (INS). Cells of the subcutaneous FA depot are specialized adipocytes having INS and GLUT4 receptors. They are regulated by the phylogenetically late humoral mechanisms at the total body level. Leptin initiates in vivo humoral, hypothalamic regulation of the size of INS-insensitive visceral adipose cells quantitatively programmed in ontogenesis; also, it prevents "endoplasmic stress" and apoptosis, regulates food consumption. Leptin initiates switching FA storage from the visceral adipocyte pool to the subcutaneous one. Adiponectin is a phylogenetically late humoral inducer of regulation of the optimal in vivo number of cells from the hypothalamus level. It is biologically predetermined to regulate the number (proliferation) of INS-dependent adipocytes in subcutaneous fat. PMID:25269205

Titov, V N

2014-01-01

291

Adiponectin is better predictor of subclinical atherosclerosis than liver function tests in patients with nonalcoholic fatty liver disease.  

PubMed

Adiponectin has recently been considered as a possible link between liver dysfunction and atherosclerosis in patients with nonalcoholic fatty liver disease (NAFLD). The present study was designed to evaluate the relation between circulating adiponectin and arterial stiffness parameters, such as pulse wave velocity (PWV) and aortic augmentation index (AI), in patients with hepatic steatosis. The study group consisted of 52 subjects with NAFLD. PWV and AI were performed using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). Metabolic parameters, homeostasis model assessment-insulin resistance, and adiponectin levels were determined. Adiponectin was significantly, positively associated with AI (r = 0.467; P < .0001) and with PWV (r = 0.348; P = .011). No association between arterial stiffness parameters and liver function tests was observed. In a multiple linear regression analysis, adiponectin remained a significant predictor of PWV even after controlling for age, gender, and MAP. Serum adiponectin levels were significantly associated with indices of subclinical atherosclerosis, such as PWV and AI in patients with NAFLD. This association was independent of age, gender, and blood pressure level and suggests an active role of adiponectin in the pathophysiology of vascular disease in this particular population group. PMID:24794207

Omelchenko, Elena; Gavish, Dov; Shargorodsky, Marina

2014-06-01

292

Adiponectin and the mediation of HDL cholesterol change with improved lifestyle: The Look AHEAD Study  

Technology Transfer Automated Retrieval System (TEKTRAN)

Adipose tissue dysfunction plays a key role in the development of the metabolic abnormalities characteristic of type 2 diabetes (T2DM) and participates actively in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of adipose health, is decreased in obese persons with T2DM. ...

293

Adiponectin normalization: a clue to the anti-metabolic syndrome action of rimonabant  

Microsoft Academic Search

Abstract: Obesity, currently associated with metabolic syndrome is characterized by an excessive fat storage in different organs, in particular adipose tissue, inducing the loss of its structural and functional integrity. The awareness of ,the importance of adipose tissue endocrine function ,and the key role of adipocytokines such as adiponectin in obesity and metabolic syndrome display, the necessity to develop ,new

Marie Maynadier; Ilaria Basile; Magali Gary-Bobo

2009-01-01

294

Adiponectin: An Attractive Marker for Metabolic Disorders in Chronic Obstructive Pulmonary Disease (COPD)  

PubMed Central

Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung disease which may be complicated by development of co-morbidities including metabolic disorders. Metabolic disorders commonly associated with this disease contribute to lung function impairment and mortality. Systemic inflammation appears to be a major factor linking COPD to metabolic alterations. Adipose tissue seems to interfere with systemic inflammation in COPD patients by producing a large number of proteins, known as “adipokines”, involved in various processes such as metabolism, immunity and inflammation. There is evidence that adiponectin is an important modulator of inflammatory processes implicated in airway pathophysiology. Increased serum levels of adiponectin and expression of its receptors on lung tissues of COPD patients have recently highlighted the importance of the adiponectin pathway in this disease. Further, in vitro studies have demonstrated an anti-inflammatory activity for this adipokine at the level of lung epithelium. This review focuses on mechanisms by which adiponectin is implicated in linking COPD with metabolic disorders. PMID:24128974

Bianco, Andrea; Mazzarella, Gennaro; Turchiarelli, Viviana; Nigro, Ersilia; Corbi, Graziamaria; Scudiero, Olga; Sofia, Matteo; Daniele, Aurora

2013-01-01

295

Maternal leptin, adiponectin, resistin, visfatin and tumor necrosis factor-alpha in normal and gestational diabetes.  

PubMed

Gestational diabetes mellitus (GDM) is a common medical complication associated with pregnancy. The present study evaluates the changes in maternal adipocytokines (leptin, adiponectin, resistin, visfatin and tumor necrosis factor-alpha; TNF-?) in pregnancy complicated with GDM compared to normal pregnancy at 2nd and 3rd trimesters. The study included total number of 142 pregnant women classified into 4 groups: normal pregnancy (n = 33) and pregnancy with GDM (n = 24) both at 2nd trimester and normal pregnancy (n = 38) and GDM (n = 47) at 3rd trimester. Both GDM groups were significantly presented with elevated body mass index, fasting blood sugar and abnormal oral glucose tolerance test compared to their matched control. Results indicated reduction in maternal serum leptin and adiponectin in GDM compared to normal pregnancy at 3rd trimester. Elevated resistin and TNF-? were evident among pregnancy complicated with GDM at both tested trimesters. On the other hand, significant elevation in maternal visfatin was noted between GDM and matched control at 2nd trimester only. Significant increase in maternal leptin and visfatin and resistin was noted by advances in gestational period in healthy pregnancy. On the other hand, reduced adiponectin and elevated visfatin mean values were noticed in GDM at 3rd compared to 2nd trimester. It could be concluded that increased insulin resistance accompanies GDM is associated with suppressed leptin and adiponectin and increased resistin and TNF-? which might suggest their involvement in the development of GDM. PMID:25298627

Noureldeen, Amani F H; Qusti, Safaa Y; Al-Seeni, Madeha N; Bagais, Maram H

2014-10-01

296

Heme Oxygenase-Mediated Increases in Adiponectin Decrease Fat Content and Inflammatory Cytokines Tumor Necrosis  

E-print Network

necrosis factor (TNF)- and interleukin (IL)-6 compared with Zucker lean (ZL) rats. Treatment of ZF animals production in adipocytes and the associated insulin resis- tance and changes in serum levels of adiponectin. Adipose tissue plays an important role in insulin resis- tance through the production and secretion

Abraham, Nader G.

297

A rabbit model of pediatric nonalcoholic steatohepatitis: The role of adiponectin  

Microsoft Academic Search

AIM: To create a rabbit model of pediatric nonalcoholic steatohepatitis (NASH) and to evaluate the role of adiponectin in the process. METHODS: Thirty-two specific pathogen-free male New Zealand rabbits were divided randomly into three groups: (1) the normal control group (n = 10) was fed with standard diet for 12 wk; (2) the model group A (n = 11); and

Jun-Fen Fu; Yan-Lan Fang; Li Liang; Chun-Lin Wang; Fang Hong; Guan-Ping Dong

2009-01-01

298

Serum adiponectin and leptin concentrations in HIV-infected children with fat redistribution syndrome.  

PubMed

Human immunodeficiency virus (HIV)-related lipodystrophy is characterized by adipose tissue redistribution, dyslipidemia, and insulin resistance. We hypothesized that fat redistribution and metabolic abnormalities in HIV-infected children are related to alterations in endocrine function of adipose tissue. A multicenter study was conducted in 130 HIV-infected children. Lipodystrophy definition was based on the central to peripheral skinfold ratio. Fasting adiponectin, leptin, insulin concentrations, glycemia, and lipid profile were measured in all children. Fat redistribution syndrome was apparent in 32 children: 14 with atrophic (LPDA) and 18 with hypertrophic lipodystrophy (LPDH). Mean serum adiponectin levels were significantly decreased in LPDA and LPDH groups compared with the group with no lipodystrophy (LPD-). Fasting insulin concentration was significantly higher in LPDA and LPDH groups versus LPD-. Mean serum leptin concentration was significantly increased only in LPDH compared with LPDA and LPD- groups. Triglyceride levels were significantly increased and high-density lipoprotein (HDL)-cholesterol concentration decreased in the LPDA versus LPD- group. Controlling for puberty stage, gender, percentage of total fat mass, serum lipids, HIV treatment, and disease severity, adiponectin was significantly and inversely associated with central obesity and insulin/glucose ratio. Fat redistribution had no significant effect on leptin concentration, which was directly related to the percentage of body fat, female gender, and insulin/glucose ratio. In conclusion, HIV-infected children with symptoms of fat redistribution have decreased levels of adiponectin, associated with insulin resistance and dyslipidemia. PMID:16864709

Verkauskiene, Rasa; Dollfus, Catherine; Levine, Martine; Faye, Albert; Deghmoun, Samia; Houang, Muriel; Chevenne, Didier; Bresson, Jean-Louis; Blanche, Stéphane; Lévy-Marchal, Claire

2006-08-01

299

New insight into adiponectin role in obesity and obesity-related diseases.  

PubMed

Obesity is a major health problem strongly increasing the risk for various severe related complications such as metabolic syndrome, cardiovascular diseases, respiratory disorders, diabetic retinopathy, and cancer. Adipose tissue is an endocrine organ that produces biologically active molecules defined "adipocytokines," protein hormones with pleiotropic functions involved in the regulation of energy metabolism as well as in appetite, insulin sensitivity, inflammation, atherosclerosis, cell proliferation, and so forth. In obesity, fat accumulation causes dysregulation of adipokine production that strongly contributes to the onset of obesity-related diseases. Several advances have been made in the treatment and prevention of obesity but current medical therapies are often unsuccessful even in compliant patients. Among the adipokines, adiponectin shows protective activity in various processes such as energy metabolism, inflammation, and cell proliferation. In this review, we will focus on the current knowledge regarding the protective properties of adiponectin and its receptors, AdipoRs ("adiponectin system"), on metabolic complications in obesity and obesity-related diseases. Adiponectin, exhibiting antihyperglycemic, antiatherogenic, and anti-inflammatory properties, could have important clinical benefits in terms of development of therapies for the prevention and/or for the treatment of obesity and obesity-related diseases. PMID:25110685

Nigro, Ersilia; Scudiero, Olga; Monaco, Maria Ludovica; Palmieri, Alessia; Mazzarella, Gennaro; Costagliola, Ciro; Bianco, Andrea; Daniele, Aurora

2014-01-01

300

Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity  

E-print Network

Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity Bulent in the circula- tion, with important effects on metabolism. We studied five lean and five obese young men [ages: 24.2 1.0 (lean) and 21.8 1.6 (obese) years (difference not significant); body mass indexes: 35.0 1

Suchard, Marc A.

301

Does dietary iodine regulate oxidative stress and adiponectin levels in human breast milk?  

PubMed

Little is known about the association between iodine and human milk composition. In this study, we investigated the association between iodine and different markers of oxidative stress and obesity-related hormones in human breast milk. This work is composed of two cross-sectional studies (in lactating women and in the general population), one prospective and one in vitro. In the cross-sectional study in lactating women, the breast milk iodine correlated negatively with superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities, and with adiponectin levels. An in vitro culture of human adipocytes with 1??M potassium iodide (KI, dose similar to the human breast milk iodine concentration) produced a significant decrease in adiponectin, GSH-Px, SOD1, and SOD2 mRNA expression. However, after 2 months of treatment with KI in the prospective study, a positive correlation was found between 24-h urinary iodine and serum adiponectin. Our observations lead to the hypothesis that iodine may be a factor directly involved in the regulation of oxidative stress and adiponectin levels in human breast milk. PMID:24001137

Gutiérrez-Repiso, Carolina; Velasco, Inés; Garcia-Escobar, Eva; Garcia-Serrano, Sara; Rodríguez-Pacheco, Francisca; Linares, Francisca; Ruiz de Adana, Maria Soledad; Rubio-Martin, Elehazara; Garrido-Sanchez, Lourdes; Cobos-Bravo, Juan Francisco; Priego-Puga, Tatiana; Rojo-Martinez, Gemma; Soriguer, Federico; García-Fuentes, Eduardo

2014-02-10

302

Ethnic Variation in Adiponectin and Leptin Levels and Their Association With Adiposity and Insulin Resistance  

PubMed Central

OBJECTIVE To investigate ethnic differences in adiponectin and leptin concentration and to determine whether these adipokines and a high–glycemic index diet account for ethnic variation in insulin resistance. RESEARCH DESIGN AND METHODS In 1,176 South Asian, Chinese, Aboriginal, and European Canadians, fasting blood samples were drawn, and clinical history and dietary habits including glycemic index/glycemic load were recorded using standardized questionnaires. Insulin resistance was defined using homeostasis model assessment–insulin resistance (HOMA-IR). RESULTS Adiponectin concentrations were significantly higher in Europeans (adjusted mean 12.94 [95% CI 2.27–13.64]) and Aboriginal people (11.87 [11.19–12.59]) than in South Asians (9.35 [8.82–9.92]) and Chinese (8.52 [8.03–9.03]) (overall P < 0.001). Serum leptin was significantly higher in South Asians (11.82 [10.72–13.04]) and Aboriginal people (11.13 [10.13–12.23]) than in Europeans (9.21 [8.38–10.12]) and Chinese (8.25 [7.48–9.10]). BMI and waist circumference were inversely associated with adiponectin in every group except the South Asians (P < 0.001 for interaction). Adiponectin was inversely and leptin was positively associated with HOMA-IR (P < 0.001). The increase in HOMA-IR for each given decrease in adiponectin was larger among South Asians (P = 0.01) and Aboriginal people (P < 0.001) than among Europeans. A high glycemic index was associated with a larger decrease in adiponectin among South Asians (P = 0.03) and Aboriginal people (P < 0.001) and a larger increase in HOMA-IR among South Asians (P < 0.05) relative to that in other groups. CONCLUSIONS South Asians have the least favorable adipokine profile and, like the Aboriginal people, display a greater increase in insulin resistance with decreasing levels of adiponectin. Differences in adipokines and responses to glycemic foods parallel the ethnic differences in insulin resistance. PMID:20413520

Mente, Andrew; Razak, Fahad; Blankenberg, Stefan; Vuksan, Vlad; Davis, A. Darlene; Miller, Ruby; Teo, Koon; Gerstein, Hertzel; Sharma, Arya M.; Yusuf, Salim; Anand, Sonia S.

2010-01-01

303

Iron Metabolism Is Associated With Adipocyte Insulin Resistance and Plasma Adiponectin  

PubMed Central

OBJECTIVE Adipocyte insulin resistance (IR) is a key feature early in the pathogenesis of type 2 diabetes mellitus (T2DM), and although scarce, data in the literature suggest a direct role for iron and iron metabolism–related factors in adipose tissue function and metabolism. Serum ferritin and transferrin were shown to be associated with muscle insulin resistance (IR) and T2DM, but little is known about the role of iron metabolism on adipose tissue. We therefore investigated whether markers of iron metabolism were associated with adipocyte IR and plasma adiponectin. RESEARCH DESIGN AND METHODS Serum ferritin, transferrin, total iron, non–transferrin-bound iron (NTBI), transferrin saturation, and plasma adiponectin were determined in 492 individuals. Adipocyte IR was defined by the product of fasting insulin and nonesterified fatty acids (NEFAs). Using linear regression analyses, we investigated the difference in adipocyte IR or adiponectin (in %) according to differences in iron metabolism markers. RESULTS Serum ferritin (? = 1.00% increase in adipocyte IR per 10 ?g/L [95% CI 0.66–1.34]), transferrin (4.18% per 0.1 g/L [2.88–5.50]), total iron (1.36% per ?mol/L [0.61–2.12]), and NTBI (5.14% per ?mol/L [1.88–8.52]) were associated with adipocyte IR after adjustment for several covariates, including inflammatory markers. All markers of iron metabolism were also associated with NEFAs (all P < 0.01). In addition, ferritin and transferrin were inversely associated with adiponectin (both P < 0.01). CONCLUSIONS The observed associations of several markers of iron metabolism with adipocyte IR and adiponectin suggest that factors related to iron and iron metabolism may contribute to adipocyte IR early in the pathogenesis of T2DM. PMID:22961568

Wlazlo, Nick; van Greevenbroek, Marleen M.J.; Ferreira, Isabel; Jansen, Eugene H.J.M.; Feskens, Edith J.M.; van der Kallen, Carla J.H.; Schalkwijk, Casper G.; Bravenboer, Bert; Stehouwer, Coen D.A.

2013-01-01

304

Integral Role of PTP1B in Adiponectin-Mediated Inhibition of Oncogenic Actions of Leptin in Breast Carcinogenesis1 2  

PubMed Central

The molecular effects of obesity are mediated by alterations in the levels of adipocytokines. High leptin level associated with obese state is a major cause of breast cancer progression and metastasis, whereas adiponectin is considered a “guardian angel adipocytokine” for its protective role against various obesity-related pathogenesis including breast cancer. In the present study, investigating the role of adiponectin as a potential inhibitor of leptin, we show that adiponectin treatment inhibits leptin-induced clonogenicity and anchorage-independent growth. Leptin-stimulated migration and invasion of breast cancer cells is also effectively inhibited by adiponectin. Analyses of the underlying molecular mechanisms reveal that adiponectin suppresses activation of two canonical signaling molecules of leptin signaling axis: extracellular signal-regulated kinase (ERK) and Akt. Pretreatment of breast cancer cells with adiponectin protects against leptin-induced activation of ERK and Akt. Adiponectin increases expression and activity of the physiological inhibitor of leptin signaling, protein tyrosine phosphatase 1B (PTP1B), which is found to be integral to leptin-antagonist function of adiponectin. Inhibition of PTP1B blocks adiponectin-mediated inhibition of leptin-induced breast cancer growth. Our in vivo studies show that adenovirus-mediated adiponectin treatment substantially reduces leptin-induced mammary tumorigenesis in nude mice. Exploring therapeutic strategies, we demonstrate that treatment of breast cancer cells with rosiglitazone results in increased adiponectin expression and inhibition of migration and invasion. Rosiglitazone treatment also inhibits leptin-induced growth of breast cancer cells. Taken together, these data show that adiponectin treatment can inhibit the oncogenic actions of leptin through blocking its downstream signaling molecules and raising adiponectin levels could be a rational therapeutic strategy for breast carcinoma in obese patients with high leptin levels. PMID:23358729

Taliaferro-Smith, LaTonia; Nagalingam, Arumugam; Knight, Brandi Brandon; Oberlick, Elaine; Saxena, Neeraj K; Sharma, Dipali

2013-01-01

305

Nucleotide sequence of a gene from chromosome 1D of wheat encoding a HMW-glutenin subunit.  

PubMed Central

A high molecular weight glutenin gene in hexaploid wheat has been isolated by cloning in bacteriophage lambda and characterized. The gene corresponds to polypeptide 12 encoded by chromosome 1D in the variety "Chinese Spring". The coding sequence predicted contains seven cysteine residues six of which flank a central repetitive region comprising more than 70% of the polypeptide. These findings are related to the role of high molecular weight subunits in the viscoelastic theory of gluten structure. Images PMID:3840588

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

1985-01-01

306

A diet supplemented with husks of Plantago ovata reduces the development of endothelial dysfunction, hypertension, and obesity by affecting adiponectin and TNF-alpha in obese Zucker rats.  

PubMed

The aim of the present study was to analyze whether consumption of a fiber-supplemented diet containing 3.5% Plantago ovata husks prevented many of the abnormalities clustered in the metabolic syndrome, including obesity, dyslipidemia, hypertension and endothelial dysfunction. For this purpose, obese Zucker rats, a model of type 2 diabetes, and their lean littermates were studied. Rats consumed a standard control diet or that diet supplemented with 3.5% P. ovata husks for 25 wk. Body weights were measured weekly. Systolic blood pressure (SBP) was measured monthly. At the end of the treatment, plasma concentrations of triglycerides, total cholesterol, FFAs, glucose, insulin, adiponectin, and tumor necrosis factor alpha (TNF-alpha) were determined, and studies on vascular function were performed using aortic rings. Rats fed the P. ovata husk-supplemented diet had a significantly reduced body weight gain compared with those fed the standard diet. Decreased endothelium-dependent relaxation in response to acetylcholine (ACh) by aortic rings from obese Zucker rats was improved in those fed the fiber-supplemented diet. The greater SBP, higher plasma concentrations of triglycerides, total cholesterol, FFA, glucose, insulin, and TNF-alpha, and the hypoadinectinemia that occurred in obese Zucker rats that consumed the control diet were significantly improved in those fed the fiber-supplemented diet. We conclude that intake of a P. ovata husk-supplemented diet prevents endothelial dysfunction, hypertension, and obesity development, and ameliorates dyslipidemia and abnormal plasma concentrations of adiponectin and TNF-alpha in obese Zucker rats. PMID:16177203

Galisteo, Milagros; Sánchez, Manuel; Vera, Rocío; González, Mercedes; Anguera, Anna; Duarte, Juan; Zarzuelo, Antonio

2005-10-01

307

Metaproteomic characterization of high molecular weight dissolved organic matter in surface seawaters in the South China Sea  

NASA Astrophysics Data System (ADS)

Dissolved organic matter (DOM) is an important reservoir of carbon and energy in the marine environment and plays a key role in regulating the global carbon cycle. This study characterized proteins of high-molecular-weight DOM (size between 5 kDa and <0.2 ?m, HMW-DOM) collected from the surface seawaters in the South China Sea using a shotgun proteomic approach in combination with the global ocean sampling combined assembly protein database. A total of 367 protein groups matched by 993 unique peptides from 1991 spectra were identified from four surface HMW-DOM samples. Proteins with unknown taxonomic classification and function dominated the dissolved protein pool (43-53%) while the remaining proteins presented close similarity in biological origin among the four sampling sites. Rhodospirillaceae, Prochlorococcus, SAR11 clade and viruses were the major contributors to dissolved proteins in the HMW-DOM from surface seawaters while very few proteins were from the eukaryotic phytoplankton and no archaeal proteins were detected. Transporters with substrate specificities for nitrogen- and carbon-containing compounds (1.5% of the total spectra for each) were highly detected while no phosphate transporters were found, suggesting that carbon and nitrogen might be more limiting than phosphorus in the surface seawater. Viral proteins were assigned into three families: Myoviridae, Podoviridae and Siphoviridae, and the Myoviridae proteins were the most abundant. Among them, structure proteins were the most abundant viral proteins. This study indicated that the dissolved proteins of HMW-DOM presented compositional and biologically original homogeneity in the surface seawaters of the South China Sea, and bacteria and viruses dominated the dissolved protein pool.

Dong, Hong-Po; Wang, Da-Zhi; Xie, Zhang-Xian; Dai, Min-Han; Hong, Hua-Sheng

2013-05-01

308

Detection of high molecular weight glutenin subunits in triticale (x Triticosecale Wittm.) Cultivars by capillary zone electrophoresis.  

PubMed

An improved method for separating and characterizing high molecular weight glutenin subunits (HMW-GS) in hexaploid triticale by capillary zone electrophoresis (CZE) was developed. A low-concentrate mixture of hydrophilic polymers, poly(vinylpyrrolidone) (PVP) and hydroxypropylmethylcellulose (HPMC), in an isoelectric buffer was employed for dynamic coating of the capillary inner wall. In separation buffer PVP with lower concentrated poly(ethylene oxide) (PEO) was replaced. The CZE electropherograms of HMW-GS showed two group peaks in accordance with x- and y-type subunits with migration times of 6.8-7.8 and 8.4-11.5 min, respectively. In total, 14 HMW subunits (2 subunits encoded by Glu-A1 locus and 12 by Glu-B1) were identified. The CZE analyses revealed that each of the subunits Bx7 and By8 determined by SDS-PAGE makes up three subunits (Bx6.8, Bx7, and Bx7* and By8, By8*, and new By8**, respectively), with different migration times. It was also shown that the subunits By18 and By20 in triticale determined by SDS-PAGE have different migration times in comparison with the same subunits in bread wheat. For these new HMW-GS, the following names were assigned: By18* instead of By18 and By20* instead of By20. The presented CZE method is an efficient alternative to the SDS-PAGE procedure for early selection of useful triticale genotypes with good breadmaking quality. PMID:18808142

Salmanowicz, Boles?aw P

2008-10-22

309

Charge-based characterisation of high-molecular-weight glutenin subunits from common wheat by capillary isoelectric focusing.  

PubMed

In this study, the capillary isoelectric focusing (CIEF) method for the separation and charge characterisation of the heterogeneity of high molecular-weight-glutenin subunits (HMW-GS) in common wheat (Triticum aestivum L.) using linear polyacrylamide (LPA) and polyvinyl alcohol (PVA) coated capillaries was developed. Particularly good repeatability and well-resolved charge isoform profiles were obtained by introducing a mixture of carrier ampholytes (pH 3-10 and pH 5-8), a high concentration of urea (6M) and SB3-12 as detergent in a sample solution during separation in a PVA-coated capillary. One major and one or two minor isoforms were observed for the individual HMW-GS. These isoforms were satisfactorily separated using a pH gradient into two groups: y-type isoforms and x-type isoforms encoded by the Glu-B1 locus with shorter migration times and remaining x-type isoforms with longer times. The method produced from eight to twelve isoforms of wheat HMW-GS with pI points in the range of 4.72-6.98. Generally, the minor isoforms were more acidic compared with the major isoform. The y-type subunits had an approximately neutral character (pI 6.70-6.98); however, x-types showed a weakly acidic character (pI 4.72-5.23), with the exception of subunits encoded by the Glu-B1 locus. The isoelectric point peak profiles were compared with capillary zone electrophoresis (CZE) electropherograms. Generally, the number of detected isoforms for the particular HMW-GS detected using both methods were similar. PMID:25127558

Salmanowicz, Boles?aw P; Langner, Monika; Franaszek, S?awomir

2014-11-01

310

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

PubMed

High molecular weight glutenin subunits (HMW-GS) are of a particular interest because of their biomechanical 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 known protein structures of this family as templates, we built three models for the N-terminal domain of HMW-GS Dy10. We analyzed these models, and we propose a number of hypotheses regarding the N-terminal domain properties that can be tested experimentally. In particular, we discuss two possible ways of interaction between the N-terminal domains of the y-type HMW glutenin subunits. The first way consists in the creation of interchain disulfide bridges. According to our models, we propose two plausible scenarios: (1) the existence of an intrachain disulfide bridge between cysteines 22 and 44, leaving the three other cysteines free of engaging in intermolecular bonds; and (2) the creation of two intrachain disulfide bridges (involving cysteines 22-44 and cysteines 10-55), leaving a single cysteine (45) for creating an intermolecular disulfide bridge. We discuss these scenarios in relation to contradictory experimental results. The second way, although less likely, is nevertheless worth considering. There might exist a possibility for the N-terminal domain of Dy10, Nt-Dy10, to create oligomers, because homologous cereal inhibitor proteins are known to exist as monomers, homodimers, and heterooligomers. We also discuss, in relation to the function of the cereal inhibitor proteins, the possibility that this N-terminal domain has retained similar inhibitory functions. PMID:12493826

Cazalis, Roland; Aussenac, Thierry; Rhazi, Larbi; Marin, Antoine; Gibrat, Jean-François

2003-01-01

311

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

PubMed Central

High molecular weight glutenin subunits (HMW-GS) are of a particular interest because of their biomechanical 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 known protein structures of this family as templates, we built three models for the N-terminal domain of HMW-GS Dy10. We analyzed these models, and we propose a number of hypotheses regarding the N-terminal domain properties that can be tested experimentally. In particular, we discuss two possible ways of interaction between the N-terminal domains of the y-type HMW glutenin subunits. The first way consists in the creation of interchain disulfide bridges. According to our models, we propose two plausible scenarios: (1) the existence of an intrachain disulfide bridge between cysteines 22 and 44, leaving the three other cysteines free of engaging in intermolecular bonds; and (2) the creation of two intrachain disulfide bridges (involving cysteines 22–44 and cysteines 10–55), leaving a single cysteine (45) for creating an intermolecular disulfide bridge. We discuss these scenarios in relation to contradictory experimental results. The second way, although less likely, is nevertheless worth considering. There might exist a possibility for the N-terminal domain of Dy10, Nt-Dy10, to create oligomers, because homologous cereal inhibitor proteins are known to exist as monomers, homodimers, and heterooligomers. We also discuss, in relation to the function of the cereal inhibitor proteins, the possibility that this N-terminal domain has retained similar inhibitory functions. PMID:12493826

Cazalis, Roland; Aussenac, Thierry; Rhazi, Larbi; Marin, Antoine; Gibrat, Jean-François

2003-01-01

312

Plasma leptin, ghrelin and adiponectin concentrations in young fit racehorses versus mature unfit standardbreds.  

PubMed

Concentrations of hormones related to energy homeostasis may differ between populations with varied body compositions, acting as signals to increase or decrease energy intake and/or expenditure. How these parameters correlate with body composition in horses and how they vary in fit (F) versus unfit (UF) Standardbred racehorses is unclear. The purpose of this study was to test the hypothesis that plasma concentrations of glucose (GLU), insulin (INS), cortisol (CORT), ghrelin (GHRL), adiponectin (ADIP) and leptin (LEP) would be correlated with body composition and differ in fit (F) versus unfit (UF) horses. Fasting plasma samples were taken from 12 unfit (11 +/- 2 years, 521 +/- 77 kg; mean +/- SD) and 34 fit (4 +/- 2 years, 475 +/- 83 kg) Standardbred horses. GHRL, LEP, ADIP, INS and CORT concentrations were measured using radioimmunoassay. GLU concentration was measured using colorometric kits. Body composition data included body weight, body condition score (BCS), and percent fat (%fat) calculated using rump fat thickness measured ultrasonically and the Westervelt equation. Data were analyzed using Pearson Product moment and Student's t tests. There were no differences (P>0.05) between F and UF horses for the plasma concentrations of CORT (69 +/- 14 versus 76 +/- 23 microg/dL), INS (7.2 +/- 3.5 versus 7.1 +/- 1.8 microIU/mL) or GLU (90 +/- 6 versus 86 +/- 7 mg/dL). Plasma GHRL and ADIP concentrations were greater (P<0.05) in F versus UF horses (54 +/- 27 versus 33 +/- 17 pg/mL and 1820 +/- 276 versus 1333 +/- 249 ng/mL, respectively), while plasma LEP was lower in F versus UF (1.0 +/- 0.6 versus 4.4 +/- 2.4 ng/mL, P<0.001). BCS and %fat were lower in F versus UF horses (4.8 +/- 0.3 versus 6.7 +/- 0.5 and 11.9 +/- 1.6 versus 15.4 +/- 2.5%, respectively), with no correlation between %fat and GHRL (-0.12, P>0.05), although there was a positive correlation between %fat and LEP (+0.72, P<0.05), and a negative correlation between %fat and ADIP (-0.40, P<0.05). The data show that in comparing fit and unfit horses, there are variations in body composition as well as concurrent and substantial differences in the concentrations of hormones, cytokines, and other parameters related to the control of appetite and feed intake. PMID:16377220

Gordon, Mary E; McKeever, Kenneth H; Betros, Cynthia L; Manso Filho, Helio C

2007-01-01

313

Effects of miglitol in platelet-derived microparticle, adiponectin, and selectin level in patients with type 2 diabetes mellitus  

PubMed Central

Background: Platelet-derived microparticles (PDMP), selectins, and adiponectin play an important role in the development of atherosclerosis in diabetes. Miglitol has been shown to have a beneficial effect on postprandial hyperglycemia in diabetic patients. However, its influence on platelet activation markers (PDMP and soluble CD40 ligand [sCD40L]), selectins, and adiponectin in these patients is poorly understood. Aim: We investigated the effect of miglitol on circulating levels of PDMP, sCD40L, selectins, and adiponectin in patients with type 2 diabetes. Methods: Miglitol (150 mg/day) was administered for 4 months. Levels of PDMP, sCD40L, soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), soluble L-selectin (sL-selectin), and adiponectin were measured by enzyme-linked immunosorbent assay at baseline, and after 1 and 4 months of treatment. Results: The levels of PDMP, sCD40L, sP-selectin, sE-selectin, and sL-selectin were higher in diabetic patients than in hypertensive patients, while there were no significant differences between hypertensive and hyperlipidemic patients. Before miglitol treatment, the adiponectin level of diabetic patients was lower than that of hypertensive patients. Miglitol therapy significantly decreased the plasma PDMP and sCD40L levels relative to baseline. Miglitol also caused a significant decrease of sP-selectin, sE-selectin, and sL-selectin. On the other hand, miglitol therapy led to a significant increase in adiponectin after 4 months of administration compared with baseline. Furthermore, the reduction of platelet activation markers and selectins during miglitol therapy was significantly greater in the responder (adiponectin-improved) group than the nonresponder group of diabetic patients. Conclusion: Miglitol has an adiponectin-dependent anti-atherothrombotic effect that may be beneficial for primary prevention of atherothrombosis in patients with type 2 diabetes. PMID:21845063

Nomura, Shosaku; Omoto, Seitaro; Yokoi, Takashi; Fujita, Shinya; Ozasa, Ryotaro; Eguchi, Noritaka; Shouzu, Akira

2011-01-01

314

Association of adiponectin with adverse outcome in coronary artery disease patients: results from the AtheroGene study  

Microsoft Academic Search

In 1890 consecutive patients with documented CAD (1130 with stable angina (SAP) and 760 with acute coronary syndrome (ACS)) baseline concentrations of adiponectin were measured by enzyme-linked immuno assay. During a median follow-up of 2.5 years cardiovascular events were registered (cardiovascular deaths 70; non-fatal myocardial infarction 46). Baseline adiponectin concentrations were similar in patients presenting with SAP (9.03 mg\\/mL (6.7,

Renate Schnabel; Claudia M. Messow; Edith Lubos; Christine Espinola-Klein; Hans J. Rupprecht; Christoph Bickel; Christoph Sinning; Stergios Tzikas; Till Keller; Sabine Genth-Zotz; Karl J. Lackner; Thomas F. Munzel; Stefan Blankenberg

2008-01-01

315

Adiponectin stimulates autophagy and reduces oxidative stress to enhance insulin sensitivity during high-fat diet feeding in mice.  

PubMed

Numerous studies have characterized the antidiabetic effects of adiponectin, yet the precise cellular mechanisms in skeletal muscle, in particular, changes in autophagy, require further clarification. In the current study, we used a high-fat diet (HFD) to induce obesity and insulin resistance in wild-type (WT) or adiponectin knockout (Ad-KO) mice with and without adiponectin replenishment. Temporal analysis of glucose tolerance and insulin sensitivity using hyperinsulinemic-euglycemic clamp and muscle insulin receptor substrate and Akt phosphorylation demonstrated exaggerated and more rapid HFD-induced insulin resistance in skeletal muscle of Ad-KO mice. Superoxide dismutase activity, the reduced glutathione-to-glutathione disulfide ratio, and lipid peroxidation indicated that HFD-induced oxidative stress was corrected by adiponectin. Gene array analysis implicated several antioxidant enzymes, including Gpxs, Prdx, Sod, and Nox4, in mediating this effect. Adiponectin also attenuated palmitate-induced reactive oxygen species production in cultured myotubes and improved insulin-stimulated glucose uptake in primary muscle cells. Increased LC3-II and decreased p62 expression suggested that HFD induced autophagy in muscle of WT mice; however, these changes were not observed in Ad-KO mice. Replenishing adiponectin in Ad-KO mice increased LC3-II and Beclin1 and decreased p62 protein levels, induced fibroblast growth factor-21 expression, and corrected HFD-induced decreases in LC3, Beclin1, and ULK1 gene expression. In vitro studies examining changes in phospho-ULK1 (Ser555), LC3-II, and lysosomal enzyme activity confirmed that adiponectin directly induced autophagic flux in cultured muscle cells in an AMPK-dependent manner. We overexpressed an inactive mutant of Atg5 to create an autophagy-deficient cell model, and together with pharmacological inhibition of autophagy, demonstrated reduced insulin sensitivity under these conditions. In summary, adiponectin stimulated skeletal muscle autophagy and antioxidant potential to reduce insulin resistance caused by HFD. PMID:25071026

Liu, Ying; Palanivel, Rengasamy; Rai, Esther; Park, Min; Gabor, Tim V; Scheid, Michael P; Xu, Aimin; Sweeney, Gary

2015-01-01

316

Association of adiponectin with hepatic steatosis: a study of 1,349 subjects in a random population sample  

PubMed Central

Background Objective of the present study was to examine the association between adiponectin and hepatic steatosis, and other biochemical and anthropometric parameters in healthy subjects. Results A total of 1349 subjects (age 18–65?years) underwent ultrasound examination of the liver. Mean adiponectin concentration for the study collective was 11.35?±?6.28??g/mL. The following parameters were assessed for their association with adiponectin: body-mass index (BMI); age; sex; arterial blood pressure; nicotine use; alcohol consumption; physical activity; metabolic syndrome; total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol; triglycerides; aspartate aminotransferase (AST); alanine aminotransferase (ALT); ?-glutamyltransferase (GGT); alkaline phosphatase (AP); C-reactive protein (CRP); insulin sensitivity according to the Homeostasis Model Assessment (HOMA); random blood glucose; and the degree of steatosis of the liver. The numerical differences in the variables influencing adiponectin returned in the descriptive analysis were confirmed at bivariate analysis for BMI, ALT, AST, GGT, AP, total and HDL cholesterol, triglycerides, CRP, arterial blood pressure, metabolic syndrome, nicotine use and alcohol consumption. The logistic regression of the multivariate analysis showed that male sex, hepatic steatosis, BMI, metabolic syndrome, tobacco smoking and CRP correlate negatively with adiponectin, while age, moderate alcohol consumption and HDL cholesterol exhibit a positive association. Conclusions The results of the present study confirm the findings of previous research. Adiponectin correlates negatively with cardiometabolic risk factors and is an independent indicator for non-alcoholic fatty liver disease (NAFLD). PMID:24693952

2014-01-01

317

ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling  

SciTech Connect

The pleiotropic effects of the insulin-sensitizing adipokine adiponectin are mediated, at least in part, by two seven-transmembrane domain receptors AdipoR1 and AdipoR2. Recent reports indicate a role for AdipoR-binding proteins, namely APPL1, RACK1 and CK2{beta}, in proximal signal transduction events. Here we demonstrate that endoplasmic reticulum protein 46 (ERp46) interacts specifically with AdipoR1 and provide evidence that ERp46 modulates adiponectin signalling. Co-immunoprecipitation followed by mass spectrometry identified ERp46 as an AdipoR1-, but not AdipoR2-, interacting protein. Analysis of truncated constructs and GST-fusion proteins revealed the interaction was mediated by the cytoplasmic, N-terminal residues (1-70) of AdipoR1. Indirect immunofluorescence microscopy and subcellular fractionation studies demonstrated that ERp46 was present in the ER and the plasma membrane (PM). Transient knockdown of ERp46 increased the levels of AdipoR1, and AdipoR2, at the PM and this correlated with increased adiponectin-stimulated phosphorylation of AMPK. In contrast, adiponectin-stimulated phosphorylation of p38MAPK was reduced following ERp46 knockdown. Collectively these results establish ERp46 as the first AdipoR1-specific interacting protein and suggest a role for ERp46 in adiponectin receptor biology and adiponectin signalling.

Charlton, Hayley K.; Webster, Julie; Kruger, Sarah; Simpson, Fiona; Richards, Ayanthi A. [Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102 (Australia)] [Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102 (Australia); Whitehead, Jonathan P., E-mail: j.whitehead1@uq.edu.au [Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102 (Australia)

2010-02-05

318

Association of adiponectin and leptin with relative telomere length in seven independent cohorts including 11,448 participants.  

PubMed

Oxidative stress and inflammation are major contributors to accelerated age-related relative telomere length (RTL) shortening. Both conditions are strongly linked to leptin and adiponectin, the most prominent adipocyte-derived protein hormones. As high leptin levels and low levels of adiponectin have been implicated in inflammation, one expects adiponectin to be positively associated with RTL while leptin should be negatively associated. Within the ENGAGE consortium, we investigated the association of RTL with adiponectin and leptin in seven independent cohorts with a total of 11,448 participants. We performed partial correlation analysis on Z-transformed RTL and LN-transformed leptin/adiponectin, adjusting for age and sex. In extended models we adjusted for body mass index (BMI) and C-reactive protein (CRP). Adiponectin showed a borderline significant association with RTL. This appeared to be determined by a single study and when the outlier study was removed, this association disappeared. The association between RTL and leptin was highly significant (r = -0.05; p = 1.81 × 10(-7)). Additional adjustment for BMI or CRP did not change the results. Sex-stratified analysis revealed no difference between men and women. Our study suggests that high leptin levels are associated with short RTL. PMID:25064619

Broer, Linda; Raschenberger, Julia; Deelen, Joris; Mangino, Massimo; Codd, Veryan; Pietiläinen, Kirsi H; Albrecht, Eva; Amin, Najaf; Beekman, Marian; de Craen, Anton J M; Gieger, Christian; Haun, Margot; Henneman, Peter; Herder, Christian; Hovatta, Iiris; Laser, Annika; Kedenko, Lyudmyla; Koenig, Wolfgang; Kollerits, Barbara; Moilanen, Eeva; Oostra, Ben A; Paulweber, Bernhard; Quaye, Lydia; Rissanen, Aila; Roden, Michael; Surakka, Ida; Valdes, Ana M; Vuolteenaho, Katriina; Thorand, Barbara; van Dijk, Ko Willems; Kaprio, Jaakko; Spector, Tim D; Slagboom, P Eline; Samani, Nilesh J; Kronenberg, Florian; van Duijn, Cornelia M; Ladwig, Karl-Heinz

2014-09-01

319

Weight set  

NSDL National Science Digital Library

Your skin covers and protects your body. Your skin can also detect pressure and weight. You can tell that a one gram weight feels lighter than a one kilogram weight because the receptors on your skin detect more pressure from a one kilogram weight compared to a one gram weight.

N/A N/A (None; )

2005-12-11

320

Elucidation of differences in N-glycosylation between different molecular weight forms of recombinant CLEC-2 by LC MALDI tandem MS.  

PubMed

C-type lectin-like receptor 2 (CLEC-2) is a newly identified receptor expressed on the platelet surface. It has been reported that CLEC-2 exists as a higher molecular weight (HMW) and a lower molecular weight (LMW) form, which share the same protein core but differ in glycans. The two forms appear to have different ligand-binding abilities, indicating that the differential glycosylation of CLEC-2 possibly produces functionally distinct glycoforms. This study aimed to explore an easy method to directly elucidate the N-glycosylation difference by employing a glycoproteomics approach. The off-line coupling of nano-LC with a MALDI-QIT-TOF mass spectrometer was demonstrated to be capable of sensitive and direct elucidation of the glycosylation difference between HMW and LMW CLEC-2, simultaneously providing information about their oligosaccharide structures and the glycosylation sites. The results reveal that a specific glycosylation site, Asn 134, is differently glycosylated in the two forms, with complex types of bi-antennary, tri-antennary and tetra-antennary, N-linked, fucosylated glycans identified at this site in the HMW form but not in the LMW form. The observed difference in glycosylation might provide new insights into the underlying mechanisms of biological functions of CLEC-2. Because of its simplicity and sensitivity, the method explored in this work suggests that it holds promise as a method of elucidating differences in direct N-glycosylation of target glycoprotein, even in small amount of samples. PMID:25498018

Zhou, Lei; Qian, Yifan; Zhang, Xingwang; Ruan, Yuanyuan; Ren, Shifang; Gu, Jianxin

2015-01-30

321

In vivo, Argonaute-bound microRNAs exist predominantly in a reservoir of low molecular weight complexes not associated with mRNA.  

PubMed

MicroRNAs repress mRNA translation by guiding Argonaute proteins to partially complementary binding sites, primarily within the 3' untranslated region (UTR) of target mRNAs. In cell lines, Argonaute-bound microRNAs exist mainly in high molecular weight RNA-induced silencing complexes (HMW-RISC) associated with target mRNA. Here we demonstrate that most adult tissues contain reservoirs of microRNAs in low molecular weight RISC (LMW-RISC) not bound to mRNA, suggesting that these microRNAs are not actively engaged in target repression. Consistent with this observation, the majority of individual microRNAs in primary T cells were enriched in LMW-RISC. During T-cell activation, signal transduction through the phosphoinositide-3 kinase-RAC-alpha serine/threonine-protein kinase-mechanistic target of rapamycin pathway increased the assembly of microRNAs into HMW-RISC, enhanced expression of the glycine-tryptophan protein of 182 kDa, an essential component of HMW-RISC, and improved the ability of microRNAs to repress partially complementary reporters, even when expression of targeting microRNAs did not increase. Overall, data presented here demonstrate that microRNA-mediated target repression in nontransformed cells depends not only on abundance of specific microRNAs, but also on regulation of RISC assembly by intracellular signaling. PMID:25568082

La Rocca, Gaspare; Olejniczak, Scott H; González, Alvaro J; Briskin, Daniel; Vidigal, Joana A; Spraggon, Lee; DeMatteo, Raymond G; Radler, Megan R; Lindsten, Tullia; Ventura, Andrea; Tuschl, Thomas; Leslie, Christina S; Thompson, Craig B

2015-01-20

322

Heme Oxygenase (HO-1) Rescue of Adipocyte Dysfunction in HO-2 Deficient Mice via Recruitment of Epoxyeicosatrienoic Acids (EETs) and Adiponectin  

PubMed Central

Background/Aims HO-1 and EETs are functionally linked and their interactions influence body weight, insulin sensitivity, and serum levels of inflammatory cytokines in metabolic syndrome phenotype of HO-2 null mice. The HO-2 isozyme is essential for regulating physiological levels of ROS. Recent studies have suggested a potential role of EET in modifying adipocyte differentiation through up-regulation of HO-1-adiponectin-AkT signaling in human mesenchymal stem cells (MSCs). Our aim was to examine the consequences of HO deficiency on MSC-derived adipogenesis in vitro using MSC derived from HO-2 null and WT mice in vivo. Methods Four-month-old HO-2 null (HO-2?/?) and B6/129SF2/J (WT) mice were divided into three groups (four mice/group): WT, HO-2?/?, and HO-2?/? +CoPP. Adipogenesis was performed on purified MSC-derived adipocytes cultured in adipogenic differentiation media and an EET-agonist was added every 3 days. Results HO-2 depletion of MSC adipocytes resulted in increased adipogenesis (p<0.01) and increased levels of inflammatory cytokines including (TNF)-alpha (p<0.05), (MCP)-1 (p<0.05), and (IL-1)-beta (p<0.05). These results were accompanied by decreases in HO-1 (p<0.05) and subsequently EET and HO activity (p<0.05). Up-regulation of HO-1 resulted in decreased MSC-derived adipocyte differentiation, decreased production of TNF-alpha and MCP-1 and increased levels of adiponectin (p<0.05). Cyp2J5 (p<0.05), HO-1 (p<0.05), and adiponectin mRNA levels (p<0.05) were also decreased in visceral adipose tissue isolated from HO-2 null compared to WT mice. EET agonist stimulation of MSC adipocytes derived from HO-2 null mice yielded similar results. Conclusion Increased levels of EET and HO-1 are essential for protection against the adverse effects of adipocyte hypertrophy and the ensuing metabolic syndrome. These results offer a portal into therapeutic approaches for the prevention of the metabolic syndrome. PMID:22415079

Burgess, Angela P.H.; Vanella, Luca; Bellner, Lars; Gotlinger, Katherine; Falck, John R.; Abraham, Nader G.; Schwartzman, Michal L.; Kappas, Attallah

2012-01-01

323

Tumor-Specific Urinary MMP Fingerprinting: Identification of High Molecular Weight Urinary MMP Species  

PubMed Central

Purpose We have previously reported that MMP-2, MMP-9 and the complex MMP-9/NGAL can be detected in urine of patients with a variety of cancers including prostate and bladder carcinoma. In addition, we also detected several unidentified urinary gelatinase activities with molecular weights >125kDa. The objective of the current study was to identify these high molecular weight (HMW) species, determine their potential as predictors of disease status and ask whether a tumor-specific pattern existed based on urinary MMP (uMMP) analysis. Experimental Design Chromatography, zymography and mass spectrometry was used to identify HMW gelatinase species of ?140, 190 and >220kDa in urine of cancer patients. To determine whether a tumor-specific pattern of appearance existed among the MMPs detected, we analyzed the urine of 189 patients with prostate or bladder cancer and controls. Results The ?140, >220kDa and ?190 HMW gelatinase species were identified as MMP-9/TIMP-1 complex, MMP-9 dimer and ADAMTS-7 respectively. The frequency of detection of any MMP species was significantly higher in urine from prostate and bladder cancer groups than controls. MMP-9 dimer and MMP-9 were independent predictors for distinguishing between patients with prostate or bladder cancer (P<0.001 for each) by multivariable analysis. Conclusions This study is the first to identify a tumor-specific uMMP fingerprint that may noninvasively facilitate identification of cancer presence and type. This information may be of diagnostic and prognostic value in the detection and/or clinical monitoring of disease progression and therapeutic efficacy in patients with bladder or prostate cancer. PMID:18927302

Roy, Roopali; Louis, Gwendolyn; Loughlin, Kevin R.; Wiederschain, Dmitri; Kilroy, Susan M.; Lamb, Carolyn C.; Zurakowski, David; Moses, Marsha A.

2009-01-01

324

Six new chalcones from Angelica keiskei inducing adiponectin production in 3T3-L1 adipocytes.  

PubMed

Angelica keiskei (Ashitaba in Japanese), a traditional herb in Japan, contains abundant prenylated chalcones. It has been reported that the chalcones from A. keiskei showed such bioactivities as anti-bacterial, anti-cancer and anti-diabetic effects. Xanthoangelol, 4-hydroxyderricin and six new chalcones were isolated in this study from an ethanol extract of A. keiskei by octadecyl silyl (ODS) and silica gel chromatography, and identified by 1D- and 2D-nuclear magnetic resonance (NMR) and high-resolution mass spectrometric analyses. The chalcones from A. keiskei markedly increased the expression of the adiponectin gene and the production of adiponectin in 3T3-L1 adipocytes. These results suggest that the chalcones from A. keiskei might be useful for preventing the metabolic syndrome. PMID:22738967

Ohnogi, Hiromu; Kudo, Yoko; Tahara, Kenichi; Sugiyama, Katsumi; Enoki, Tatsuji; Hayami, Shoko; Sagawa, Hiroaki; Tanimura, Yuko; Aoi, Wataru; Naito, Yuji; Kato, Ikunoshin; Yoshikawa, Toshikazu

2012-01-01

325

Low adiponectin concentration during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia  

Microsoft Academic Search

Aims\\/hypothesis  The postpartum phase following gestational diabetes (GDM) is characterised by subtle metabolic defects, including the beta\\u000a cell dysfunction that is believed to mediate the increased future risk of type 2 diabetes in this patient population. Low\\u000a circulating levels of adiponectin and increased leptin and C-reactive protein (CRP) have recently emerged as novel diabetic\\u000a risk factors, although their relevance to GDM

R. Retnakaran; Y. Qi; P. W. Connelly; M. Sermer; A. J. Hanley; B. Zinman

2010-01-01

326

Association between Plasma Adiponectin Concentration and Visceral Fat Accumulation in Hemodialysis Patients  

Microsoft Academic Search

Background: Cardiovascular diseases resulting from atherosclerotic complications are major causes of death in hemodialysis (HD) patients. Adiponectin (ADPN) is a recently discovered adipocyte-derived protein that appears to have protective role against atherosclerosis. HD patients have an excess accumulation of intra-abdominal fat mass in association with an atherogenic serum lipid profile despite low body mass index; however, the role of intra-abdominal

Mari Odamaki; Ryuichi Furuya; Yumie Kinumura; Naoki Ikegaya; Hiromichi Kumagai

2006-01-01

327

Ghrelin, leptin, adiponectin, and resistin levels in sleep apnea syndrome: Role of obesity  

PubMed Central

AIM: The aim of this study was to investigate the relationship among plasma leptin, ghrelin, adiponectin, resistin levels, and obstructive sleep apnea syndrome (OSAS). METHODS: Fifty-five consecutive newly diagnosed OSAS patients and 15 age-matched nonapneic controls were enrolled in this study. After sleep study between 8:00 AM and 9:00 AM on the morning, venous blood was obtained in the fasting state to measure ghrelin and adipokines. RESULTS: Serum ghrelin levels of OSAS group were significantly (P < 0.05) higher than those of the control group. No significant difference was noted in the levels of leptin, adiponectin, and resistin in OSAS group when compared to controls. There was a significant positive correlation between ghrelin and apnea–hypopnea index (AHI) (r = 0.237, P < 0.05) or the Epworth sleepiness scale (ESS) (r = 0.28, P < 0.05). There was also a significant positive correlation between leptin and body mass index (r = 0.592, P < 0.0001). No significant correlation was observed between leptin, adiponectin, resistin, and any polysomnographic parameters. CONCLUSION: Our findings demonstrated that serum ghrelin levels were higher in OSAS patients than those of control group and correlated with AHI and ESS. Further studies are needed to clarify the complex relation among OSAS, obesity, adipokines, and ghrelin. PMID:20835311

Ursavas, Ahmet; Ilcol, Yesim Ozarda; Nalci, Nazan; Karadag, Mehmet; Ege, Ercument

2010-01-01

328

Serum Leptin, Adiponectin and Tumor Necrosis Factor-? in Hyperlipidemic Rats with/without Concomitant Diabetes Mellitus  

PubMed Central

We compared the lipid profiles and serum levels of leptin, adiponectin and tumor necrosis factor-? (TNF-?) in rats with/without hyperlipidemia and with/without concomitant diabetes mellitus. Forty 10-wk-old male Wistar rats were divided into four groups. Groups A and C received standard food for 12 wks. Groups B and D received a high-fat diet enriched with 2% additional cholesterol. Moreover, insulin-deficient (type I) diabetes mellitus was induced in rats in groups C and D with intraperitoneal injections of streptozotocin. Fasting serum leptin levels were decreased in diabetic groups (groups C and D) compared with controls. Fasting serum adiponectin levels were decreased in groups C and D compared with group A. Serum TNF-? levels were augmented in groups B and D, those fed with an atherogenic diet. By contrast, TNF-? levels were decreased in group C. Our data suggest that serum leptin, adiponectin and TNF-? levels may serve as markers of obesity and type I diabetes mellitus. PMID:20838752

Margoni, Angeliki; Perrea, Despoina N; Vlachos, Ioannis; Prokopaki, Georgia; Pantopoulou, Alkistis; Fotis, Lambros; Kostaki, Maria; Papavassiliou, Athanasios G

2011-01-01

329

Omentin-1, visfatin and adiponectin levels in relation to bone mineral density in Iranian postmenopausal women.  

PubMed

The bone and fat interface is implicated in the pathogenesis of postmenopausal osteoporosis. The association between circulating omentin-1 levels and bone mineral density (BMD) in postmenopausal women has never been assessed. A total of 382 healthy postmenopausal women were randomly selected. Omentin-1, visfatin, adiponectin, the receptor activator of nuclear factor-?B ligand (RANKL), osteoprotegerin, high sensitivity C-reactive protein, degradation products of C-terminal telopeptides of type I collagen, and osteocalcin were measured by highly specific enzyme-linked immunosorbent assay methods. BMD was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy X-ray absorptiometry. In multivariable-adjusted linear regression, serum omentin-1 levels were inversely correlated with BMD at the lumbar spine (?=-0.11, p=0.020). In multiple regression analyses, serum visfatin and adiponectin levels were not significantly correlated with BMD at different skeletal sites after controlling for age, body mass index, and bone-related markers. However, the highest quartile of adiponectin compared to the lowest quartile, after adjusting for potential confounders, revealed an inverse association with BMD in the lumbar spine (?=-0.19, p=0.010). In conclusion, circulating omentin-1 levels had an inverse correlation with BMD at the lumbar spine in Iranian postmenopausal women. To further understand the role of omentin-1 in bone and mineral metabolism, large-scale longitudinal studies focusing on BMD and osteoporotic fractures are warranted. PMID:22971441

Tohidi, Maasumeh; Akbarzadeh, Samad; Larijani, Bagher; Kalantarhormozi, Mohammadreza; Ostovar, Afshin; Assadi, Majid; Vahdat, Katayoun; Farrokhnia, Maryam; Sanjdideh, Zahra; Amirinejad, Roya; Nabipour, Iraj

2012-11-01

330

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin  

PubMed Central

Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood–brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

Yau, Suk Yu; Li, Ang; Hoo, Ruby L. C.; Ching, Yick Pang; Christie, Brian R.; Lee, Tatia M. C.; Xu, Aimin; So, Kwok-Fai

2014-01-01

331

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin.  

PubMed

Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood-brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

Yau, Suk Yu; Li, Ang; Hoo, Ruby L C; Ching, Yick Pang; Christie, Brian R; Lee, Tatia M C; Xu, Aimin; So, Kwok-Fai

2014-11-01

332

Effects of short-term lifestyle activity modification on adiponectin mRNA expression and plasma concentrations.  

PubMed

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 plasma concentrations. Sixteen obese and overweight middle-aged men (age, 35-50 years) with type 2 diabetes participated in this study. The subjects were randomly assigned to LAM group (n=8) or control group (n=8). The subjects in LAM group walked two miles in 30 min on a treadmill on 4 days per week for 12 weeks according to the guidelines of the Centers for Disease Control and Prevention and American College of Sports Medicine. The results showed that body mass, body mass index, central visceral adipose tissue and subcutaneous adipose tissue volume and hip and thigh subcutaneous adipose tissue (hip and thigh SAT) volume were decreased in the LAM group compared to the control group (P<0.05). Adiponectin mRNA in abdominal and gluteal subcutaneous AT were increased significantly in the LAM group compared to the control group (P<0.05), while plasma adiponectin concentrations, hs-CRP and insulin resistance did not change significantly. In conclusion, adiponectin mRNA levels increase after 12 weeks of LAM; however, plasma adiponectin levels were not affected by this protocol in obese and overweight middle-aged men with type 2 diabetes. PMID:23834543

Moghadasi, Mehrzad; Mohebbi, Hamid; Rahmani-Nia, Farhad; Hassan-Nia, Sadegh; Noroozi, Hamid

2013-01-01

333

Effect of dietary lipids on circulating adiponectin: a systematic review with meta-analysis of randomised controlled trials.  

PubMed

Different dietary interventions have been identified as potential modifiers of adiponectin concentrations, and they may be influenced by lipid intake. We identified studies investigating the effect of dietary lipids (type/amount) on adiponectin concentrations in a systematic review with meta-analysis. A literature search was conducted until July 2013 using databases such as Medline, Embase and Scopus (MeSH terms: 'adiponectin', 'dietary lipid', 'randomized controlled trials (RCT)'). Inclusion criteria were RCT in adults analysing adiponectin concentrations with modification of dietary lipids. Among the 4930 studies retrieved, fifty-three fulfilled the inclusion criteria and were grouped as follows: (1) total dietary lipid intake; (2) dietary/supplementary n-3 PUFA; (3) conjugated linoleic acid (CLA) supplementation; (4) other dietary lipid interventions. Diets with a low fat content in comparison to diets with a high-fat content were not associated with positive changes in adiponectin concentrations (twelve studies; pooled estimate of the difference in means: -0·04 (95% CI -0·82, 0·74) ?g/ml). A modest increase in adiponectin concentrations with n-3 PUFA supplementation was observed (thirteen studies; 0·27 (95% CI 0·07, 0·47) ?g/ml). Publication bias was found by using Egger's test (P= 0·01) and funnel plot asymmetry. In contrast, CLA supplementation reduced the circulating concentrations of adiponectin compared with unsaturated fat supplementation (seven studies; -0·74 (95% CI -1·38, -0·10) ?g/ml). However, important sources of heterogeneity were found as revealed by the meta-regression analyses of both n-3 PUFA and CLA supplementation. Results of new RCT would be necessary to confirm these findings. PMID:25192422

von Frankenberg, Anize D; Silva, Flávia M; de Almeida, Jussara C; Piccoli, Vanessa; do Nascimento, Filipe V; Sost, Mônica M; Leitão, Cristiane B; Remonti, Luciana L R; Umpierre, Daniel; Reis, André F; Canani, Luis H; de Azevedo, Mirela J; Gerchman, Fernando

2014-10-28

334

Constitutively-active TRPC channels of adipocytes confer a mechanism for sensing dietary fatty acids and regulating adiponectin  

PubMed Central

Rationale Calcium entry is pivotal in the heart and blood vessels but its significance and mechanisms in adipose tissue are largely unknown. An important factor produced by adipocytes is adiponectin, which confers myocardial protection, insulin-sensitisation, and anti-atherosclerotic effects. Objective To investigate the relevance of calcium channels to adipocytes and the production of adiponectin. Methods and Results Micro-array analysis led to identification of TRPC1 and TRPC5 as channel subunits that are induced when adipocytes mature. Both subunits were found in perivascular fat of patients with atherosclerosis. Intracellular calcium and patch-clamp measurements showed that adipocytes exhibit constitutively-active calcium-permeable non-selective cationic channels that depend on TRPC1 and TRPC5. The activity could be enhanced by lanthanum or rosiglitazone, known stimulators of TRPC5 and TRPC5-containing channels. Screening identified lipid modulators of the channels that are relevant to adipose biology. Dietary ?-3 fatty acids (e.g. ?-linolenic acid) were inhibitory at concentrations that are achieved by ingestion. The adipocyte TRPC1/TRPC5-containing channel was functionally negative for the generation of adiponectin because channel blockade by antibodies, knock-down of TRPC1-TRPC5 in vitro, or conditional disruption of calcium permeability in TRPC5-incorporating channels in vivo increased the generation of adiponectin. The previously recognised capability of ?-linolenic acid to stimulate the generation of adiponectin was lost when calcium permeability in the channels was disrupted. Conclusions The data suggest that TRPC1 and TRPC5 contribute a constitutively-active heteromultimeric channel of adipocytes that negatively regulates adiponectin and through which ?-3 fatty acids enhance the anti-inflammatory adipokine, adiponectin. PMID:22668831

Sukumar, Piruthivi; Sedo, Alicia; Li, Jing; Wilson, Lesley A; O’Regan, David; Lippiat, Jonathan D; Porter, Karen E; Kearney, Mark T; Ainscough, Justin FX; Beech, David J

2012-01-01

335

Stellar Rotation and Variability in IC 348 and Indication of a 4.75 Year Period for the Unique, Apparently Eclipsing Pre-Main Sequence Star HMW 15  

NASA Astrophysics Data System (ADS)

During the past two years of a seven-year photometric variability study of the young stellar cluster IC 348, numerous periodically variable T Tauri stars were discovered, bringing the total number of identified periodic variables in IC 348 to 69, or about 45 % of all cluster stars observed by us. This includes data from Herbst, Maley & Williams (2000, AJ 120, 394), Cohen, Herbst & Williams (2004, AJ 127, 1602) and Littlefair et al. (2005 MNRAS 358, 341). In addition to these photometric data, spectra of 30 cluster members were obtained with the WIYN 3.5m telescope and used to calculate radial velocities and v sin i rotation measurements, offering a generally complementary view of stellar rotation in IC 348. A mean heliocentric radial velocity for the cluster has been determined, and two radial velocity outliers discovered, which are possible spectroscopic binaries. The distribution of rotation periods, their relationship to v sin i measurements and the implications of these results for the rotation and radii of pre-main sequence stars in IC 348 will be presented. In addition, we discuss the recent behavior of the peculiar variable HMW 15 (Cohen, Herbst & Williams 2003 ApJ 596, L243), which now appears to be undergoing a periodic eclipse on a time scale of 4.75 years. We discuss possible origins for this extraordinarily long periodicity. S. Nordhagen was an undergraduate summer student at Wesleyan University, sponsored by the Keck Northeast Astronomy Consortium. Their REU program is supported by NSF grant AST-0353997.

Nordhagen, S. C. J.; Rhode, K. L.; Herbst, W.; Williams, E. C.

2005-12-01

336

Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects  

PubMed Central

Objective High fat, low carbohydrate (HFLC) diets have become popular tools for weight management. We sought to determine the effects of a HFLC diet compared to a low fat high carbohydrate (LFHC) diet on the change in weight loss, cardiovascular risk factors and inflammation in subjects with obesity. Methods Obese subjects (29.0–44.6 kg/m2) recruited from Boston Medical Center were randomized to a hypocaloric LFHC (n=26) or HFLC (n=29) diet for 12 weeks. Results The age range of subjects was 21–62 years. As a percentage of daily calories, the HFLC group consumed 33.5% protein, 56.0% fat and 9.6% carbohydrate and the LFHC group consumed 22.0% protein, 25.0% fat and 55.7% carbohydrate. The change in percent body weight, lean and fat mass, blood pressure, flow mediated dilation, hip:waist ratio, hemoglobin A1C, fasting insulin and glucose, and glucose and insulin response to a 2 h oral glucose tolerance test did not differ (P>0.05) between diets after 12 weeks. The HFLC group had greater mean decreases in serum triglyceride (P=0.07), and hs-CRP (P=0.03), and greater mean increases in HDL cholesterol (P=0.004), and total adiponectin (P=0.045) relative to the LFHC. Secreted adipose tissue adiponectin or TNF-? did not differ after weight loss for either diet. Conclusions Relative to the LFHC group, the HFLC group had greater improvements in blood lipids and systemic inflammation with similar changes in body weight and composition. This small-scale study suggests that HFLC diets may be more beneficial to cardiovascular health and inflammation in free-living obese adults compared to LFHC diets. PMID:24075505

Ruth, Megan R.; Port, Ava M.; Shah, Mitali; Bourland, Ashley C.; Istfan, Nawfal W.; Nelson, Kerrie P.; Gokce, Noyan; Apovian, Caroline M.

2013-01-01

337

Fish oil N-3 Fatty acids increase adiponectin and decrease leptin levels in patients with systemic lupus erythematosus.  

PubMed

Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ? 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ? 0.026) and decreased leptin levels (p ? 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE. PMID:25690094

Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Morimoto, Helena Kaminami; Scavuzzi, Bruna Miglioranza; Iriyoda, Tathiana Veiga Mayumi; Reiche, Edna Maria Vissoci; Cecchini, Rubens; Dichi, Isaias

2015-01-01

338

The impact of metformin treatment on adiponectin and resistin levels in women with polycystic ovary syndrome: a prospective clinical study.  

PubMed

Abstract Women with polycystic ovary syndrome (PCOS) are often characterized by adiposity and insulin resistance (IR). Recent studies in patients with obesity and diabetes mellitus type 2 (DMt2) indicate that adiponectin and resistin may play a role in the pathophysiology of IR. The aim of this study was to identify a possible correlation between the plasma levels of adiponectin and resistin and IR in patients with PCOS. Thirty-one women of reproductive age were enrolled in this prospective study after being diagnosed with PCOS and IR according to Rotterdam and American Diabetes Association (ADA) criteria, respectively. Every patient was treated with a daily dose of 1275?mg metformin for 6 months. Adiponectin, resistin, and the primary hormonal and metabolic parameters of the syndrome were evaluated at entry and endpoint of treatment. Adiponectin plasma levels were reduced after metformin treatment, but resistin levels were not significantly affected. Our study suggests that circulating levels of adiponectin should be evaluated with skepticism in patients with PCOS. The adipokine's role in the manifestation of IR in PCOS remains unclear and needs further investigation. PMID:25377599

Basios, G; Trakakis, E; Chrelias, Ch; Panagopoulos, P; Vaggopoulos, V; Skarpas, P; Kassanos, D; Dimitriadis, G; Hatziagelaki, E

2015-02-01

339

Adiponectin Enhances IL6 Production in Human Synovial Fibroblast via an AdipoR1 Receptor, AMPK, p38, and NF-B Pathway1  

Microsoft Academic Search

Articular adipose tissue is a ubiquitous component of human joints, and adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and involved in energy homeostasis. We investigated the signaling pathway involved in IL-6 produc- tion caused by adiponectin in both rheumatoid arthritis synovial fibroblasts and osteoarthritis synovial fibroblasts. Rheumatoid arthritis synovial fibroblasts and osteoarthritis synovial fibroblasts expressed the AdipoR1

Chih-Hsin Tang; Yung-Cheng Chiu; Tzu-Wei Tan; Rong-Sen Yang; Wen-Mei Fu

2007-01-01

340

Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: Results of genome-wide association analyses including 4659 European individuals  

Microsoft Academic Search

ObjectivePlasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women.

Iris M. Heid; Peter Henneman; Andrew Hicks; Stefan Coassin; Thomas Winkler; Yurii S. Aulchenko; Christian Fuchsberger; Kijoung Song; Marie-France Hivert; Dawn M. Waterworth; Nicholas J. Timpson; J. Brent Richards; John R. B. Perry; Toshiko Tanaka; Najaf Amin; Barbara Kollerits; Irene Pichler; Ben A. Oostra; Barbara Thorand; Rune R. Frants; Thomas Illig; Josée Dupuis; Beate Glaser; Tim Spector; Jack Guralnik; Josephine M. Egan; Jose C. Florez; David M. Evans; Nicole Soranzo; Stefania Bandinelli; Olga D. Carlson; Timothy M. Frayling; Keith Burling; George Davey Smith; Vincent Mooser; Luigi Ferrucci; James B. Meigs; Peter Vollenweider; Ko Willems van Dijk; Peter Pramstaller; Florian Kronenberg; Cornelia M. van Duijn

2010-01-01

341

Serum Adiponectin is Related to Plasma HDL-Cholesterol but not to Plasma Insulin-Concentration in Healthy Children. The FLVS II Study.  

E-print Network

1 Serum Adiponectin is Related to Plasma HDL-Cholesterol but not to Plasma Insulin- Concentration circumference (WC, and percent body fat (bioimpedance)), blood pressure, plasma glucose, triglycerides, HDL-cholesterol.04) but not with other adiposity variables. After taking into account WC, adiponectin was positively correlated with HDL-cholesterol

342

Characterization of a new wheat-Aegilops biuncialis addition line conferring quality-associated HMW glutenin subunits.  

PubMed

In this study, a new disomic addition line, 12-5-2, with 44 chromosomes that was derived from BC3F2 descendants of the hybridization between Triticum aestivum cv. CN19 and Aegilops biuncialis was created and reported. 12-5-2 was immune to both powdery mildew and stripe rust and has stable fertility. Fluorescence in situ hybridization and C-banding revealed that 12-5-2 was a 1U(b) disomic addition line (ADL1U(b)). The seed storage protein electrophoresis showed that 12-5-2 presented all high molecular weight glutenin subunits (7 + 8 and 2 + 12) of CN19 and 2 new subunits that were designated Ux and Uy. Additionally, the flour quality parameters showed that the protein content, Zeleny sedimentation value, wet gluten content, and grain hardness of 12-5-2 were significantly higher than those of its parent CN19. Moreover, 5 pairs of the chromosome 1U(b)-specific polymerase chain reaction-based landmark unique gene markers, TNAC1021, TNAC1041, TNAC1071, TNAC1-01, and TNAC1-04, were also obtained. The new ADL1U(b) 12-5-2 could be a valuable source for wheat improvement, especially for wheat end-product quality and resistance to disease. PMID:24615031

Zhou, J P; Yao, C H; Yang, E N; Yin, M Q; Liu, C; Ren, Z L

2014-01-01

343

Relation between augmentation index and adiponectin during one-year metformin treatment for nonalcoholic steatohepatosis: effects beyond glucose lowering?  

PubMed Central

Background Insulin resistance (IR) is the major driving force behind development and progression of atherosclerosis in patients with nonalcoholic fatty liver disease (NAFLD). Therefore, correction of IR is a relevant therapeutic target. We performed the current trial to evaluate whether 12- month metformin therapy improves vascular stiffness in patients with NAFLD and to assess if this improvement is associated with change in glucose control, insulin resistance or circulating adiponectin. Methods In randomized, placebo controlled study, 63 patients with NAFLD were assigned to one of two groups: Group 1 received daily metformin; Group 2 received placebo. Central aortic augmentation index (AI) was performed using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia) at baseline, at 4-and 12-month treatment period. Metabolic parameters, insulin resistance markers and serum adiponectin levels were determined. Results In placebo group: AI did not improve during the treatment period. Liver function and adiponectin levels did not change during the study. In multiple linear regression analysis, the independent predictors of arterial stiffness improvement were metformin treatment and increase in circulating adiponectin levels. Among metformin treated patients: AI decreased significantly during the study. ALP and ALT decreased during initial 4-month treatment period, however raised to the pretreatment levels after 12?months. Serum adiponectin level tended to increase during treatment period with metformin. Conclusions Metformin treatment was associated with significant decrease in AI during one year treatment in NAFLD patients. These beneficial vascular effects was associated with exposure to metformin per se as well as change in adiponectin levels suggesting that metformin may mediate its vascular effects via glicemic control-independent mechanisms. Trial registry no: NCT01084486 PMID:22676459

2012-01-01

344

Correlation study on adiponectin gene SNP45 and long-term oxidative stress in patients with diabetes and carotid atherosclerosis  

PubMed Central

The aim of the present study was to investigate the correlation between the adiponectin gene single nucleotide polymorphism (SNP)45 T/G and long-term oxidative stress in type II diabetes mellitus (T2DM) patients with carotid atherosclerosis. Patients with T2DM were divided into non-carotid atherosclerosis and carotid atherosclerosis groups, which were then subsequently divided into TT and TG + GG groups according to the adiponectin SNP45 T/G genotypes. Enzyme-linked immunosorbent assay, TaqMan probe quantitative polymerase chain reaction (PCR), PCR-TaqMan, color Doppler and other methods were used to determine the adiponectin levels, gene polymorphisms, acquired mitochondrial DNA (mtDNA) A3243G somatic cell mutation rates and the carotid intima-media thickness. The somatic cell mutation rate of acquired mtDNA A3243A/G in the T2DM carotid atherosclerosis group was significantly higher compared with the group without carotid atherosclerosis. In addition, the acquired mtDNA A3243A/G somatic cell mutation rate in the T2DM carotid atherosclerosis group with the adiponectin gene SNP45 TT genotype was significantly lower compared with the SNP45 TG/GG genotype group. T2DM combined with carotid atherosclerosis was associated with long-term oxidative stress. In addition, adiponectin gene SNP45 T/G was associated with increased mtDNA A3243A/G somatic mutation rates in T2DM patients with carotid atherosclerosis. Therefore, adiponectin gene polymorphisms may lead to diabetes atherosclerosis through oxidative stress. PMID:25120586

PIAO, LIANSHAN; HAN, YANHUA; LI, DAN

2014-01-01

345

Overexpression of the Adiponectin Receptor AdipoR1 in Rat Skeletal Muscle Amplifies Local Insulin Sensitivity  

PubMed Central

Adiponectin is an adipokine whose plasma levels are inversely related to degrees of insulin resistance (IR) or obesity. It enhances glucose disposal and mitochondrial substrate oxidation in skeletal muscle and its actions are mediated through binding to receptors, especially adiponectin receptor 1 (AdipoR1). However, the in vivo significance of adiponectin sensitivity and the molecular mechanisms of muscle insulin sensitization by adiponectin have not been fully established. We used in vivo electrotransfer to overexpress AdipoR1 in single muscles of rats, some of which were fed for 6 wk with chow or high-fat diet (HFD) and then subjected to hyperinsulinemic-euglycemic clamp. After 1 wk, the effects on glucose disposal, signaling, and sphingolipid metabolism were investigated in test vs. contralateral control muscles. AdipoR1 overexpression (OE) increased glucose uptake and glycogen accumulation in the basal and insulin-treated rat muscle and also in the HFD-fed rats, locally ameliorating muscle IR. These effects were associated with increased phosphorylation of insulin receptor substrate-1, Akt, and glycogen synthase kinase-3?. AdipoR1 OE also caused increased phosphorylation of p70S6 kinase, AMP-activated protein kinase, and acetyl-coA carboxylase as well as increased protein levels of adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif-1 and adiponectin, peroxisome proliferator activated receptor-? coactivator-1?, and uncoupling protein-3, indicative of increased mitochondrial biogenesis. Although neither HFD feeding nor AdipoR1 OE caused generalized changes in sphingolipids, AdipoR1 OE did reduce levels of sphingosine 1-phosphate, ceramide 18:1, ceramide 20:2, and dihydroceramide 20:0, plus mRNA levels of the ceramide synthetic enzymes serine palmitoyl transferase and sphingolipid ?-4 desaturase, changes that are associated with increased insulin sensitivity. These data demonstrate that enhancement of local adiponectin sensitivity is sufficient to improve skeletal muscle IR. PMID:22989629

Patel, S. A.; Hoehn, K. L.; Lawrence, R. T.; Sawbridge, L.; Talbot, N. A.; Tomsig, J. L.; Turner, N.; Cooney, G. J.; Whitehead, J. P.; Kraegen, E. W.

2012-01-01

346

Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes  

SciTech Connect

Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1{alpha} (HIF-1{alpha}), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H{sub 2}O{sub 2})-induced dysregulation of adiponectin and PAI-1 production. H{sub 2}O{sub 2} treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPAR{gamma}) and CCAAT/enhancer binding protein (C/EBP{alpha}), but had no effect on HIF-1{alpha}, whereas hypoxia stabilized HIF-1{alpha} and decreased expression of C/EBP{alpha}, but not PPAR{gamma}. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases.

Chen Baoying [Department of Medicine, University of Hong Kong, Hong Kong (China); Department of Radiology, Tangdu Hospital, Fourth Military Medical University (China); Lam, Karen S.L. [Department of Medicine, University of Hong Kong, Hong Kong (China); Wang Yu [Genome Research Center, University of Hong Kong, Hong Kong (China); Wu Donghai [Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences (China); Lam, Michael C. [Department of Medicine, University of Hong Kong, Hong Kong (China); Shen Jiangang [School of Chinese Medicine, University of Hong Kong (China); Wong Laiching [Department of Medicine, University of Hong Kong, Hong Kong (China); Hoo, Ruby L.C. [Department of Medicine, University of Hong Kong, Hong Kong (China); Zhang Jialiang [Department of Medicine, University of Hong Kong, Hong Kong (China); Xu Aimin [Department of Medicine, University of Hong Kong, Hong Kong (China) and Genome Research Center, University of Hong Kong, Hong Kong (China)]. E-mail: amxu@hkucc.hku.hk

2006-03-10

347

Effects of a low-fat diet on the hepatic expression of adiponectin and its receptors in rats with NAFLD.  

PubMed

Background. Non-alcoholic fatty liver disease (NAFLD) is correlated with obesity, but specific therapeutic interventions are lacking. Adiponectin is an adipokine with anti-inflammatory activity and is considered a hepatic protector. We aimed to investigate effects of a low-fat diet on the hepatic expression of adiponectin and its receptors in rats with NAFLD. Materials and methods. Sixteen male SD rats were fed a high-fat diet for 8 weeks (HFD1 group) or 16 weeks (HFD2 group) to induce NAFLD, and these rats were compared with rats on a normal diet for 8 weeks (NC1 group) or 16 weeks (NC2 group). Another group of 8 rats was fed an HFD for 8 weeks and then switched to a low-fat diet (DIET group) until the 16th week. The expression of hepatic adiponectin and its receptors was detected by western blotting, immunohistochemistry and RT-qPCR. Results. The NAFLD activity score (NAS) in the HFD groups increased from 3.2 ± 0.45 (8th week) to 6.2 ± 0.84 (16th week) (P < 0.001), reflecting the progression in the NAFLD histology. In contrast to the HFD2 group, the low-fat diet ameliorated the steatosis, ballooning degeneration and inflammation. Dietary intervention augmented the expression of adiponectin and its receptors, which was down-regulated in the HFD2 group. Conclusions. The NAFLD rat model was successfully developed by feeding the animals a high-fat diet. Adiponectin may play a role in the pathogenesis of NAFLD, especially in the progression from steatosis to NASH. The low-fat diet alleviated the histological lesions associated with NAFLD by up-regulating the expression of adiponectin and its receptors. PMID:25536648

Ma, Hong; You, Guo-Ping; Cui, Fan; Chen, Lu-Fang; Yang, Xiang-Jiu; Chen, Li-Gang; Lu, Hua-Dong; Zhang, Wen-Qiang

2015-01-01

348

Synergistic Steatohepatitis by Moderate Obesity and Alcohol in Mice Despite Increased Adiponectin and p-AMPK  

PubMed Central

Background & Aims Mechanisms underlying synergistic liver injury caused by alcohol and obesity are not clear. We have produced a mouse model of synergistic steatohepatitis by recapitulating the natural history of the synergism seen in patients for mechanistic studies. Methods Moderate obesity was induced in mice by 170% overnutrition in calories using intragastric overfeeding of high fat diet. Alcohol (low or high dose) was then co-administrated to determine its effects. Results Moderate obesity plus alcohol intake causes synergistic steatohepatitis in an alcohol dose-dependent manner. A heightened synergism is observed when a high alcohol dose (32g/kg/day) is used, resulting in plasma ALT reaching 392 ± 28 U/L, severe steatohepatitis with pericellular fibrosis, marked M1 macrophage activation, a 40-fold induction of iNos, and intensified nitrosative stress in the liver. Hepatic expression of genes for mitochondrial biogenesis and metabolism are significantly downregulated, and hepatic ATP level is decreased. Synergistic ER stress evident by elevated XBP-1, GRP78 and CHOP, is accompanied by hyperhomocysteinemia. Despite increased caspase 3/7 cleavage, their activities are decreased in a redox-dependent manner. Neither increased PARP cleavage nor TUNEL positive hepatocytes are found, suggesting a shift of apoptosis to necrosis. Surprisingly, the synergism mice have increased plasma adiponectin and hepatic p-AMPK, but adiponectin resistance is shown downstream of p-AMPK. Conclusions Nitrosative stress mediated by M1 macrophage activation, adiponectin resistance, accentuated ER and mitochondrial stress underlie potential mechanisms for synergistic steatohepatitis caused by moderate obesity and alcohol. PMID:21256905

Xu, Jun; Lai, Keane K.Y.; Verlinsky, Alla; Lugea, Aurelia; French, Samuel W.; Cooper, Marcus P.; Ji, Cheng; Tsukamoto, Hidekazu

2011-01-01

349

Smoking and Diabetes: Is the Association Mediated by Adiponectin, Leptin, or C-reactive Protein?  

PubMed Central

Background Although the association between cigarette smoking and risk of type 2 diabetes is well established, its mechanisms are yet to be clarified. This study examined the possible mediating effects of adiponectin, leptin, and C-reactive protein (CRP) concentrations on the smoking-diabetes association. Methods Between 2002 and 2011, we followed 3338 Japanese workers, aged 35–66 years, who were enrolled in the second Aichi workers’ cohort study. We used multivariable-adjusted Cox regression models to determine the hazard ratios and respective 95% confidence intervals (CIs) of the association between smoking status and risk of diabetes. A multiple mediation model with bootstrapping was used to estimate the magnitude and the respective bias-corrected (BC) 95% CIs of the indirect effects of smoking on diabetes through the three biomarkers. Results Relative to never smokers, the risk of diabetes was significantly elevated in current (hazard ratio 1.75, 95% CI 1.25–2.46) and ex-smokers (hazard ratio 1.54, 95% CI 1.07–2.22). The indirect effects of smoking on diabetes through adiponectin levels were statistically significant among light (point estimate 0.033, BC 95% CI 0.005–0.082), moderate (point estimate 0.044, BC 95% CI 0.010–0.094), and heavy smokers (point estimate 0.054, BC 95% CI 0.013–0.113). In contrast, neither the indirect effects of smoking on diabetes through leptin nor CRP levels were significant, as the corresponding BC 95% CIs included zero. Conclusions In our analysis, adiponectin concentration appeared to partially mediate the effect of smoking on diabetes, while leptin and CRP levels did not.

Hilawe, Esayas Haregot; Yatsuya, Hiroshi; Li, Yuanying; Uemura, Mayu; Wang, Chaochen; Chiang, Chifa; Toyoshima, Hideaki; Tamakoshi, Koji; Zhang, Yan; Kawazoe, Nobuo; Aoyama, Atsuko

2015-01-01

350

Relationship between epicardial adipose tissue, coronary artery disease and adiponectin in a Mexican population  

PubMed Central

Background The amount of epicardial adipose tissue (EAT) around the heart has been identified as an independent predictor of coronary artery disease (CAD), potentially through local release of inflammatory cytokines. Ethnic differences have been observed, but no studies have investigated this relationship in the Mexican population. The objective of the present study was to evaluate whether a relationship exist between EAT thickness assessed via echocardiography with CAD and adiponectin levels in a Mexican population. Methods We studied 153 consecutive patients who underwent coronary angiography and transthoracic echocardiography (TTE). EAT thickness on the free wall of the right ventricle was measured at the end of systole from parasternal long and short axis views of three consecutive cardiac cycles. Coronary angiograms were analyzed for the presence, extent and severity of CAD. Serum adiponectin, lipids, glucose, C-reactive protein and fibrinogen were determined. Results EAT thickness was greater in patients with CAD than in those without CAD from both parasternal long (5.39?±?1.75 mm vs 4.00?±?1.67 mm p?adiponectin or with the severity of CAD. Conclusions EAT thickness was greater in patients with CAD. However, no correlation was observed with the severity of the disease or with serum adiponectin levels. EAT thickness measured by echocardiography might provide additional information for risk assessment and prediction of CAD. PMID:25200587

2014-01-01

351

Ethnic differences in leptin and adiponectin levels between Greenlandic Inuit and Danish children  

PubMed Central

Objective In a recent study, we found that Greenlandic Inuit children had a more adverse metabolic profile than Danish children. Aerobic fitness and adiposity could only partly account for the differences. Therefore, we set out to evaluate and compare plasma leptin and adiponectin levels in Danish and Inuit children. Methods In total, 187 Inuit and 132 Danish children (5.7–17.1 years) had examinations of anthropometrics, body fat content, pubertal staging, fasting blood and aerobic fitness. Results Plasma leptin was higher in Danish boys [3,774 (4,741–3,005)] [pg/mL unadjusted geometric mean (95% CI)] compared to both northern [2,076 (2,525–1,706)] (p<0.001) and southern (2,515 (3,137–2,016)) (p<0.001) living Inuit boys and higher in Danish girls [6,988 (8,353–5,847)] compared to southern living Inuit girls [4,910 (6,370–3,785)] (p=0.021) and tended to be higher compared to northern living Inuit girls [5,131 (6,444–4,085)] (p=0.052). Plasma adiponectin was higher for both Danish boys [22,359 (2,573–19,428)] [ng/mL unadjusted geometric mean (95% CI)] and girls [26,609 (28,994–24,420)] compared to southern living Inuit boys [15,306 (18,406–12,728)] and girls [18,864 (22,640–15,717)] (both p<0.001), respectively. All differences remained after adjustment for body fat percentage (BF%), aerobic fitness, age and puberty. The leptin/adiponectin ratio was higher in Danish boys and tended to be higher in Danish girls compared to northern living Inuit boys and girls, respectively. These differences were eliminated after adjustment for BF%, aerobic fitness, age and puberty. Conclusions In contrast to our hypothesis, plasma leptin was higher in Danish children despite a more healthy metabolic profile compared to Inuit children. As expected, plasma adiponectin was lowest in Inuit children with the most adverse metabolic profile. PMID:23940841

Munch-Andersen, Thor; Sorensen, Kaspar; Aachmann-Andersen, Niels-Jacob; Aksglaede, Lise; Juul, Anders; Helge, Jørn W.

2013-01-01

352

Integrated ozone and biotreatment of pulp mill effluent and changes in biodegradability and molecular weight distribution of organic compounds.  

PubMed

The overall effectiveness of integrating ozonation with biological treatment on the biodegradability enhancement and recalcitrant organic matter (ROM) removal from pulp mill alkaline bleach plant effluent was investigated. Ozonation was performed in a semi-batch bubble column reactor at pH of 11 and 4.5. Batch biological treatment was conducted in shake flasks. Samples obtained during the treatments were monitored for BOD5, COD, TOC, and molecular weight distribution. At an ozone dosage of 0.7-0.8 mg O3/mL wastewater, integrated treatment showed about 30% higher TOC mineralization compared to individual ozonation or biotreatment. Ozone treatment enhanced the biodegradability of the effluent (monitored as 21% COD reduction and 13% BOD5 enhancement), allowing for a higher removal of pollutants. The conversion of high molecular weight (HMW) to low molecular weight (LMW) compounds was an important factor in the overall biodegradability enhancement of the alkaline effluent. The overall biodegradability of the LMW compounds did not change over the course of ozonation, but it increased from 5% to 50% (measured as COD removal) for the HMW portion. Ozonation at pH of 11 was more effective than that at pH of 4.5 in terms of generating more biodegradable compounds. PMID:16139863

Bijan, Leila; Mohseni, Madjid

2005-10-01

353

Serum adiponectin is associated with homocysteine in elderly men and women, and with 5,10-methylenetetrahydrofolate reductase (MTHFR) in a sex-dependent manner.  

PubMed

Plasma homocysteine associates positively with cardiovascular disease. C-to-T substitution at base 677 of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene associates with increased plasma homocysteine. The association of adiponectin with cardiovascular disease is unclear. This study of survivors of a 30-year cohort of the Jewish Israeli population, 310 men and 273 women (mean age, 70.5 ± 7.0 years for both), investigated the relationship between adiponectin and homocysteine, and between adiponectin and the MTHFR C677T genotype. Serum adiponectin associated positively with total homocysteine in both men (r = 0.27, P < .001) and women (r = 0.22, P < .001). In women, the TT MTHFR genotype associated with lower median adiponectin levels, 8.98 mg/L, compared with 9.88 and 10.57 mg/L for TC and CC, respectively (P = .05; CC vs TT, P = .01). In men, the trend was opposite, but not statistically significant: 7.90, 7.03, and 6.88 mg/L for TT, TC, and CC genotypes, respectively (P = .5). This study demonstrated a positive association between homocysteine and adiponectin in both elderly men and women and a statistically significant association between adiponectin and MTHFR C677T genotypes in women only. PMID:20580032

Dankner, Rachel; Chetrit, Angela; Murad, Havi; Sela, Ben-Ami; Frystyk, Jan; Raz, Itamar; Flyvbjerg, Allan

2010-12-01

354

Antibodies Specific for the High-Molecular-Weight Adhesion Proteins of Nontypeable Haemophilus influenzae Are Opsonophagocytic for both Homologous and Heterologous Strains?  

PubMed Central

The HMW1/HMW2-like adhesion proteins of nontypeable Haemophilus influenzae (NTHI) are expressed by 75% of NTHI strains. Antibodies directed against these proteins are opsonophagocytic in vitro and are protective in an animal model of infection. The objective of the present study was to determine the opsonophagocytic activity of high-titer anti-HMW1/HMW2 immune sera against both homologous and heterologous NTHI strains. Chinchillas were immunized with purified HMW1/HMW2-like proteins from five prototype NTHI strains. Serum opsonophagocytic activity was monitored in an assay that uses a human promyelocytic cell line, HL-60, as the source of phagocytic cells. Preimmune sera did not demonstrate opsonophagocytic killing of any strains. In contrast, the immune sera demonstrated killing of the five homologous NTHI strains at titers ranging from 1:320 to 1:640. The immune sera also demonstrated killing of eight heterologous NTHI strains that express HMW1/HMW2-like proteins at titers ranging from 0 to 1:640. Killing of heterologous strains sometimes demonstrated a prozone phenomenon. None of the immune sera killed NTHI strains that did not express HMW1/HMW2-like proteins. Adsorption of immune sera with HMW1/HMW2-like proteins purified from either homologous or heterologous NTHI strains eliminated opsonophagocytic killing of homologous strains in most cases. These data demonstrate that antibodies produced following immunization with the HMW1/HMW2-like proteins are opsonophagocytic for both homologous and heterologous NTHI and strongly suggest that common epitopes recognized by functionally active antibodies exist on the HMW1/HMW2-like proteins of unrelated NTHI strains. The results argue for the continued investigation of the HMW1/HMW2-like proteins as potential vaccine candidates for the prevention of NTHI disease. PMID:17021246

Winter, Linda E.; Barenkamp, Stephen J.

2006-01-01

355

Weight Control  

MedlinePLUS

Keeping a healthy weight is crucial. If you are underweight, overweight, or obese, you may have a higher risk of certain health problems. ... U.S. are overweight or obese. Achieving a healthy weight can help you control your cholesterol, blood pressure ...

356

Globular Adiponectin Activates Motility and Regenerative Traits of Muscle Satellite Cells  

PubMed Central

Regeneration of adult injured skeletal muscle is due to activation of satellite cells, a population of stem cells resident beneath the basal lamina. Thus, information on soluble factors affecting satellite cell activation, as well as migration towards injury and fusion into new myofibers are essential. Here, we show that globular adiponectin (gAd), positively affects several features of muscle satellite cells. gAd activates satellite cells to exit quiescence and increases their recruitment towards myotubes. gAd elicits in satellite cells a specific motility program, involving activation of the small GTPase Rac1, as well as expression of Snail and Twist transcription factors driving a proteolytic motility, useful to reach the site of injury. We show that satellite cells produce autocrine full length adiponectin (fAd), which is converted to gAd by activated macrophages. In turns, gAd concurs to attract to the site of injury both satellite cells and macrophages and induces myogenesis in muscle satellite cells. Thus, these findings add a further role for gAd in skeletal muscle, including the hormone among factors participating in muscle regeneration. PMID:22629295

Fiaschi, Tania; Giannoni, Elisa; Taddei, Maria Letizia; Chiarugi, Paola

2012-01-01

357

Cloning and partial characterization of a gene in Bombyx mori homologous to a human adiponectin receptor.  

PubMed

In this study, we report the cloning and characteristics of an adiponectin-like receptor gene from Bombyx mori (BmAdipoR) with highly conserved deduced amino-acid sequences and similar structure to the human adiponectin receptor (AdipoR). Structural analysis of the translated cDNA suggested it encoded a membrane protein with seven transmembrane domains. BmAdipoR was found to be expressed in multiple tissues and highly expressed in Malpighian tubules, fat body and testis. BmNPV (Bombyx mori nucleopolyhedrovirus) bacmid system combined with confocal microscopy revealed that BmAdipoR was targeted to the cell membrane. We also found that infection with BmNPV did not have an effect on BmAdipoR mRNA quantity in the midgut of susceptible Bombyx mori strain (306) at 48 h, but BmAdipoR mRNA quantity increased significantly at 72 h. We concluded that BmAdipoR gene was a membrane protein ubiquitously expressed in Bombyx mori tissues and that its expression was altered by treating with BmNPV. PMID:18560604

Zhu, Minfeng; Chen, Keping; Wang, Yong; Guo, Zhongjian; Yin, Huijuan; Yao, Qin; Chen, Huiqin

2008-01-01

358

Puerarin enhances adipocyte differentiation, adiponectin expression, and antioxidant response in 3T3-L1 cells.  

PubMed

Puerarin, a major isoflavone glycoside from Kudzu root (Pueraria lobata), has been reported to exert antihyperglycemic and antioxidant effects and thus have pharmacological actions in the treatment of diabetes and cardiovascular diseases. We investigated the effects of puerarin on the changes of key gene expression associated with adipocyte differentiation and insulin sensitivity and link to cellular antioxidant response pathways. Puerarin treatment significantly enhanced differentiation of 3T3-L1 preadipocytes accompanying increased lipid accumulation and glucose-6-phosphate dehydrogenase (G6PDH) activity. At a molecular level, puerarin upregulated mRNA expression of peroxisome proliferator-activated receptor ? (PPAR?) and its target genes, an adipocyte-specific fatty acid binding protein (aP2) and GLUT4. Puerarin also caused a significant increase in mRNA level of adiponectin, an important insulin-sensitizing adipocytokine that is downregulated in insulin-resistant and diabetic states. In addition, treatment with puerarin was found to upregulate mRNA levels of G6PDH, glutathione reductase, and catalase, all of which are important for endogenous antioxidant responses. These data suggest that the hypoglycemic effects of puerarin can be attributed to the upregulation of PPAR? and its downstream target genes, GLUT4 and adiponectin expression, leading to increased glucose utilization. Puerarin may also be effective in preventing the rise of oxidative stress during adipocyte differentiation by increasing endogenous antioxidant responses. PMID:20806284

Lee, Ok-Hwan; Seo, Dong-Ho; Park, Cheon-Seok; Kim, Young-Cheul

2010-01-01

359

Adiponectin, a downstream target gene of peroxisome proliferator-activated receptor {gamma}, controls hepatitis B virus replication  

SciTech Connect

In this study, HepG2-hepatitis B virus (HBV)-stable cells that did not overexpress HBx and HBx-deficient mutant-transfected cells were analyzed for their expression of HBV-induced, upregulated adipogenic and lipogenic genes. The mRNAs of CCAAT enhancer binding protein {alpha} (C/EBP{alpha}), peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), adiponectin, liver X receptor {alpha} (LXR{alpha}), sterol regulatory element binding protein 1c (SREBP1c), and fatty acid synthase (FAS) were expressed at higher levels in HepG2-HBV and lamivudine-treated stable cells and HBx-deficient mutant-transfected cells than in the HepG2 cells. Lamivudine treatment reduced the mRNA levels of PPAR{gamma} and C/EBP{alpha}. Conversely, HBV replication was upregulated by adiponectin and PPAR{gamma} agonist rosiglitazone treatments and was downregulated by adiponectin siRNAs. Collectively, our results demonstrate that HBV replication and/or protein expression, even in the absence of HBx, upregulated adipogenic or lipogenic genes, and that the control of adiponectin might prove useful as a therapeutic modality for the treatment of chronic hepatitis B.

Yoon, Sarah; Jung, Jaesung; Kim, Taeyeung; Park, Sun; Chwae, Yong-Joon; Shin, Ho-Joon; Kim, Kyongmin, E-mail: kimkm@ajou.ac.k

2011-01-20

360

Perinatal BPA Exposure Induces Hyperglycemia, Oxidative Stress and Decreased Adiponectin Production in Later Life of Male Rat Offspring  

PubMed Central

The main object of the present study was to explore the effect of perinatal bisphenol A (BPA) exposure on glucose metabolism in early and later life of male rat offspring, and to establish the potential mechanism of BPA-induced dysglycemia. Pregnant rats were treated with either vehicle or BPA by drinking water at concentrations of 1 and 10 µg/mL BPA from gestation day 6 through the end of lactation. We measured the levels of fasting serum glucose, insulin, adiponectin and parameters of oxidative stress on postnatal day (PND) 50 and PND100 in male offspring, and adiponectin mRNA and protein expression in adipose tissue were also examined. Our results showed that perinatal exposure to 1 or 10 µg/mL BPA induced hyperglycemia with insulin resistance on PND100, but only 10 µg/mL BPA exposure had similar effects as early as PND50. In addition, increased oxidative stress and decreased adiponectin production were also observed in BPA exposed male offspring. Our findings indicated that perinatal exposure to BPA resulted in abnormal glucose metabolism in later life of male offspring, with an earlier and more exacerbated effect at higher doses. Down-regulated expression of adiponectin gene and increased oxidative stress induced by BPA may be associated with insulin resistance. PMID:24705360

Song, Shunzhe; Zhang, Ling; Zhang, Hongyuan; Wei, Wei; Jia, Lihong

2014-01-01

361

Serum from Calorie-Restricted Rats Activates Vascular Cell eNOS through Enhanced Insulin Signaling Mediated by Adiponectin  

Microsoft Academic Search

eNOS activation resulting in mitochondrial biogenesis is believed to play a central role in life span extension promoted by calorie restriction (CR). We investigated the mechanism of this activation by treating vascular cells with serum from CR rats and found increased Akt and eNOS phosphorylation, in addition to enhanced nitrite release. Inhibiting Akt phosphorylation or immunoprecipitating adiponectin (found in high

Fernanda M. Cerqueira; Laura I. Brandizzi; Fernanda M. Cunha; Francisco R. M. Laurindo; Alicia J. Kowaltowski

2012-01-01