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1

Ovarian HMW adiponectin is associated with folliculogenesis in women with polycystic ovary syndrome  

PubMed Central

Background Adiponectin may regulate ovarian steroidogenesis, folliculogenesis and ovulation. The alterations in the distribution of adiponectin multimers in follicular fluid (FF) and the relationship between adiponectin multimers and folliculogenesis in women with polycystic ovary syndrome (PCOS) remain unclear. In this study, we aimed to investigate the association between the levels of total and high molecular weight (HMW) adiponectin in serum and FF and folliculogenesis in women undergoing in vitro fertilisation (IVF). Methods This prospective study included ten Chinese women with PCOS and ten controls undergoing IVF. The levels of the total and HMW adiponectin in serum and FF were determined by ELISA. Insulin resistance (IR) was estimated using the homeostasis model assessment insulin resistance index (HOMA-IR). Results After controlling for the body mass index (BMI), the levels of the total, and the HMW adiponectin in the serum and FF were significantly lower in the women with PCOS compared with the normovulatory women undergoing IVF (P?HMW adiponectin were significantly lower in the FF than in the serum (P?adiponectin levels in the serum and in the FF (P?>?0.05). Decreased HMW adiponectin in the FF was associated with an increased number of follicles and decreased follicular diameters in the normovulatory and PCOS women, and this association was independent of the overall adiposity. A strong positive linear correlation was observed between the number of the follicles and the IR estimated by HOMA-IR (r?=?0.784, P?HMW adiponectin levels (r?=??0.726, P?adiponectin levels (r?=??0.759, P?adiponectin and the HMW adiponectin in the FF and serum were decreased in the Chinese women with PCOS compared with the normovulatory women undergoing IVF, and the differences persisted after controlling for the BMI. Ovarian HMW adiponectin is negatively correlated to folliculogenesis.

2013-01-01

2

Analytical Validation and Biological Evaluation of a High-Molecular-Weight Adiponectin ELISA  

Microsoft Academic Search

Background: Of the 3 circulating multimeric forms of adiponectin, the high-molecular-weight (HMW) form, as measured by size-exclusion and\\/or immunoblotting tech- niques, is a better index of insulin sensitivity for monitor- ing health and disease than is total adiponectin. We aimed to develop a simple ELISA to measure HMW adiponectin. Methods: We pretreated serum or plasma samples with digestion solution containing

Madhur K. Sinha; Traci Songer; Qiang Xiao; John H. Sloan; Jin Wang; Shaoquen Ji; William E. Alborn; Randy A. Davis; Michael M. Swarbrick; Kimber L. Stanhope; Bruce M. Wolfe; Peter J. Havel; Todd Schraw; Robert J. Konrad; Philipp E. Scherer; Jehangir S. Mistry

2007-01-01

3

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

Microsoft Academic Search

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

Akihiko Kato; Mari Odamaki; Junko Ishida; Akira Hishida

2008-01-01

4

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

Microsoft Academic Search

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

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

2006-01-01

5

The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes  

Microsoft Academic Search

Aims\\/hypothesis  Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. We studied the role played by total adiponectin and by the bioactive high-molecular-weight (HMW) oligomeric complexes of adiponectin in vascular function in offspring whose parents both had type 2 diabetes, a population at high risk of diabetes and atherosclerosis.Methods  Total and %HMW adiponectin, the cytokines C-reactive protein, interleukin-6 and plasminogen activator inhibitor-1

F. Halperin; J. A. Beckman; M. E. Patti; M. E. Trujillo; M. Garvin; M. A. Creager; P. E. Scherer; A. B. Goldfine

2005-01-01

6

Inherent insulin sensitivity is a major determinant of multimeric adiponectin responsiveness to short-term weight loss in extreme obesity  

PubMed Central

High molecular weight (HMW-A) adiponectin levels mirror alterations in glucose homeostasis better than medium (MMW-A) and low molecular weight (LMW-A) components. In 25 patients with wide-range extreme obesity (BMI 40-77?kg/m2), we aimed to explore if improvements of multimeric adiponectin following 4-wk weight loss reflect baseline OGTT-derived insulin sensitivity (ISIOGTT) and disposition index (DIOGTT). Compared to 40 lean controls, adiponectin oligomers were lower in extreme obesity (p < 0.001) and, within this group, HMW-A levels were higher in insulin-sensitive (p < 0.05) than -resistant patients. In obese patients, short-term weight loss did not change total adiponectin levels and insulin resistance, while the distribution pattern of adiponectin oligomers changed due to significant increment of HMW-A (p < 0.01) and reduction of MMW-A (p < 0.05). By multivariate analysis, final HMW-A levels were significantly related to baseline ISIOGTT and final body weight (adjusted R2 = 0.41). Our data suggest that HMW adiponectin may reflect baseline insulin sensitivity appropriately in the context of extreme obesity. Especially, we documented that HMW-A is promptly responsive to short-term weight loss prior to changes in insulin resistance, by a magnitude that is proportioned to whole body insulin sensitivity. This may suggest an insulin sensitivity-dependent control operated by HMW-A on metabolic dynamics of patients with extreme obesity.

Mai, Stefania; Walker, Gillian E.; Brunani, Amelia; Guzzaloni, Gabriele; Grossi, Glenda; Oldani, Alberto; Aimaretti, Gianluca; Scacchi, Massimo; Marzullo, Paolo

2014-01-01

7

Inherent insulin sensitivity is a major determinant of multimeric adiponectin responsiveness to short-term weight loss in extreme obesity.  

PubMed

High molecular weight (HMW-A) adiponectin levels mirror alterations in glucose homeostasis better than medium (MMW-A) and low molecular weight (LMW-A) components. In 25 patients with wide-range extreme obesity (BMI 40-77?kg/m(2)), we aimed to explore if improvements of multimeric adiponectin following 4-wk weight loss reflect baseline OGTT-derived insulin sensitivity (ISIOGTT) and disposition index (DIOGTT). Compared to 40 lean controls, adiponectin oligomers were lower in extreme obesity (p < 0.001) and, within this group, HMW-A levels were higher in insulin-sensitive (p < 0.05) than -resistant patients. In obese patients, short-term weight loss did not change total adiponectin levels and insulin resistance, while the distribution pattern of adiponectin oligomers changed due to significant increment of HMW-A (p < 0.01) and reduction of MMW-A (p < 0.05). By multivariate analysis, final HMW-A levels were significantly related to baseline ISIOGTT and final body weight (adjusted R(2) = 0.41). Our data suggest that HMW adiponectin may reflect baseline insulin sensitivity appropriately in the context of extreme obesity. Especially, we documented that HMW-A is promptly responsive to short-term weight loss prior to changes in insulin resistance, by a magnitude that is proportioned to whole body insulin sensitivity. This may suggest an insulin sensitivity-dependent control operated by HMW-A on metabolic dynamics of patients with extreme obesity. PMID:25056918

Mai, Stefania; Walker, Gillian E; Brunani, Amelia; Guzzaloni, Gabriele; Grossi, Glenda; Oldani, Alberto; Aimaretti, Gianluca; Scacchi, Massimo; Marzullo, Paolo

2014-01-01

8

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

PubMed Central

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

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

2010-01-01

9

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

PubMed Central

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

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

2012-01-01

10

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

PubMed

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

2012-06-01

11

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

National Technical Information Service (NTIS)

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

L. I. Aluwihare

1999-01-01

12

High-molecular-weight adiponectin is selectively reduced in women with polycystic ovary syndrome independent of body mass index and severity of insulin resistance.  

PubMed

Context: High-molecular-weight (HMW) adiponectin contributes to insulin resistance (IR), which is closely associated with the pathophysiology of polycystic ovary syndrome (PCOS). Abnormalities in adipocyte function have been identified in PCOS and potentially contribute to lower adiponectin concentrations. Objective: Our objective was to determine which variables in plasma and adipose tissue influence HMW adiponectin in a well characterized cohort of women with PCOS. Design: This was a cross-sectional study. Settings and Participants: A teaching hospital. Women with PCOS (n = 98) and body mass index (BMI)-matched controls (n = 103) (including 68 age-, BMI-, and IR-matched pairs). Interventions: A standard 75-g oral glucose tolerance test was performed for each participant. Subcutaneous adipose tissue samples were taken by needle biopsy for a subset of PCOS women (n = 9) and controls (n = 8). Main Outcome Measures: Serum levels of HMW adiponectin and their relation to indices of insulin sensitivity, body composition, and circulating androgens as well as adipose tissue expression levels of ADIPOQ, TNFalpha, PPARgamma, and AR were assessed. Results: HMW adiponectin was significantly lower in women with PCOS compared with both BMI- and BMI- and IR-matched controls (P = 0.009 and P = 0.027, respectively). Although BMI and IR were the main predictors of HMW adiponectin, an interaction between waist to hip ratio and plasma testosterone contributed to its variance (P = 0.026). Adipose tissue gene expression analysis demonstrated that AR and TNFalpha (P = 0.008 and P = 0.035, respectively) but not ADIPOQ mRNA levels were increased in PCOS compared with controls. Conclusions: HMW adiponectin is selectively reduced in women with PCOS, independent of BMI and IR. Gene expression analysis suggests that posttranscriptional/translational modification contributes to reduced HMW adiponectin in PCOS. PMID:20080859

O'Connor, A; Phelan, N; Tun, T Kyaw; Boran, G; Gibney, J; Roche, H M

2010-03-01

13

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

2014-06-01

14

Preatherosclerosis and adiponectin subfractions in obese adolescents.  

PubMed

We evaluated total adiponectin, high-molecular weight (HMW), medium-molecular weight (MMW), low-molecular weight (LMW) adiponectin subfractions, clinical parameters, routine lab parameters, lipids, metabolic, inflammatory biomarkers, and intima-media thickness (IMT) of common carotid arteries in 70 obese juveniles and adolescents with preatherosclerosis and 55 normal weight controls of similar age and gender distribution. Compared with the controls, the obese probands had a significantly increased IMT (P < 0.001) and elevated ultra-sensitive C-reactive protein (P < 0.001) indicating early vascular burden. Total and HMW adiponectin were significantly decreased in the obese cohort. The ratio between HMW and total adiponectin was significantly decreased in obese probands whereas the LMW/total adiponectin ratio was increased. Overall, total-, HMW, and MMW adiponectin were significantly negatively correlated with carotid IMT. The HMW/total adiponectin ratio correlated significantly negatively, and the LMW/total adiponectin ratio significantly positively with the IMT. Furthermore, HMW adiponectin was significantly positively correlated with high-density lipoprotein (HDL)-cholesterol and serum apolipoprotein A1, and negatively with BMI, triglycerides, homeostatic model assessment (HOMA)-index, leptin, liver transaminases, and uric acid. This remained stable after controlling for gender. Multiple regression analysis of body measures and all other lab parameters showed the strongest correlation between HMW adiponectin and carotid IMT (beta = -0.35, P < 0.001). Taken together, our study provides the first evidence that preatherosclerosis in obese juveniles and adolescents is associated with altered subfractions of adiponectin, whereas after multiple testing the HMW subfraction showed a better correlation to IMT compared with total adiponectin. PMID:18846045

Mangge, Harald; Almer, Gunter; Haj-Yahya, Samih; Pilz, Stefan; Gasser, Robert; Möller, Reinhard; Horejsi, Renate

2008-12-01

15

Adding glimepiride to current insulin therapy increases high-molecular weight adiponectin levels to improve glycemic control in poorly controlled type 2 diabetes  

PubMed Central

Background To observe the efficacy and safety of adding glimepiride to established insulin therapy in poorly controlled type 2 diabetes (T2D) and to assess the relationship of changes in the serum high-molecular weight (HMW) adiponectin levels and glycemic control after glimepiride treatment. Methods Fifty-six subjects with poorly controlled insulin-treated T2D were randomly assigned to either the glimepiride-added group (the group A, n?=?29) or the insulin-increasing group (the group B, n?=?27) while continuing current insulin-based therapy. Glycosylated hemoglobin (HbA1c) value, daily insulin dose, body weight, waist circumference, plasma lipid concentration, serum HMW adiponectin level and the number of hypoglycemic events were evaluated before and after treatment. Results At the end of study, insulin doses were significantly reduced, and the mean HbA1c, fasting blood glucose (FBG) and 2-hour postprandial blood glucose (P2BG) were improved greater in the group A compared with the group B. The serum HMW adiponectin levels were significantly increased in the group A compared with the group B. Most importantly, we found that changes in HbA1c were inversely correlated with changes in serum HMW adiponectin in the group A (r?=??0.452, p?=?0.02). Conclusions Adding glimepiride to current insulin treatment led to better improvement in glycemic control with a significant smaller daily insulin dose, and the increases in the serum HMW adiponectin levels may directly contribute to improvement glycemic control.

2014-01-01

16

Extracellular conversion of adiponectin hexamers into trimers.  

PubMed

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

2012-12-01

17

Differential effects of endurance training and weight loss on plasma adiponectin multimers and adipose tissue macrophages in younger, moderately overweight men.  

PubMed

Obese individuals are characterized by low circulating adiponectin concentrations and an increased number of macrophages in adipose tissue, which is believed to be causally associated with chronic low-grade inflammation and insulin resistance. Regular physical exercise decreases overall morbidity in obese subjects, which may be due to modulations of inflammatory pathways. In this randomized clinical trial we investigated the separate effects of endurance training-induced weight loss, diet-induced weight loss, and endurance training per se (without weight loss) on plasma adiponectin multimer composition (Western blotting) and adipose tissue macrophage content (immunohistochemistry) in young, moderately overweight men. Weight loss and endurance training per se decreased whole body fat percentage in an additive manner. No intervention-induced changes were observed for plasma total adiponectin. Surprisingly, endurance training, irrespectively of any associated weight loss, shifted the adiponectin multimer distribution toward a lower molecular weight (21% decrease in HMW/LMW, P = 0.015), whereas diet-induced weight loss shifted the distribution toward a higher molecular weight (42% increase in HMW/MMW, P < 0.001). Furthermore, endurance training per se increased the number of anti-inflammatory CD163? macrophages [from 12.7 ± 2.1 (means ± SE) to 16.1 ± 3.1 CD163? cells/100 adipocytes, P = 0.013], whereas diet-induced weight loss tended to decrease CD68? macrophages in subcutaneous abdominal adipose tissue. Thus regular physical exercise influences systemic and adipose tissue inflammatory pathways differently than diet-induced weight loss in younger, moderately overweight men. Our data suggest that some of the health benefits of a physically active lifestyle may occur through modulations of anti- rather than pro-inflammatory pathways in young, overweight men. PMID:23842679

Auerbach, Pernille; Nordby, Pernille; Bendtsen, Line Q; Mehlsen, Jesper L; Basnet, Smita K; Vestergaard, Henrik; Ploug, Thorkil; Stallknecht, Bente

2013-09-01

18

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

PubMed

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

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

2013-03-01

19

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

20

Small angle X-ray scattering of wheat seed-storage proteins: alpha-, gamma- and omega-gliadins and the high molecular weight (HMW) subunits of glutenin.  

PubMed

Small angle X-ray scattering in solution was performed on seed-storage proteins from wheat. Three different groups of gliadins (alpha-, gamma- and omega-) and a high molecular weight (HMW) subunit of glutenin (1Bx20) were studied to determine molecular size parameters. All the gliadins could be modelled as prolate ellipsoids with extended conformations. The HMW subunit existed as a highly extended rod-like particle in solution with a length of about 69 nm and a diameter of about 6.4 nm. Specific aggregation effects were observed which may reflect mechanisms of self-assembly that contribute to the unique viscoelastic properties of wheat dough. PMID:10082963

Thomson, N H; Miles, M J; Popineau, Y; Harries, J; Shewry, P; Tatham, A S

1999-03-19

21

A large molecular size fraction of riverine high molecular weight dissolved organic matter (HMW DOM) stimulates growth of the harmful dinoflagellate Alexandrium minutum  

Microsoft Academic Search

An increase in the concentration of riverine dissolved organic matter (DOM) has been observed during the last decades, and this material can stimulate marine plankton in coastal waters with significant freshwater input. We studied the effect of two size fractions of riverine high molecular weight dissolved organic matter (HMW DOM), isolated with tangential ultrafiltration, on the harmful dinoflagellate Alexandrium minutum

Tony Fagerberg; Per Carlsson; Mikael Lundgren

2009-01-01

22

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

PubMed

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. We investigated whether the changes in adiponectin with an intensive lifestyle intervention (ILI) for weight loss could potentially mediate the increase in low HDL-cholesterol (HDL-C) with ILI. Adiponectin and its fractions were determined using an ELISA with selective protease treatment in 1,397 participants from Look AHEAD, a trial examining whether ILI will reduce cardiovascular events in overweight/obese subjects with T2DM when compared with a control arm, diabetes support and education (DSE). Multivariable regression and mediational analyses were performed for adiponectin and its high-molecular-weight (HMW) and non-HMW fractions. ILI increased baseline HDL-C by 9.7% and adiponectin by 11.9%; changes with DSE were 1.3% and 0.2%, respectively (P < 0.0001). In a model including changes in weight, fitness, triglycerides, and glucose control and that adjusted for demographics and medical history, adiponectin changes remained significantly associated with HDL-C change. Data supported the contribution of changes in both HMW- and non-HMW-adiponectin to the improvement in HDL-C with ILI. PMID:22956782

Belalcazar, L Maria; Lang, Wei; Haffner, Steven M; Hoogeveen, Ron C; Pi-Sunyer, F Xavier; Schwenke, Dawn C; Balasubramanyam, Ashok; Tracy, Russell P; Kriska, Andrea P; Ballantyne, Christie M

2012-12-01

23

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

PubMed Central

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

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

2013-01-01

24

Adiponectin and markers of metabolic syndrome in obese children and adolescents: impact of 8-mo regular physical exercise program.  

PubMed

Background:Adiponectin circulates as low-, medium-, and high-molecular-weight multimers (LMW, MMW, and HMW) and influences lipid profile and insulin resistance (IR), HMW being considered as the most biologically active form. We aimed to study the relation between adiponectin and markers of metabolic syndrome (MS) in pediatric obesity, and the impact of physical exercise.Methods:The study consisted of a cross-sectional part and an 8-mo physical exercise program. Lipid profile, insulin, glucose, C-reactive protein (CRP), total adiponectin (TA), and homeostasis model assessment IR (HOMA-IR) were measured. Adiponectin multimers were studied in a prepubertal group.Results:Obesity is associated with increased dyslipidemia, IR, and inflammation. TA is correlated inversely with adiposity, triglycerides, HOMA-IR, and CRP, and positively with high-density lipoprotein cholesterol (HDLc)/total cholesterol (TC) ratio. HMW mimicked TA associations. The intervention program led to a reduction of TC, low-density lipoprotein cholesterol (LDLc), insulin, HOMA-IR, and trunk percentage of fat, and an increase of HDLc/TC ratio, in the obese group. BMI improvements prevented adiponectin reduction and correlated with increments in HMW and MMW.Conclusion:Obesity-related increase in MS features might be linked to lower adiponectin. HMW and MMW were the multimers that most explained the MS features. The intervention program improved the lipid profile and IR, and prevented the reduction of adiponectin. PMID:24819375

Nascimento, Henrique; Costa, Elísio; Rocha, Susana; Lucena, Clarice; Rocha-Pereira, Petronila; Rêgo, Carla; Mansilha, Helena Ferreira; Quintanilha, Alexandre; Aires, Luísa; Mota, Jorge; Santos-Silva, Alice; Belo, Luís

2014-08-01

25

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

26

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

PubMed

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

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

2013-03-01

27

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

PubMed Central

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

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

2009-01-01

28

Disulfide-dependent self-assembly of adiponectin octadecamers from trimers and presence of stable octadecameric adiponectin lacking disulfide bonds in vitro.  

PubMed

Adiponectin is a circulating insulin-sensitizing hormone that homooligomerizes into trimers, hexamers, and higher molecular weight (HMW) species. Low levels of circulating HMW adiponectin appear to increase the risk for insulin resistance. Currently, assembly of adiponectin oligomers and, consequently, mechanisms responsible for decreased HMW adiponectin in insulin resistance are not well understood. In the work reported here, we analyzed the reassembly of the most abundant HMW adiponectin species, the octadecamer, following its collapse to smaller oligomers in vitro. Purified bovine serum adiponectin octadecamer was treated with reducing agents at pH 5 to obtain trimers. These reduced trimers partially and spontaneously reassembled into octadecamers upon oxidative formation of disulfide bonds. Disulfide bonds appear to occupy a greater role in the process of oligomerization than in the structural stabilization of mature octadecamer. Stable octadecamers lacking virtually all disulfide bonds could be observed in abundance using native gel electrophoresis, dynamic light scattering, and collision-induced dissociation nanoelectrospray ionization mass spectrometry. These findings indicate that while disulfide bonds help to maintain the mature octadecameric adiponectin structure, their more important function is to stabilize intermediates during the assembly of octadecamer. Adiponectin oligomerization must proceed through intermediates that are at least partially reduced. Accordingly, fully oxidized adiponectin hexamers failed to reassemble into octadecamers at a rate comparable to that of reduced trimers. As the findings from the present study are based on in vitro experiments, their in vivo relevance remains unclear. Nevertheless, they describe a redox environment-dependent model of adiponectin oligomerization that can be tested using cell-based approaches. PMID:19943704

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

2009-12-29

29

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

PubMed Central

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

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

2013-01-01

30

Influence of Androgens on Circulating Adiponectin in Male and Female Rodents  

PubMed Central

Several endocrine factors, including sex-steroid hormones are known to influence adiponectin secretion. Our purpose was to evaluate the influence of testosterone and of the synthetic non-aromatizable/non-5? reducible androgen 17?-hydroxyestra-4,9,11-trien-3-one (trenbolone) on circulating adiponectin and adiponectin protein expression within visceral fat. Young male and female F344 rats underwent sham surgery (SHAM), gonadectomy (GX), or GX plus supraphysiologic testosterone-enanthate (TE) administration. Total circulating adiponectin was 39% higher in intact SHAM females than SHAM males (p<0.05). GX increased total adiponectin by 29–34% in both sexes (p<0.05), while TE reduced adiponectin to concentrations that were 46–53% below respective SHAMs (p?0.001) and ablated the difference in adiponectin between sexes. No differences in high molecular weight (HMW) adiponectin were observed between sexes or treatments. Adiponectin concentrations were highly and negatively associated with serum testosterone (males: r?=??0.746 and females: r?=??0.742, p?0.001); however, no association was present between adiponectin and estradiol. In separate experiments, trenbolone-enanthate (TREN) prevented the GX-induced increase in serum adiponectin (p?0.001) in young animals, with Low-dose TREN restoring adiponectin to the level of SHAMs and higher doses of TREN reducing adiponectin to below SHAM concentrations (p?0.001). Similarly, TREN reduced adiponectin protein expression within visceral fat (p<0.05). In adult GX males, Low-dose TREN also reduced total adiponectin and visceral fat mass to a similar magnitude as TE, while increasing serum HMW adiponectin above SHAM and GX animals (p<0.05). Serum adiponectin was positively associated with visceral fat mass in young (r?=?0.596, p?0.001) and adult animals (r?=?0.657, p?0.001). Our results indicate that androgens reduce circulating total adiponectin concentrations in a dose-dependent manner, while maintaining HMW adiponectin. This change is directionally similar to the androgen-induced lipolytic effects on visceral adiposity and equal in magnitude between TE and TREN, suggesting that neither the aromatization nor the 5? reduction of androgens is required for this effect.

Yarrow, Joshua F.; Beggs, Luke A.; Conover, Christine F.; McCoy, Sean C.; Beck, Darren T.; Borst, Stephen E.

2012-01-01

31

Influence of androgens on circulating adiponectin in male and female rodents.  

PubMed

Several endocrine factors, including sex-steroid hormones are known to influence adiponectin secretion. Our purpose was to evaluate the influence of testosterone and of the synthetic non-aromatizable/non-5? reducible androgen 17?-hydroxyestra-4,9,11-trien-3-one (trenbolone) on circulating adiponectin and adiponectin protein expression within visceral fat. Young male and female F344 rats underwent sham surgery (SHAM), gonadectomy (GX), or GX plus supraphysiologic testosterone-enanthate (TE) administration. Total circulating adiponectin was 39% higher in intact SHAM females than SHAM males (p<0.05). GX increased total adiponectin by 29-34% in both sexes (p<0.05), while TE reduced adiponectin to concentrations that were 46-53% below respective SHAMs (p?0.001) and ablated the difference in adiponectin between sexes. No differences in high molecular weight (HMW) adiponectin were observed between sexes or treatments. Adiponectin concentrations were highly and negatively associated with serum testosterone (males: r = -0.746 and females: r = -0.742, p?0.001); however, no association was present between adiponectin and estradiol. In separate experiments, trenbolone-enanthate (TREN) prevented the GX-induced increase in serum adiponectin (p?0.001) in young animals, with Low-dose TREN restoring adiponectin to the level of SHAMs and higher doses of TREN reducing adiponectin to below SHAM concentrations (p?0.001). Similarly, TREN reduced adiponectin protein expression within visceral fat (p<0.05). In adult GX males, Low-dose TREN also reduced total adiponectin and visceral fat mass to a similar magnitude as TE, while increasing serum HMW adiponectin above SHAM and GX animals (p<0.05). Serum adiponectin was positively associated with visceral fat mass in young (r = 0.596, p?0.001) and adult animals (r = 0.657, p?0.001). Our results indicate that androgens reduce circulating total adiponectin concentrations in a dose-dependent manner, while maintaining HMW adiponectin. This change is directionally similar to the androgen-induced lipolytic effects on visceral adiposity and equal in magnitude between TE and TREN, suggesting that neither the aromatization nor the 5? reduction of androgens is required for this effect. PMID:23071783

Yarrow, Joshua F; Beggs, Luke A; Conover, Christine F; McCoy, Sean C; Beck, Darren T; Borst, Stephen E

2012-01-01

32

Reduced adiponectin signaling due to weight gain results in nonalcoholic steatohepatitis through impaired mitochondrial biogenesis.  

PubMed

Obesity and adiponectin depletion have been associated with the occurrence of nonalcoholic fatty liver disease (NAFLD). The goal of this study was to identify the relationship between weight gain, adiponectin signaling, and development of nonalcoholic steatohepatitis (NASH) in an obese, diabetic mouse model. Leptin-receptor deficient (Lepr(db/db) ) and C57BL/6 mice were administered a diet high in unsaturated fat (HF) (61%) or normal chow for 5 or 10 weeks. Liver histology was evaluated using steatosis, inflammation, and ballooning scores. Serum, adipose tissue, and liver were analyzed for changes in metabolic parameters, messenger RNA (mRNA), and protein levels. Lepr(db/db) HF mice developed marked obesity, hepatic steatosis, and more than 50% progressed to NASH at each timepoint. Serum adiponectin level demonstrated a strong inverse relationship with body mass (r?=?-0.82; P?adiponectin level was an independent predictor of NASH (13.6 ?g/mL; P?adiponectin, and impaired lipid metabolism. HF lepr (db/db) NASH mice exhibited diminished hepatic adiponectin signaling evidenced by reduced levels of adiponectin receptor-2, inactivation of adenosine monophosphate activated protein kinase (AMPK), and decreased expression of genes involved in mitochondrial biogenesis and ?-oxidation (Cox4, Nrf1, Pgc1?, Pgc1? and Tfam). In contrast, recombinant adiponectin administration up-regulated the expression of mitochondrial genes in AML-12 hepatocytes, with or without lipid-loading. Conclusion: Lepr(db/db) mice fed a diet high in unsaturated fat develop weight gain and NASH through adiponectin depletion, which is associated with adipose tissue inflammation and hepatic mitochondrial dysfunction. We propose that this murine model of NASH may provide novel insights into the mechanism for development of human NASH. (Hepatology 2014;60:133-145). PMID:24464605

Handa, Priya; Maliken, Bryan D; Nelson, James E; Morgan-Stevenson, Vicki; Messner, Donald J; Dhillon, Barjinderjit K; Klintworth, Heather M; Beauchamp, Mary; Yeh, Matthew M; Elfers, Clinton T; Roth, Christian L; Kowdley, Kris V

2014-07-01

33

Ghrelin, Leptin, Adiponectin, and Insulin Levels and Concurrent and Future Weight Change in Overweight Postmenopausal Women  

PubMed Central

Objective Weight loss and maintenance can be particularly challenging for postmenopausal women given the changes in body composition, metabolism, and lifestyle that can accompany the menopausal transition. Peptides mediating energy homeostasis (i.e., ghrelin, leptin, adiponectin, and insulin) may play an important role in the weight and body composition changes of postmenopausal women, and may in turn be affected by hormone therapy (HT) use. This study examines how success with weight loss may be related to peptides mediating energy homeostasis and HT use. Methods The present analysis involves 200 women from a lifestyle intervention trial in overweight, postmenopausal women for whom data on the peptides ghrelin, leptin, adiponectin, and insulin were collected at 0 and 18 months. Peptide levels were compared to changes in weight from 0-18 and18-30 months. Results Baseline peptide levels were not significantly related to future weight change. From 0-18 months, ghrelin (p=0.0005) and adiponectin (p=<0.0001) levels increased, while leptin (p=<0.0001), and insulin (p=0.0003) decreased with increasing amount of weight loss. However, only leptin change was related to 18-30 month weight change. Women who were on HT at 0 months but discontinued by 18 months had a greater increase in ghrelin from 0-18 months compared to women with continuous HT use or non-use. Conclusions In overweight, postmenopausal women, changes in energy homeostasis peptides relate to both concurrent and future weight change. Future studies should continue to address the how ghrelin, leptin, insulin, and adiponectin contribute to body composition changes and weight loss maintenance after menopause.

Soni, Amy C.; Conroy, Molly B.; Mackey, Rachel H.; Kuller, Lewis H.

2010-01-01

34

Process For Autoclaving HMW PMR-II Composites  

NASA Technical Reports Server (NTRS)

Parts made of graphite-reinforced, high-molecular-weight (HMW) PMR-II polyimide easy to fabricate by autoclaving. Study showed autoclaved HMW PMR-II parts equal in quality to those made by compression molding. Well suited to use at temperatures up to 700 degrees F (371 degrees C). In aircraft engines, they offer advantages of strength and light weight.

Vannucci, Raymond D.; Cifani, Diane

1990-01-01

35

Increased serum C1q-binding adiponectin complex to total-adiponectin ratio in men with multi-vessel coronary disease  

PubMed Central

Background Adiponectin plays a role as a positive contributor to the stabilization of atherosclerotic plaques. Circulating total adiponectin (Total-APN) levels associates with the number of coronary vessels in men with coronary artery disease (CAD). We recently reported that adiponectin binds to C1q in human blood, and serum C1q-binding adiponectin (C1q-APN) /Total-APN levels are associated with CAD in type 2 diabetic subjects. The present study investigated the relationship between circulating C1q-APN levels and the number of angiographic coronary artery vessel in male subjects. Methods The study subjects were 53 male Japanese patients who underwent diagnostic coronary angiography. Blood total adiponectin (Total-APN), high-molecular weight adiponectin (HMW-APN), C1q-APN and C1q were measured by enzyme-linked immunosorbent assays. Results Serum C1q-APN/Total-APN ratio significantly increased in subjects with single and multi-vessel coronary diseases (p?=?0.029 for trend, the Kruskal-Wallis test). However, serum Total-APN, HMW-APN, C1q-APN and C1q levels did not correlate with number of diseased coronary vessels. Conclusion Serum C1q-APN/Total-APN ratio progressively increases in men with single and multi-vessel coronary disease. Trial registration UMIN000002997

2014-01-01

36

Adiponectin and Atherosclerosis in Rheumatoid Arthritis  

PubMed Central

In the present study, we examined the potential impact of adiponectin on carotid ultrasound determined atherosclerosis in 210 (119 black and 91 white) RA patients in mixed regression models. Total adiponectin concentrations were smaller in patients with compared to those without the metabolic syndrome (MetS) defined waist criterion (median (range) = 6.47 (1.23–34.54) versus 8.38 (0.82–85.30)?ng/mL, P = 0.02, resp.); both total and high molecular weight (HMW) adiponectin concentrations were larger in patients with compared to those without joint deformities (7.97 (0.82–85.30) and 3.51 (0.01–35.40) versus 5.36 (1.29–19.49) and 2.34 (0.01–19.49)?ng/mL, P = 0.003 and 0.02, resp.). Total and HMW adiponectin concentrations were associated with carotid artery plaque in patients with MetS waist (odds ratio (95% CI) = 0.87 (0.76–0.99) and 0.92 (0.85–0.99) per 1-standard deviation increment, P = 0.02 for both) and those without joint deformities (odds ratio (95% CI) = 0.94 (0.88–0.99) and 0.94 (0.89–0.99), P = 0.03 for both). Plaque prevalence was lower in patients without compared to those with joint deformities (23.4% versus 42.6, P = 0.004 in multivariable analysis). In RA patients with abdominal obesity or no clinically evident joint damage, adiponectin concentrations are reduced but nevertheless associated with decreased carotid atherosclerosis.

Dessein, Patrick H.; Tsang, Linda; Solomon, Ahmed; Woodiwiss, Angela J.; Millen, Aletta M. E.; Norton, Gavin R.

2014-01-01

37

Association of Leptin and Adiponectin Levels with Three-year Weight Change among Japanese Male Workers.  

PubMed

The purpose of this study was to clarify, through a prospective study, the relationship between leptin and adiponectin levels, and subsequent weight change. The study subjects were 2,485 male office workers aged 35-64 employed by a company in Fukuoka Prefecture, Japan. Of these men, 1,936 (77.9%) received health check-ups both in 2005-2007 and 3 years later, in 2008-2010. Of the subjects who received both health check-ups, 352 were excluded duo to cancer, cardiac infarction, stroke or diabetes mellitus, leaving a total of 1,584. We divided them into tertiles according to baseline leptin and adiponectin levels, and compared the subsequent change in body mass index (BMI) over 3 years. The subjects with the lowest leptin levels showed a significantly greater increase in BMI (difference in change in BMI?0.178kg/m2, 95% CI:0.025-0.331kg/m2) over 3 years when those with the highest leptin levels were regarded as the reference even after adjusting for age, baseline BMI, smoking status, drinking status and exercise. The subjects with the highest adiponectin levels showed a greater increase in BMI (difference in change in BMI?0.099kg/m2, 95% CI:?0.034-0.231kg/m2) over 3 years when those with the lowest adiponectin levels were regarded as the reference, but this association was not statistically significant after adjusting for age, baseline BMI, smoking status, drinking status and exercise. Our findings suggest that higher leptin levels may suppress weight gain in Japanese male workers. PMID:24942792

Yamaguchi, Junichi; Imatoh, Takuya; Une, Hiroshi

2014-06-01

38

Adiponectin levels do not change with moderate dietary induced weight loss and exercise in obese postmenopausal women  

Microsoft Academic Search

OBJECTIVE: The purpose of this study was to determine changes in adiponectin levels with moderate weight loss, weight loss plus aerobic exercise, or weight loss plus resistive exercise in overweight and obese, sedentary postmenopausal women.DESIGN: Longitudinal, clinical intervention study of 6-month (3 × \\/week) program of either weight loss (WL, n=15), weight loss + aerobic exercise (WL+AEX, n=16), or weight

A S Ryan; B J Nicklas; D M Berman; D Elahi

2003-01-01

39

The Haemophilus influenzae HMW1C Protein Is a Glycosyltransferase That Transfers Hexose Residues to Asparagine Sites in the HMW1 Adhesin  

PubMed Central

The Haemophilus influenzae HMW1 adhesin is a high-molecular weight protein that is secreted by the bacterial two-partner secretion pathway and mediates adherence to respiratory epithelium, an essential early step in the pathogenesis of H. influenzae disease. In recent work, we discovered that HMW1 is a glycoprotein and undergoes N-linked glycosylation at multiple asparagine residues with simple hexose units rather than N-acetylated hexose units, revealing an unusual N-glycosidic linkage and suggesting a new glycosyltransferase activity. Glycosylation protects HMW1 against premature degradation during the process of secretion and facilitates HMW1 tethering to the bacterial surface, a prerequisite for HMW1-mediated adherence. In the current study, we establish that the enzyme responsible for glycosylation of HMW1 is a protein called HMW1C, which is encoded by the hmw1 gene cluster and shares homology with a group of bacterial proteins that are generally associated with two-partner secretion systems. In addition, we demonstrate that HMW1C is capable of transferring glucose and galactose to HMW1 and is also able to generate hexose-hexose bonds. Our results define a new family of bacterial glycosyltransferases.

Grass, Susan; Lichti, Cheryl F.; Townsend, R. Reid; Gross, Julia; St. Geme, Joseph W.

2010-01-01

40

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.

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

2014-01-01

41

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

PubMed Central

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

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

1992-01-01

42

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.

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

2014-01-01

43

Nuchal thickness of subcutaneous adipose tissue is tightly associated with an increased LMW/total adiponectin ratio in obese juveniles.  

PubMed

Subcutaneous adipose tissue (SAT) topography contributes significantly to metabolic risk profiles and atherosclerotic vascular burden in obese adults. However, little information exists concerning individual risk profiles in early phases of obesity found in childhood and adolescence. Thus, the rationale of this study was to evaluate possible impacts of SAT topography in obese juveniles on adiponectin subfractions, with special emphasis on low molecular weight (LMW) adiponectin. To address this, we analysed associations between lipometry, early metabolic and preatherosclerotic symptoms and adiponectin subfractions in 71 obese juveniles and 75 normal weight controls of similar age and gender distribution. Compared to the controls, obese juveniles had a significantly decreased ratio between high molecular weight (HMW) and total adiponectin whereas the LMW/total adiponectin ratio was increased. The LMW/total adiponectin ratio correlated significantly positively with the SAT thickness of trunk-located lipometer measure points neck, biceps, upper back, lower back, body mass index (BMI), and waist circumference. Further significant positive correlations were seen with systolic blood pressure, intima media thickness (IMT) of common carotid arteries, and metabolic parameters such as HOMA-index, leptin, oxidized LDL (oxLDL), liver transaminases, and HDL-triglycerides. This remained stable after controlling for gender. A stepwise multiple regression analysis encompassing all these variables revealed a robust positive association between LMW/total adiponectin ratio and nuchal SAT thickness defined by the lipometer measure point neck. Taken together, our data provide the first evidence that nuchal SAT thickness is tightly positively associated with an increased LMW/total adiponectin ratio. PMID:18656877

Mangge, Harald; Almer, Gunter; Haj-Yahya, Samih; Grandits, Nadja; Gasser, Robert; Pilz, Stefan; Möller, Reinhard; Horejsi, Renate

2009-03-01

44

Transformation of wheat with the HMW-GS 1Bx14 gene without markers  

Microsoft Academic Search

High molecular weight (HMW) glutenin polypeptides are critical contributors to the visco\\/elastic properties responsible for\\u000a the processing characteristics and utilizations of wheat flour. In order to improve bread making quality of flour and produce\\u000a transgenic plants free of selectable markers, a linear DNA construct consisting of a minimal expression cassette with the\\u000a HMW-GS 1Bx14 gene was transformed into wheat cultivar

X. Liu; W. Jin; J. Liu; H. Zhao; A. Guo

2011-01-01

45

Impact of high-/middle-molecular-weight adiponectin on the synthesis and regulation of extracellular matrix in dermal fibroblasts.  

PubMed

Adiponectin has been shown to play a critical role in immunity. Recently, we reported that the adiponectin levels after allogeneic stem cell transplantation were higher in recipients with chronic graft-versus-host disease (cGVHD). However, the effects of adiponectin on extracellular matrix (ECM) and regulatory factors in dermal fibroblasts remain unclear. We compared the messenger RNA (mRNA) levels of collagen type1 (COL1A), fibronectin 1 (FN1), matrix metalloproteinase (MMP)1, MMP3, tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, transforming growth factor-? (TGF-?), and TGF-? receptor 2 (TGF-?R2) in human normal dermal fibroblasts cultured with and without adiponectin, and we assessed the degree of synthesis of ECMs by immunofluorescent microscopy. Furthermore, we also assessed these mRNA levels after blocking of TGF-?R2. Adiponectin induced higher mRNA levels of FN1, MMP1, MMP3, TIMP1, TIMP3, and TGF-?R2 in a dose-dependent manner, but did not significantly affect COL1A or TGF-?. In addition, adiponectin was shown to upregulate FN1, MMPs, and TIMPs after blocking of TGF-?R2. Immunofluorescent microscopy revealed that adiponectin promoted a greater synthesis of ECMs than in the control in vitro. The finding that adiponectin upregulated ECM-associated factors might mean that high levels of adiponectin could modulate dermal fibrosis was observed in recipients with cGVHD. Further basic investigation is warranted to elucidate whether the adiponectin-pathway could be a target for the treatment of sclerotic cGVHD. PMID:24407161

Nakasone, Hideki; Terasako-Saito, Kiriko; Yamazaki, Rie; Sato, Miki; Tanaka, Yukie; Sakamoto, Kana; Kurita, Masakazu; Yamasaki, Ryoko; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Machishima, Tomohito; Ashizawa, Masahiro; Kimura, Shun-Ichi; Kikuchi, Misato; Tanihara, Aki; Kanda, Junya; Kako, Shinichi; Nishida, Junji; Yamada, Shigeki; Kanda, Yoshinobu

2014-04-01

46

Serum C1q- binding adiponectin in maintenance hemodialysis patients  

PubMed Central

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

2013-01-01

47

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.

2014-01-01

48

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

49

Pediatric obesity and vitamin D deficiency: a proteomic approach identifies multimeric adiponectin as a key link between these conditions.  

PubMed

Key circulating molecules that link vitamin D (VD) to pediatric obesity and its co-morbidities remain unclear. Using a proteomic approach, our objective was to identify key molecules in obese children dichotomized according to 25OH-vitamin D (25OHD) levels. A total of 42 obese children (M/F?=?18/24) were divided according to their 25OHD3 levels into 25OHD3 deficient (VDD; n?=?18; 25OHD<15 ng/ml) or normal subjects (NVD; n?=?24; >30 ng/ml). Plasma proteomic analyses by two dimensional (2D)-electrophoresis were performed at baseline in all subjects. VDD subjects underwent a 12mo treatment with 3000 IU vitamin D3 once a week to confirm the proteomic analyses. The proteomic analyses identified 53 "spots" that differed between VDD and NVD (p<0.05), amongst which adiponectin was identified. Adiponectin was selected for confirmational studies due to its tight association with obesity and diabetes mellitus. Western Immunoblot (WIB) analyses of 2D-gels demonstrated a downregulation of adiponectin in VDD subjects, which was confirmed in the plasma from VDD with respect to NVD subjects (p<0.035) and increased following 12mo vitamin D3 supplementation in VDD subjects (p<0.02). High molecular weight (HMW) adiponectin, a surrogate indicator of insulin sensitivity, was significantly lower in VDD subjects (p<0.02) and improved with vitamin D3 supplementation (p<0.042). A direct effect in vitro of 1?,25-(OH)2D3 on adipocyte adiponectin synthesis was demonstrated, with adiponectin and its multimeric forms upregulated, even at low pharmacological doses (10(-9) M) of 1?,25-(OH)2D3. This upregulation was paralleled by the adiponectin interactive protein, DsbA-L, suggesting that the VD regulation of adiponectin involves post-transciptional events. Using a proteomic approach, multimeric adiponectin has been identified as a key plasma protein that links VDD to pediatric obesity. PMID:24404137

Walker, Gillian E; Ricotti, Roberta; Roccio, Marta; Moia, Stefania; Bellone, Simonetta; Prodam, Flavia; Bona, Gianni

2014-01-01

50

The Relationships Between IGF-1 and CRP, NO, Leptin, and Adiponectin During Weight Loss in the Morbidly Obese  

Microsoft Academic Search

Background  The relationship between C-reactive protein (CRP), nitric oxide (NO), leptin, adiponectin, and insulin growth factor 1 (IGF-1)\\u000a is poorly defined in morbidly obese patients before and after gastric bypass and, in some cases, is controversial.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We examined the plasma of 34 morbidly obese patients before and 1, 6, and 12 months after Roux-en-Y gastric bypass surgery.\\u000a \\u000a \\u000a \\u000a Results  Obese people had more CRP

Eva Pardina; Roser Ferrer; Juan Antonio Baena-Fustegueras; Albert Lecube; Jose Manuel Fort; Víctor Vargas; Roberto Catalán; Julia Peinado-Onsurbe

2010-01-01

51

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

52

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

53

Adiponectin as a routine clinical biomarker.  

PubMed

Adiponectin is a protein synthesized and secreted predominantly by adipocytes into the peripheral blood. However, circulating adiponectin level is inversely related with body weight, especially visceral fat accumulation. The mechanism of this paradoxical relation remains obscure. Low circulating adiponectin concentrations (hypoadiponectinemia; <4 ?g/mL) are associated with a variety of diseases, including dysmetabolism (type 2 diabetes, insulin resistance, hypertension, dyslipidemia, metabolic syndrome, hyperuricemia), atherosclerosis (coronary artery disease, stroke, peripheral artery disease), sleep apnea, non-alcoholic fatty liver disease, gastritis and gastro-esophageal reflux disease, inflammatory bowel diseases, pancreatitis, osteoporosis, and cancer (endometrial cancer, postmenopausal breast cancer, leukemia, colon cancer, gastric cancer, prostate cancer). On the other hand, hyperadiponectinemia is associated with cardiac, renal and pulmonary diseases. This review article focuses on the significance of adiponectin as a clinical biomarker of obesity-related diseases. Routine measurement of adiponectin in patients with lifestyle-related diseases is highly recommended. PMID:24417951

Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

2014-01-01

54

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

55

Adiponectin and lipoprotein metabolism.  

PubMed

Adiponectin is secreted by the adipose tissue and it has been shown to be down-regulated in states of insulin resistance and in cardiovascular disease. It has also been found to be correlated with various parameters of lipoprotein metabolism, and in particular, it is associated with the metabolism of high-density lipoprotein (HDL) and triglycerides; adiponectin appears to induce an increase in serum HDL, and conversely, HDL can up-regulate adiponectin levels, and in addition, adiponectin lowers serum triglycerides through enhancement of the catabolism of triglyceride-rich lipoproteins. Studies investigating whether adiponectin is causally linked with lipoprotein metabolism have yielded conflicting data, and the mechanisms underlying the interplay between adiponectin and lipoproteins remain to be elucidated. The adiponectin-HDL relationship can explain at least in part the presumed protective role of adiponectin in cardiovascular disease and the adiponectin changes observed after dieting, exercise and lipid-lowering treatment. Statins, fibrates, niacin and n-3 fatty acids may influence circulating adiponectin levels, indicating that adiponectin may mediate some of the metabolic effects of these agents. Further studies to investigate more thoroughly the role of adiponectin in lipoprotein metabolism in the human setting should be carefully planned, focusing on causality and the possible impact of adiponectin on the pathogenesis of cardiovascular disease. PMID:23957239

Christou, G A; Kiortsis, D N

2013-12-01

56

High sputum total adiponectin is associated with low odds for asthma.  

PubMed

Abstract Objective: Adipose tissue produces adiponectin, an anti-inflammatory protein. High systemic total adiponectin is associated with a low risk for incident asthma but the association with lung adiponectin is not known. Our objective was to evaluate the association between sputum total adiponectin and asthma. Methods: This case-control study included 44 cases with objectively-confirmed asthma and an equal number of body mass index (BMI) and sex-matched controls. Serum and sputum adiponectin were estimated by ELISA and Western Blot technique, respectively. While Fisher's exact test, t-test and Spearman's correlations were used for univariate analyses, Spearman and regression analyses were performed for multivariable analyses. Results: While high-molecular-weight adiponectin was the dominant isoform in serum, medium-molecular-weight isoform was dominant in sputum. Sputum total adiponectin was not correlated with serum adiponectin or BMI. Sputum total adiponectin was lower among asthmatics than controls (p?=?0.03), although individual sputum isoforms were not similarly associated. High sputum total adiponectin was associated with lower odds for asthma (OR 0.33, 95% C.I. 0.12, 0.91), even after adjustment for systemic adiposity measures including serum adiponectin. Conclusions: High sputum total adiponectin predicted lower odds for asthma, even after adjustment for serum adiponectin. Although not studied, it is possible that pharmacological modulation of sputum adiponectin may suggest new ways to prevent and/or treat asthma. PMID:24447284

Sood, Akshay; Seagrave, JeanClare; Herbert, Guy; Harkins, Michelle; Alam, Yasir; Chiavaroli, Annalisa; Shohreh, Rugia; Montuschi, Paolo; Campen, Matthew; Harmon, Molly; Qualls, Clifford; Berwick, Marianne; Schuyler, Mark

2014-06-01

57

Genetics of adiponectin.  

PubMed

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

Breitfeld, Jana; Stumvoll, Michael; Kovacs, Peter

2012-10-01

58

Adiponectin and energy homeostasis.  

PubMed

White adipose tissue (WAT) is the premier energy depot. Since the discovery of the hormonal properties of adipose-secreted proteins such as leptin and adiponectin, WAT has been classified as an endocrine organ. Although many regulatory effects of the adipocyte-derived hormones on various biological systems have been identified, maintaining systemic energy homeostasis is still the essential function of most adipocyte-derived hormones. Adiponectin is one adipocyte-derived hormone and well known for its effect in improving insulin sensitivity in liver and skeletal muscle. Unlike most other adipocyte-derived hormones, adiponectin gene expression and blood concentration are inversely associated with adiposity. Interestingly, recent studies have demonstrated that, in addition to its insulin sensitizing effects, adiponectin plays an important role in maintaining energy homeostasis. In this review, we summarize the progress of research about 1) the causal relationship of adiposity, energy intake, and adiponectin gene expression; and 2) the regulatory role of adiponectin in systemic energy metabolism. PMID:24170312

Lee, Bonggi; Shao, Jianhua

2014-06-01

59

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

60

Vagal hyperactivity due to ventromedial hypothalamic lesions increases adiponectin production and release.  

PubMed

In obese humans and animals, adiponectin production and release in adipose tissue are downregulated by feedback inhibition, resulting in decreased serum adiponectin. We investigated adiponectin production and release in ventromedial hypothalamic (VMH)-lesioned animals. VMH-lesioned mice showed significant increases in food intake and body weight gain, with hyperinsulinemia and hyperleptinemia at 1 and 4 weeks after VMH-lesioning. Serum adiponectin was elevated in VMH-lesioned mice at 1 and 4 weeks, despite adipocyte hypertrophy in subcutaneous and visceral adipose tissues and increased body fat. Adiponectin production and mRNA were also increased in both adipose tissues in VMH-lesioned mice at 1 week. These results were replicated in VMH-lesioned rats at 1 week. Daily atropine administration for 5 days or subdiaphragmatic vagotomy completely reversed the body weight gain and eliminated the increased adiponectin production and release in these rats, with reversal to a normal serum adiponectin level. Parasympathetic nerve activation by carbachol infusion for 5 days in rats increased serum adiponectin, with increased adiponectin production in visceral and subcutaneous adipose tissues without changes of body weight. These results demonstrate that activation of the parasympathetic nerve by VMH lesions stimulates production of adiponectin in visceral and subcutaneous adipose tissues and adiponectin release, resulting in elevated serum adiponectin. PMID:24487025

Suzuki, Yoko; Shimizu, Hiroyuki; Ishizuka, Noriko; Kubota, Naoto; Kubota, Tetsuya; Senoo, Akira; Kageyama, Haruaki; Osaka, Toshimasa; Hirako, Satoshi; Kim, Hyoun-Ju; Matsumoto, Akiyo; Shioda, Seiji; Mori, Masatomo; Kadowaki, Takashi; Inoue, Shuji

2014-05-01

61

PLASMA ADIPONECTIN CONCENTRATIONS IN NON PREGNANT, NORMAL PREGNANCY AND OVERWEIGHT PREGNANT WOMEN  

PubMed Central

Aims Adiponectin is an adipokine that has anti-diabetic, anti-atherogenic, anti-inflammatory and angiogenic properties. This hormone has been implicated in both the physiological adaptation to normal pregnancy and obstetrical complications. The aims of this study were to determine normal maternal plasma concentrations of adiponectin throughout gestation and to explore the relationships between plasma adiponectin concentration, pregnancy, and maternal overweight. Study design A cross-sectional study was designed to include normal pregnant women (normal weight and overweight; 11–42 weeks of gestation), and non-pregnant women. Plasma adiponectin concentration was determined by immunoassay. Non-parametric statistics were used for analysis. Results (1) Adiponectin was detectable in the plasma of all patients; (2) there was no significant difference in the median adiponectin concentrations between pregnant and non-pregnant women; (3) plasma adiponectin concentrations were negatively correlated with gestational age only among normal weight pregnant women; and (4) overweight patients had significantly lower adiponectin concentrations than normal weight women. Conclusion Consistent with the increased insulin resistance and weight gain that occur in pregnancy, adiponectin concentrations were negatively correlated with gestational age. The results of this study and the nomogram herein presented can serve as the basis to explore the relationship between adiponectin and pregnancy complications and facilitate the clinical use of this important adipokine. Condensation Plasma adiponectin concentrations decrease with advancing gestational age only in nonobese women.

Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Gomez, Ricardo; Edwin, Samuel; Mazor, Moshe; Espinoza, Jimmy; Yoon, Bo Hyun; Hassan, Sonia S.

2008-01-01

62

Adiponectin and bariatric surgery: associations with diabetes and cardiovascular disease in the Swedish obese subjects study.  

PubMed

OBJECTIVE Adiponectin has been implicated in the pathogenesis of type 2 diabetes, but its role for incident diabetes, myocardial infarction, or stroke in obesity is unclear. The aim of this study was to analyze the associations between systemic levels of adiponectin and the aforementioned outcomes in a population with severe obesity at high risk of diabetes and cardiovascular events. RESEARCH DESIGN AND METHODS We measured serum concentrations of total adiponectin in 3,299 participants of the prospective controlled Swedish Obese Subjects (SOS) Study (bariatric surgery group, n = 1,570; control group given usual care, n = 1,729). Median follow-up periods ranged between 10 and 13 years for different outcomes. RESULTS In models containing both baseline adiponectin and 2-year changes in adiponectin, high baseline adiponectin and 2-year increases in adiponectin were associated with decreased risk of diabetes and myocardial infarction among controls. In the surgery group, the 2-year weight loss was paralleled by substantial increase in circulating adiponectin (1,807-1,958 ng/mL per 10-kg weight loss). However, neither baseline adiponectin nor 2-year increases in adiponectin were associated with risk of diabetes or myocardial infarction in the fully adjusted models in the surgery group. No associations were found for stroke in either group. CONCLUSIONS Taken together, baseline adiponectin and 2-year changes were associated with incident diabetes and myocardial infarction in the control group but not in the surgery group. Baseline adiponectin did not predict treatment benefit of bariatric surgery. PMID:24574342

Herder, Christian; Peltonen, Markku; Svensson, Per-Arne; Carstensen, Maren; Jacobson, Peter; Roden, Michael; Sjöström, Lars; Carlsson, Lena

2014-05-01

63

ADIPONECTIN IN SEVERE PREECLAMPSIA  

PubMed Central

Aims Adiponectin is an adipokine with insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic properties. The aims of this study were to determine whether maternal plasma adiponectin concentrations differ between patients with severe preeclampsia and those with normal pregnancies, and to explore the relationship between plasma adiponectin and the results of Doppler velocimetry of the uterine arteries. Methods This case-control study included two groups: (1) patients with severe preeclampsia (n=50) and (2) patients with normal pregnancies (n=150). Pulsed-wave and color Doppler ultrasound examination of the uterine arteries were performed. Plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results (1) Patients with severe preeclampsia had a higher median plasma concentration of adiponectin than that of normal pregnant women. (2) The median plasma adiponectin concentration did not differ between women with severe preeclampsia who had a high impedance to blood flow in the uterine arteries and those with normal impedance to blood flow. (3) Among patients with normal pregnancies, plasma adiponectin concentrations were negatively correlated with BMI in the first trimester and at sampling. Conclusions Women with severe preeclampsia have a higher median plasma concentration of adiponectin than that of normal pregnant women. This may reflect a compensatory feedback mechanism to the metabolically-altered, anti-angiogenic and pro-atherogenic state of severe preeclampsia.

Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Gomez, Ricardo; Edwin, Samuel; Mazor, Moshe; Espinoza, Jimmy; Yoon, Bo Hyun; Hassan, Sonia S.

2008-01-01

64

Prostate cancer and adiponectin  

Microsoft Academic Search

ObjectivesTo search for any relation between plasma adiponectin levels and the cellular differentiation or progression of prostate cancer (PCa). PCa is becoming an increasingly important public health problem, particularly for those countries with a trend toward an aging population. Because insulin resistance in the setting of obesity is associated with the development of PCa, we hypothesized that decreased adiponectin levels

Serdar Goktas; Mahmut Ilker Yilmaz; Kayser Caglar; Alper Sonmez; Selim Kilic; Selahattin Bedir

2005-01-01

65

Adiponectin and Arterial Stiffness  

Microsoft Academic Search

Background: Adiponectin, an anti-inflammatory adipocytokine, is reduced in hypertension, diabetes, and coronary artery disease (CAD). Arterial stiffness, as aortic pulse wave velocity (PWV) in hypertension and diabetes, and as augmentation index (AIx) in CAD, is independently associated with cardiovascular mortality. We explored the relationship between adiponectin and arterial stiffness in essential hypertension.Methods: Seventy-six untreated patients, 34 women, aged 47 ±

Azra Mahmud; John Feely

2005-01-01

66

Adiponectin and Polycystic Ovary Syndrome  

PubMed Central

Introduction Polycystic ovary syndrome (PCOS) has a prevalence of 5–8% in women of reproductive age. Women with PCOS have an increased risk of metabolic syndrome and associated comorbidities. Adiponectin is a circulating protein produced by adipocytes. Circulating levels of adiponectin are inversely related to adipocyte mass. Low levels occur with insulin resistance, type 2 diabetes, metabolic syndrome, and obesity-related cardiovascular disease. This article reviews the literature on the link between adiponectin and PCOS and the potential use of adiponectin as a biomarker for PCOS. Method Data-based studies on adiponectin and PCOS and adiponectin measurement were identified through the Medline (1950–2009) and ISI Web of Knowledge (1973–2009) databases. Results Fifteen studies related to adiponectin and PCOS met inclusion criteria and were included in this review. These studies present evidence that adiponectin is linked to insulin resistance, insulin sensitivity, body mass index (BMI), and adiposity. In women with PCOS, lower levels, as opposed to higher levels, of adiponectin occur in the absence of adiposity. Conclusion The relationships between adiponectin and insulin resistance and sensitivity, metabolic syndrome, and BMI in women with PCOS suggest that adiponectin potentially could serve as a marker for disease risk and provide opportunity for earlier intervention if knowledge is successfully translated from laboratory to clinical practice. However, further study of the relationship between adiponectin and PCOS is required before there can be direct application to clinical practice.

Groth, Susan W.

2013-01-01

67

Adiponectin and IL-6  

PubMed Central

Aim The objective of the study was to identify the association if any, of inflammatory markers (adiponectin and IL-6) with fasting glucose in normoglycemic (healthy), prediabetic (impaired fasting glucose), and hyperglycemic (diabetic) people in Indian population. Methods Total 162 volunteers were distributed into 3 groups (normoglycemic, individuals with impaired fasting glucose, and hyperglycemic) as per ADA criterion. The blood chemistry parameters were analyzed and serum adiponectin and IL-6 levels were measured by ELISA. Results Significant reduction was observed in serum adiponectin level in hyperglycemic and impaired fasting glucose population compared with normoglycemic population. Significant reduction in adiponectin was also observed in impaired fasting glucose group compared with hyperglycemic group. Similarly significant increase was also observed in IL-6 level in hyperglycemic and impaired fasting glucose groups compared with normoglycemic group. Conclusions From our data it can be summarized that there is a significant change in both adiponectin (reduction) and IL-6 (increase) levels in normoglycemic (healthy), prediabetic (impaired fasting glucose), and hyperglycemic (diabetic) population in Indian population. There is a significant but gradual change during the progression of healthy toward diabetic population via pre-diabetic condition.

Upadhyaya, Smitha; Kadamkode, Vinitha; Mahammed, Rafi; Doraiswami, Chandraprabha; Banerjee, Gautam

2014-01-01

68

The activities of lysyl hydroxylase 3 (LH3) regulate the amount and oligomerization status of adiponectin.  

PubMed

Lysyl hydroxylase 3 (LH3) has lysyl hydroxylase, galactosyltransferase, and glucosyltransferase activities, which are sequentially required for the formation of glucosylgalactosyl hydroxylysines in collagens. Here we demonstrate for the first time that LH3 also modifies the lysine residues in the collagenous domain of adiponectin, which has important roles in glucose and lipid metabolism and inflammation. Hydroxylation and, especially, glycosylation of the lysine residues of adiponectin have been shown to be essential for the formation of the more active high molecular weight adiponectin oligomers and thus for its function. In cells that totally lack LH3 enzyme, the galactosylhydroxylysine residues of adiponectin were not glucosylated to glucosylgalactosylhydroxylysine residues and the formation of high and middle molecular weight adiponectin oligomers was impaired. Circulating adiponectin levels in mutant mice lacking the lysyl hydroxylase activity of LH3 were significantly reduced, which indicates that LH3 is required for complete modification of lysine residues in adiponectin and the loss of some of the glycosylated hydroxylysine residues severely affects the secretion of adiponectin. LH mutant mice with reduced adiponectin level showed a high fat diet-induced increase in glucose, triglyceride, and LDL-cholesterol levels, hallmarks of the metabolic syndrome in humans. Our results reveal the first indication that LH3 is an important regulator of adiponectin biosynthesis, secretion and activity and thus might be a potential candidate for therapeutic applications in diseases associated with obesity and insulin resistance. PMID:23209641

Ruotsalainen, Heli; Risteli, Maija; Wang, Chunguang; Wang, Yu; Karppinen, Marjo; Bergmann, Ulrich; Kvist, Ari-Pekka; Pospiech, Helmut; Herzig, Karl-Heinz; Myllylä, Raili

2012-01-01

69

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.

Lee, Sewon; Kwak, Hyo-Bum

2014-01-01

70

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

PubMed

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-D(t)1 subunits. Genetic variability at Glu-D(t)1 locus was greater than Glu-A1 and Glu-B1 loci. The relative high frequency of superior alleles, Glu-B1b and Glu-D(t)1d 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-D(t)1 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

2012-12-01

71

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

72

The influence of the high and low molecular weight fractions of a bleach kraft mill effluent on the microbial activity of activated sludge  

Microsoft Academic Search

The high molecular weight (HMW) fraction (> 1000 Da) of bleached kraft mill effluent (BKME) is the principal source of adsorbable organic halide (AOX), colour and chemical oxygen demand in treated effluent. The influence of HMW material on the microbial activity of activated sludge microorganisms was studied in a series of batch growth experiments using fractionated effluent. The HMW material

C. M. Bullock; P. A. Bicho; J. N. Saddler

1996-01-01

73

Mycoplasma pneumoniae cytadherence phase-variable protein HMW3 is a component of the attachment organelle.  

PubMed

The subcellular location of the phase-variable cytadherence-accessory protein HMW3 in Mycoplasma pneumoniae has been examined by biochemical and immunoelectron microscopic techniques. Analysis by Western blot (immunoblot) with HMW3-specific antiserum established the presence of this protein within the M. pneumoniae Triton X-100-insoluble fraction or triton shell. Immunogold labeling of Triton-extracted mycoplasmas with affinity-purified antibodies localized HMW3 to the terminal knob on the rodlike extensions of the triton shell, a location that would correspond to the adherence organelle in whole mycoplasmas. Treatment of triton shells with KI resulted in the selective removal of the adherence-accessory proteins HMW1 to HMW4. Analysis of these triton shells by transmission electron microscopy revealed dramatic ultrastructural changes in the filamentous network and core structure. Immunogold labeling of KI-extracted shells reflected the removal of HMW3 from the disrupted tip structure. An examination of ultrathin sections of wild-type cells by transmission electron microscopy following labeling with HMW3-specific antibodies provided further evidence for the nonrandom distribution of HMW3 and its localization to the terminal portion of filamentous cell extensions. Most colloidal gold molecules were associated with the cell interior, but limited peripheral labeling of the terminal region was also observed. Postfixation antibody labeling of whole cells suggested limited exposure of HMW3 on the mycoplasma surface at the tip structure. However, prefixation antibody labeling failed to indicate surface exposure, raising some uncertainty regarding the relationship of HMW3 with the mycoplasma membrane. PMID:1624421

Stevens, M K; Krause, D C

1992-07-01

74

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

PubMed Central

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

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

2012-01-01

75

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

PubMed Central

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

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

1989-01-01

76

The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice.  

PubMed

Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases. PMID:12840063

Xu, Aimin; Wang, Yu; Keshaw, Hussila; Xu, Lance Yi; Lam, Karen S L; Cooper, Garth J S

2003-07-01

77

Physiological, Pharmacological, and Nutritional Regulation of Circulating Adiponectin Concentrations in Humans  

PubMed Central

Abstract Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans.

Swarbrick, Michael M.

2008-01-01

78

Lactation driven dynamics of adiponectin supply from different fat depots to circulation in cows.  

PubMed

Adipose tissue (AT) depots are heterogeneous in terms of morphology and adipocyte metabolism. Adiponectin, one of the most abundant adipokines, is known for its insulin sensitizing effects and its role in glucose and lipid metabolism. Little is known about the presence of adiponectin protein in visceral (vc) and subcutaneous (sc) AT depots. We assessed serum adiponectin and adiponectin protein concentrations and the molecular weight forms in vc (mesenterial, omental, and retroperitoneal) and sc (sternum, tail-head, and withers) AT of primiparous dairy cows during early lactation. Primiparous German Holstein cows (n = 25) were divided into a control (CON) and a conjugated linoleic acid (CLA) group. From day 1 of lactation until slaughter, CLA cows were fed 100 g of a CLA supplement/d (approximately 6% of cis-9, trans-11 and trans-10, cis-12 isomers each), whereas the CON cows received 100 g of a fatty acid mixture/d instead of CLA. Blood samples from all animals were collected from 3 wk before calving until slaughter on day 1 (n = 5, CON cows), 42 (n = 5 each of CON and CLA cows), and 105 (n = 5 each of CON and CLA cows) of lactation when samples from different AT depots were obtained. Adiponectin was measured in serum and tissue by ELISA. In all AT depots adiponectin concentrations were lowest on day 1 than on day 42 and day 105, and circulating adiponectin reached a nadir around parturition. Retroperitoneal AT had the lowest adiponectin concentrations; however, when taking total depot mass into consideration, the portion of circulating adiponectin was higher in vc than sc AT. Serum adiponectin was positively correlated with adiponectin protein concentrations but not with the mRNA abundance in all fat depots. The CLA supplementation did not affect adiponectin concentrations in AT depots. Furthermore, inverse associations between circulating adiponectin and measures of body condition (empty body weight, back fat thickness, and vc AT mass) were observed. In all AT depots at each time, adiponectin was present as high (approximately 300 kDa) and medium (approximately 150 kDa) molecular weight complexes similar to that of the blood serum. These data suggest differential contribution of AT depots to circulating adiponectin. PMID:24462180

Singh, S P; Häussler, S; Heinz, J F L; Akter, S H; Saremi, B; Müller, U; Rehage, J; Dänicke, S; Mielenz, M; Sauerwein, H

2014-04-01

79

Purification to homogeneity of a high molecular weight human B cell growth factor; demonstration of specific binding to activated B cells; and development of a monoclonal antibody to the factor  

PubMed Central

High molecular weight B cell growth factor (HMW-BCGF) produced by a T cell line was purified to homogeneity and demonstrated to bind specifically to activated human B cells. A monoclonal antibody to HMW- BCGF was developed that (a) specifically inhibited the activity of HMW- BCGF in enhancing B cell proliferation, (b) specifically bound to HMW- BCGF in Western blots, (c) specifically absorbed HMW-BCGF activity from culture supernatants, and (d) specifically absorbed an internally labeled protein from T-ALL supernatant which comigrates with HMW-BCGF on sodium dodecyl sulfate-polyacrylamide gels. This antibody should help in cloning the gene for HMW-BCGF and further exploring the physiologic roles of HMW-BCGF.

1985-01-01

80

Enhanced adiponectin actions by overexpression of adiponectin receptor 1 in macrophages  

PubMed Central

Objective Adiponectin is one of several important, metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type II diabetes, and cardiovascular disease. To investigate how enhanced adiponectin-mediated changes in metabolism in vivo, we generated transgenic mice which specifically overexpress the gene coding for adiponectin receptor 1 (AdipoR1) in mouse macrophages using the human scavenger receptor A-I gene (SR-AI) enhancer/promoter. We found that macrophage-specific AdipoR1 transgenic mice (AdR1-TG) presented reduced whole body weight, fat accumulation and liver steatosis when these transgenic mice were fed with a high fat diet. Moreover, these macrophage AdR1-TG mice exhibited enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-?, both in the serum and in the insulin target metabolic tissues. Additional studies demonstrated that these macrophage AdR1-TG animals exhibited reduced macrophage foam cell formation in the arterial wall when these transgenic mice were crossed with a low-density lipoprotein receptor (Ldlr) deficient mouse model. Conclusions These results suggest that AdipoR1 overexpressed in macrophages can physiologically modulate metabolic activities in vivo by enhancing adiponectin actions in distal metabolically active tissues. The AdipoR1 modified macrophages provide unique interactions with the residented tissues/cells, suggesting a novel role of macrophage adiponectin receptor in improving metabolic disorders in vivo.

Luo, Nanlan; Chung, B Hong; Wang, Xiangdong; Klein, Richard L.; Tang, Chao-Ke; Garvey, W. Timothy; Fu, Yuchang

2013-01-01

81

Adiponectin signaling in the liver.  

PubMed

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, fatty liver disease and decreased life expectancy. The future development of "adiponectin sensitizers", medications that correct the deficiency in adiponectin signaling, 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

2014-06-01

82

Correlation between serum adiponectin and clinical characteristics, biochemical parameters in Indian women with polycystic ovary syndrome  

PubMed Central

Background: Polycystic ovary syndrome (PCOS) is a common disorder. PCOS women are at a high risk for insulin resistance and metabolic syndrome (MS). Adiponectin is positively related to insulin sensitivity. It has a preventive role in atherogenesis and MS. The present work was conducted to study the correlation between serum adiponectin levels and clinical characteristics and biochemical parameters in PCOS patients. Materials and Methods: A prospective study in 49 newly diagnosed (as per Rotterdam criteria) Indian PCOS women was conducted. PCOS women were clinically examined and investigated for biochemical parameters. Results: The mean serum adiponectin was 12 ± 9.4 ?g/mL (range 0.47-45). Hypoadiponectinemia (serum adiponectin <4 ?g/mL) was present in 22% patients. Age and adiponectin correlated significantly and inversely (r = ?0.42, P = 0.027). Overweight/obese patients had lower mean adiponectin levels than normal weight (11.62 ± 9.5 vs 13.58 ± 9.5, P = 0.56). It was significantly lower in patients with acanthosis nigricans (AN) as compared with those without AN (8.4 ± 5.9 vs 15 ± 11, P = 0.038). Hirsute patients showed lower mean adiponectin levels than nonhirsute (10 ± 7.3 vs 13 ± 10, P = 0.57). A positive, insignificant correlation was observed between serum adiponectin and cholesterol, low-density lipoprotein, follicle stimulating hormone (FSH), thyroid stimulating hormone, levels. A negative insignificant correlation existed between serum adiponectin and luteinizing hormone (LH), LH: FSH ratio, prolactin, dehydroepiandrosterone, testosterone, triglyceride, high-density lipoprotein, fasting blood glucose, fasting insulin, and Homeostasis Model Assessment. Conclusion: Hypoadiponectinemia is present in one-fifth of women with PCOS. Adiponectin levels decrease as age advances. Low levels of adiponectin possibly contributes to the development of dermal manifestation (AN) of insulin resistance.

Ramanand, Sunita J.; Ramanand, Jaiprakash B.; Ghongane, Balasaheb B.; Patwardhan, Milind H.; Patwardhan, Varsha M.; Ghanghas, Ravi; Halasawadekar, Nimish R.; Patil, Praveenkumar

2014-01-01

83

Intake of mulberry 1-deoxynojirimycin prevents diet-induced obesity through increases in adiponectin in mice.  

PubMed

In this study, the anti-obesity effect of 1-deoxynojirimycin (DNJ) was examined in the diet-induced obese mouse model. Mulberry DNJ was administered to the obese mice for 12 weeks. As a result, DNJ decreased both the visceral fat weight and adipocyte size. To determine the influence of DNJ on lipid metabolism, lipid parameters of the plasma and the liver and the activities of several molecules related to lipid metabolism in the liver were measured. DNJ activated the ?-oxidation system, suppressed lipid accumulation in the liver and reduced plasma triacylglycerol. Since it was thought that the factor activated in the ?-oxidation system was adiponectin, plasma adiponectin levels were measured and it was shown that plasma adiponectin was increased with DNJ. Therefore, it was suggested that DNJ promoted an increase in plasma adiponectin and activated the ?-oxidation system. Overall, it was shown that DNJ prevents diet-induced obesity through an increase in adiponectin. PMID:23561072

Tsuduki, Tsuyoshi; Kikuchi, Ikuko; Kimura, Toshiyuki; Nakagawa, Kiyotaka; Miyazawa, Teruo

2013-08-15

84

Adiponectin and visfatin concentrations in children treated with valproic acid.  

PubMed

Chronic antiepileptic therapy with valproic acid (VPA) is associated with increased body weight and insulin resistance in adults and children. Attempts to determine the underlying pathophysiologic mechanisms have failed. Adipocytokines have recently been defined as a link between glucose and fat metabolism. We herein demonstrate that VPA-associated overweight is accompanied by lower adiponectin and higher leptin concentrations in children. The absence of any relationship with visfatin concentration does not suggest a role of this novel insulin-mimetic hormone in VPA-associated metabolic alterations. Therefore, adiponectin and leptin but not visfatin may be considered as potential regulators of glucose and fat metabolism during VPA-therapy. PMID:18070089

Rauchenzauner, Markus; Haberlandt, Edda; Scholl-Bürgi, Sabine; Ernst, Barbara; Hoppichler, Fritz; Karall, Daniela; Ebenbichler, Christoph F; Rostasy, Kevin; Luef, Gerhard

2008-02-01

85

Stability of Mycoplasma pneumoniae Cytadherence-Accessory Protein HMW1 Correlates with Its Association with the Triton Shell  

PubMed Central

Mycoplasma pneumoniae adsorbs to host respiratory epithelium primarily by its attachment organelle, the proper function of which depends upon mycoplasma adhesin and cytoskeletal proteins. Among the latter are the cytadherence-associated proteins HMW1 and HMW2, whose specific roles in this process are unknown. In the M. pneumoniae cytadherence mutant I-2, loss of HMW2 results in accelerated turnover of HMW1 and other cytadherence-accessory proteins, probably by proteolysis. However, both the mechanism of degradation and the means by which these proteins are rendered susceptible to it are not understood. In this study, we addressed whether HMW1 degradation is a function of its presence among specific subcellular fractions and established that HMW1 is a peripheral membrane protein that is antibody accessible on the outer surfaces of both wild-type and mutant I-2 M. pneumoniae but to a considerably lesser extent in the mutant. Quantitation of HMW1 in Triton X-100-fractionated extracts from cells pulse-labeled with [35S]methionine indicated that HMW1 is synthesized in a Triton X-100-soluble form that exists in equilibrium with an insoluble (cytoskeletal) form. Pulse-chase analysis demonstrated that over time, HMW1 becomes stabilized in the cytoskeletal fraction and associated with the cell surface in wild-type M. pneumoniae. The less efficient transition to the cytoskeleton and mycoplasma cell surface in mutant I-2 leads to accelerated degradation of HMW1. These data suggest a role for HMW2 in promoting export of HMW1 to the cell surface, where it is stable and fully functional.

Balish, Mitchell F.; Hahn, Tae-Wook; Popham, Phillip L.; Krause, Duncan C.

2001-01-01

86

Serum Adiponectin and Cardiometabolic Risk in Patients with Acute Coronary Syndromes  

PubMed Central

Background The adipose tissue is considered not only a storable energy source, but mainly an endocrine organ that secretes several cytokines. Adiponectin, a novel protein similar to collagen, has been found to be an adipocyte-specific cytokine and a promising cardiovascular risk marker. Objectives To evaluate the association between serum adiponectin levels and the risk for cardiovascular events in patients with acute coronary syndromes (ACS), as well as the correlations between adiponectin and metabolic, inflammatory, and myocardial biomarkers. Methods We recruited 114 patients with ACS and a mean 1.13-year follow-up to measure clinical outcomes. Clinical characteristics and biomarkers were compared according to adiponectin quartiles. Cox proportional hazard regression models with Firth's penalization were applied to assess the independent association between adiponectin and the subsequent risk for both primary (composite of cardiovascular death/non-fatal acute myocardial infarction (AMI)/non-fatal stroke) and co-primary outcomes (composite of cardiovascular death/non-fatal AMI/non-fatal stroke/ rehospitalization requiring revascularization). Results There were significant direct correlations between adiponectin and age, HDL-cholesterol, and B-type natriuretic peptide (BNP), and significant inverse correlations between adiponectin and waist circumference, body weight, body mass index, Homeostasis Model Assessment (HOMA) index, triglycerides, and insulin. Adiponectin was associated with higher risk for primary and co-primary outcomes (adjusted HR 1.08 and 1.07/increment of 1000; p = 0.01 and p = 0.02, respectively). Conclusion In ACS patients, serum adiponectin was an independent predictor of cardiovascular events. In addition to the anthropometric and metabolic correlations, there was a significant direct correlation between adiponectin and BNP.

Oliveira, Gustavo Bernardes de Figueiredo; Franca, Joao Italo Dias; Piegas, Leopoldo Soares

2013-01-01

87

Expression system for production of bioactive compounds, recombinant human adiponectin, in the silk glands of transgenic silkworms.  

PubMed

Adiponectin is an adipocyte hormone involved in glucose and lipid metabolism. The aim of this study was to develop a human adiponectin expression system in transgenic silkworm using a human adiponectin expression vector. The silk gland of the silkworm is a highly specialized organ that has the wonderful ability to synthesize and secrete silk protein. To express human adiponectin in the silk gland of transgenic silkworm, targeting vectors pB-A3-adiponectin-IRES-RFP and pB-Ser1-adiponectin-IRES-RFP were constructed and then introduced into the silkworm pupa. The transgenic silkworms were verified by PCR and then generated. The level of adiponectin in the transgenic silkworm was 6-10 ng/50 mg of freeze-dried powder, and western blotting using an antibody against human adiponectin demonstrated a specific band with a molecular weight of 30 kDa in the silkworm. These results showed that human adiponectin introduced into the silkworm genome was expressed successfully on a large-scale. PMID:24272890

Shin, Seulmee; Kim, Bong-Yoon; Jeon, Hyung-Yook; Lee, Aeri; Lee, Sungwon; Sung, Seung-Hyun; Park, Chan-Su; Lee, Chong-Kil; Kong, Hyunseok; Song, Youngcheon; Kim, Kyungjae

2014-05-01

88

HMW and LMW glutenin alleles among putative tetraploid and hexaploid European spelt wheat (Triticum spelta L.) progenitors.  

PubMed

The allelic compositions of high- and low-molecular-weight subunits of glutenins (HMW-GS and LMW-GS) among European spelt ( Triticum spelta L.) and related hexaploid and tetraploid Triticum species were investigated by one- and two-dimensional polyacrylamide-gel electrophoresis (PAGE) and capillary electrophoresis (CE). A total of seven novel glutenin alleles (designated A1a*, B1d*, B1g*, B1f*, B1j*, D1a* at Glu-1 and A3h at the Glu-3 loci, respectively) in European spelt wheat were detected by SDS-PAGE, which were confirmed further by employing A-PAGE and CE methods. Particularly, two HMW-GS alleles, Glu-B1d* coding the subunits 6.1 and 22.1, and Glu-B1f* coding the subunits 13 and 22*, were found to occur in European spelt with frequencies of 32.34% and 5.11%, respectively. These two alleles were present in cultivated emmer (Triticum dicoccum), but they were not observed in bread wheat (Triticum aestivum L.). The allele Glu-B1g* coding for 13* and 19* subunits found in spelt wheat was also detected in club wheat (Triticum compactum L.). Additionally, two alleles coding for LMW-GS, Glu-A3h and Glu-B3d, occurred with high frequencies in spelt, club and cultivated emmer wheat, whereas these were not found or present with very low frequencies in bread wheat. Our results strongly support the secondary origin hypothesis, namely European spelt wheat originated from hybridization between cultivated emmer and club wheat. This is also confirmed experimentally by the artificial synthesis of spelt through crossing between old European emmer wheat, T. dicoccum and club wheat, T. compactum. PMID:13679994

Yan, Y; Hsam, S L K; Yu, J Z; Jiang, Y; Ohtsuka, I; Zeller, F J

2003-11-01

89

Sources and composition of high-molecular-weight dissolved organic carbon in a southern Louisiana tidal stream (Bayou Trepagnier)  

Microsoft Academic Search

The composition and cycling of high-molecular-weight dissolved organic carbon (HMW-DOC) were examined in a tidal stream (Bayou Trepagnier) with seasonally high DOC concentrations (1.0-5.6 mM). 13 C nuclear magnetic resonance ( 13 C NMR) was used to examine the bulk chemical composition of natural HMW-DOC from two field sites over 1.5 yr. The HMW-DOC at both sites was dominated by

Erika Engelhaupt; Thomas S. Bianchi

2001-01-01

90

Epicardial adipose tissue adiponectin expression is related to intracoronary adiponectin levels.  

PubMed

The role of adiponectin and epicardial adipose tissue in coronary artery disease (CAD) is a subject of debate. Whether plasma adiponectin concentration in the coronary circulation is locally modulated by the epicardial fat is still unexplored. We evaluated the hypothesis whether intracoronary plasma adiponectin levels are related to adiponectin expression in epicardial adipose tissue in vivo in patients with CAD and without CAD (non-CAD). We examined 12 patients with CAD who required CABG and 10 patients with non-CAD who underwent cardiac surgery for valve replacement. Plasma levels of adiponectin were measured in peripheral vein circulation and in left coronary artery (LCA) during coronary angiography. Epicardial adipose tissue biopsy for adiponectin protein extraction was performed during cardiac surgery in both CAD and non-CAD subjects. Adiponectin protein expression in epicardial adipose tissue was lower in patients with CAD than in those with non-CAD (0.45+/-0.4 vs. 1.1+/-1.0, p<0.05). LCA plasma adiponectin levels significantly correlated with epicardial adipose tissue adiponectin protein expression (r=0.68, p=0.02) in all subjects. Peripheral adiponectin levels and epicardial fat adiponectin protein expression were the best correlates of LCA adiponectin, r (2)=0.49, p<0.01, p<0.05, respectively). Our study showed that intracoronary adiponectin levels reflect systemic adiponectin levels. Epicardial adipose tissue could partially contribute to adiponectin levels in the coronary circulation. PMID:19003726

Iacobellis, G; di Gioia, Cira Rosaria Tiziana; di Gioia, C R Tiziana; Cotesta, D; Petramala, L; Travaglini, C; De Santis, V; Vitale, D; Tritapepe, L; Letizia, C

2009-03-01

91

High-power DPSS Laser hosted on a HMW-THS  

Microsoft Academic Search

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

Maurizio Checchetti

2007-01-01

92

Changes of Plasma Adiponectin Levels after Smoking Cessation  

PubMed Central

Objective Cigarette smoking is associated with a variety of health problems including cardiovascular, pulmonary, neoplasms, endocrinopathies including diabetes, the metabolic syndrome, and chronic inflammation. Adiponectin is an adipocyte-derived plasma protein that is closely associated with insulin sensitivity and the metabolic syndrome. The aim of this study was to evaluate the changes of plasma adiponectin levels after smoking cessation. Methods Thirty seven smokers that wanted to stop smoking without any nicotine replacement therapy or medication were recruited for this study. Fifteen smokers succeeded in stopping smoking (validated by urine cotinine levels ?50 ng/mL) and 22 smokers failed. Therefore, only the 15 that succeeded were included in the analysis. The plasma adiponectin levels were determined using a commercially available enzyme-linked immunosorbent assay. Results The mean age of the successful 15 was 35±9.3 years old. They were all males. The daily smoking habit was a mean of 13.5±5.4 cigarettes per day. The mean Nicotine Dependence Syndrome Scale (NDSS) and Fagerstrom Test for Nicotine Dependence (FTND) scores were 55.6±9.6 and 2.9±1.9. During the study period of three months, the mean body mass index (BMI), body fat mass (BFM), waist-hip ratio (WHR) and body weight increased by 1.1 kg/m2, 3.0%, 0.02%, and 2.9 kg, respectively. The baseline mean adiponectin level in the subjects was 11.9±5.2 mg/L. The mean adiponectin levels measured at one and three months were 16.0±5.1 mg/L and 14.7±4.5 mg/L respectively. The mean plasma adiponectin levels of the successful group was significantly increased after four weeks when compared to the baseline (z=-2.401, p=0.016). However, the decrease in plasma adiponectin levels at one and three months was not statistically significant. Conclusion Even though the decrease over the next two months was not significant, these findings, the increase of plasma level of adiponectin after smoking cessation, provide preliminary data for future research on the possible mechanisms associated with smoking cessation and changes in body metabolism.

Won, Wang-Youn; Lee, Chang-Uk; Chae, Jeong-Ho; Kim, Jung-Jin; Lee, Chul

2014-01-01

93

Serum adiponectin in gestational diabetes and its relation to pregnancy outcome.  

PubMed

Abstract We investigated adiponectin levels in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) at 24-28 gestational weeks. Fasting serum adiponectin, glucose and glycated haemoglobin (HbA1c) were determined in 88 pregnant women, 44 with GDM and 44 with NGT. Pre-pregnancy and current body mass indices (BMI), weight gain and pregnancy outcomes were investigated. Serum adiponectin was significantly reduced in GDM compared with the NGT group (p = 0.000). Adiponectin was negatively correlated with age (r = -0.419, p = 0.000); glucose (r = -0.263, p = 0.013); HbA1c (r = -0.274, p = 0.01); BMI (pre-pregnancy and current) (r = -0.317, p = 0.003 and r = -0.303, p = 0.004) and positively correlated with gestational age at delivery (r = 0.278, p = 0.009). The GDM group delivered significantly earlier than the NGT group (p = 0.001). Adverse pregnancy outcomes and abdominal delivery were higher in the GDM group (p = 0.000, p = 0.033, respectively), and adiponectin was significantly reduced in patients with adverse outcomes (p = 0.003) and abdominal delivery (p = 0.032). Adiponectin is reduced in patients with GDM. Association of adiponectin with adverse pregnancy outcomes remains to be elucidated. PMID:24738829

Doruk, M; U?ur, M; Oruç, A S; Demirel, N; Yildiz, Y

2014-08-01

94

[The role of adiponectin in atherosclerosis].  

PubMed

Adiponectin is a adipose tissue-derived protein. In the light of current investigations, the role of adiponectin goes far beyond only adipose tissue regulatory factor, being involved in some pathological processes as endothelium damage or atherosclerosis. Unique properties of adiponectin make it a very promising agent that posses ability to slow down the progression of atherosclerosis. In this article, a structure and a function of adiponectin have been reviewed. The special emphasis was put upon the role of adiponectin in atherosclerosis. PMID:16886584

Lewicki, Maciej; Kotyla, Przemys?aw; Jankiewicz-Ziobro, Katarzyna; Kucharz, Eugeniusz Józef

2006-04-01

95

Adiponectin Lowers Glucose Production by Increasing SOGA  

PubMed Central

Adiponectin is a hormone that lowers glucose production by increasing liver insulin sensitivity. Insulin blocks the generation of biochemical intermediates for glucose production by inhibiting autophagy. However, autophagy is stimulated by an essential mediator of adiponectin action, AMPK. This deadlock led to our hypothesis that adiponectin inhibits autophagy through a novel mediator. Mass spectrometry revealed a novel protein that we call suppressor of glucose by autophagy (SOGA) in adiponectin-treated hepatoma cells. Adiponectin increased SOGA in hepatocytes, and siRNA knockdown of SOGA blocked adiponectin inhibition of glucose production. Furthermore, knockdown of SOGA increased late autophagosome and lysosome staining and the secretion of valine, an amino acid that cannot be synthesized or metabolized by liver cells, suggesting that SOGA inhibits autophagy. SOGA decreased in response to AICAR, an activator of AMPK, and LY294002, an inhibitor of the insulin signaling intermediate, PI3K. AICAR reduction of SOGA was blocked by adiponectin; however, adiponectin did not increase SOGA during PI3K inhibition, suggesting that adiponectin increases SOGA through the insulin signaling pathway. SOGA contains an internal signal peptide that enables the secretion of a circulating fragment of SOGA, providing a surrogate marker for intracellular SOGA levels. Circulating SOGA increased in parallel with adiponectin and insulin activity in both humans and mice. These results suggest that adiponectin-mediated increases in SOGA contribute to the inhibition of glucose production.

Cowerd, Rachael B.; Asmar, Melissa M.; Alderman, J. McKee; Alderman, Elizabeth A.; Garland, Alaina L.; Busby, Walker H.; Bodnar, Wanda M.; Rusyn, Ivan; Medoff, Benjamin D.; Tisch, Roland; Mayer-Davis, Elizabeth; Swenberg, James A.; Zeisel, Steven H.; Combs, Terry P.

2010-01-01

96

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

PubMed Central

Adiponectin has a variety of metabolic effects on obesity, insulin sensitivity, and atherosclerosis. To identify genes influencing variation in plasma adiponectin levels, we performed genome-wide linkage and association scans of adiponectin in two cohorts of subjects recruited in the Genetic Epidemiology of Metabolic Syndrome Study. The genome-wide linkage scan was conducted in families of Turkish and southern European (TSE, n = 789) and Northern and Western European (NWE, N = 2,280) origin. A whole genome association (WGA) analysis (500K Affymetrix platform) was carried out in a set of unrelated NWE subjects consisting of approximately 1,000 subjects with dyslipidemia and 1,000 overweight subjects with normal lipids. Peak evidence for linkage occurred at chromosome 8p23 in NWE subjects (lod = 3.10) and at chromosome 3q28 near ADIPOQ, the adiponectin structural gene, in TSE subjects (lod = 1.70). In the WGA analysis, the single-nucleotide polymorphisms (SNPs) most strongly associated with adiponectin were rs3774261 and rs6773957 (P < 10?7). These two SNPs were in high linkage disequilibrium (r2 = 0.98) and located within ADIPOQ. Interestingly, our fourth strongest region of association (P < 2 × 10?5) was to an SNP within CDH13, whose protein product is a newly identified receptor for high-molecular-weight species of adiponectin. Through WGA analysis, we confirmed previous studies showing SNPs within ADIPOQ to be strongly associated with variation in adiponectin levels and further observed these to have the strongest effects on adiponectin levels throughout the genome. We additionally identified a second gene (CDH13) possibly influencing variation in adiponectin levels. The impact of these SNPs on health and disease has yet to be determined.

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

2014-01-01

97

Adiponectin retards the progression of diabetic nephropathy in db/db mice by counteracting angiotensin II  

PubMed Central

Abstract Adiponectin is a multifunctional adipokine with insulin?sensitizing, anti?inflammatory, and vasoprotective properties. Epidemiology studies have, however, shown that high levels of serum adiponectin are associated with kidney disease progression. We, therefore, examined the effect of adiponectin administration on the progression of glomerulosclerosis in the obese diabetic (db/db) mouse, a model of type II diabetes. Recombinant human adiponectin was administered intraperitoneally at a dose of 30 or 150 ?g per day from weeks 18 to 20. Rosiglitazone administered by gavage at 20 mg/kg body weight (BW) daily served as a therapeutic control. Untreated uninephrectomized db/db mice developed progressive albuminuria and glomerular matrix expansion, associated with increased expression of transforming growth factor beta 1 (TGF?1), plasminogen activator inhibitor type 1 (PAI?1), collagen I (Col I), and fibronectin (FN). Treatment with adiponectin at either dose reduced the increases in albuminuria and markers of renal fibrosis seen in db/db mice, without affecting BW and blood glucose. Renal expressions of tumor necrosis factor?? (TNF??) and monocyte?chemoattractant protein?1 (MCP?1) and urinary TNF?? levels, the markers of renal inflammation, were increased in diabetic mice, whereas adiponectin treatment significantly reduced the levels of these markers. Furthermore, adiponectin obliterated the stimulatory effects of angiotensin II (Ang II), but not the total effect of TGF?1, on the mRNA expression of PAI?1, Col I, and FN by cultured glomerular mesangial cells. These observations suggest that adiponectin treatment reduces glomerulosclerosis resulting from type II diabetes probably through its anti?inflammatory and angiotensin–antagonistic effects. Thus, adiponectin has therapeutic implications in the prevention of progression of diabetic nephropathy.

Guo, Xiaohua; Zhou, Guangyu; Guo, Meizi; Cheung, Alfred K; Huang, Yufeng; Beddhu, Srinivasan

2014-01-01

98

Cord blood resistin and adiponectin in term newborns of diabetic mothers  

PubMed Central

Introduction Adipose tissue can release hormones into the blood stream in response to specific extracellular stimuli or changes in metabolic status. Resistin, an adipose-secreted factor, is primarily involved in the modulation of insulin sensitivity and adipocyte differentiation. Adiponectin, an adipocyte-specific hormone with insulin sensitizing, anti-inflammatory and anti-atherogenic effects, is reduced in obesity and type II diabetes. The aim of the study was to assess the influence of maternal pre-existing diabetes on cord blood resistin and adiponectin at birth in relation to neonatal anthropometric parameters and cord blood insulin levels. Material and methods A total of 60 term newborns were prospectively enrolled and categorized into three groups: 20 were macrosomic infants of pre-gestational diabetic mothers (group I), 20 were non-macrosomic infants of pre-gestational diabetic mothers (group II) and 20 were healthy non-macrosomic infants born to non-diabetic mothers serving as controls (group III). Infants’ anthropometric indices were recorded. Cord blood samples for glucose, insulin, resistin and adiponectin assay, together with maternal glycosylated haemoglobin were obtained. Results Serum insulin was increased while resistin and adiponectin were significantly decreased in infants of diabetic mothers (IDMs) compared to the control group. Serum glucose, insulin, resistin and adiponectin were comparable in group I and II. Cord serum resistin correlated positively with cord blood glucose in IDMs in both macrosomic and non-macrosomic groups. Cord serum insulin correlated positively with triceps skinfold thickness in all studied neonates. Cord serum resistin and adiponectin showed no correlation with neonatal anthropometric indices. Multiple regression analysis demonstrated that insulin, resistin and adiponectin together were highly correlated with birth weight, with adiponectin as the one responsible for this positive correlation. Conclusions Infants of diabetic mothers had elevated levels of cord serum insulin and suppressed levels of cord serum resistin and adiponectin, suggesting that the regulation of these metabolic pathways is probably operational before birth. Levels were comparable in both macrosomic and non-macrosomic neonates.

Mohamed, Maha H.; Gad, Ghada I.; Ibrahim, Hala Y.; El Shemi, Mohamed S.; Atef, Shereen H.; Ramadan, Naglaa M.; El Saeid, Shimaa M.

2010-01-01

99

Screening and degrading characteristics and community structure of a high molecular weight polycyclic aromatic hydrocarbon-degrading bacterial consortium from contaminated soil  

Microsoft Academic Search

Inoculation with efficient microbes had been proved to be the most important way for the bioremediation of polluted environments. For the treatment of abandoned site of Beijing Coking Chemical Plant contaminated with high level of high-molecular-weight polycyclic aromatic hydrocarbons (HMW-PAHs), a bacterial consortium capable of degrading HMW-PAHs, designated 1-18-1, was enriched and screened from HMW-PAHs contaminated soil. Its degrading ability

Run Sun; Jinghua Jin; Guangdong Sun; Ying Liu; Zhipei Liu

2010-01-01

100

Fetuin-A Induces Cytokine Expression and Suppresses Adiponectin Production  

PubMed Central

Background The secreted liver protein fetuin-A (AHSG) is up-regulated in hepatic steatosis and the metabolic syndrome. These states are strongly associated with low-grade inflammation and hypoadiponectinemia. We, therefore, hypothesized that fetuin-A may play a role in the regulation of cytokine expression, the modulation of adipose tissue expression and plasma concentration of the insulin-sensitizing and atheroprotective adipokine adiponectin. Methodology and Principal Findings Human monocytic THP1 cells and human in vitro differenttiated adipocytes as well as C57BL/6 mice were treated with fetuin-A. mRNA expression of the genes encoding inflammatory cytokines and the adipokine adiponectin (ADIPOQ) was assessed by real-time RT-PCR. In 122 subjects, plasma levels of fetuin-A, adiponectin and, in a subgroup, the multimeric forms of adiponectin were determined. Fetuin-A treatment induced TNF and IL1B mRNA expression in THP1 cells (p<0.05). Treatment of mice with fetuin-A, analogously, resulted in a marked increase in adipose tissue Tnf mRNA as well as Il6 expression (27- and 174-fold, respectively). These effects were accompanied by a decrease in adipose tissue Adipoq mRNA expression and lower circulating adiponectin levels (p<0.05, both). Furthermore, fetuin-A repressed ADIPOQ mRNA expression of human in vitro differentiated adipocytes (p<0.02) and induced inflammatory cytokine expression. In humans in plasma, fetuin-A correlated positively with high-sensitivity C-reactive protein, a marker of subclinical inflammation (r?=?0.26, p?=?0.01), and negatively with total- (r?=??0.28, p?=?0.02) and, particularly, high molecular weight adiponectin (r?=??0.36, p?=?0.01). Conclusions and Significance We provide novel evidence that the secreted liver protein fetuin-A induces low-grade inflammation and represses adiponectin production in animals and in humans. These data suggest an important role of fatty liver in the pathophysiology of insulin resistance and atherosclerosis.

Wicke, Corinna; Machicao, Fausto; Fritsche, Andreas; Haring, Hans-Ulrich; Stefan, Norbert

2008-01-01

101

Characterization of a Mycoplasma pneumoniae hmw3 Mutant: Implications for Attachment Organelle Assembly  

PubMed Central

The proteins required for adherence of the pathogen Mycoplasma pneumoniae to host respiratory epithelial cells are localized to a polar structure, the attachment organelle. A number of these proteins have been characterized functionally by analysis of noncytadhering mutants, and many are components of the mycoplasma cytoskeleton. Mutations in some cytadherence-associated proteins have pleiotropic effects, including decreased stability of other proteins, loss of adherence and motility, and abnormal morphology. The function of protein HMW3, a component of the attachment organelle, has been difficult to discern due to lack of an appropriate mutant. In this paper, we report that loss of HMW3 resulted in decreased levels and more diffuse localization of cytoskeletal protein P65, subtle changes in morphology, inability to cluster the adhesin P1 consistently at the terminal organelle, reduced cytadherence, and, in some cells, an atypical electron-dense core in the attachment organelle. This phenotype suggests a role for HMW3 in the architecture and stability of the attachment organelle.

Willby, Melisa J.; Krause, Duncan C.

2002-01-01

102

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

103

Serum Adiponectin Level and Clinical, Metabolic, and Hormonal Markers in Patients with Polycystic Ovary Syndrome  

PubMed Central

Background: To investigate the relationship between adiponectin, metabolic and hor- monal parameters, and insulin resistance in patients with non-treated polycystic ovary syndrome. Materials and Methods: In this cross-sectional observational study, 81 patients admitted to out-patient clinic with complaints of menstrual irregularity, hirsutism and obesity were enrolled. Serum adiponectin, biochemical and hormonal parameters, and 75 gram oral glu- cose tolerance test (OGTT) were measured. Spearman’s correlation coefficient was used for statistical analysis. Results: We observed inverse correlations between serum adiponectin level and body mass index, homeostasis model assessment insulin-resistance score, insulin level, fast- ing glucose level, and prolactin level (p=0.001, p=0.02, p=0.04, p=0.02, and p=0.005, respectively). No significant correlations were found between serum adiponectin level and age, height, weight, Ferriman-Gallwey score, 2 hours OGTT test value and free tes- tosterone level (p=0.3, p=0.6, p=0.2, p=0.8, p=0.9, and p=0.01, respectively). Conclusion: The present study demonstrated that in polycystic ovary syndrome patients, when serum adiponectin level decreased, degree of insulin resistance increased. Our find- ings indicate that serum adiponectin level is likely to be an adequate marker for deter- mination of the degree of insulin resistance, and may be a predictor of diseases, such as type 2 diabetes mellitus (T2DM) and metabolic syndrome, which develop on the basis of insulin resistance.

Yildiz, Yunus; Ozaksit, Gulnur; Serdar Unlu, Bekir; Ozgu, Emre; Energin, Hasan; Kaba, Metin; Ugur, Mustafa

2014-01-01

104

Serum adiponectin and resistin in rats under three isocaloric diets: The effect of sibutramine.  

PubMed

The aim of the study was to investigate the effects of (1) macronutrients on food intake, body composition and serum resistin and adiponectin and (2) sibutramine(S) on the above parameters in rats fed with isocaloric diets. Three groups of male Wistar rats (n=63) were fed with high fat diet (HFD), high carbohydrate diet (HCD) or high protein diet (HPD) for 13weeks. In the last 3weeks each group was divided into three subgroups and received S 5mg/kg or 10mg/kg, or vehicle. Body weight was measured weekly, gastrocnemius muscle, perirenal, retroperitoneal and epididymal fat were isolated, fat/lean ratio was calculated and serum adiponectin and resistin were assayed. S did not affect lean body mass in any group. HFD was associated with elevated fat/lean ratio regardless of S administration. S at 10mg/Kg decreased fat/lean ratio in the HCD and HPD and adiponectin in the HFD group. S did not affect resistin in any group. Adiponectin was paradoxically elevated in the HFDS10 compared to the HCD or HPD S10 groups. Resistin was lower in the HCD compared to the HPD and HFD groups. Results suggest a preferential effect of S on body fat. The detrimental effect of S on adiponectin can be attributed to its sympathomimetic properties. Adiponectin was paradoxically elevated in the HFD and resistin in the HPD group, results that require further investigation. PMID:19251435

Stroubini, Th; Perelas, A; Liapi, C; Perrea, D; Dontas, I; Tzavara, Ch; Galanopoulou, P

2009-05-01

105

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.

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

106

Supplementation with conjugated linoleic acids extends the adiponectin deficit during early lactation in dairy cows.  

PubMed

Decreasing insulin sensitivity (IS) in peripheral tissues allows for partitioning nutrients towards the mammary gland. In dairy cows, extensive lipid mobilization and continued insulin resistance (IR) are typical for early lactation. Adiponectin, an adipokine, promotes IS. Supplementation with conjugated linoleic acids (CLA) in rodents and humans reduces fat mass whereby IR and hyperinsulinemia may occur. In dairy cows, CLA reduce milk fat, whereas body fat, serum free fatty acids and leptin are not affected. We aimed to investigate the effects of CLA supplementation on serum and adipose tissue (AT) adiponectin concentrations in dairy cows during the lactation driven and parity modulated changes of metabolism. High yielding cows (n=33) were allocated on day 1 post partum to either 100 g/day of a CLA mixture or a control fat supplement (CON) until day 182 post partum. Blood and subcutaneous (sc) AT (AT) biopsy samples were collected until day 252 post partum to measure adiponectin. Serum adiponectin decreased from day 21 pre partum reaching a nadir at calving and thereafter increased gradually. The distribution of adiponectin molecular weight forms was neither affected by time, parity nor treatment. Cows receiving CLA had decreased serum adiponectin concentrations whereby primiparous cows responded about 4 weeks earlier than multiparous cows. The time course of adiponectin concentrations in sc AT (corrected for residual blood) was similar to serum concentrations, without differences between CLA and CON. CLA supplementation attenuated the post partum increase of circulating adiponectin thus acting towards prolongation of peripartal IR and drain of nutrients towards the mammary gland. PMID:24384531

Singh, Shiva P; Häussler, Susanne; Heinz, Johanna F L; Saremi, Behnam; Mielenz, Birgit; Rehage, Jürgen; Dänicke, Sven; Mielenz, Manfred; Sauerwein, Helga

2014-03-01

107

Adiponectin and leptin in relation to insulin sensitivity.  

PubMed

An increased amount of adipose tissue or its disproportionate distribution between central and peripheral body regions is related to the development of insulin resistance, type 2 diabetes mellitus, dyslipidemia, atherosclerosis, and coronary artery disease. Until recently, adipose tissue was regarded as a storage depot for lipids. It is now viewed as a hormonally active organ that plays a crucial metabolic role. The most important products of adipose tissue collectively referred to as adipocytokines, include adiponectin, leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), resistin, plasminogen-activating inhibitor-I (PAI-1), and angiotensinogen. These low and medium molecular weight proteins play an important role in the adipose tissue physiology and are believed to be a link between obesity, insulin resistance and endothelial dysfunction. This review describes the metabolic role of two of these proteins, adiponectin and leptin, in relation to insulin sensitivity. PMID:18370642

Soodini, Geetha R

2004-06-01

108

The Effects of Adiponectin and Leptin on Changes in Bone Mineral Density  

PubMed Central

Introduction Adiponectin and leptin are hormones secreted by adipose cells that may impact bone mineral density (BMD). Few studies have evaluated the longitudinal association of leptin and adiponectin levels with rates of BMD change. Methods Hip and whole body areal BMD (aBMD) were measured 5 times using dual energy x-ray absorptiometry (DXA) over 10 years. Trabecular lumbar spine volumetric BMD (vBMD) was measured using quantitative computed topography (QCT) at baseline and year 6 in the Pittsburgh cohort only. Random slope and intercept models were used to account for within person correlation as a result of repeated measures of hip and whole body aBMD. Linear regression was used to model changes in spine trabecular vBMD. Results Among women, the annualized rate of hip aBMD loss in the highest tertile of adiponectin was ?0.67% (95% CI: ?0.77, ?0.58) compared to ?0.43% (95% CI: ?0.51, ?0.35)] in the lowest tertile (p trend=0.019) after adjusting for age, race, BMI, diabetes, baseline hip aBMD, and weight change. In men, hip aBMD loss was greatest in the high adiponectin group (tertile 3), however this association was not significant, p trend=0.148. After adjusting for weight change in women, the association between higher leptin and lower hip aBMD loss was attenuated and no longer significant, p trend=0.134. Leptin and adiponectin levels were not associated with whole body aBMD or trabecular lumbar spine vBMD loss. Conclusions Adiponectin was associated with increased hip aBMD loss in women only; supporting evidence that adiponectin may have an important role in bone health.

Barbour, Kamil E.; Zmuda, Joseph M.; Boudreau, Robert; Strotmeyer, Elsa S.; Horwitz, Mara J; Evans, Rhobert W.; Kanaya, Alka M.; Harris, Tamara B.; Cauley, Jane A.

2012-01-01

109

Adiponectin and cardiovascular health: an update  

PubMed Central

The global epidemic of obesity is accompanied by an increased prevalence of cardiovascular disease (CVD), in particular stroke and heart attack. Dysfunctional adipose tissue links obesity to CVD by secreting a multitude of bioactive lipids and pro-inflammatory factors (adipokines) with detrimental effects on the cardiovascular system. Adiponectin is one of the few adipokines that possesses multiple salutary effects on insulin sensitivity and cardiovascular health. Clinical investigations have identified adiponectin deficiency (hypoadiponectinaemia) as an independent risk factor for CVD. In animals, elevation of plasma adiponectin by either pharmacological or genetic approaches alleviates obesity-induced endothelial dysfunction and hypertension, and also prevents atherosclerosis, myocardial infarction and diabetic cardiomyopathy. Furthermore, many therapeutic benefits of the peroxisome-proliferator activated receptor gamma agonists, the thiazolidinediones, are mediated by induction of adiponectin. Adiponectin protects cardiovascular health through its vasodilator, anti-apoptotic, anti-inflammatory and anti-oxidative activities in both cardiac and vascular cells. This review summarizes recent findings in the understanding of the physiological role and clinical relevance of adiponectin in cardiovascular health, and in the identification of the receptor and postreceptor signalling events that mediate the cardiovascular actions of adiponectin. It also discusses adiponectin-targeted drug discovery strategies for treating obesity, diabetes and CVD. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3

Hui, Xiaoyan; Lam, Karen SL; Vanhoutte, Paul M; Xu, Aimin

2012-01-01

110

Identification of Intact High Molecular Weight Glutenin Subunits from the Wheat Proteome Using Combined Liquid Chromatography-Electrospray Ionization Mass Spectrometry  

PubMed Central

The present paper describes a method for the identification of intact high molecular weight glutenin subunits (HMW-GS), the quality determining proteins from the wheat storage proteome. The method includes isolation of HMW-GS from wheat flour, further separation of HMW-GS by reversed-phase high-performance liquid chromatography (RP-HPLC), and their subsequent molecular identification with electrospray ionization mass spectrometry using a quadrupole-time-of-flight mass analyzer. For HMW-GS isolation, wheat proteins were reduced and extracted from flour with 50% 1-propanol containing 1% dithiothreitol. HMW-GS were then selectively precipitated from the protein mixture by adjusting the 1-propanol concentration to 60%. The composition of the precipitated proteins was first evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Coomassie staining and RP-HPLC with ultraviolet detection. Besides HMW-GS (?65%), the isolated proteins mainly contained ?5-gliadins. Secondly, the isolated protein fraction was analyzed by liquid chromatography-mass spectrometry. Optimal chromatographic separation of HMW-GS from the other proteins in the isolated fraction was obtained when the mobile phase contained 0.1% trifluoroacetic acid as ion-pairing agent. Individual HMW-GS were then identified by determining their molecular masses from the high-resolution mass spectra and comparing these with theoretical masses calculated from amino acid sequences. Using formic acid instead of trifluoroacetic acid in the mobile phase increased protein peak intensities in the base peak mass chromatogram. This allowed the detection of even traces of other wheat proteins than HMW-GS in the isolated fraction, but the chromatographic separation was inferior with a major overlap between the elution ranges of HMW-GS and ?-gliadins. Overall, the described method allows a rapid assessment of wheat quality through the direct determination of the HMW-GS composition and offers a basis for further top-down proteomics of individual HMW-GS and the entire wheat glutenin fraction.

Lagrain, Bert; Brunnbauer, Markus; Rombouts, Ine; Koehler, Peter

2013-01-01

111

Evaluation of Serum Adiponectin Concentrations Among Drug Abusers on Methadone Maintenance Treatment  

PubMed Central

Background: Adiponectin, an adipocyte-derived protein, modulates a number of metabolic processes. Methadone maintenance treatment (MMT) changes the level of hormones produced by adipose tissue in addicts. However, current data remains contradictory. Objectives: The aim of this study was to evaluate the effect of MMT on serum adiponectin levels in drug addicts. Materials and Methods: Twenty-five drug abusers with a mean age of 37.4 ± 8.7 years were referred to the Baharan Hospital, Zahedan, and 22 healthy age-matched control subjects with a mean age of 35 ± 9.5 years were enrolled in the study. Addicts were treated with methadone at (40 to 120 mg/d) for six months. Measurement of anthropometric parameters, serum adiponectin, and biochemical parameter levels, were assessed in the addicts, before and after six months of MMT, but only once in the healthy controls. Results: The mean basal serum adiponectin level was not significantly lower in the drug abuser group compared to the healthy subjects (P > 0.05). After six months of MMT, the mean serum adiponectin level of the drug addicts was not significantly different from their mean baseline level or that of the healthy subjects (P > 0.05). However, the mean baseline serum adiponectin level was significantly lower in overweight/obese addicts when compared to underweight patients and healthy individuals (P < 0.001). After six months of MMT, the mean level of serum adiponectin increased significantly in the underweight subjects compared to the normal weight and overweight/obese subjects (P < 0.0001) and the control group (P < 0.001). Adiponectin concentration was correlated inversely with body mass index and positively correlated with waist circumference and serum high-density lipoprotein levels. Conclusions: This study showed that MMT did not markedly alter the concentration of serum adiponectin in drug abusers. However, in regard to the variations in the serum lipid profiles and anthropometric parameters, the findings indicated that low concentrations of serum adiponectin might play a role in the pathogenesis of obesity and other metabolic abnormalities. Thus, more long-term studies with larger sample sizes are recommended.

Montazerifar, Farzaneh; Karajibani, Mansour; Lashkaripour, Kobra; Yousefi, Maryam

2013-01-01

112

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

PubMed Central

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

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

2011-01-01

113

Leptin to adiponectin ratio in preeclampsia.  

PubMed

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

Khosrowbeygi, A; Ahmadvand, H

2013-04-01

114

Biodegradation of high molecular weight lignin under sulfate reducing conditions: lignin degradability and degradation by-products.  

PubMed

This study is designed to investigate the biodegradation of high molecular weight (HMW) lignin under sulfate reducing conditions. With a continuously mesophilic operated reactor in the presence of co-substrates of cellulose, the changes in HMW lignin concentration and chemical structure were analyzed. The acid precipitable polymeric lignin (APPL) and lignin monomers, which are known as degradation by-products, were isolated and detected. The results showed that HMW lignin decreased and showed a maximum degradation capacity of 3.49 mg/l/day. APPL was confirmed as a polymeric degradation by-product and was accumulated in accordance with HMW lignin reduction. We also observed non-linear accumulation of aromatic lignin monomers such as hydrocinnamic acid. Through our experimental results, it was determined that HMW lignin, when provided with a co-substrate of cellulose, is biodegraded through production of APPL and aromatic monomers under anaerobic sulfate reducing conditions with a co-substrate of cellulose. PMID:18977138

Ko, Jae-Jung; Shimizu, Yoshihisa; Ikeda, Kazuhiro; Kim, Seog-Ku; Park, Chul-Hwi; Matsui, Saburo

2009-02-01

115

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

116

Insulin regulates the expression of adiponectin and adiponectin receptors in porcine adipocytes  

Microsoft Academic Search

Adiponectin is an adipocyte-derived hormone that can improve insulin sensitivity. Its functions in regulating glucose utilization and fatty acid metabolism in mammals are mediated by two subtypes of adiponectin receptors (AdipoR1 and AdipoR2). This study was conducted to determine the effect of insulin on the expression of adiponectin and its receptors. We demonstrated that in the presence of 10nM insulin,

Bing Hsien Liu; Ya Chin Wang; Shinn Chih Wu; Harry John Mersmann; Winston Teng Kuei Cheng; Shih Torng Ding

2008-01-01

117

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.

2012-01-01

118

Association between Risk Factors for Vascular Dementia and Adiponectin  

PubMed Central

Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia.

Lee, Won Taek; Park, Kyung Ah

2014-01-01

119

Adiponectin Promotes Functional Recovery after Podocyte Ablation  

PubMed Central

Low levels of the adipocyte-secreted protein adiponectin correlate with albuminuria in both mice and humans, but whether adiponectin has a causative role in modulating renal disease is unknown. Here, we first generated a mouse model that allows induction of caspase-8–mediated apoptosis specifically in podocytes upon injection of a construct-specific agent. These POD-ATTAC mice exhibited significant kidney damage, mimicking aspects of human renal disease, such as foot process effacement, mesangial expansion, and glomerulosclerosis. After the initial induction, both podocytes and filtration function recovered. Next, we crossed POD-ATTAC mice with mice lacking or overexpressing adiponectin. POD-ATTAC mice lacking adiponectin developed irreversible albuminuria and renal failure; conversely, POD-ATTAC mice overexpressing adiponectin recovered more rapidly and exhibited less interstitial fibrosis. In conclusion, these results suggest that adiponectin is a renoprotective protein after podocyte injury. Furthermore, the POD-ATTAC mouse provides a platform for further studies, allowing precise timing of podocyte injury and regeneration.

Rutkowski, Joseph M.; Wang, Zhao V.; Park, Ae Seo Deok; Zhang, Jianning; Zhang, Dihua; Hu, Ming Chang; Moe, Orson W.; Susztak, Katalin

2013-01-01

120

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.

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

121

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

122

Influence of Exercise Intensity on Abdominal Fat and Adiponectin in Elderly Adults  

PubMed Central

Abstract To examine the influence of moderate-intensity (50% of VO2peak) exercise training (MI) versus high-intensity (75% of VO2peak) exercise training (HI) on regional fat distribution and plasma adiponectin, we randomized 18 overweight (body mass index [BMI]?=?30?±?1 kg/m2) elderly (71?±?1 years) to HI, MI, or a control group (CON). Subjects enrolled in HI or MI completed a 12-week exercise training protocol designed to expend 1000 kcal/week. Body composition testing was completed prior to and following the exercise training using dual energy X-ray absorptiometry and a computed tomography scan. Plasma adiponectin was measured using enzyme-linked immunoassay (ELISA). VO2peak improved in HI and MI, whereas there was no change in VO2peak in CON. No significant change in body weight, BMI, and % fat occurred in MI, HI, or CON. Although there was a significant reduction in visceral fat with HI (?39 cm2), there was no change in the MI or CON groups. In addition, there was a significant increase in thigh muscle attenuation in the HI group. There were no changes in thigh muscle attenuation in the MI and CON groups. Also, there was no change in plasma adiponectin in the MI, HI, or CON groups. In summary, our direct comparison of exercise intensity without weight loss promotes the efficacy of HI in the reduction in visceral fat, even without changes in adiponectin.

Williams, Rick H.; Kortebein, Patrick M.; Sullivan, Dennis H.; Evans, William J.

2009-01-01

123

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

124

The role of adiponectin in mammary gland development  

Microsoft Academic Search

Adiponectin is an insulin-sensitizing hormone that is secreted from adipocytes. Clinical studies have linked low adiponectin levels to increased risk of atherosclerosis, type II diabetes, metabolic syndrome and many forms of cancer. Subsequent studies have shown adiponectin has anti-atherogenic, anti-diabetic and anti-inflammatory effects. Recent evidence also reveals adiponectin inhibits proliferation of breast cancer and nonmalignant mammary epithelial cell lines in

Michael Karadimos

2010-01-01

125

Correlation between atherogenic risk and adiponectin in gestational diabetes mellitus.  

PubMed

Introduction and objective. Gestational diabetes mellitus (GDM) is a pregnancy complication which increases the risk for maternal and foetal complications during pregnancy, and also significantly increases the cardiovascular risk for women's health in the postpartum. Current literature provides contradictory information on the role of adiponectin (AdipoQ) in the course of GDM. The aim of the study was to measure AdipoQ concentration in blood of women with GDM and to find correlations between this adipokine and clinical and biochemical parameters of the atherogenic risk. Material and methods. The GDM group included 50 women diagnosed with GDM between 24 - 28 weeks of gestation who underwent routine prenatal tests for GDM in compliance with the guidelines of the Polish Diabetes Association. All patients underwent clinical and laboratory evaluation at GDM diagnosis. Laboratory tests included serum AdipoQ concentration, fasting glucose and insulin, OGTT, lipid parameters, C-reactive protein and fibrinogen in serum. Results. The GDM group showed significantly elevated fasting glucose, insulin, HOMA-IR values, total cholesterol, LDLcholesterol and triglicerydes as compared with the control group (p<0.05). The atherogenic index, CRP, fibrinogen in women with GDM were significantly higher than in the control group (p<0.05). AdipoQ concentrations did not differ significantly between the groups during gestation (p=0.7054). No correlations, except with the neonatal weight (r= - 0.29, p<0.05), were found between AdipoQ and the studied parameters. Conclusions. Based on the conducted studies, it may be conclude that women with early diagnosed and promptly treated GDM have a normal adiponectin level, although insulin resistant changes and increased cardiovascular risk in basic metabolic parameters are observed. Moreover, adiponectin does not reflect the atherogenic risk in pregnant women with GDM. PMID:24738514

Matyjaszek-Matuszek, Beata; Lenart-Lipi?ska, Monika; Kowalczyk-Bo?tu?, Jolanta; Szlichtyng, Wojciech; Paszkowski, Tomasz

2014-03-31

126

Plasma adiponectin response to acute exercise in healthy subjects  

Microsoft Academic Search

Adipose tissue secretes adiponectin, an adipocytokine that is involved in the regulation of insulin sensitivity. Following acute exercise, insulin sensitivity has been shown to increase. Increased adiponectin following exercise may be related to the change in insulin sensitivity. The purpose of the present study was to characterize the effect of a single cycle exercise session on adiponectin and to compare

Michael A. Ferguson; Lesley J. White; Sean McCoy; Hee-Won Kim; Theresa Petty; Jared Wilsey

2004-01-01

127

Adiponectin and Leptin Trajectories in Mexican-American Children from Birth to 9 Years of Age  

PubMed Central

Objectives To address molecular mechanisms underlying obesity development, we examined patterns of critical metabolism-related hormones, adiponectin and leptin (adipokines), over childhood. Subjects and Design Plasma adiponectin and leptin were measured in 80 Mexican-American children at birth and again at 2, 5, and 9 years from the ongoing prospective cohort followed by the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). We used a mixture modeling approach to identify patterns in adipokine trajectories from birth to 9 years. Results Leptin was positively related to child body size within all ages, however adiponectin had inverse and weaker associations with BMI at 2, 5, and 9 years. Correlations between adipokine levels over the 0–2, 2–5, and 5–9-year periods increased for both leptin (r?=?0.06, 0.31 and 0.62) and adiponectin (r?=?0.25, 0.41 and 0.46). Our mixture modeling approach identified three trajectory clusters for both leptin (1L [slowly-rising], 2L [rapidly-rising], and 3L [stable]) and adiponectin (1A [steep-dropping and rebounding], 2A [moderately-dropping], and 3A [stable]). While leptin groups were most separated over the 2–9-year period, adiponectin trajectories displayed greatest heterogeneity from birth to 2 years. Children in the rapidly-rising 2L group had highest BMI and waist circumference at 9 years. Further, children with greater birth weight had increased odds of belonging to this high risk group (OR?=?1.21 95% CI 1.03, 1.43, compared to stable group 3L). Children whose mothers consumed more sugar-sweetened beverages during pregnancy were at risk of being in the steep-dropping 1A group (OR?=?1.08, 95% CI 1.01, 1.17, compared to stable group 3A). Conclusion Our results highlight developmental differences in leptin and adiponectin over the childhood period. Leptin closely reflects child body size however factors affecting adiponectin and long-term consequences of its changes over infancy need to be further explored.

Volberg, Vitaly; Heggeseth, Brianna; Harley, Kim; Huen, Karen; Yousefi, Paul; Dave, Veronica; Tyler, Kristin; Vedar, Michelle; Eskenazi, Brenda; Holland, Nina

2013-01-01

128

A highly conserved tryptophan in the N-terminal variable domain regulates disulfide bond formation and oligomeric assembly of adiponectin.  

PubMed

Adiponectin is a collagenous adipokine with direct anti-diabetic and anti-atherogenic properties. It can assume an ensemble of oligomeric states, e.g. trimers, hexamers and octadecamers, each being involved in distinct signaling pathways relevant to adiponectin's diverse biological function in metabolism, immunity, inflammation and cellular homeostasis. Assembly of the active variants principally the octadecameric high molecular weight form is achieved via the tightly controlled oxidation of cysteine 39 located in the adiponectin hyper-variable domain (AHD, residues 18-44) between the signal sequence and the collagen-like domain. We show that mutation of a highly conserved tryptophan (W42A) in the AHD profoundly affects assembly by trapping full-length adiponectin in the oxidized trimeric or hexameric states with a concomitant major reduction in the high molecular weight form. Our biophysical measurements on synthesized analogues of the AHD suggests that the aberrant oligomer distribution can be explained based on the fact that the proximity of W42 to C39 causes a reduction in the rate of C39 oxidation, an effect that to our knowledge has not been documented before. At the biological level, the perturbed oligomer distribution of full-length mutant adiponectin leads to a major reduction in the AMP-activated protein kinase activation in endothelial cells and liver tissues. PMID:22583869

Radjainia, Mazdak; Huang, Bosheng; Bai, Bo; Schmitz, Michael; Yang, Sung H; Harris, Paul W R; Griffin, Michael D W; Brimble, Margaret A; Wang, Yu; Mitra, Alok K

2012-07-01

129

Central adiponectin acutely improves glucose tolerance in male mice.  

PubMed

Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 ?g) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 ?(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin. PMID:24564394

Koch, Christiane E; Lowe, Chrishanthi; Legler, Karen; Benzler, Jonas; Boucsein, Alisa; Böttiger, Gregor; Grattan, David R; Williams, Lynda M; Tups, Alexander

2014-05-01

130

Lipid-lowering drugs and circulating adiponectin.  

PubMed

Pharmacological agents used to treat primary and combined hyperlipidemia reduce cardiovascular disease morbidity and mortality. Risk reduction has been attributed to improvements in blood lipid and lipoprotein characteristics. However, each class of available lipid-lowering drugs has been shown to exhibit pleiotropic effects that broaden their anticipated actions. Indeed, the results of a growing number of available studies suggest that a strong relationship exists between pharmacological reductions in blood lipids and circulating concentrations of the adipose tissue derived protein, adiponectin. Adiponectin is the most abundantly secreted protein from adipose tissue and has been shown to decrease hepatic glucose production, increase fatty acid oxidation in liver and skeletal muscle, and decrease vascular inflammation. In this chapter, we present a comprehensive analysis of the effects of the available classes of lipid-lowering drugs (statins, fibrates, niacin, and omega-3-fatty acids) on circulating adiponectin and the known mechanisms which produce these important events. PMID:23017722

Wanders, Desiree; Plaisance, Eric P; Judd, Robert L

2012-01-01

131

Adiponectin: mechanistic insights and clinical implications.  

PubMed

Adiponectin is an adipocyte-derived secretory protein that has been very widely studied over the past 15 years. A multitude of different functions have been attributed to this adipokine. It has been characterised in vitro at the level of tissue culture systems and in vivo through genetic manipulation of rodent models. It is also widely accepted as a biomarker in clinical studies. Originating in adipose tissue, generally positive metabolic effects have been attributed to adiponectin. In this review, we briefly discuss the key characteristics of this interesting but very complex molecule, highlight recent results in the context of its mechanism of action and summarise some of the key epidemiological data that helped establish adiponectin as a robust biomarker for insulin sensitivity, cardiovascular disease and many additional disease phenomena. PMID:22688349

Turer, A T; Scherer, P E

2012-09-01

132

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

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

1990-01-01

133

The association of circulating adiponectin levels with pancreatic cancer risk: a study within the prospective EPIC cohort.  

PubMed

Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a case-control study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.23-0.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.67-3.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development. PMID:21681743

Grote, Verena A; Rohrmann, Sabine; Dossus, Laure; Nieters, Alexandra; Halkjaer, Jytte; Tjønneland, Anne; Overvad, Kim; Stegger, Jakob; Chabbert-Buffet, Nathalie; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Teucher, Birgit; Becker, Susen; Montonen, Jukka; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Argüelles, Marcial; Duell, Eric J; Molina-Montes, Esther; Larrañaga, Nerea; Chirlaque, María-Dolores; Gurrea, Aurelio Barricarte; Jeurnink, Suzanne M; Peeters, Petra Hm; Ye, Weimin; Sund, Malin; Lindkvist, Björn; Johansen, Dorthe; Khaw, Kay-Tee; Wareham, Nick; Crowe, Francesca L; Romieu, Isabelle; Rinaldi, Sabina; Jenab, Mazda; Romaguera, Dora; Michaud, Dominique S; Riboli, Elio; Bas Bueno-de-Mesquita, H; Kaaks, Rudolf

2012-05-15

134

Chemical and isotopic composition of high-molecular-weight dissolved organic matter from the Mississippi River plume  

Microsoft Academic Search

In order to examine the source and transformation of high-molecular-weight dissolved organic matter (HMW-DOM) in the mixing zone of the Mississippi River plume, HMW-DOM with sizes between 1 kDa and 0.2 ?m was collected along a salinity gradient using cross-flow ultrafiltration. Isolated OM samples were desalted, freeze-dried and characterized for elemental (C and N) and biochemical composition (proteins, carbohydrates and uronic acids),

Laodong Guo; Daniel M. White; Chen Xu; Peter H. Santschi

2009-01-01

135

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

136

Adiponectin ameliorates experimental periodontitis in diet-induced obesity mice.  

PubMed

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

137

Adiponectin Upregulates SHBG Production: Molecular Mechanisms and Potential Implications.  

PubMed

Epidemiological studies have shown that plasma SHBG levels correlate with plasma adiponectin levels, both in men and women. There are no reports describing any molecular mechanism by which adiponectin regulates hepatic SHBG production. The aim of the present study is to explore whether adiponectin regulates SHBG production by increasing HNF-4? levels through reducing hepatic lipid content. For this purpose, in vitro studies using human HepG2 cells, as well as human liver biopsies, were performed. Our results show that adiponectin treatment increased SHBG production via AMPK activation in HepG2 cells. Adiponectin treatment decreased the mRNA and protein levels of enzymes related to hepatic lipogenesis (ACC) and increased those related to fatty acid oxidation (ACOX and CPTI). These adiponectin-induced changes in hepatic enzymes resulted in a reduction of total TG and FFA and an increase of HNF-4?. When HNF-4? expression was silenced by using siRNA, adiponectin-induced SHBG overexpression was blocked. Furthermore, adiponectin-induced upregulation of SHBG production via HNF-4? overexpression was abrogated by the inhibition of fatty acid oxidation or by the induction of lipogenesis with a 30mM glucose treatment in HepG2 cells. Finally, adiponectin levels correlated positively and significantly with both HNF-4? and SHBG mRNA levels in human liver biopsies. Our results suggest for the first time that adiponectin increases SHBG production by activating AMPK, which reduces hepatic lipid content and increases HNF-4? levels. PMID:24828613

Simó, Rafael; Saez-Lopez, Cristina; Lecube, Albert; Hernandez, Cristina; Fort, Jose Manuel; Selva, David M

2014-08-01

138

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.

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

139

Study of adiponectin in chronic liver disease and cholestasis  

PubMed Central

Purpose Adiponectin is an adipocytokine suggested to have a hepatoprotective effect. To date, little information is available in the literature regarding changes in serum adiponectin levels in cirrhosis and cholestasis and the associated metabolic disturbances. In order to elucidate the role of adiponectin in chronic liver disease our aim was to determine serum adiponectin in patients with different grades of cirrhosis and cholestasis and to correlate it with markers of liver injury, inflammation and cholestasis. We also aimed to correlate adiponectin with markers of metabolic syndrome such as body mass index and insulin resistance. Methods Forty patients with cirrhosis; 30 patients with cirrhosis and cholestasis; and 20 matched controls were studied. They were subjected to clinical assessment, laboratory investigations: serum bilirubin, ALT, AST, alkaline phosphatase, GGT, albumin, C-reactive protein, prothrombin activity, fasting blood sugar, insulin. HOMA index was calculated. Abdominal ultrasonography and upper GI endoscopy were performed. Results Adiponectin was elevated in patients with cirrhosis and cirrhosis/cholestasis and was significantly higher in Child A and B. Adiponectin showed correlation with liver cell injury, marker of inflammation, synthetic liver function and markers of cholestasis. Adiponectin did not correlate with complications of cirrhosis as ascites and esophageal varices nor did it correlate with BMI or HOMA. Conclusions Adiponectin is elevated in cirrhosis and shows correlation with degree of hepatocellular injury and cholestasis. Finally, adiponectin levels in cirrhosis do not correlate with parameters of body composition or metabolism but exclusively with reduced liver function.

Salman, Tary A.; Azab, Gasser I.; Shaarawy, Ahmed A.; Hassouna, Mona M.; El-haddad, Omkolsoum M.

2010-01-01

140

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

PubMed Central

Background The control of growth and nutritional status in the foetus and neonate is a complex mechanism, in which also hormones produced by adipose tissue, such as adiponectin and leptin are involved. The aim of this study was to evaluate levels of adiponectin, leptin and insulin in appropriate (AGA) and small for gestational age (SGA) children during the 1st year of life and to correlate these with auxological parameters. Methods In 33 AGA and 29 SGA infants, weight, length, head circumference, glucose, insulin, adiponectin and leptin levels were evaluated at the second day of life, and at one, six and twelve months, during which a portion of SGA could show catch-up growth (rapid growth in infants born small for their gestational age). Results Both total and isoform adiponectin levels were comparable between AGA and SGA infants at birth and until age one year. These levels significantly increased from birth to the first month of life and then decreased to lower values at 1 year of age in all subjects. Circulating leptin concentrations were higher in AGA (2.1 ± 4.1 ng/ml) than in SGA neonates (0.88 ± 1.03 ng/ml, p < 0.05) at birth, then similar at the 1st and the 6th month of age, but they increased in SGA from six months to one year, when they showed catch-up growth. Circulating insulin levels were not statistically different in AGA and SGA neonates at any study time point. Insulin levels in both AGA and SGA infants increased over the study period, and were significantly lower at birth compared to one, six and 12 months of age. Conclusions During the first year of life, in both AGA and SGA infants a progressive decrease in adiponectin levels was observed, while a difference in leptin values was correlated with the nutritional status.

2010-01-01

141

Low circulating adiponectin levels in women with polycystic ovary syndrome: an updated meta-analysis.  

PubMed

Adiponectin, as an important adipocytokine, plays a pivotal role in the regulation of insulin sensitivity and metabolism. It has been reported that circulating adiponectin levels were decreased in women with polycystic ovary syndrome (PCOS). However, the results remained inconsistent. In order to derive a more precise estimation of this relationship, a large meta-analysis was performed in this study. A comprehensive systematic electronic search was conducted in electronic databases PubMed, EMBASE, and Web of Science up to November 30, 2013. Pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association. A meta-analysis technique was used to study 38 trials involving 1,944 PCOS women and 1,654 healthy controls. Overall pooled adiponectin levels in women with PCOS were significantly reduced compared with healthy controls (WMD -2.67, 95% CI -3.22 to -2.13; P?=?0.000), yet with significant heterogeneity across studies (I(2)?=?95.9%, P?=?0.000). In subgroup analysis by HOMA-IR ratio and total testosterone ratio, inconsistent results were presented. No single study was found to affect the overall results by sensitivity testing. Meta-regression suggested that BMI might contribute little to the heterogeneity between including studies. Cumulative meta-analysis demonstrated the reliability and stability of the meta-analysis results. No evidence of publication bias was observed. Our meta-analysis suggested that circulating adiponectin levels in women with PCOS were significantly lower than those in healthy controls, which indicated that circulating adiponectin might play a role in the development of PCOS. PMID:24414393

Li, Shan; Huang, Xiamei; Zhong, Huizhi; Peng, Qiliu; Chen, Siyuan; Xie, Yantong; Qin, Xue; Qin, Aiping

2014-05-01

142

Adiponectin-Mediated Modulation of Lymphatic Vessel Formation and Lymphedema  

PubMed Central

Background Obesity is linked with an increased risk of lymphedema, which is a serious clinical problem. Adiponectin is a circulating adipokine that is down?regulated in obese states. We investigated the effects of adiponectin on lymphatic vessel formation in a model of lymphedema and dissected its mechanisms. Methods and Results A mouse model of lymphedema was created via ablation of tail surface lymphatic network. Adiponectin?knockout mice showed the greater diameter of the injured tail compared with wild?type mice, which was associated with lower numbers of lymphatic endothelial cells (LECs). Systemic delivery of adiponectin reduced the thickness of the injured tail and enhanced LEC formation in wild?type and adiponectin?knockout mice. Adiponectin administration also improved the edema of injured tails in obese KKAy mice. Treatment with adiponectin protein stimulated the differentiation of human LECs into tubelike structures and increased LEC viability. Adiponectin treatment promoted the phosphorylation of AMP?activated protein kinase (AMPK), Akt, and endothelial nitric oxide synthase n LECs. Blockade of AMPK or Akt activity abolished adiponectin?stimulated increase in LEC differentiation and viability and endothelial nitric oxide synthase phosphorylation. Inhibition of AMPK activation also suppressed adiponectin?induced Akt phosphorylation in LECs. In contrast, inactivation of Akt signaling had no effects on adiponectin?mediated AMPK phosphorylation in LECs. Furthermore, adiponectin administration did not affect the thickening of the damaged tail in endothelial nitric oxide synthase–knockout mice. Conclusions Adiponectin can promote lymphatic vessel formation via activation of AMPK/Akt/endothelial nitric oxide synthase signaling within LECs, thereby leading to amelioration of lymphedema.

Shimizu, Yuuki; Shibata, Rei; Ishii, Masakazu; Ohashi, Koji; Kambara, Takahiro; Uemura, Yusuke; Yuasa, Daisuke; Kataoka, Yoshiyuki; Kihara, Shinji; Murohara, Toyoaki; Ouchi, Noriyuki

2013-01-01

143

Effect of a combined estrogen and progesterone oral contraceptive on circulating adipocytokines adiponectin, resistin and DLK-1 in normal and obese female rhesus monkeys?  

PubMed Central

Background Hormonal contraception is the most common medication used by reproductive aged women but there is little understanding of the impact of hormonal contraception on obesity and metabolism. Adipokine levels (adiponectin, resistin) and markers of adipocyte development (DLK-1) are altered in obese animals and humans and are associated with increased cardiovascular risk. We sought to determine the effect of combined hormonal oral contraceptive pills (COCs) on circulating adiponectin, resistin and DLK-1 levels in obese and normal-weight rhesus macaque monkeys. Methods Serum adiponectin, resistin and DLK-1 levels in reproductive-age female rhesus macaques of normal (n = 5, mean = 5.76 kg) and inherently obese (n = 5, mean = 8.11 kg) weight were determined before, during and 2 months after cessation of 8 months of continuous treatment with COCs. Results The obese group alone showed a significant decrease (p<.01) in weight with COC use, which returned to baseline after COC cessation. Baseline adiponectin levels prior to COC treatment were lower in the obese group (p<.05). Adiponectin levels increased from baseline in both groups, but more so in the obese group (p<.05). Resistin levels were similar at baseline, with an increase in both groups following treatment. Circulating resistin remained elevated above baseline levels after COC cessation, particularly in the obese group (p<.05). While DLK-1 levels did not change significantly in either group, a trend for higher levels in obese animals was observed. Conclusions COC use may alter metabolic processes via direct (resistin) or indirect (adiponectin) means, while unchanging DLK1 levels suggest they do not affect adipocyte development. COCs may directly increase resistin levels, as observed in both groups. As adiponectin is inversely related to adipocyte mass, increased levels in the obese group are likely attributed to weight loss.

Shaw, Kate A.; Hennebold, Jon D.; Edelman, Alison B.

2012-01-01

144

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

145

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.

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

2013-01-01

146

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

NASA Astrophysics Data System (ADS)

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

Kaufman, Darrell S.; Miller, Gifford H.

1995-07-01

147

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.

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

2013-01-01

148

Role of adiponectin in metabolic and cardiovascular disease  

PubMed Central

Under disease conditions including obesity (insulin resistance) and diabetes, dysregulation of adipokines such as tumor necrosis factor (TNF)-?, leptin, resistin, and adiponectin contribute to the development of metabolic and cardiovascular disease. Unlike other adipokines, adiponectin has been shown to be a therapeutic target for metabolic syndrome and cardiovascular disease. Circulating levels of adiponectin are markedly reduced in obese, diabetic, hypertensive, and coronary artery disease patients as well as experimental animal models of insulin resistance and diabetes. Recently, the small molecule adiponectin receptors (AdipoRs) agonist was discovered and suggested that the agonist is a novel therapeutic target for the treatment of type 2 diabetes linked to obesity in an experimental mouse model. This review will focus on signaling pathways involved in adiponectin and its receptors and the role of adiponectin in metabolic and cardiovascular disease including insulin resistance, cardiomyopathy, and cardiovascular dysfunction.

Lee, Sewon; Kwak, Hyo-Bum

2014-01-01

149

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

150

p63 as a complimentary basal cell specific marker to high molecular weight-cytokeratin in distinguishing prostatic carcinoma from benign prostatic lesions.  

PubMed

The diagnosis of prostatic carcinoma (Pca) on routine biopsies may be challenging, and to date the commonly used marker to distinguish prostate carcinoma from benign prostatic lesions has been High Molecular Weight-Cytokeratin (HMW-CK). However, the antigen of HMW-CK is susceptible to the effect of formalin fixation and causes frequent loss or patchy staining in the obviously benign glands. More recently, antibodies to p63 have been reported to be more sensitive than HMW-CK for the detection of prostatic basal cells. p63, a homologue of tumour suppressor gene p53, is essential for prostate development and is selectively expressed in the nuclei of basal cells of normal prostate glands. The objective of this study is to compare the sensitivity and specificity of HMW-CK and p63 in distinguishing prostatic carcinomas from benign prostatic lesions, as well as determining their positive predictive values. Seventy-two cases from HUKM (comprising 29 prostatic carcinomas and 43 benign prostatic hyperplasias) were stained for both HMW-CK and p63. The sensitivity of p63 and HMW-CK in identifying basal cells in benign glands was 88.37% and 90.70% respectively. The specificity of both reagents was 100%, and the positive predictive value for both reagents was also 100%. Thus, p63 is a useful complementary basal cell specific stain to HMW-CK, and would be very helpful to practicing pathologists in dealing with difficult cases. PMID:17682568

Shiran, M S; Tan, G C; Sabariah, A R; Rampal, L; Phang, K S

2007-03-01

151

Associations between Endothelin1 and Adiponectin in Chronic Heart Failure  

Microsoft Academic Search

Objectives: Endothelin-1 (ET-1) induces cardiac hypertrophy, whereas adiponectin may elicit protective effects in the vasculature and myocardium. We therefore evaluated the relationship between plasma ET-1 and adiponectin levels in heart failure (HF) patients, and the association between adiponectin expression and ET-1-induced hypertrophy of human cardiomyocytes (HCM) in vitro. Methods: One hundred seventeen patients with chronic HF were enrolled into this

Wei-Hsian Yin; Yung-Hsiang Chen; Jeng Wei; Hsu-Lung Jen; Wen-Ping Huang; Mason Shing Young; Der-Cherng Chen; Po-Len Liu

2011-01-01

152

ATF3 negatively regulates adiponectin receptor 1 expression  

Microsoft Academic Search

Adiponectin is an adipocyte-derived hormone that has antidiabetic and antiatherogenic effects through two membrane receptors, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). Although it has been reported that the expression of AdipoR1 and AdipoR2 is regulated under physiological and pathophysiological states, their regulation is largely unknown. Previously, we demonstrated that endoplasmic reticulum (ER) stress or obesity-inducible ATF3 negatively

Hyun Jin Park; Young Mi Kang; Cho Hee Kim; Myeong Ho Jung

2010-01-01

153

Chemerin and adiponectin contribute reciprocally to metabolic syndrome.  

PubMed

Obesity and metabolic syndrome (MetS) are considered chronic inflammatory states. Chemerin, a novel adipokine, may play an important role in linking MetS and inflammation. We investigated the association of chemerin with inflammatory markers and with characteristics of MetS in apparently healthy overweight and obese adults. We studied 92 adults; 59 men and 33 women whose average body mass index (BMI) was 28.15 ± 5.08 kg/m(2). Anthropometric parameters, insulin resistance indices, lipid profiles, and inflammatory markers including high sensitivity C-reactive protein (hsCRP), pentraxin 3 (PTX3), adiponectin, and chemerin were measured. Controlling for age, gender, and BMI, serum chemerin level was positively correlated with body fat and serum triglyceride, and negatively correlated with adiponectin and high density lipoprotein cholesterol (HDL- C), and was not correlated with altered hsCRP or PTX3 levels. Among the low, moderate and high chemerin groups, high chemerin individuals are more likely to have lower HDL-C. Conversely, individuals in the low adiponectin group are more likely to have lower HDL-C and show more MetS phenotypic traits than moderate and high adiponectin subjects. To determine the relationships of chemerin and adiponectin to MetS and its components, participants were stratified into four groups based on their chemerin and adiponectin levels (high chemerin/high adiponectin, high chemerin/low adiponectin, low chemerin/high adiponectin, or low chemerin/low adiponectin). Participants who were in the high chemerin/low adiponectin group more likely to have dyslipidemia and MetS (OR: 5.79, 95% CI:1.00-33.70) compared to the other three group. Our findings suggest that chemerin and adiponectin may reciprocally participate in the development of MetS. PMID:22509348

Chu, Sang Hui; Lee, Mi Kyung; Ahn, Ki Yong; Im, Jee-Aee; Park, Min Soo; Lee, Duk-Chul; Jeon, Justin Y; Lee, Ji Won

2012-01-01

154

The cardio-protective signaling and mechanisms of adiponectin  

PubMed Central

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

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

2012-01-01

155

Adiponectin as a new paradigm for approaching Alzheimer's disease  

PubMed Central

Adiponectin is an adipocytokine released by the adipose tissue and has multiple roles in the immune system and in the metabolic syndromes such as cardiovascular disease, Type 2 diabetes, obesity and also in the neurodegenerative disorders including Alzheimer's disease. Adiponectin regulates the sensitivity of insulin, fatty acid catabolism, glucose homeostasis and anti-inflammatory system through various mechanisms. Previous studies demonstrated that adiponectin modulates memory and cognitive impairment and contributes to the deregulated glucose metabolism and mitochondrial dysfunction observed in Alzheimer's disease. Here, we aim to summarize recent studies that suggest the potential correlation between adiponectin and Alzheimer's disease.

Song, Juhyun

2013-01-01

156

Effects of Sugar-sweetened Beverages on plasma Acylation Stimulating Protein, Leptin & Adiponectin and Metabolic Parameters  

PubMed Central

Objective We determined 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. Design and Methods 32 overweight/obese adults consumed glucose- or fructose-sweetened beverages (25% energy requirement) with their ad libitum diets for 8 weeks, followed by sweetened beverage consumption for 2 weeks with a standardized, energy-balanced diet. Plasma variables were measured at baseline, 2, 8 and 10 weeks, and body adiposity and insulin sensitivity at baseline and 10 weeks. Results Fasting and postprandial ASP concentrations increased at 2 and/or 8 weeks. ASP increases correlated with changes in late-evening triglyceride concentrations. At 10 weeks, fasting adiponectin levels decreased in both groups, and decreases were inversely associated with baseline intra-abdominal fat volume. Sugar consumption increased fasting leptin concentrations; increases were associated with body weight changes. 24-h leptin profiles increased during glucose consumption and decreased during fructose consumption. These changes correlated with changes of 24-h insulin levels. Conclusions The consumption of fructose and glucose beverages induced changes in plasma concentrations of ASP, adiponectin and leptin. Further study is required to determine if these changes contribute to the metabolic dysfunction observed during fructose consumption.

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

2013-01-01

157

Association of genetic variants in the adiponectin gene with adiponectin level and hypertension in Hong Kong Chinese  

Microsoft Academic Search

Low plasma adiponectin level can predict the development of hypertension after 5 years in our population. We therefore investigated whether single-nucleotide polymorphisms (SNPs) in the adiponectin gene influenced plasma adiponectin level and whether they were associated with hypertension.\\\\\\\\ We genotyped 14 tagging SNPs in 1616 subjects with persistent normotensive or hypertensive status during a 6.4-year follow-up period in the Hong

K. L. Ong; M. Li; A. W. Tso; A. Xu; S. S. Cherny; P. C. Sham; H. F. Tse; T. H. Lam; B. M. Cheung; K. S. Lam

2010-01-01

158

Adiponectin and Leptin in African Americans  

Microsoft Academic Search

Objective:African Americans (AAs) have less visceral and more subcutaneous fat than whites, thus the relationship of adiponectin and leptin to body fat and insulin sensitivity in AA may be different from that in whites.Methods and Procedures:Sixty-nine non-diabetic AA (37 men and 32 women), aged 33 ± 1 year participated. The percent fat was determined by dual-energy X-ray absorptiometry, abdominal visceral

Robert V. Considine; Ahalya Premkumar; James C. Reynolds; Nancy G. Sebring; Madia Ricks; Anne E. Sumner

2008-01-01

159

Adiponectin: Systemic contributor to insulin sensitivity  

Microsoft Academic Search

Adipocyte-specific secreted molecules, termed adipokines, have dispelled the notion of adipose tissue as an inert storage\\u000a depot for lipids, and highlighted its role as an active endocrine organ that monitors and alters whole-body metabolism and\\u000a maintains energy homeostasis. One of these adipokines, adiponectin (also known as Acrp30, AdipoQ, and GBP28), has gained significant\\u000a attention recently as a mediator of insulin

Utpal B. Pajvani; Philipp E. Scherer

2003-01-01

160

Tracing the movement of adiponectin in a parabiosis model of wild-type and adiponectin-knockout mice  

PubMed Central

Adiponectin is exclusively synthesized by adipocytes and exhibits anti-diabetic, anti-atherosclerotic and anti-inflammatory properties. Hypoadiponectinemia is associated in obese individuals with insulin resistance and atherosclerosis. However, the mechanisms responsible for hypoadiponectinemia remain unclear. Here, we investigated adiponectin movement using hetero parabiosis model of wild type (WT) and adiponectin-deficient (KO) mice. WT mice were parabiosed with WT mice (WT–WT) or KO mice (WT–KO) and adiponectin levels were measured serially up to 63 days after surgery. In the WT–KO parabiosis model, circulating adiponectin levels of the WT partners decreased rapidly, on the other hand, those of KO partners increased, and then these reached comparable levels each other at day 7. Circulating adiponectin levels decreased further to the detection limit of assay, and remained low up to day 63. However, adiponectin protein was detected in the adipose tissues of not only the WT partner but also WT–KO mice. In the diet-induced obesity model, high adiponectin protein levels were detected in adipose stromal vascular fraction of diet-induced obese KO partner, without changes in its binding proteins. The use of parabiosis experiments shed light on movement of native adiponectin among different tissues such as the state of hypoadiponectinemia in obesity.

Nakatsuji, Hideaki; Kishida, Ken; Sekimoto, Ryohei; Funahashi, Tohru; Shimomura, Iichiro

2014-01-01

161

Serum adiponectin in patients with coronary heart disease.  

PubMed

Adiponectin is an adipocyte derived hormone, a modulator of lipid metabolism and systemic inflammation. It has potential anti-atherogenic property. Adiponectin is present in low concentration in patients with obesity, insulin resistance (IR), Type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). In this case control study, we studied the association of Serum adiponectin with CHD. Sixty-four subjects were enrolled. Consecutive 31 CHD patients (Group I) and 33 healthy controls (Group II) were included. Serum adiponectin & lipid profile were estimated in all. Serum adiponectin was significantly lower in CHD patients (3.90±2.21?g/ml) in comparison with controls (5.09±2.13?g/ml)(P<0.05). There was no significant difference of any fraction of lipid profile between cases and controls. Significant negative correlation was observed between Serum adiponectin and Serum triacylglyceride (STG) in cases (P<0.01). It may be concluded that low serum adiponectin may have some important role in development of CHD and probably low adiponectin and dyslipidemia are linked in the development of atherosclerosis. Further study is recommended with larger sample size to explore the role of hypoadiponectinemia in the causation of CHD. PMID:21240167

Parul, S S; Mazumder, M; Debnath, B C; Haque, M E

2011-01-01

162

Effects of Pitavastatin on Adiponectin in Patients with Hyperlipidemia  

Microsoft Academic Search

The effects of treatment with pitavastatin on inflammatory and platelet activation markers and adiponectin in 117 patients with hyperlipidemia were investigated to determine whether pitavastatin may prevent the progression of atherosclerotic changes in hyperlipidemic patients. Adiponectin levels prior to pitavastatin treatment in hyperlipidemic patients with and without diabetes were lower than levels in normolipidemic controls. Both total cholesterol and the

N. Inami; S. Nomura; A. Shouzu; S. Omoto; Y. Kimura; N. Takahashi; A. Tanaka; M. Nanba; Y. Shouda; T. Iwasaka

2008-01-01

163

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

164

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

165

Adiponectin is partially associated with exosomes in mouse serum.  

PubMed

Exosomes are membrane vesicles 30-120nm 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

166

Effects of the traditional Mediterranean diet on adiponectin and leptin concentrations in men and premenopausal women: do sex differences exist?  

PubMed

Background/Objectives:Most of the interventional studies have investigated the impact of the diet on adiponectin and leptin concentrations only in men or in women. Consequently, it is still unknown whether the consumption of a healthy diet influences in a sex-specific manner these adipocytokines. We examined sex differences in the effects of the Mediterranean diet (MedDiet) on adiponectin and leptin concentrations, and determined whether changes in these adipocytokines are associated with changes in cardiovascular risk factors in both sexes.Subjects/Methods:Participants were 38 men and 32 premenopausal women (24-53 years) with slightly elevated low-density lipoprotein cholestrol concentrations (3.4-4.9?mmol/l) or total cholesterol/high-density lipoprotein cholestrol (HDL-C)?5.0. Adiponectin, leptin and cardiovascular risk factors were measured before and after a 4-week fully controlled isoenergetic MedDiet.Results:Adiponectin concentration decreased in response to the MedDiet, but this decrease reached statistical significance only in men (P<0.001 for men and P=0.260 for women; sex-by-time interaction, P=0.072). Adjustments for body weight or waist circumference did not change results obtained. Changes in adiponectin were positively associated with concomitant variations in HDL-C in men (r=0.52, P=0.003) and with variations in apolipoprotein A-1 and insulin sensitivity as calculated by both the homeostasis model assessment index for insulin sensitivity and Cederholm indices in women (respectively, r=0.44, P=0.021; r=0.79, P<0.001 and r=0.47, P=0.020). The MedDiet had no impact on leptin and the leptin-to-adiponectin ratio in both sexes.Conclusions:Results suggest a sex difference in adiponectin response to the short-term consumption of the MedDiet, with only men experiencing a decrease. Also sex-specific patterns of associations between changes in adiponectin concentration and changes in cardiovascular risk factors were observed. PMID:24595221

Bédard, A; Tchernof, A; Lamarche, B; Corneau, L; Dodin, S; Lemieux, S

2014-05-01

167

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

168

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

SciTech Connect

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

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

1993-11-05

169

Adiponectin and resistin concentrations after glucose load in adolescents with polycystic ovary syndrome.  

PubMed

Our aims were to evaluate the serum adiponectin and resistin levels at fasting and after glucose load and their interaction with risk of cardiovascular disease (CVD) in adolescents with polycystic ovary syndrome (PCOS). Twenty-two adolescents with PCOS and 16 healthy controls were included in the study. Oral glucose tolerance test (OGTT) was performed in all adolescents. Fasting lipids was measured. Insulin, glucose, adiponectin, and resistin levels were measured at 0 and 120 min of OGTT. Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), fasting glucose-to-insulin ratio (FGIR), and the whole -body insulin sensitivity index (ISI) were calculated. Fasting adiponectin was correlated with ISI (r = 0.729, p < 0.0001), FGIR (r = 0.696, p < 0.0001), QUICKI (r = 0.592, p = 0.004) and HDL-C (r = 0.516, p = 0.028), systolic blood pressure (r = -0.732, p < 0.0001), body mass index (r = -0.738, p < 0.0001), waist circumference (r = -0.706, p < 0.0001), and HOMA-IR (r = -0.595, p = 0.003). No correlation was found between resistin and insulin resistance indexes. Obese adolescents with PCOS have increased CVD risk such as dyslipidemia, hypertension, and insulin resistance than normo-weight PCOS. Hypoadiponectinaemia could be increase risks levels in obese girls with PCOS. PMID:19639497

Güven, Ayla; Ozgen, Tolga; Aliyazicio?lu, Yüksel

2010-01-01

170

The effects of exercise and adipose tissue lipolysis on plasma adiponectin concentration and adiponectin receptor expression in human skeletal muscle  

Microsoft Academic Search

Objective: It has been suggested that adiponectin regulates plasma free fatty acid (FFA) clearance by stimulating FFA uptake and\\/or oxidation in muscle. We aimed to determine changes in plasma adi- ponectin concentration and adiponectin receptor 1 and 2 mRNA expression in skeletal muscle during and after prolonged exercise under normal, fasting conditions (high FFA trial; HFA) and following pharmacological inhibition

Chamindie Punyadeera; Antoine H G Zorenc; Andrew J McAinch; Egbert Smit; Ralph Manders; Hans A Keizer; David Cameron-Smith; Luc J C van Loon

2005-01-01

171

Adiponectin Action: A Combination of Endocrine and Autocrine/Paracrine Effects  

PubMed Central

The widespread physiological actions of adiponectin have now been well characterized as clinical studies and works in animal models have established strong correlations between circulating adiponectin level and various disease-related outcomes. Thus, conventional thinking attributes many of adiponectin’s beneficial effects to endocrine actions of adipose-derived adiponectin. However, it is now clear that several tissues can themselves produce adiponectin and there is growing evidence that locally produced adiponectin can mediate functionally important autocrine or paracrine effects. In this review article we discuss regulation of adiponectin production, its mechanism of action via receptor isoforms and signaling pathways, and its principal physiological effects (i.e., metabolic and cardiovascular). The role of endocrine actions of adiponectin and changes in local production of adiponectin or its receptors in whole body physiology is discussed.

Dadson, Keith; Liu, Ying; Sweeney, Gary

2011-01-01

172

Low-dose dietary resveratrol has differential effects on colorectal tumorigenesis in adiponectin knockout and wild-type mice.  

PubMed

Obesity is associated with a decrease in the antiinflammatory hormone, adiponectin, and increases in the circulating concentrations of multiple proinflammatory cytokines. These changes contribute to colon tumorigenesis. Resveratrol increases adiponectin production in adipocytes and attenuates the development of colon cancer. Thus, we hypothesized that adiponectin is an integral component of the mechanism by which resveratrol antagonizes colorectal tumorigenesis. To investigate this, we induced tumorigenesis in adiponectin knockout (KO) and wild-type (Wt) C57BL/6 mice through combined azoxymethane and dextran sodium sulfate treatment during which mice were fed a high-fat, lard-based diet, or the same diet containing 20 mg/kg resveratrol. After 14 wk on diet, Wt mice gained more weight and, on a percentage basis, had higher fat mass and lower lean mass than KO mice. Resveratrol tended to attenuate this response in male Wt mice. Resveratrol also tended to reduce aberrant crypt foci development and decrease circulating interleukin 6 and insulin concentrations in male but not female Wt mice. Taken together, resveratrol improved overall health of obese Wt but not KO mice as hypothesized with a differential sex response. PMID:21958119

Boddicker, Rebecca L; Whitley, Elizabeth M; Davis, Jeremy E; Birt, Diane F; Spurlock, Michael E

2011-11-01

173

Adiponectin Provides Cardiovascular Protection in Metabolic Syndrome  

PubMed Central

Adipose tissue plays a central role in the pathogenesis of metabolic syndrome. Adiponectin (APN) is a bioactive adipocytokine secreted from adipocytes. Low plasma APN levels (hypoadiponectinemia) are observed among obese individuals and in those with related disorders such as diabetes, hypertension, and dyslipidemia. APN ameliorates such disorders. Hypoadiponectinemia is also associated with major cardiovascular diseases including atherosclerosis and cardiac hypertrophy. Accumulating evidence indicates that APN directly interacts with cardiovascular tissue and prevents cardiovascular pathology. Increasing plasma APN or enhancing APN signal transduction may be an ideal strategy to prevent and treat the cardiovascular diseases associated with metabolic syndrome. However, further studies are required to uncover the precise biological actions of APN.

Okamoto, Yoshihisa

2011-01-01

174

Adiponectin in Cardiovascular Inflammation and Obesity  

PubMed Central

Inflammation is widely known to play a key role in the development and progression of cardiovascular diseases. It is becoming increasingly evident that obesity is linked to many proinflammatory and obesity-associated cardiovascular conditions (e.g., metabolic syndrome, acute coronary syndrome, and congestive heart failure). It has been observed that adipokines play an increasingly large role in systemic and local inflammation. Therefore, adipose tissue may have a more important role than previously thought in the pathogenesis of several disease types. This review explores the recently described role of adiponectin as an immunomodulatory factor and how it intersects with the inflammation associated with both cardiovascular and autoimmune pathologies.

Aprahamian, Tamar R.; Sam, Flora

2011-01-01

175

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

PubMed Central

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.

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

2010-01-01

176

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.

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

2014-01-01

177

Effect of Persea americana (avocado) fruit extract on the level of expression of adiponectin and PPAR-? in rats subjected to experimental hyperlipidemia and obesity.  

PubMed

Abstract Background: Persea americana, commonly known as avocado, is traditionally consumed fruit which possesses body fat lowering capacity. Adiponectin plays an important role in regulating obesity. In this study, the effect of hydro-alcoholic fruit extract of P. americana (HAEPA) on the level of blood lipids, glutathione, lipid peroxidation products, adiponectin and peroxisome proliferator activated receptor (PPAR)-? expressions was investigated in rats fed a high-fat diet (HFD). Methods: Male Sprague Dawley rats were divided into four groups: groups 1 and 2 were fed normal rat chow (5% fat) and groups 3 and 4 were fed HFD (23% fat) for a period of 14 weeks. In addition, groups 2 and 4 rats were administered orally with 100 mg/kg body weight of HAEPA from third week. After 14 weeks, rats were sacrificed, and serum/plasma levels of total cholesterol, phospholipids, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and adiponectin were determined. The mRNA expression of adiponectin, PPAR-? and protein expression of PPAR-? were also evaluated. Results: The body mass index (BMI), total fat pad mass and adiposity index were significantly decreased in HAEPA co-administered rats than in HFD-fed rats. The levels of LDL and lipid peroxides were significantly higher in HFD group than in HFD+HAEPA group. Levels of reduced glutathione, adiponectin, mRNA expression of adiponectin, PPAR-? and protein expression of PPAR-? were found to be increased in HFD+HAEPA group than in HFD group. The hypolipidemic effect of HAEPA is also evidenced by the histological observations in liver, heart and adipose tissue. Conclusions: The results indicate that HAEPA exhibits hypolipidemic activity probably by increasing the mRNA expression of adiponectin and PPAR-?, which reduce the risk of hyperlipidemia and obesity. PMID:24770838

Padmanabhan, Monika; Arumugam, Geetha

2014-06-01

178

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

PubMed

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

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

2010-12-15

179

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

2014-01-01

180

Effect of the diet components on adiponectin levels.  

PubMed

The prevalence of obesity has reached epidemic proportions worldwide, which requires nutritional interventions for its effective control. Adiponectin has antiinflammatory capacity, improves glucose tolerance and presents decreased plasma expression and concentration in obese individuals. Studies with animals reveal improvement in insulin resistance after the infusion of adiponectin; in humans, caloric restriction increases its levels. The present study aimed to analyze the effects of dietary components on gene expression and plasma concentration of adiponectin. Sixteen articles were found following a literature review--seven with interventions in animal models and nine in human. The results in animal models demonstrate that the consumption of hyperlipidemic diets, rich in saturated fat, reduces the levels of adiponectin, while the diets rich in polyunsaturated fatty acids and supplementation with omega-3 and eicosapentaenoic acid increase its gene expression and plasma levels. In humans, the consumption of a healthy and Mediterranean diet are positively associated with adiponectin levels, although the mechanisms are not fully understood. Due to the importance of adiponectin in preventing metabolic diseases and reducing cardiovascular risk, more research are needed on food strategies to promote the increase of adiponectin levels. Therefore, studies must be carried out to evaluate the response to different sources and levels of various dietary components and the safety of the supplementation of specific nutrients. PMID:21519758

Reis, C E G; Bressan, J; Alfenas, R C G

2010-01-01

181

Impact of Adiponectin Overexpression on Allergic Airways Responses in Mice  

PubMed Central

Obesity is an important risk factor for asthma. Obese individuals have decreased circulating adiponectin, an adipose-derived hormone with anti-inflammatory properties. We hypothesized that transgenic overexpression of adiponectin would attenuate allergic airways inflammation and mucous hyperplasia in mice. To test this hypothesis, we used mice overexpressing adiponectin (Adipo Tg). Adipo Tg mice had marked increases in both serum adiponectin and bronchoalveolar lavage (BAL) fluid adiponectin. Both acute and chronic ovalbumin (OVA) sensitization and challenge protocols were used. In both protocols, OVA-induced increases in total BAL cells were attenuated in Adipo Tg versus WT mice. In the acute protocol, OVA-induced increases in several IL-13 dependent genes were attenuated in Adipo Tg versus WT mice, even though IL-13 per se was not affected. With chronic exposure, though OVA-induced increases in goblet cells numbers per millimeter of basement membrane were greater in Adipo Tg versus WT mice, mRNA abundance of mucous genes in lungs was not different. Also, adiponectin overexpression did not induce M2 polarization in alveolar macrophages. Our results indicate that adiponectin protects against allergen-induced inflammatory cell recruitment to the airspaces, but not development of goblet cell hyperplasia.

Verbout, Norah G.; Williams, Alison S.; Kasahara, David I.; Wurmbrand, Allison P.; Halayko, Andrew J.; Shore, Stephanie A.

2013-01-01

182

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

PubMed Central

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

2011-01-01

183

PEGylation-aided refolding of globular adiponectin.  

PubMed

Globular adiponectin (GAD) as the active domain of adiponectin is a promising candidate for anti-diabetic drug development. The recombinant production of GAD in Escherichia coli, however, is difficult because it is mainly expressed as inclusion bodies which need to be refolded to regain function. In this study we developed a novel method for refolding of GAD with a high efficiency by using polyethylene glycol (PEG) conjugation. An artificially designed DNA sequence encoding for GAD was synthesized and inserted into the pET28a vector to construct an expression plasmid which was thereafter transformed into E. coli BL21 (DE3) host cells for heterologous expression. After bacterial cell culture employing auto-induction medium, the inclusion bodies were collected, washed and dissolved in guanidine hydrochloride before PEG conjugation. Then the PEG-conjugated GAD was refolded by dialysis and purified by two steps of chromatography. The refolded conjugate showed a marked glucose-lowering activity in mice, demonstrating that it had been successfully refolded. As a convenient method, PEGylation-aided refolding could also be tested on other proteins to explore its suitability. PMID:23512209

Gao, Mingming; Tong, Yue; Gao, Xiangdong; Yao, Wenbing

2013-08-01

184

Adiponectin is a potential catabolic mediator in osteoarthritis cartilage  

PubMed Central

Introduction Adiponectin has been implicated in the pathogenesis of osteoarthritis (OA). We studied the effects of adiponectin on the OA cartilage homeostasis. Methods Immunohistochemical analysis was performed to evaluate differential expression of adiponectin receptors (AdipoRs) in nonlesional and lesional areas of OA cartilage. Cartilage and chondrocytes from the knee joints of primary OA patients were cultured in the presence of adiponectin (0~30 ?g/ml). The levels of total nitric oxide (NO), matrix metalloproteinase (MMP)-1, -3, and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in the conditioned media. The levels of inducible NO synthase (iNOS) and MMPs were determined with the quantitative real-time reverse transcription-polymerase chain reaction. The concentrations of collagenase-cleaved type II collagen neoepitope (C1-2C) were determined in the supernatant of adiponectin-stimulated OA cartilage explants. The effects of kinase and NOS inhibitors were evaluated in the adiponectin-stimulated chondrocytes. Results The expression levels of both AdipoR1 and AdipoR2 were significantly higher in lesional than in nonlesional areas of OA cartilage. The increased rate of AdipoR1-positive chondrocytes was twice that of AdipoR2-positive chondrocytes when compared between nonlesional and lesional areas. Adiponectin-stimulated OA chondrocytes showed increased total NO and MMP-1, -3, and -13 levels compared with nonstimulated cells. The TIMP-1 level was not affected. The C1-2C levels were increased by adiponectin in OA cartilage explant culture. AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) inhibitors (compound C and SP600125) significantly suppressed adiponectin-induced production of total NO and MMP-1, -3, and -13. Inducible NOS inhibitors enhanced the expression of the adiponectin-induced MMPs. Conclusions Adiponectin causes matrix degradation in OA cartilage and increases MMPs and iNOS expression via the AMPK and JNK pathways in human OA chondrocytes. The catabolic effects of adiponectin may be counteracted by NO.

2010-01-01

185

OLIGOMERIC ADIPONECTIN FORMS AND THEIR COMPLEXES IN THE BLOOD OF HEALTHY DONORS AND PATIENTS WITH TYPE 2 DIABETES MELLITUS  

Microsoft Academic Search

Adiponectin (Adn) is a protein that circulates in the blood in several oligomeric forms named low-, medium-, and high-molecular-weight forms. Adn may serve as a risk factor for type 2 diabetes mellitus (T2DM). The aims of this work were 1) to produce monoclonal antibodies (MAbs) specific to different Adn oligomeric forms, 2) to design immunoassays suitable for measuring the Adn

Alexander E. Kogan; Vladimir L. Filatov; Olga V. Kolosova; Ivan A. Katrukha; Ekaterina V. Mironova; Natalya S. Zhuravleva; Oleg A. Nagibin; Andrei N. Kara; Anastasiya V. Bereznikova; Alexey G. Katrukha

2012-01-01

186

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.

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

2014-01-01

187

Common polymorphisms (single-nucleotide polymorphisms SNP+45 and SNP+276) of the adiponectin gene regulate serum adiponectin concentrations and blood pressure in young Finnish men  

Microsoft Academic Search

Epidemiologic studies have shown that serum level of adiponectin, a circulating protein secreted by adipocytes, predicts the risk of type 2 diabetes and cardiovascular events. Two single-nucleotide polymorphisms (SNPs) at the adiponectin locus (T45G or G276T) of the adiponectin gene (APM1) have been associated with insulin resistance, low serum adiponectin levels, and diabetes. In the present study, the association of

Firoozeh Mousavinasab; Tuula Tähtinen; Jari Jokelainen; Pentti Koskela; Mauno Vanhala; Jorma Oikarinen; Sirkka Keinänen-Kiukaanniemi; Markku Laakso

2006-01-01

188

Omental fat expression of adiponectin and adiponectin receptors in non-obese women with PCOS: a preliminary study.  

PubMed

Adiponectin is regarded as a possible link between adiposity and insulin resistance. The aim of the study was to determine adipose levels of mRNA for adiponectin and adiponectin receptors (AdipoR) in non-obese women with polycystic ovary syndrome (PCOS), and to assess whether the cytokine and receptors are related to insulin resistance in PCOS. Adipose tissue obtained from eight non-obese women with PCOS [body mass index (BMI) <27 kg/m(2) as cut-off point] was analysed. Levels of mRNA for adiponectin, AdipoR1 and 2 were quantified using the semi-quantitative reverse transcriptase-polymerase chain reaction. Eight non-obese, age- and BMI-matched healthy women served as controls. The level of adiponectin mRNA in non-obese women with PCOS were lower than in controls, but the difference was not statistically significant. However, AdipoR1 and 2 mRNA levels in non-obese women with PCOS were significantly lower than in controls. There was a significant negative correlation between 2 h insulin levels and AdipoR1 or AdipoR2 mRNA levels in non-obese women with PCOS ( r = 0.45 and 0.52 respectively, P < 0.05). The present study demonstrates that adiponectin receptor expression is down-regulated by hyperinsulinaemia in non-obese women with PCOS, resulting in adiponectin resistance. PMID:19909601

Seow, Kok-Min; Tsai, Yieh-Loong; Juan, Chi-Chang; Lin, Yu-Hung; Hwang, Jiann-Loung; Ho, Low-Tone

2009-10-01

189

The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians.  

PubMed

Low concentrations of adiponectin, the protein product of the APM1 gene, have been reported to be associated with obesity and insulin resistance. However, contrasting results have been described on the genetic variability in APM1 and characteristics of the metabolic syndrome and adiponectin serum concentrations. In the present study, we investigated the association of the two most well-known SNPs of APM1 (+45T>G and +276G>T) and their haplotypes, with serum adiponectin concentrations, metabolic parameters and intima-media thickness of the carotid arteries in 1,745 well-phenotyped asymptomatic unrelated Caucasian subjects of the SAPHIR cohort. The common T-allele (88.5%) of SNP +45T>G and the common G-allele (70.5%) of SNP +276G>T were associated with significantly lower serum adiponectin levels (P = 0.0008 and P = 0.00005, respectively). The most frequent haplotype TG (59.0%) defined by both loci showed a strong association with lower serum adiponectin concentrations (P = 0.000000002). A clear effect per copy of the respective haplotype was observed. This association was most pronounced in lean and insulin-sensitive subjects. The two less common haplotypes TT (29.5%) and GG (11.5%) were associated with higher serum adiponectin levels in a dose-dependent association. Interestingly, no significant association between the adiponectin 45-276 haplotypes and the majority of parameters of the metabolic syndrome or intima-media thickness of the carotid arteries was found in our study. In summary, we replicated a strong association of the adiponectin 45-276 genotypes and haplotypes with adiponectin levels in healthy Caucasians. However, we could not confirm an association of this gene locus with metabolic parameters of the insulin resistance syndrome. PMID:16418740

Mackevics, Vitolds; Heid, Iris M; Wagner, Stefanie A; Cip, Paula; Doppelmayr, Hildegard; Lejnieks, Aivars; Gohlke, Henning; Ladurner, Günther; Illig, Thomas; Iglseder, Bernhard; Kronenberg, Florian; Paulweber, Bernhard

2006-03-01

190

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

PubMed

A deficit in adiponectin plays an important causal role in insulin resistance and metabolic syndrome. We hypothesized that as seen during the fasting state, the intake of a walnut-enriched meal increased postprandial adiponectin. Twenty-one healthy white men followed a 4-week baseline diet and then consumed 3 fat-loaded meals that included 1 g fat/kg body weight (65% fat) according to a randomized crossover design: olive oil-enriched meal (22% saturated fatty acids [SFA], 38% monounsaturated fatty acids [MUFA], 4% polyunsaturated fatty acids [PUFA]), butter-enriched meal (35% SFA, 22% MUFA, 4% PUFA), and walnut-enriched meal (20% SFA, 24% MUFA, 16% PUFA, and 4% ?-linolenic acid). Leptin, resistin, adiponectin, and free fatty acids were determined at 0, 3, 6, and 8.5 hours after the fat load. After the walnut-enriched meal, plasma adiponectin concentrations were higher at 3 and 6 hours (P = .011, P = .046, respectively) compared with the butter-enriched meal and higher at 6 hours compared with the olive oil-enriched meal (P = .036). Free fatty acid levels decreased from baseline at 3 hours after the walnut-enriched meal (P = .001). No differences were observed between the 3 meals for leptin and resistin responses. Our data confirmed a beneficial profile in the postprandial response to walnuts, source of omega-3 PUFA with an increased postprandial adiponectin and lower postprandial free fatty acid responses. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with omega-3 PUFA dietary fat. PMID:24267040

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

2013-12-01

191

Capillary electrophoresis separation of high molecular weight glutenin subunits in bread wheat (Triticum aestivum L.) and related species with phosphate-based buffers.  

PubMed

This study focused on optimizing phosphate-based buffers and other capillary electrophoresis (CE) parameters for separating and characterizing high molecular weight glutenin subunits (HMW-GS) in bread wheat (Triticum aestivum L., AABBDD, 2n = 6x = 42), emmer (Triticum dicoccum, AABB, 2n = 4x = 28) and Aegilops tauschii (DD, 2n = 2x = 14). The fast and high-resolution separation of HMW-GS was achieved using 0.1 M phosphate-glycine buffer (pH 2.5, containing 20% acetonitrile and 0.05% hydroxypropylmethylcellulose) at 12.5 kV and 40 degrees C with 25 microm inside diameter (ID)x27 cm uncoated fused-silica capillary. In general, one sample separation can be analyzed in 15 min. The good run-to-run repeatable separation of HMW-GS could be obtained with a relative standard deviation of less than 1% when capillaries were rinsed with 1 M phosphoric acid for 2 min, followed by separation buffer for 2 min after each separation. The HMW-GS from some bread wheat cultivars as well as tetraploid and diploid accessions was separated by the CE method described above, and all subunits detected were well characterized and readily identified. Some HMW-GS showed reversed mobilities and elution order compared to the methods of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and SDS-CE. Particularly, most of the HMW-GS analyzed with the CE buffer used were separated into multiple peaks, generally a high peak plus a minor peak. CE appears to be capable of separating and characterizing HMW-GS with fast and high-resolution features, therefore it is expected to be useful for specific germplasm screening and desirable HMW-GS identification in wheat quality improvement. PMID:12731030

Yan, Yueming; Yu, Jianzhong; Jiang, Yi; Hu, Yingkao; Cai, Minhua; Hsam, Sai L K; Zeller, Friedrich J

2003-05-01

192

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

PubMed Central

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

Ye, Risheng; Scherer, Philipp E.

2013-01-01

193

Adiponectin Enhances the Responsiveness of the Olfactory System  

PubMed Central

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

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

2013-01-01

194

AICAR stimulates adiponectin and inhibits cytokines in adipose tissue  

Microsoft Academic Search

5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) can be used as an experimental tool to activate 5?-AMP-activated protein kinase (AMPK) and has been shown to improve insulin sensitivity. In parallel adiponectin also seems to activate AMPK and to improve insulin sensitivity. We have investigated the effects of AICAR on the gene expression of adiponectin and on gene expression and release of cytokines in human

Aina S Lihn; Niels Jessen; Steen B Pedersen; Sten Lund; Bjørn Richelsen

2004-01-01

195

Molecular mechanisms of leptin and adiponectin in breast cancer  

Microsoft Academic Search

Obesity is associated with an increased risk of breast cancer in postmenopausal women. Accumulating evidence suggests that adipose tissue, which is an endocrine organ producing a large range of factors, may interfere with breast cancer development. Leptin and adiponectin are two major adipocyte-secreted hormones. The pro-carcinogenic effect of leptin and conversely, the anti-carcinogenic effect of adiponectin result from two main

Thierry Jardé; Stéphane Perrier; Marie-Paule Vasson; Florence Caldefie-Chézet

2011-01-01

196

Lower Serum Adiponectin Levels in African-American Boys  

Microsoft Academic Search

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

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

2003-01-01

197

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

198

Adiponectin as a Biomarker of Osteoporosis in Postmenopausal Women: Controversies  

PubMed Central

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.

Dobek, Aleksandra; Garczynski, Wojciech; Chlubek, Dariusz

2014-01-01

199

Effects of lipid-lowering drugs on adiponectin.  

PubMed

Adiponectin has been implicated in the pathogenesis of coronary heart disease. We review the literature describing the effect of lipid-lowering agents on adiponectin bioavailability. Statins exert variable effects that can be influenced by patient-dependent characteristics (i.e. diabetes or insulin resistance). Fibrates and especially niacin can raise adiponectin levels. The impact of plant sterols, ezetimibe and ?-3 fish oils on adiponectin in humans remains to be defined. There was no literature on whether resins can alter adiponectin levels. As far as mechanisms are concerned, statins enhance peroxisome proliferator-activator receptor (PPAR)-? activation and have antioxidant or anti-inflammatory potential. Niacin, ?-3 fatty acids, plant sterols and bezafibrate primarily act by increasing PPAR-? activity and possibly by reducing oxidative stress or inflammation. Both fibrates and ?-3 fish oils act as synthetic ligands for PPAR-?. Hypolipidaemic drugs can affect adiponectin bioavailability, although the impact depends on the individual drug administered and patient characteristics. However, with the exception of niacin, the results observed are not conclusive. PMID:20180775

Perelas, Apostolos; Tsoulkani, Anna; Perrea, Despina

2010-11-01

200

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

PubMed Central

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 (3) model group B (n = 11) were fed with a high-fat diet (standard diet + 10% lard + 2% cholesterol) for 8 and 12 wk, respectively. Hepatic histological changes were observed and biochemical parameters as well as serum levels of adiponectin, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-? were measured. RESULTS: Typical histological hepatic lesions of NASH were observed in both model groups described as liver steatosis, liver inflammatory infiltration, cytologic ballooning, perisinusoidal fibrosis and overall fibrosis. Compared with the normal control group, there were significant increases in model groups A and B in weight gain (1097.2 ± 72.3, 1360.5 ± 107.6 vs 928.0 ± 58.1, P < 0.05, P < 0.01), liver weight (93.81 ± 6.64, 104.6 ± 4.42 vs 54.4 ± 1.71, P < 0.01), Lg (ALT) (1.9 ± 0.29, 1.84 ± 0.28 vs 1.60 ± 0.17, P < 0.01), and Lg (TG) (1.03 ± 0.24, 1.16 ± 0.33 vs 0.00 ± 0.16, P < 0.01). Weight gain was much more in model group B than in model group A (1360.5 ± 107.6 vs 1097.2 ± 72.3, P < 0.05). But, there was no significant difference between the two groups concerning the other indexes. Pro-inflammatory cytokines (IL-6 and TNF-?) increased in model group B compared with that of control and model group A (IL-6: 1.86 ± 0.21 vs 1.41 ± 0.33, 1.38 ± 0.42, P < 0.01; TNF-?: 1.18 ± 0.07 vs 0.66 ± 0.08, 0.86 ± 0.43, P < 0.01, P < 0.05), whereas serum adiponectin and IL-10 decreased in model groups compared with that in the control (adiponectin: A: 21.87 ± 4.84 and B: 21.48 ± 4.60 vs 27.36 ± 7.29, P < 0.05. IL-10: A: 1.72 ± 0.38 and B: 1.83 ± 0.39 vs 2.26 ± 0.24, P < 0.01). Lg (TC) and the degree of liver fatty infiltration was an independent determinant of serum adiponectin level analyzed by stepwise multiple regressions, resulting in 29.4% of variances. CONCLUSION: This rabbit model produces the key features of pediatric NASH and may provide a realistic model for future studies. Adiponectin level partially reflects the severity of liver steatosis, but not the degree of liver inflammation.

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

2009-01-01

201

The Liposuction-Induced Effects on Adiponectin and Selected Cytokines Are Not Affected by Exercise Training in Women  

PubMed Central

It has been suggested that the abrupt liposuction-induced decrease in adipose tissue could affect adipokine secretion pattern. We hypothesized that exercise training could positively impact adipokine metabolism following liposuction. The aim of this study was to investigate the effects of liposuction on inflammation-related adipokines in women who were either exercise-trained or remained sedentary after surgery. Thirty-six healthy normal-weight women underwent an abdominal liposuction and two months after surgery were randomly allocated into two groups: trained (TR, n = 18, four-month exercise program) and nontrained (NT, n = 18). Inflammation-related adipokine serum levels (TNF-?, IL-6, IL-10, and adiponectin) and abdominal and thigh subcutaneous adipose tissue (scAT) mRNA levels were assessed before (PRE) and six months after surgery (POST6). TNF-?, IL-6, and IL-10 serum levels were unchanged in both groups. In contrast, TNF-?, IL-6, and IL-10 mRNA levels in scAT were increased, whereas adiponectin scAT mRNA and serum levels were decreased at POST6 (P < 0.05, main effect for time). No changes were observed in mRNA levels of MCP-1, CD14, and CD68 in any of the groups. In conclusion, liposuction downregulates adiponectin scAT gene expression and serum levels and upregulates scAT gene expression of inflammation-related genes six months after surgery in normal-weight women, irrespective of exercise training.

Yazigi Solis, Marina; Artioli, Guilherme Giannini; Montag, Eduardo; de Salles Painelli, Vitor; Saito, Fabio Lopes; Lima, Fernanda Rodrigues; Roschel, Hamilton; Gualano, Bruno; Lancha Junior, Antonio Herbert; Benatti, Fabiana Braga

2014-01-01

202

Adiponectin and inflammatory markers in peripheral arterial occlusive disease.  

PubMed

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

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

2006-10-01

203

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).

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

2014-01-01

204

Plasma adiponectin concentrations in children: relationships with obesity and insulinemia.  

PubMed

Adiponectin, a novel adipokine with anti-inflammatory and insulin-sensitizing properties, has been found to have independent negative associations with obesity and hyperinsulinemia/insulin resistance in adults. We measured fasting plasma adiponectin and insulin concentrations and body composition (dual-energy x-ray absorptiometry or doubly labeled water) in 30 5-yr-old (11 boys and 19 girls) and 53 10-yr-old (17 boys and 36 girls) Pima Indian children. A subgroup of 20 children (5 boys and 15 girls) had all measurements at both 5 and 10 yr of age. Cross-sectionally, plasma adiponectin concentrations were negatively correlated with percentage body fat and fasting plasma insulin concentrations at both 5 yr (r = -0.35, P = 0.06, r = -0.42, P = 0.02) and 10 yr (r = -0.46, P = 0.001, r = -0.38, P = 0.005) of age. At age 10 yr, percentage body fat (P = 0.03) but not fasting plasma insulin (P = 0.59) was independently associated with fasting plasma adiponectin concentrations. Longitudinally, plasma adiponectin concentrations decreased with increasing adiposity. In summary, these results confirm our previously reported findings in adults of an inverse relationship between plasma adiponectin concentrations and adiposity in children. Longitudinal analyses indicated that hypoadiponectinemia is a consequence of the development of obesity in childhood. We did not find evidence that adiponectin is an early mediator of obesity-induced insulin resistance, a preliminary observation that needs to be confirmed in studies using a more direct measurement of insulin action than the one used in this investigation. PMID:12364452

Stefan, Norbert; Bunt, Joy C; Salbe, Arline D; Funahashi, Tohru; Matsuzawa, Yuji; Tataranni, P Antonio

2002-10-01

205

High molecular weight polyethylene glycol cellular distribution and PEG-associated cytoplasmic vacuolation is molecular weight dependent and does not require conjugation to proteins.  

PubMed

Conjugation of therapeutic proteins with high molecular weight polyethylene glycols (HMW PEGs) is used to extend the half-life of biologics. To evaluate the effects of HMW PEGs in animals, we used an immunohistochemical procedure to study the tissue distribution and toxicity of unconjugated HMW PEGs in rats given 100 mg/kg (10K)PEG, (20K)PEG, or (40K)PEG intravenously. Both the PEG cellular distribution and the histology were different between groups. In (10K)PEG and (20K)PEG groups, PEG immunoreactivity was most prominent in the renal tubule epithelium and in alveolar macrophages and hepatic Kupffer cells and cellular vacuolation was absent. In contrast, rats given (40K)PEG had strong PEG immunoreactivity in splenic subcapsular red pulp macrophages, renal interstitial macrophages, and choroid plexus epithelial cells that was frequently associated with cytoplasmic vacuolation. While the vacuolation appeared to be an adaptive response, there was focal renal tubular epithelial degeneration associated with strong PEG immunoreactivity in one rat given (40K)PEG. These data indicate that both the tissue distribution and the vacuolation observed with unconjugated HMW PEGs are markedly influenced by the molecular weight of the PEG and that when vacuolation is observed it is likely an adaptive change that is associated with PEG cytoplasmic immunoreactivity. PMID:23788571

Rudmann, Daniel G; Alston, James T; Hanson, Jeffrey C; Heidel, Shawn

2013-01-01

206

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

Microsoft Academic Search

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

Rebecca L. Boddicker

2011-01-01

207

Adiponectin signals in prostate cancer cells through Akt to activate the mammalian target of rapamycin pathway  

Microsoft Academic Search

Adiponectin has received much attention due to its beneficial effects on insulin sensitivity, and epidemiologic studies have further shown an inverse association between adiponectin levels and risk for multiple tumors, which is independent of the IGF system or other risk factors. Previous studies have shown that adiponectin can activate AMP-activated protein kinase (AMPK) in myocytes, hepatocytes, and adipocytes, suggesting that

D Barb; A Neuwirth; C S Mantzoros; S P Balk

2007-01-01

208

Decreased adiponectin levels in familial combined hyperlipidemia patients contribute to the atherogenic lipid profile  

Microsoft Academic Search

Familial combined hyperlipidemia (FCH) is characterized by increased levels of total cholesterol, triglycerides, and\\/or apolipoprotein B. Other features of FCH are obesity and insulin resistance. Adiponectin is a secretory product of the adipose tissue. Low levels of adiponectin are associated with insulin resistance and accelerated atherosclerosis. The aim of this study was to determine whether decreased adiponectin levels are associated

Gerly M. van der Vleuten; Martin den Heijer; H. L. M. Hak-Lemmers; Anton F. H. Stalenhoef; Jacqueline de Graaf

2005-01-01

209

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

210

Evidence that adiponectin receptor 1 activation exacerbates ischemic neuronal death  

PubMed Central

Background- Adiponectin is a hormone produced in and released from adipose cells, which has been shown to have anti-diabetic and anti-inflammatory actions in peripheral cells. Two cell surface adiponectin receptors (ADRs) mediate the majority of the known biological actions of adiponectin. Thus far, ADR expression in the brain has been demonstrated in the arcuate and the paraventricular nucleus of hypothalamus, where its activation affects food intake. Recent findings suggest that levels of circulating adiponectin increase after an ischemic stroke, but the role of adiponectin receptor activation in stroke pathogenesis and its functional outcome is unclear. Methods- Ischemic stroke was induced in C57BL/6 mice by middle cerebral artery occlusion (MCAO) for 1 h, followed by reperfusion. Primary cortical neuronal cultures were established from individual embryonic neocortex. For glucose deprivation (GD), cultured neurons were incubated in glucose-free Locke's medium for 6, 12 or 24 h. For combined oxygen and glucose deprivation (OGD), neurons were incubated in glucose-free Locke's medium in an oxygen-free chamber with 95% N2/5% CO2 atmosphere for either 3, 6, 9, 12 or 24 h. Primary neurons and brain tissues were analysed for Adiponectin and ADRs using reverse transcriptase polymerase chain reaction (RT-PCR), immunoblot and immunochemistry methods. Results- Cortical neurons express ADR1 and ADR2, and that the levels of ADR1 are increased in neurons in response to in vitro or in vivo ischemic conditions. Neurons treated with either globular or trimeric adiponectin exhibited increased vulnerability to oxygen and glucose deprivation which was associated with increased activation of a pro-apoptotic signaling cascade involving p38 mitogen-activated protein kinase (p38MAPK) and AMP-activated protein kinase (AMPK). Conclusions- This study reveals a novel pathogenic role for adiponectin and adiponectin receptor activation in ischemic stroke. We show that cortical neurons express ADRs and reveal a pro-apoptotic role for ADR1 activation in neurons, which may render them vulnerable to ischemic death.

2010-01-01

211

Plasma adiponectin before and after kidney transplantation.  

PubMed

The role of plasma adiponectin (ADPN) in patients with impaired kidney function and following kidney transplantation (Tx) is debated. We aimed to: (i) determine whether pretransplant ADPN level is an independent risk factor for deterioration of glucose tolerance including development of new-onset diabetes mellitus after Tx, (ii) describe which parameters that influence the ADPN concentration before and after Tx. Fifty-seven nondiabetic kidney allograft recipients and 40 nondiabetic uraemic patients were included. The Tx group was examined at baseline and 3 and 12 months after Tx. The uraemic control group was examined twice, separated by 12 months. ADPN levels declined significantly following Tx (P < 0.0001), while estimated glomerular filtration rate (eGFR) increased (P < 0.0005). eGFR, BMI and insulin sensitivity index were independently associated with ADPN in a multivariate regression analysis, whereas an ordinal logistic regression analysis revealed no predictive characteristic of ADPN for aggravation of the glucose tolerance after Tx. In conclusion, kidney transplantation is accompanied by a significant reduction in ADPN concentration. Several factors determine the ADPN concentration before and after Tx including kidney function, insulin resistance, use of immunosuppressive agents and BMI. Pretransplant ADPN level did not predict development of new-onset diabetes mellitus or even deterioration of the glucose tolerance following Tx. PMID:22994569

Idorn, Thomas; Hornum, Mads; Bjerre, Mette; Jørgensen, Kaj Anker; Nielsen, Finn Thomsen; Hansen, Jesper Melchior; Flyvbjerg, Allan; Feldt-Rasmussen, Bo

2012-11-01

212

Effects of soy protein and isoflavones on insulin resistance and adiponectin in male monkeys.  

PubMed

Isoflavones may influence insulin action by means of their well-known receptor-mediated estrogenic activity. However, isoflavones also bind to peroxisome proliferator-activated receptors (PPARs) that are strongly associated with insulin action. Soy protein with its isoflavones has previously been shown to improve glycemic control in diabetic postmenopausal women and to improve insulin sensitivity in ovariectomized monkeys. The purpose of the current report was to extend our studies of dietary soy protein to male monkeys and determine effects of the soy isoflavones on insulin resistance. Two studies are reported here. Study one involved 91 male monkeys consuming 3 diets differing only by the source of protein (casein-lactalbumin, soy protein with a low isoflavone concentration, or soy protein with a high isoflavone concentration). Intravenous glucose tolerance tests were done, and plasma adiponectin and lipoprotein concentrations were determined after 25 months of study. Samples of visceral fat were obtained at 31 months for assessment of adiponectin and PPARgamma expression. The second study involved 8 monkeys in a Latin-square design that compared the effects of diets with casein/lactalbumin, soy protein with a high isoflavone concentration, or soy protein that was alcohol-washed to deplete the isoflavones. After 8 weeks of treatment, insulin sensitivity and plasma lipoproteins were assessed. At 10 weeks, a biopsy of the skeletal muscle was performed for determination of insulin receptor, PPARalpha, and PPARgamma content. The major findings were that consumption of isoflavone-containing soy protein dose-dependently increased insulin responses to the glucose challenge and decreased plasma adiponectin, whereas isoflavone-depleted soy protein decreased body weight and had no effect on plasma adiponectin concentrations. Muscle PPARalpha and gamma expression was also increased with the isoflavone-depleted soy relative to either casein or soy protein containing the isoflavones. Further studies are needed to determine the mechanisms involved in these effects of a high-soy isoflavone diet and to optimize dietary isoflavone content for maximal health benefits in male subjects. PMID:18555850

Wagner, Janice D; Zhang, Li; Shadoan, Melanie K; Kavanagh, Kylie; Chen, Haiying; Tresnasari, Kristianti; Kaplan, Jay R; Adams, Michael R

2008-07-01

213

Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management.  

PubMed

An increase in adiposity is associated with altered levels of biologically active proteins. These include the hormones adiponectin and leptin. The marked change in circulating concentrations of these hormones in obesity has been associated with the development of insulin resistance and metabolic syndrome. Variations in dietary lipid consumption have also been shown to impact obesity. Specifically, omega-3 fatty acids have been correlated with the prevention of obesity and subsequent development of chronic disease sequalae. This review explores animal and human data relating to the effects of omega-3 fatty acids (marine lipids) on adiponectin and leptin, considering plausible mechanisms and potential implications for obesity management. Current evidence suggests a positive, dose-dependent relationship between omega-3 fatty acid intake and circulating levels of adiponectin. In obese subjects, this may translate into a reduced risk of developing cardiovascular disease, metabolic syndrome and diabetes. In non-obese subjects, omega-3 is observed to decrease circulating levels of leptin; however, omega-3-associated increases in leptin levels have been observed in obese subjects. This may pose benefits in the prevention of weight regain in these subjects following calorie restriction. PMID:24129365

Gray, B; Steyn, F; Davies, P S W; Vitetta, L

2013-12-01

214

A Study of Adiponectin in Children with Diabetes Mellitus  

PubMed Central

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

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

2013-01-01

215

Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice  

PubMed Central

Aims/hypothesis Adiponectin is an adipocyte-derived hormone that plays an important role in energy homeostasis. The main objective of this study was to investigate whether or not adiponectin regulates brown adipose tissue (BAT) activation and thermogenesis. Methods Core body temperatures (CBTs) of genetic mouse models were monitored at room temperature and during cold exposure. Cultured brown adipocytes and viral vector-mediated gene transduction were used to study the regulatory effects of adiponectin on Ucp1 gene expression and the underlying mechanisms. Results The CBTs of adiponectin knockout mice (Adipoq?/?) were significantly higher than those of wild type (WT) mice both at room temperature and during the cold (4°C) challenge. Conversely, reconstitution of adiponectin in Adipoq?/? mice significantly blunted ? adrenergic receptor agonist-induced thermogenesis of interscapular BAT. After 10 days of intermittent cold exposure, Adipoq?/? mice exhibited higher UCP1 expression and more brown-like structure in inguinal fat than WT mice. Paradoxically, we found that the anti-thermogenic effect of adiponectin requires neither AdipoR1 nor AdipoR2, two well-known adiponectin receptors. In sharp contrast to the anti-thermogenic effects of adiponectin, AdipoR1 and especially AdipoR2 promote BAT activation. Mechanistically, adiponectin was found to inhibit Ucp1 gene expression by suppressing ?3-adrenergic receptor expression in brown adipocytes. Conclusions/interpretation This study demonstrates that adiponectin suppresses thermogenesis, which is likely to be a mechanism whereby adiponectin reduces energy expenditure.

Qiao, Liping; Yoo, Hyung sun; Bosco, Chris; Lee, Bonggi; Feng, Gen-Sheng; Schaack, Jerome; Chi, Nai-Wen; Shao, Jianhua

2014-01-01

216

Adiponectin Expression in the Porcine Ovary during the Oestrous Cycle and Its Effect on Ovarian Steroidogenesis  

PubMed Central

Adiponectin is an adipose-secreted hormone that regulates energy homeostasis and is also involved in the control of the reproductive system. The goal of the present study was to investigate changes in adiponectin gene and protein expression in porcine ovarian structures during the oestrous cycle and to examine the effects of in vitro administration of adiponectin on basal and gonadotrophin- and/or insulin-induced secretion of ovarian steroid hormones. Both gene and protein expression of adiponectin were enhanced during the luteal phase of the cycle. Adiponectin affected basal secretion of progesterone by luteal cells, oestradiol by granulosa cells, and testosterone by theca interna cells. The gonadotrophin/insulin-induced release of progesterone from granulosa and theca interna cells and the release of oestradiol and androstenedione from theca cells was also modified by adiponectin. In conclusion, the presence of adiponectin mRNA and protein in the porcine ovary coupled with our previous results indicating adiponectin receptors expression suggest that adiponectin may locally affect ovarian functions. The changes in adiponectin expression throughout the oestrous cycle seem to be dependent on the hormonal status of pigs related to the stage of the oestrous cycle. The effect of adiponectin on ovarian steroidogenesis suggests that this adipokine influences reproductive functions in pigs.

Maleszka, Anna; Smolinska, Nina; Nitkiewicz, Anna; Chojnowska, Katarzyna; Dobrzyn, Kamil; Szwaczek, Hubert; Kaminski, Tadeusz

2014-01-01

217

Adiponectin Expression in the Porcine Ovary during the Oestrous Cycle and Its Effect on Ovarian Steroidogenesis.  

PubMed

Adiponectin is an adipose-secreted hormone that regulates energy homeostasis and is also involved in the control of the reproductive system. The goal of the present study was to investigate changes in adiponectin gene and protein expression in porcine ovarian structures during the oestrous cycle and to examine the effects of in vitro administration of adiponectin on basal and gonadotrophin- and/or insulin-induced secretion of ovarian steroid hormones. Both gene and protein expression of adiponectin were enhanced during the luteal phase of the cycle. Adiponectin affected basal secretion of progesterone by luteal cells, oestradiol by granulosa cells, and testosterone by theca interna cells. The gonadotrophin/insulin-induced release of progesterone from granulosa and theca interna cells and the release of oestradiol and androstenedione from theca cells was also modified by adiponectin. In conclusion, the presence of adiponectin mRNA and protein in the porcine ovary coupled with our previous results indicating adiponectin receptors expression suggest that adiponectin may locally affect ovarian functions. The changes in adiponectin expression throughout the oestrous cycle seem to be dependent on the hormonal status of pigs related to the stage of the oestrous cycle. The effect of adiponectin on ovarian steroidogenesis suggests that this adipokine influences reproductive functions in pigs. PMID:24790602

Maleszka, Anna; Smolinska, Nina; Nitkiewicz, Anna; Kiezun, Marta; Chojnowska, Katarzyna; Dobrzyn, Kamil; Szwaczek, Hubert; Kaminski, Tadeusz

2014-01-01

218

Clinical implication of changes in serum adiponectin in patients with hepatogenic diabetes  

PubMed Central

Adiponectin is a protein hormone that modulates glucose metabolism and fatty acid oxidation. We explored the clinical implication of serum adiponectin in hepatogenic diabetes. Serum adiponectin levels were determined using enzyme–linked immunochemistry assay in 78 individuals including 19 hepatogenic diabetes, 20 type 2 diabetes (T2D), 20 chronic liver disease and 19 healthy controls. Cases and controls were matched by gender and body mass index (BMI). There is no difference in serum adiponectin levels among hepatogenic diabetic, T2D and healthy control groups. The levels of adiponectin are highest in chronic liver disease and lowest in T2D. Insulin levels are highest in hepatic diabetics and lowest in T2D. Hepatic diabetics have the lowest insulin sensitivity index (ISI). Serum adiponectin levels were negatively correlated with triglycerides and total cholesterol in T2D. Serum adiponectin is significantly increased in chronic liver disease, but lacks association with hepatogenic diabetes.

Bao, Zhongying; Yuan, Xiaodong; Duan, Shuhong; Dong, Xiaoqun

2014-01-01

219

Clinical implication of changes in serum adiponectin in patients with hepatogenic diabetes.  

PubMed

Adiponectin is a protein hormone that modulates glucose metabolism and fatty acid oxidation. We explored the clinical implication of serum adiponectin in hepatogenic diabetes. Serum adiponectin levels were determined using enzyme-linked immunochemistry assay in 78 individuals including 19 hepatogenic diabetes, 20 type 2 diabetes (T2D), 20 chronic liver disease and 19 healthy controls. Cases and controls were matched by gender and body mass index (BMI). There is no difference in serum adiponectin levels among hepatogenic diabetic, T2D and healthy control groups. The levels of adiponectin are highest in chronic liver disease and lowest in T2D. Insulin levels are highest in hepatic diabetics and lowest in T2D. Hepatic diabetics have the lowest insulin sensitivity index (ISI). Serum adiponectin levels were negatively correlated with triglycerides and total cholesterol in T2D. Serum adiponectin is significantly increased in chronic liver disease, but lacks association with hepatogenic diabetes. PMID:24990535

Bao, Zhongying; Yuan, Xiaodong; Duan, Shuhong; Dong, Xiaoqun

2014-01-01

220

Biological effects of high molecular weight lignin derivatives.  

PubMed

A number of high molecular weight (HMW) lignin derivatives possessing varied chemical properties were screened for their biological effects in order to obtain more information on the possible structural features of HMW lignin-related effects. The studied compounds were both commercial and in-house extracted lignin derivatives. Bioassays used include reverse electron transport (RET), Vibrio fischeri, Daphnia magna, and juvenile rainbow trout (Oncorhynchus mykiss) hepatocytes. The studied lignin derivatives inhibited the in vitro systems and luminescence of V. fischeri bacteria to some extent-daphnids were not affected. It seems that, at least in the RET assay, certain pH-dependent functional groups in lignin may be of importance regarding the biological effects. PMID:20494440

Pessala, Piia; Schultz, Eija; Kukkola, Jukka; Nakari, Tarja; Knuutinen, Juha; Herve, Sirpa; Paasivirta, Jaakko

2010-10-01

221

Electrophoretic High Molecular Weight DNA Purification Enables Optical Mapping  

PubMed Central

Optical mapping generates an ordered restriction map from single, long DNA molecules. By overlapping restriction maps from multiple molecules, a physical map of entire chromosomes and genomes is constructed, greatly facilitating genome assembly in next generation sequencing projects, comparative genomics and strain typing. However, optical mapping relies on a method of preparing high quality DNA >250 kb in length, which can be challenging from some organisms and sample types. Here we demonstrate the ability of Boreal Genomics' Aurora instrument to provide pure, high molecular weight (HMW) DNA 250-1,100 kb in length, ideally suited for optical mapping. The Aurora performs electrophoretic DNA purification within an agarose gel in reusable cartridges, protecting long DNA molecules from shearing forces associated with liquid handling steps common to other purification methods. DNA can be purified directly from intact cells embedded and lysed within an agarose gel, preserving the highest molecular weight DNA possible while achieving exceptional levels of purity. The Aurora delivers DNA in a buffer solution, where DNA can be condensed and protected from shearing during recovery with a pipette. DNA is then returned to its regular coiled state by simple dilution prior to optical mapping. Here we present images showing HMW DNA purification taking place in the Aurora and subsequent images of single DNA molecules on OpGen's Argus® Optical Mapping System. Future work will focus on further optimizing Aurora HMW DNA purification to bias DNA recovery in favor of only the longest molecules in a sample, maximizing the benefits of optical mapping.

Maydan, Jason; Thomas, Matthew; Tabanfar, Leyla; Mai, Laura; Poon, Hau-Ling; Pe, Joel; Hahn, Kristen; Goji, Noriko; Amoako, Kingsley; Marziali, Andre; Hanson, Dan

2013-01-01

222

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

PubMed

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

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

2013-02-01

223

Potentiated macrophage activation by acid sensing under low adiponectin levels.  

PubMed

Adiponectin can protect against inflammation; one of the mechanisms involves direct, inhibition of macrophages (M?). We postulated that adiponectin anti-sense transgenic (AsTg) mice raised in our laboratory are prone to inflammation because of systemic low adiponectin levels. The writhing response to acetic acid was utilized as an in vivo inflammatory model, and using Ca(2)(+), response to the acid was exploited in vitro to evaluate the function of resident peritoneal M?. The in vivo response to the acid was increased and the Ca(2)(+) response of M? was enhanced in AsTg mice, compared with those in wild type (WT) mice. In parallel with these enhanced responses, M? from AsTg mice augmented TNF-? and IL-6 mRNA expression. We further analyzed the enhancement in activity of M? from AsTg mice by acid sensing using specific inhibitors, amiloride for acid-sensing ion channels (ASICs) and KB-R7943 for Na(+)/Ca(2)(+) exchangers (NCXs). Our results indicated that in AsTg mice, the Ca(2)(+) response to the acid was facilitated in M? by a low threshold of ASIC1 and NCX1 molecules and the activity of these channel was possibly regulated by adiponectin. PMID:24084100

Negoro, Takaharu; Kin, Masaoki; Takuma, Akitoshi; Saito, Kiyomi; Shimizu, Shunichi; Nakano, Yasuko

2014-02-01

224

Naringenin chalcone improves adipocyte functions by enhancing adiponectin production.  

PubMed

Naringenin chalcone is a flavonoid contained in tomato peel. In this study, we investigated its effects on adipocyte functions related to metabolic processes, including adipocytokine production. Naringenin chalcone promoted the gene expression (8.0-fold, p<0.001) and protein secretion (2.2-fold, p<0.001) of adiponectin from 3T3-L1 adipocytes. Reporter gene assays revealed that naringenin enhanced the activity of peroxisome proliferator-activated receptor gamma. DNA microarray experiments and Gene Ontology analysis revealed that naringenin chalcone also up-regulated the genes associated with mitochondrial energy metabolism, reflecting its insulin-sensitizing effects. Conversely, genes in categories such as those for cell adhesion were down-regulated. The expression of one adiponectin receptor, AdipoR2, was also increased (1.8-fold, p<0.01), suggesting that naringenin chalcone could activate the adiponectin pathway through the elevation of both the ligand and its receptor. These results indicate that naringenin chalcone is a potent tomato flavonoid that improves adipocyte metabolic functions and exerts insulin-sensitizing effects by activating an adiponectin-related pathway. PMID:20363289

Horiba, Taro; Nishimura, Ikuko; Nakai, Yuji; Abe, Keiko; Sato, Ryuichiro

2010-07-29

225

Globular and full-length forms of adiponectin mediate specific changes in glucose and fatty acid uptake and metabolism in cardiomyocytes  

Microsoft Academic Search

Objective: Our aim was to investigate the regulation of glucose and fatty acid metabolism in cardiomyocytes by the globular (gAd) and full- length (fAd) forms of adiponectin. Methods: We produced fAd (consisting of high, medium and low molecular weight oligomers) in a mammalian expression system and gAd in bacteria. These were used to treat primary neonatal rat cardiomyocytes (up to

Rengasamy Palanivel; Xiangping Fang; Min Park; Megumi Eguchi; Shelley Pallan; Sabrina De Girolamo; Ying Liu; Yu Wang; Aimin Xu; Gary Sweeney

2007-01-01

226

Adiponectin Regulation of Stellate Cell Activation via PPAR?-Dependent and -Independent Mechanisms  

PubMed Central

In this study, we elucidated the mechanism by which adiponectin modulates hepatic stellate cell activation and fibrogenesis. Adiponectin-overexpressing transgenic mice receiving thioacetamide were resistant to fibrosis, compared with controls. In contrast, adiponectin-null animals developed severe fibrosis. Expression of collagen ?1(I) and ?-smooth muscle actin (?-SMA) mRNAs were significantly lower in adiponectin-overexpressing mice, compared with controls. In wild-type stellate cells exposed to a lentivirus encoding adiponectin, expression of peroxisome proliferator-activated receptor-? (PPAR?), SREBP1c, and CEBP? mRNAs was significantly increased (3.2-, 4.1-, and 2.2-fold, respectively; n = 3; P < 0.05, adiponectin virus versus control), consistent with possible activation of an adipogenic transcriptional program. Troglitazone, a PPAR? agonist, strongly suppressed up-regulation of collagen ?1(I) and ?-SMA mRNA in stellate cells isolated from wild-type mice; however, stellate cells from adiponectin-null animals failed to respond to troglitazone. Furthermore, in isolated stellate cells in which PPAR? was depleted using an adenovirus-Cre-recombinase system and in which adiponectin was also overexpressed, collagen ?1(I) and ?-SMA were significantly inhibited. We conclude that the PPAR? effect on stellate cell activation and the fibrogenic cascade appears to be adiponectin-dependent; however, the inhibitory effect of adiponectin on stellate cell activation was not dependent on PPAR?, suggesting the presence of PPAR?-dependent as well as independent pathways in stellate cells.

Shafiei, Mahnoush S.; Shetty, Shoba; Scherer, Philipp E.; Rockey, Don C.

2011-01-01

227

Estradiol stimulates mitochondrial biogenesis and adiponectin expression in skeletal muscle.  

PubMed

Sexual dimorphism has been found in mitochondrial features of skeletal muscle, with female rats showing greater mitochondrial mass and function compared with males. Adiponectin is an insulin-sensitizing adipokine whose expression has been related to mitochondrial function and that is also expressed in skeletal muscle, where it exerts local metabolic effects. The aim of this research was to elucidate the role of sex hormones in modulation of mitochondrial function, as well as its relationship with adiponectin production in rat skeletal muscle. An in vivo study with ovariectomized Wistar rats receiving or not receiving 17?-estradiol (E2) (10??g/kg per 48?h for 4 weeks) was carried out, in parallel with an assay of cultured myotubes (L6E9) treated with E2 (10?nM), progesterone (Pg; 1??M), or testosterone (1??M). E2 upregulated the markers of mitochondrial biogenesis and dynamics, and also of mitochondrial function in skeletal muscle and L6E9. Although in vivo E2 supplementation only partially restored the decreased adiponectin expression levels induced by ovariectomy, these were enhanced by E2 and Pg treatment in cultured myotubes, whereas testosterone showed no effects. Adiponectin receptor 1 expression was increased by E2 treatment, both in vivo and in vitro, but testosterone decreased it. In conclusion, our results are in agreement with the sexual dimorphism previously reported in skeletal muscle mitochondrial function and indicate E2 to be its main effector, as it enhances mitochondrial function and diminishes oxidative stress. Moreover, our data support the idea of the existence of a link between mitochondrial function and adiponectin expression in skeletal muscle, which could be modulated by sex hormones. PMID:24681828

Capllonch-Amer, Gabriela; Sbert-Roig, Miquel; Galmés-Pascual, Bel M; Proenza, Ana M; Lladó, Isabel; Gianotti, Magdalena; García-Palmer, Francisco J

2014-06-01

228

Enhanced fatty acid flux triggered by adiponectin overexpression.  

PubMed

Adiponectin overexpression in mice increases insulin sensitivity independent of adiposity. Here, we combined stable isotope infusion and in vivo measurements of lipid flux with transcriptomic analysis to characterize fatty acid metabolism in transgenic mice that overexpress adiponectin via the aP2-promoter (ADNTg). Compared with controls, fasted ADNTg mice demonstrated a 31% reduction in plasma free fatty acid concentrations (P = 0.008), a doubling of ketones (P = 0.028), and a 68% increase in free fatty acid turnover in plasma (15.1 ± 1.5 vs. 25.3 ± 6.8 mg/kg · min, P = 0.011). ADNTg mice had 2-fold more brown adipose tissue mass, and triglyceride synthesis and turnover were 5-fold greater in this organ (P = 0.046). Epididymal white adipose tissue was slightly reduced, possibly due to the approximately 1.5-fold increase in the expression of genes involved in oxidation (peroxisome proliferator-activated receptor ?, peroxisome proliferator-activated receptor-? coactivator 1?, and uncoupling protein 3). In ADNTg liver, lipogenic gene expression was reduced, but there was an unexpected increase in the expression of retinoid pathway genes (hepatic retinol binding protein 1 and retinoic acid receptor beta and adipose Cyp26A1) and liver retinyl ester content (64% higher, P < 0.02). Combined, these data support a physiological link between adiponectin signaling and increased efficiency of triglyceride synthesis and hydrolysis, a process that can be controlled by retinoids. Interactions between adiponectin and retinoids may underlie adiponectin's effects on intermediary metabolism. PMID:22045665

Shetty, Shoba; Ramos-Roman, Maria A; Cho, You-Ree; Brown, Jonathan; Plutzky, Jorge; Muise, Eric S; Horton, Jay D; Scherer, Philipp E; Parks, Elizabeth J

2012-01-01

229

Evaluating vaspin and adiponectin in postmenopausal women with endometrial cancer.  

PubMed

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

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

2013-10-01

230

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

NASA Astrophysics Data System (ADS)

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

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

2012-11-01

231

Advances in the field of high-molecular-weight polycyclic aromatic hydrocarbon biodegradation by bacteria  

PubMed Central

Summary Interest in understanding prokaryotic biotransformation of high?molecular?weight polycyclic aromatic hydrocarbons (HMW PAHs) has continued to grow and the scientific literature shows that studies in this field are originating from research groups from many different locations throughout the world. In the last 10 years, research in regard to HMW PAH biodegradation by bacteria has been further advanced through the documentation of new isolates that represent diverse bacterial types that have been isolated from different environments and that possess different metabolic capabilities. This has occurred in addition to the continuation of in?depth comprehensive characterizations of previously isolated organisms, such as Mycobacterium vanbaalenii PYR?1. New metabolites derived from prokaryotic biodegradation of four? and five?ring PAHs have been characterized, our knowledge of the enzymes involved in these transformations has been advanced and HMW PAH biodegradation pathways have been further developed, expanded upon and refined. At the same time, investigation of prokaryotic consortia has furthered our understanding of the capabilities of microorganisms functioning as communities during HMW PAH biodegradation.

Kanaly, Robert A.; Harayama, Shigeaki

2010-01-01

232

Kinetics of cellular trafficking and cytotoxicity of 9.2.27-gelonin immunotoxins targeted against the high-molecular-weight melanoma-associated antigen  

Microsoft Academic Search

The high-molecular-weight melanoma-associated antigen (HMW-MAA) is expressed on a large majority of melanoma tissues but\\u000a not on most normal or other neoplastic tissues. Monoclonal antibody 9.2.27 binds with high affinity and specificity to the\\u000a HMW-MAA, making it an attractive choice as an agent for targeting toxins or chemotherapeutic agents specifically towards melanomas.\\u000a To characterize the interactions between 9.2.27 and melanoma

Michael C. Chan; Regina M. Murphy

1999-01-01

233

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.

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

2014-01-01

234

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

PubMed

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

Cinar, Nese; Gurlek, Alper

2013-01-01

235

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

PubMed Central

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

Cinar, Nese; Gurlek, Alper

2013-01-01

236

DETECTION OF HIGH MOLECULAR WEIGHT ORGANIC TRACERS IN VEGETATION SMOKE SAMPLES BY HIGH-TEMPERATURE GAS CHROMATOGRAPHY-MASS SPECTROMETRY. (R823990)  

EPA Science Inventory

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 wit...

237

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

238

The unusual pre-main-sequence star V718 Persei (HMW 15). Photometry and spectroscopy across the eclipse  

NASA Astrophysics Data System (ADS)

Context: The remarkable pre-main-sequence object V718 Per (HMW 15, H187) in the young cluster IC 348 periodically undergoes long-lasting eclipses caused by variable amounts of circumstellar dust in the line-of-sight to the star. It has been speculated that the star is a close binary and similar to another unusual eclipsing object, KH 15D. Aims: We have submitted V718 Per to a detailed photometric and spectroscopic study to investigate how regular the recurrent eclipses are, to find out more about the properties of the stellar object and the occulting circumstellar material, and to look for signatures of a possible binary component. Methods: V718 Per was monitored photometrically from the optical to the near-infrared (NIR). We also obtained high-resolution optical spectra with the Keck telescope at minimum as well as at maximum brightness. We derived the fundamental photospheric parameters of this star by comparing with synthetic spectra. Results: Our photometric data show that the eclipses are very symmetric and persistent, and that the extinction law of the foreground occulting dust deviates only little from what is expected for “normal” interstellar material. The stellar parameters of V718 Per indicate a primordial abundance of Li and a surface temperature of T_eff ? 5200 K. Remarkably, the in-eclipse spectrum shows a significant broadening of the photospheric absorption lines, as well as a slightly lower stellar surface temperature. In addition, weak emission components appear in the absorption lines of H? and the Ca II IR triplet lines. We did not detect any signs of atomic or molecular features related to the occulting body in the in-eclipse spectrum. We also found no evidence of any radial velocity changes in V718 Per to within about ± 80 m s-1, which for an edge-on system corresponds to a maximum companion mass of ~ 6 M_Jup. Conclusions: Our observations suggest that V718 Per is a single star, and thus very different from the related binary system KH 15D. We conclude that V718 Per is surrounded by an edge-on circumstellar disk with an irregular mass distribution orbiting at a distance of 3.3 AU from the star, presumably at the inner disk edge. To produce the prolonged eclipses, the occulting feature must extend along more than half of the inner disk edge. The change in stellar surface temperature and the emission line activity observed could be related to spot activity. We ascribe the broadening of photospheric absorption lines during the eclipse to forward scattering of stellar light in the circumstellar dust feature. Based on observations collected at the Crimean Astrophysical Observatory, Ukraine; the W. M. Keck Observatory, Hawaii, USA and the Campo Imperatore Observatory, Italy.

Grinin, V.; Stempels, H. C.; Gahm, G. F.; Sergeev, S.; Arkharov, A.; Barsunova, O.; Tambovtseva, L.

2008-10-01

239

Orlistat for obesity: benefits beyond weight loss  

Microsoft Academic Search

Orlistat lowers lipids and improves insulin sensitivity, but its effect on other metabolic syndrome related parameters is not known. To assess its influence on adiponectin, high sensitive C-reactive protein (hs-CRP) and other metabolic syndrome related parameters, this study enrolled 106 participants in a weight-reduction program and categorized them into a group of 51 who had been treated with orlistat 360mg\\/day

Ching-Jung Hsieh; Pei-Wen Wang; Rue-Tsuan Liu; Shih-Chen Tung; Wen-Yen Chien; Jung-Fu Chen; Chen-Hsiong Chen; Ming-Chun Kuo; Ya-Hui Hu

2005-01-01

240

Downregulation of GPR83 in the hypothalamic preoptic area reduces core body temperature and elevates circulating level of adiponectin  

PubMed Central

Objective The G protein-coupled receptor 83 (GPR83) was recently demonstrated in warm sensitive neurons (WSN) of the hypothalamic preoptic area (POA) that participate in temperature homeostasis. Thus, we investigated whether GPR83 may have a role in regulating core body temperature (CBT) by reducing its expression in the POA. D issipation of energy in the form of heat is the primary mode of energy expenditure in mammals and can ultimately affect energy homeostasis. Thus, we also measured the level of important regulators of metabolism. Matherials/Methods Downregulation of GPR83 was obtained by lentiviral short-hairpin RNAs (shGPR83) vectors designed and selected for their ability to reduce GPR83 levels in vitro. Mice received POA injection of shGPR83 or non-silencing vectors and were monitored for CBT, motor activity, food intake body weight and circulating levels of IGF-1, insulin, leptin and adiponectin. Results Down-regulation of GPR83 in the POA resulted in a small (0.15°C) but significant reduction of CBT during the dark/active cycle of the day. Temperature reduction was followed by increased body weight gain independent of caloric intake. shGPR83 mice also had increased level of circulating adiponectin (31916 ± 952 pg/ml vs. 23474 ± 1507 pg/ml, p<0.01) while no change was observed for insulin, IGF-1 or leptin. Conclusions GPR83 may participate in central thermoregulation and the central control of circulating adiponectin. Further work is required to determine how GPR83 can affect POA WSN and what are the long term metabolic consequences of it down-regulation.

Dubins, Jeffrey S.; Sanchez-Alavez, Manuel; Zhukov, Viktor; Sanchez-Gonzalez, Alejandro; Moroncini, Gianluca; Carvajal-Gonzalez, Santos; Hadcock, John R; Bartfai, Tamas; Conti, Bruno

2012-01-01

241

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.

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

2014-01-01

242

The emerging roles of adiponectin in female reproductive system-associated disorders and pregnancy.  

PubMed

Adiponectin, the most abundant adipose-released cytokine, has an important role in metabolism, primarily through reducing insulin resistance. Reproductive functions are known to be influenced by energy balance and adiponectin may be involved in the underlying mechanisms connecting reproduction and metabolism. Interestingly, adiponectin has been shown to exert actions in the female reproductive system, including the hypothalamic-pituitary-ovarian axis and the endometrium. The peripheral effects of this adipocytokine are mediated mainly via 2 receptors, AdipoR1 and AdipoR2. The expression of these receptors has been reported in the brain, ovaries, endometrium, and the placenta. Thus, adiponectin may influence fertility and pregnancy. Furthermore, adiponectin concentrations and effects have been assessed in some pregnancy-associated disorders and gynecological conditions. The findings may lead to the use of adiponectin or its receptors as therapeutic targets in novel treatment strategies of these disorders. PMID:23271161

Angelidis, George; Dafopoulos, Konstantinos; Messini, Christina I; Valotassiou, Varvara; Tsikouras, Panagiotis; Vrachnis, Nikolaos; Psimadas, Dimitrios; Georgoulias, Panagiotis; Messinis, Ioannis E

2013-08-01

243

Expression of adiponectin and adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) in the porcine uterus during the oestrous cycle.  

PubMed

Adiponectin is a hormone secreted primarily by white adipose tissue. Recent studies have shown that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in different reproductive tissues, including the ovary and uterus. This newly discovered endocrine system plays an important role in the regulation of reproductive processes. The expression of the adiponectin system in the porcine uterus during the oestrous cycle has not been researched to date. The aim of the present study was to investigate the presence and changes in adiponectin system expression in the porcine uterus on days 2-3, 10-12, 14-16, and 17-19 of the oestrous cycle. The expression of the adiponectin gene was highest on days 14-16 and 2-3 in the endometrium and myometrium, respectively. In the endometrium, the content of AdipoR1 and AdipoR2 mRNAs was highest on days 10-12, whereas significantly higher expression levels of both genes were noted in the myometrium on days 17-19. The highest content of adiponectin and AdipoR1 protein in the endometrium was reported on days 2-3. In the myometrium, the expression levels of both receptor proteins were significantly higher on days 17-19. Adiponectin system proteins were localized in endometrial epithelial glandular cells, luminal epithelial cells and stromal cells as well as in longitudinal and circular muscles of the myometrium. This study demonstrated the presence of adiponectin, AdipoR1 and AdipoR2 genes and proteins in the porcine uterus and the effect of the stage of the oestrous cycle on the expression of the adiponectin system. Our results suggest that locally synthesized adiponectin directly affects uterine functions. PMID:24598213

Smolinska, Nina; Dobrzyn, Kamil; Maleszka, Anna; Kiezun, Marta; Szeszko, Karol; Kaminski, Tadeusz

2014-04-01

244

Pharmacological ceramide reduction alleviates alcohol-induced steatosis and hepatomegaly in adiponectin knockout mice.  

PubMed

Hepatosteatosis, the ectopic accumulation of lipid in the liver, is one of the earliest clinical signs of alcoholic liver disease (ALD). Alcohol-dependent deregulation of liver ceramide levels as well as inhibition of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor ? (PPAR-?) activity are thought to contribute to hepatosteatosis development. Adiponectin can regulate lipid handling in the liver and has been shown to reduce ceramide levels and activate AMPK and PPAR-?. However, the mechanisms by which adiponectin prevents alcoholic hepatosteatosis remain incompletely characterized. To address this question, we assessed ALD progression in wild-type (WT) and adiponectin knockout (KO) mice fed an ethanol-containing liquid diet or isocaloric control diet. Adiponectin KO mice relative to WT had increased alcohol-induced hepatosteatosis and hepatomegaly, similar modest increases in serum alanine aminotransferase, and reduced liver TNF. Restoring circulating adiponectin levels using recombinant adiponectin ameliorated alcohol-induced hepatosteatosis and hepatomegaly in adiponectin KO mice. Alcohol-fed WT and adiponectin KO animals had equivalent reductions in AMPK protein and PPAR-? DNA binding activity compared with control-fed animals. No difference in P-AMPK/AMPK ratio was detected, suggesting that alcohol-dependent deregulation of AMPK and PPAR-? in the absence of adiponectin are not primary causes of the observed increase in hepatosteatosis in these animals. By contrast, alcohol treatment increased liver ceramide levels in adiponectin KO but not WT mice. Importantly, pharmacological inhibition of de novo ceramide synthesis in adiponectin KO mice abrogated alcohol-mediated increases in liver ceramides, steatosis, and hepatomegaly. These data suggest that adiponectin reduces alcohol-induced steatosis and hepatomegaly through regulation of liver ceramides, but its absence does not exacerbate alcohol-induced liver damage. PMID:24742988

Correnti, Jason M; Juskeviciute, Egle; Swarup, Aditi; Hoek, Jan B

2014-06-01

245

The Rab11 Effector Protein FIP1 Regulates Adiponectin Trafficking and Secretion  

PubMed Central

Adiponectin is an adipokine secreted by white adipocytes involved in regulating insulin sensitivity in peripheral tissues. Secretion of adiponectin in adipocytes relies on the endosomal system, however, the intracellular machinery involved in mediating adiponectin release is unknown. We have previously reported that intracellular adiponectin partially compartmentalizes with rab 5 and rab11, markers for the early/sorting and recycling compartments respectively. Here we have examined the role of several rab11 downstream effector proteins (rab11 FIPs) in regulating adiponectin trafficking and secretion. Overexpression of wild type rab11 FIP1, FIP3 and FIP5 decreased the amount of secreted adiponectin expressed in HEK293 cells, whereas overexpression of rab11 FIP2 or FIP4 had no effect. Furthermore shRNA-mediated depletion of FIP1 enhanced adiponectin release whereas knock down of FIP5 decreased adiponectin secretion. Knock down of FIP3 had no effect. In 3T3L1 adipocytes, endogenous FIP1 co-distributed intracellularly with endogenous adiponectin and FIP1 depletion enhanced adiponectin release without altering insulin-mediated trafficking of the glucose transporter Glut4. While adiponectin receptors internalized with transferrin receptors, there were no differences in transferrin receptor recycling between wild type and FIP1 depleted adipocytes. Consistent with its inhibitory role, FIP1 expression was decreased during adipocyte differentiation, by treatment with thiazolidinediones, and with increased BMI in humans. In contrast, FIP1 expression increased upon exposure of adipocytes to TNF?. In all, our findings identify FIP1 as a novel protein involved in the regulation of adiponectin trafficking and release.

Moreno-Navarrete, Jose Maria; Fernandez-Real, Jose Manuel; Mora, Silvia

2013-01-01

246

Insulin resistance, adiponectin and adverse outcomes following elective cardiac surgery: a prospective follow-up study  

Microsoft Academic Search

BACKGROUND: Insulin resistance and adiponectin are markers of cardio-metabolic disease and associated with adverse cardiovascular outcomes. The present study examined whether preoperative insulin resistance or adiponectin were associated with short- and long-term adverse outcomes in non-diabetic patients undergoing elective cardiac surgery. METHODS: In a prospective study, we assessed insulin resistance and adiponectin levels from preoperative fasting blood samples in 836

Martin M Mikkelsen; Troels K Hansen; Jakob Gjedsted; Niels H Andersen; Thomas D Christensen; Vibeke E Hjortdal; Søren P Johnsen

2010-01-01

247

Corticosteroid-binding globulin affects the relationship between circulating adiponectin and cortisol in men and women  

Microsoft Academic Search

Inflammatory pathways are increasingly recognized to be tightly associated with insulin resistance in humans. The promoter region of the adiponectin gene—Apm1—encompasses consensus sequences for glucocorticosteroid receptor responsive element. Dexamethasone induced downregulation of adiponectin secretion in vitro, whereas prednisolone administration increased circulating adiponectin concentrations. As previous studies have demonstrated an inverse relationship between corticosteroid-binding globulin (CBG), body mass index, and insulin

José-Manuel Fernandez-Real; Michel Pugeat; Abel López-Bermejo; Hubert Bornet; Wifredo Ricart

2005-01-01

248

Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin  

Microsoft Academic Search

The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity, decreases inflammation and promotes cell survival. No unifying mechanism has yet explained how adiponectin can exert such a variety of beneficial systemic effects. Here, we show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, AdipoR1 and AdipoR2, and enhances ceramide catabolism and formation of its antiapoptotic metabolite—sphingosine-1-phosphate (S1P)—independently

William L Holland; Russell A Miller; Zhao V Wang; Kai Sun; Brian M Barth; Hai H Bui; Kathryn E Davis; Benjamin T Bikman; Nils Halberg; Joseph M Rutkowski; Mark R Wade; Vincent M Tenorio; Ming-Shang Kuo; Joseph T Brozinick; Bei B Zhang; Morris J Birnbaum; Scott A Summers; Philipp E Scherer

2010-01-01

249

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

Microsoft Academic Search

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

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

2006-01-01

250

DsbA-L Alleviates Endoplasmic Reticulum Stress-Induced Adiponectin Downregulation  

PubMed Central

OBJECTIVE Obesity impairs adiponectin expression, assembly, and secretion, yet the underlying mechanisms remain elusive. The aims of this study were 1) to determine the molecular mechanisms by which obesity impairs adiponectin multimerization and stability, and 2) to determine the potential role of disulfide-bond-A oxidoreductase-like protein (DsbA-L), a recently identified adiponectin interactive protein that promotes adiponectin multimerization and stability in obesity-induced endoplasmic reticulum (ER) stress and adiponectin downregulation. RESEARCH DESIGN AND METHODS Tauroursodeoxycholic acid (TUDCA), a chemical chaperone that alleviates ER stress, was used to study the mechanism underlying obesity-induced adiponectin downregulation in db/db mice, high-fat diet-induced obese mice, and in ER-stressed 3T3-L1 adipocytes. The cellular levels of DsbA-L were altered by RNAi-mediated suppression or adenovirus-mediated overexpression. The protective role of DsbA-L in obesity- and ER stress–induced adiponectin downregulation was characterized. RESULTS Treating db/db mice and diet-induced obese mice with TUDCA increased the cellular and serum levels of adiponectin. In addition, inducing ER stress is sufficient to downregulate adiponectin levels in 3T3-L1 adipocytes, which could be protected by treating cells with the autophagy inhibitor 3-methyladenine or by overexpression of DsbA-L. CONCLUSIONS ER stress plays a key role in obesity-induced adiponectin downregulation. In addition, DsbA-L facilitates adiponectin folding and assembly and provides a protective effect against ER stress–mediated adiponectin downregulation in obesity.

Zhou, Lijun; Liu, Meilian; Zhang, Jingjing; Chen, Hongzhi; Dong, Lily Q.; Liu, Feng

2010-01-01

251

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

Microsoft Academic Search

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

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

252

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

253

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

PubMed Central

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

Blaslov, Kristina; Zibar, Karin; Duvnjak, Lea

2013-01-01

254

Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies  

PubMed Central

Obesity and type 2 diabetes are associated with chronic inflammation. Adiponectin is an adipocyte-derived hormone with antidiabetic and antiinflammatory actions. Here, we demonstrate what we believe to be a previously undocumented activity of adiponectin, facilitating the uptake of early apoptotic cells by macrophages, an essential feature of immune system function. Adiponectin-deficient (APN-KO) mice were impaired in their ability to clear apoptotic thymocytes in response to dexamethasone treatment, and these animals displayed a reduced ability to clear early apoptotic cells that were injected into their intraperitoneal cavities. Conversely, adiponectin administration promoted the clearance of apoptotic cells by macrophages in both APN-KO and wild-type mice. Adiponectin overexpression also promoted apoptotic cell clearance and reduced features of autoimmunity in lpr mice whereas adiponectin deficiency in lpr mice led to a further reduction in apoptotic cell clearance, which was accompanied by exacerbated systemic inflammation. Adiponectin was capable of opsonizing apoptotic cells, and phagocytosis of cell corpses was mediated by the binding of adiponectin to calreticulin on the macrophage cell surface. We propose that adiponectin protects the organism from systemic inflammation by promoting the clearance of early apoptotic cells by macrophages through a receptor-dependent pathway involving calreticulin.

Takemura, Yukihiro; Ouchi, Noriyuki; Shibata, Rei; Aprahamian, Tamar; Kirber, Michael T.; Summer, Ross S.; Kihara, Shinji; Walsh, Kenneth

2007-01-01

255

Modulation of Lupus Phenotype by Adiponectin Deficiency in Autoimmune Mouse Models  

PubMed Central

Adiponectin is an adipocyte-derived cytokine with anti-inflammatory properties. Paradoxically, circulating adiponectin levels are increased in a number of inflammatory diseases. Thus, we sought to define the role of adiponectin deficiency in mouse models of autoimmunity. Adiponectin-deficient mice on a C57BL/6 background do not develop an autoimmune phenotype. Autoimmunity was also not observed in adiponectin-deficient mice generated on the permissive MRL background. However, adiponectin deficiency exacerbated the autoimmune phenotype of MRL-lpr mice. Compared with MRL-lpr mice, MRL-lpr.apn?/? mice displayed greater lymphadenopathy and splenomegaly, as well as increased anti-nuclear antibody and anti-dsDNA production. In addition, evaluation of the kidney revealed larger glomerular tuft size, crescent formation, increased IgG and C3 deposits, and mesangial expansion in the MRL-lpr.apn?/? mice. The effects of adiponectin deficiency on the autoimmune phenotypes were more pronounced in female versus male mice. These data show that, while adiponectin deficiency is not sufficient to confer autoimmunity, adiponectin acts as a negative modulator of the autoimmune phenotype in a murine model of lupus.

Parker, Jennifer; Menn-Josephy, Hanni; Laskow, Bari; Takemura, Yukihiro

2012-01-01

256

Effects of weight loss in obese cats on biochemical analytes related to inflammation and glucose homeostasis.  

PubMed

The aim of the current study was to measure circulating metabolic and inflammation-related biochemical analytes in obese cats before and after weight loss. Thirty-seven overweight neutered cats were studied, median body weight 6.85 kg (range, 4.70 to 10.30 kg), representing a range of ages and both sexes. An individualized weight-loss program was devised for each cat and monitored until completion. Body fat mass was determined by dual-energy x-ray absorptiometry, whereas plasma concentrations of acute-phase proteins (APPs; eg, haptoglobin and serum amyloid A), hormones (eg, insulin, IGF-1, and adiponectin), and enzymes (eg, butyrylcholinesterase and paraoxonase type 1 [PON-1]) associated with inflammation and metabolic compounds (eg, glucose) were also measured. No significant changes were found in APPs after weight loss (P > 0.3), but significant increases in plasma adiponectin (P = 0.021) and IGF-1 (P = 0.036) were seen, whereas insulin (P < 0.001) and homeostasis model assessment (P = 0.005) decreased significantly. Plasma concentrations before weight loss of PON-1 (P = 0.004), adiponectin (P = 0.02), and IGF-1 (P = 0.048) were less in cats that failed to complete weight loss than cats that were successful, whereas glucose concentration was greater. Finally, multivariable linear regression analysis showed that lean tissue loss during weight management was associated with percentage weight loss (greater weight loss, greater lean tissue loss; R = 0.71, P < 0.001) and plasma adiponectin concentration before weight loss (lesser adiponectin, more lean tissue loss; R = -0.52, P = 0.023). In conclusion, various metabolic abnormalities occur in feline obesity, and these can be linked to outcomes of weight-loss programs. The changes that occur with weight loss suggest an improved metabolic status. PMID:22177629

Tvarijonaviciute, A; Ceron, J J; Holden, S L; Morris, P J; Biourge, V; German, A J

2012-04-01

257

Mixing properties and dough functionality of transgenic lines of a commercial wheat cultivar expressing the 1Ax1, 1Dx5 and 1Dy10 HMW glutenin subunit genes  

Microsoft Academic Search

In this work we report the effects of the HMW-GS 1Ax1, 1Dx5 and 1Dy10 on the breadmaking quality of the bread wheat cultivar Anza that contains the HMW-GS pairs 1Dx2+1Dy12 and 1Bx7*+1By8, and is null for the Glu-A1 locus. This allows the characterization of individual subunits 1Dx5 and 1Dy10 in the absence of subunit 1Dx5, and the interactions between these

Elena León; Santiago Marín; María J. Giménez; Fernando Piston; Marta Rodríguez-Quijano; Peter R. Shewry; Francisco Barro

2009-01-01

258

Natural killer cell-dependent immunoglobulin G2a anti-bovine serum albumin (BSA) response elicited by high molecular weight dextran-BSA conjugates associated with dextran-mediated macrophage-natural killer cell interaction  

PubMed Central

The roles of the interferon-? (IFN-?) and interleukin-12 (IL-12) produced during natural killer (NK) cell interaction with macrophages (M?) were investigated as the basis for the induction of immunoglobulin G2a (IgG2a) anti-bovine serum albumin (BSA) responses by high molecular weight dextran conjugated to BSA (HMW-DEX–BSA). BALB/c mice immunized with HMW-DEX–BSA produced significantly higher levels of both IgG1 and IgG2a anti-BSA than did mice immunized with BSA alone. Both IgG1 and IgG2a anti-BSA levels were higher in mice immunized with BSA conjugated to dextran of molecular weight (MW) 5 000 000–40 000 000 compared with dextran of MW 10 000–60 000. The enhancement of anti-BSA IgG2a levels but not of anti-BSA IgG1 levels was inhibited when free BSA was added to the HMW-DEX–BSA conjugate. NK cell depletion during HMW-DEX–BSA immunization of mice resulted in significantly lower anti-BSA IgG2a levels without affecting anti-BSA IgG1 levels. Naive splenocytes or M? + NK cell co-cultures incubated with HMW-DEX or HMW-DEX–BSA produced higher IFN-? levels than splenocytes or co-cultures incubated with BSA alone. HMW-DEX stimulated both IFN-? and IL-12 production by M? + NK cell co-cultures in a dose-dependent manner. DEX-induced IFN-? production by NK cells was dependent upon the presence of IL-12, and IL-12 production by M? was dependent upon the presence of IFN-? in these co-cultures. Both M? and NK cells bound DEX to their surfaces. These data demonstrate that BSA linked to HMW-DEX enhanced both T-helper-1- and T-helper-2-associated antibody responses to BSA. The results also indicate an IL-12-dependent positive feedback interaction between NK cells and M? that supports a NK cell/IFN-?-dependent mechanism for enhancement of anti-BSA IgG2a antibody responses in mice immunized with HMW-DEX–BSA protein conjugates.

Ediriwickrema, C P; Tonkonogy, S L; Hammerberg, B

2000-01-01

259

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.

2014-01-01

260

Molecular Pathways: Adiponectin and Leptin Signaling in Cancer  

PubMed Central

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

VanSaun, Michael N.

2013-01-01

261

Adiponectin regulates ACTH secretion and the HPAA in an AMPK-dependent manner in pituitary corticotroph cells.  

PubMed

It is known that adipokines can regulate the hypothalamic-pituitary-adrenal axis (HPAA). In this study, we confirmed that adiponectin regulates the HPAA by affecting pituitary corticotroph cells. Using RT-PCR and immunofluorescence, we determined that adiponectin receptors were expressed in pituitary corticotroph tumour cells (AtT-20 cells and human corticotroph tumours). Adiponectin stimulated calcium influx and increased basal ACTH secretion without affecting corticotrophin-releasing hormone (CRH)-stimulated ACTH secretion, which was most likely due to the expression of adiponectin repressing CRH receptor 1 (CRHR1). Adiponectin also acutely stimulated ACTH release in primary culture pituitary cells. Lastly, adiponectin directly phosphorylated 5' AMP-activated protein kinase (AMPK) in AtT-20 cells. The effects of adiponectin were mimicked by AICAR, which was blocked by compound C. Taken together, our results suggested that adiponectin stimulated ACTH secretion and down-regulated CRHR1, possibly via an AMPK-dependent mechanism in pituitary corticotroph cells. PMID:24361598

Chen, Maopei; Wang, Zhiquan; Zhan, Ming; Liu, Ruixin; Nie, Aifang; Wang, Jiqiu; Ning, Guang; Ma, Qinyun

2014-03-01

262

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

PubMed Central

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

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

2013-01-01

263

In vitro phosphorylation of high molecular weight glutenin subunits from wheat endosperm  

Microsoft Academic Search

We have investigated the in vitro phosphorylation of high molecular weight glutenin subunits (HMW-GS), a group of non-soluble proteins present in wheat endosperm. Computer aided searches of potential biological sites in the known sequences of these proteins have evidenced the presence of sequence motifs specific for protein kinase C (PKC), calcium-dependent protein kinase from wheat, casein kinase II, tyrosine protein

Angelo M Facchiano; Giovanni Colonna; Emilio Chiosi; Gennaro Illiano; Annamaria Spina; Domenico Lafiandra; Francesco Buonocore

1999-01-01

264

Low-Dose Dietary Resveratrol Has Differential Effects on Colorectal Tumorigenesis in Adiponectin Knockout and Wild-Type Mice  

Microsoft Academic Search

Obesity is associated with a decrease in the antiinflammatory hormone, adiponectin, and increases in the circulating concentrations of multiple proinflammatory cytokines. These changes contribute to colon tumorigenesis. Resveratrol increases adiponectin production in adipocytes and attenuates the development of colon cancer. Thus, we hypothesized that adiponectin is an integral component of the mechanism by which resveratrol antagonizes colorectal tumorigenesis. To investigate

Rebecca L. Boddicker; Elizabeth M. Whitley; Jeremy E. Davis; Diane F. Birt; Michael E. Spurlock

2011-01-01

265

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

Microsoft Academic Search

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

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

2010-01-01

266

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

PubMed Central

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

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

2007-01-01

267

Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin  

Microsoft Academic Search

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

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

2003-01-01

268

Diabetic and nondiabetic patients express similar adipose tissue adiponectin and leptin levels  

Microsoft Academic Search

Objective:Epicardial adipose tissue (EAT) is an interesting visceral fat pad with a particular location. EAT and subcutaneous adipose tissue (SAT) produce a wide range of adipokines. Some of them, including adiponectin and leptin, can influence the risk of development of diabetes and other associated metabolic and cardiovascular conditions. We sought to assess whether EAT and SAT adiponectin and leptin expression

E Teijeira-Fernandez; S Eiras; L Grigorian-Shamagian; A Salgado-Somoza; J M Martinez-Comendador; J R Gonzalez-Juanatey

2010-01-01

269

Epicardial adipose tissue expression of adiponectin is lower in patients with hypertension  

Microsoft Academic Search

Low plasma adiponectin levels are related to a higher risk of development of metabolic and cardiovascular disorders, including hypertension (HT). To date, there have been no studies supporting the relationship between epicardial adipose tissue (EAT) expression of adiponectin and HT. We collected samples of EAT from 116 patients undergoing elective cardiac surgery, mostly for coronary artery bypass grafting (n=54), valve

E Teijeira-Fernandez; S Eiras; L Grigorian-Shamagian; A Fernandez; B Adrio; J R Gonzalez-Juanatey

2008-01-01

270

Serum Adiponectin and Resistin Levels in de Novo and Relapsed Acute Lymphoblastic Leukemia Children Patients  

PubMed Central

Background Adipose tissue secretes a large number of adipocytokines such as leptin, resistin, and adiponectin. Many of these hormones and cytokines are altered in obese individuals and may lead to disruption of the normal balance between cell proliferation, differentiation, and apoptosis. The aim of our work was to investigate the disturbance of secretion of adiponectin and resistin in de novo and relapsed acute lymphoblastic leukemia (ALL) in Egyptian children and determine whether adiponectin and resistin are implicated in increased risk relapse compared to healthy individuals. Methods: Measurements of adiponectin and resistin were performed at diagnosis, in 32 patients with de novo ALL aged 3 to 18 years (mean 9.8 y) and 19 children with relapsed ALL aged 5 to 17 (mean 9.9 yr). 10 apparently healthy children with matched age and sex were used as controls. Results: Mean adiponectin levels were low (P < 0.05), whereas mean resistin levels were high (P<0.05) at diagnosis and relapsed ALL (compared to healthy controls). A significant decrease of adiponectin levels was observed in relapsed ALL compared to de novo ALL. In contrast resistin was significantly increased in relapsed ALL compared to de novo patients. Adiponectin in ALL subjects inversely correlated with resistin level (r = ?0.51, P < 0.001). Conclusion: Low adiponectin and high resistin level at diagnosis suggest their implication in ALL pathogenesis and may serve as potential clinically significant diagnostic markers to detect leukemic relapse.

EL-BAZ, Hatim A; MOSA, Tamer E; ELABD, Elham M; RAMADAN, Amal; ELHAROUN, Ahmed S; ELMORSY, Elsayed A; FOUDA, Manal I

2013-01-01

271

Negative regulation of adiponectin secretion by receptor interacting protein 140 (RIP140)  

PubMed Central

RIP140 (Receptor-interacting protein 140) is highly expressed in mature adipocytes and functions as a co-repressor for gene expression involved in lipid and glucose metabolism. In adipocytes, activated PKC? (Protein kinase C epsilon) phosphorylates nuclear RIP140 which is then subsequently arginine methylated and exported to the cytoplasm. In the cytoplasm, RI140 can elicit additional activities. Here we report a new functional role for cytoplasmic RIP140 in adipocyte in regulating adiponectin secretion. Targeting cytoplasmic RIP140 by knocking down RIP140 itself or its nuclear export trigger, PKC?, promotes the secretion of adiponectin without affecting the production or oligomerization of adiponectin. Consequentially, conditioned media from either RIP140- or PKC?-silenced adipocytes, which contain higher levels of adiponectin, enhance glucose uptake in C2C12 cells and reduce gluconeogenesis in HepG2 cells. Further, these effects can be inhibited by an adiponectin-neutralizing antibody. The effect of cytoplasmic RIP140 in regulating adiponectin secretion is via interacting with AS160, a known RIP140-interacting protein. This study reveals a new functional role for cytoplasmic RIP140 in modulating adiponectin vesicle secretion, and suggests that targeting cytoplasmic RIP140 may be a potentially effective therapeutic strategy to improve adiponectin secretion and possibly to manage metabolic disorders.

Ho, Ping-Chih; Wei, Li-Na

2011-01-01

272

Adiponectin promotes syncytialisation of BeWo cell line and primary trophoblast cells  

Microsoft Academic Search

BACKGROUND: In human pregnancy, a correct placentation depends on trophoblast proliferation, differentiation, migration and invasion. These processes are highly regulated by placental hormones, growth factors and cytokines. Recently, we have shown that adiponectin, an adipokine, has anti-proliferative effects on trophoblastic cells. Here, we complete this study by demonstrating that adiponectin modulates BeWo and human villous cytotrophoblast cell differentiation. RESULTS: We

Delphine Benaitreau; Esther Dos Santos; Marie-Christine Leneveu; Philippe De Mazancourt; René Pecquery; Marie-Noëlle Dieudonné

2010-01-01

273

Association of Plasma Adiponectin Levels with Oxidative Stress in Hemodialysis Patients  

Microsoft Academic Search

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

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

2007-01-01

274

Adiponectin decreases plasma glucose and improves insulin sensitivity in diabetic Swine.  

PubMed

To investigate the effects of recombinant human adiponectin on the metabolism of diabetic swine induced by feeding a high-fat/high-sucrose diet (HFSD), diabetic animal models were constructed by feeding swine with HFSD for 6 months. The effects of recombinant adiponectin were assessed by detecting the change of plasma glucose levels by commercially available enzymatic method test kits and evaluating the insulin sensitivity by oral glucose tolerance test (OGTT). About 1.5 g purified recombinant adiponectin was produced using a 15-liter fermenter. A single injection of purified recombinant human adiponectin to diabetic swine led to a 2- to 3-fold elevation in circulating adiponectin, which triggered a transient decrease in basal glucose level (P<0.05). This effect on glucose was not associated with an increase in insulin level. Moreover, after adiponectin injection, swine also showed improved insulin sensitivity compared with the control (P<0.05). Adiponectin might have the potential to be a glucose-lowering agent for metabolic disease. Adiponectin as a potent insulin enhancer linking adipose tissue and glucose metabolism could be useful to treat insulin resistance. PMID:17277888

Hu, Xiaobo; She, Meihua; Hou, Hongjie; Li, Qinkai; Shen, Qingyun; Luo, Yi; Yin, Weidong

2007-02-01

275

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.

Liu, Meilian; Liu, Feng

2012-01-01

276

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.

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

2014-01-01

277

Corticosteroid-binding globulin affects the relationship between circulating adiponectin and cortisol in men and women.  

PubMed

Inflammatory pathways are increasingly recognized to be tightly associated with insulin resistance in humans. The promoter region of the adiponectin gene--Apm1--encompasses consensus sequences for glucocorticosteroid receptor responsive element. Dexamethasone induced downregulation of adiponectin secretion in vitro, whereas prednisolone administration increased circulating adiponectin concentrations. As previous studies have demonstrated an inverse relationship between corticosteroid-binding globulin (CBG), body mass index, and insulin resistance, we studied whether CBG could explain cortisol-to-adiponectin relationship. One hundred twenty-two healthy subjects were enrolled in a cross-sectional study. Plasma CBG and serum cortisol concentration were measured by radioimmunoassay. The cortisol-to-CBG ratio was used to calculate free cortisol. An RIA kit (Linco Research, St Louis, MO) was used to measure adiponectin levels. Insulin resistance was calculated using the homeostatis model of assessment (HOMA) value. Circulating adiponectin was associated with serum CBG ( r = 0.38, P < .00001), both in men ( r = 0.26, P = .03, n = 79) and women ( r = 0.48, P = .003, n = 43), and with insulin resistance (HOMA index) ( r = -0.30, P < .0001) in both. Free cortisol correlated negatively with adiponectin only in women ( r = -0.32, P = .04), but not in men ( r = 0.01, P = .89). Serum CBG concentration was significantly lower among men in the lowest quartile of adiponectin when compared with the remaining subjects (37.3 +/- 5.7 vs 40.6 +/- 5.1, P = .016), whereas men in the highest quartile of adiponectin showed significantly increased free cortisol index (14.2 +/- 3.3 vs 12.2 +/- 3.1, P = .039). Women in the lowest quartile of adiponectin also displayed significantly lower CBG concentration than that present in the remaining subjects (38.6 +/- 6.9 vs 44.4 +/- 5.5, P = .016), whereas free cortisol index was not significantly different across adiponectin quartiles ( P = .1). In a stepwise regression analysis, body mass index ( P = .0011), CBG ( P = .0047), and sex ( P = .04) contributed to 15%, 8%, and 3%, respectively, of adiponectin variance. Using CBG as dependent variable, both adiponectin ( P = .0002) and fasting cortisol ( P = .019) contributed to 14% and 4%, respectively, of CBG variance. In summary, circulating adiponectin, CBG concentration, and fasting cortisol were significantly interrelated in healthy subjects. A significant sexual dimorphism exists in this association. PMID:15877287

Fernandez-Real, José-Manuel; Pugeat, Michel; López-Bermejo, Abel; Bornet, Hubert; Ricart, Wifredo

2005-05-01

278

Particulate-dissolved transformations as a sink for semi-labile dissolved organic matter: Chemical characterization of high molecular weight dissolved and surface-active organic matter in seawater and in diatom cultures  

Microsoft Academic Search

Chemical characterizations of high molecular weight dissolved organic matter (HMW DOM) have shown that a compositionally well-defined family of acylated polysaccharides (APS) contributes a large fraction of DOM in the surface ocean. One process that might affect APS cycling is physical removal by aggregation. To investigate the importance of this mechanism, we compared the chemical composition and transparent exopolymer particle

Alexandra Gogou; Daniel J. Repeta

2010-01-01

279

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

280

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

281

A high-molecular-weight fraction of smooth lipopolysaccharide in Klebsiella serotype O1:K20 contains a unique O-antigen epitope and determines resistance to nonspecific serum killing.  

PubMed Central

The lipopolysaccharide (LPS) O-antigen side chains of Klebsiella serotype O1 have been studied by using mutants selected by resistance to a Klebsiella bacteriophage designated O1-A. Two classes of LPS mutants were identified. The major group (90%) synthesized rough LPS. The remaining 10% of the mutants produced a novel LPS profile that lacked the highest-molecular-weight O-substituted molecules (HMW-LPS) but still produced lower-molecular-weight O-substituted species (LMW-LPS). By using antisera raised against mutant Klebsiella strains and antiserum specific for Pasteurella haemolytica serotype 4, it was demonstrated that HMW-LPS and LMW-LPS contain shared epitopes. HMW-LPS also contained an epitope absent in LMW-LPS. This unique epitope was recognized by a monoclonal antibody (O1-52.6) and appears to be responsible for the serological cross-reaction between the O antigens of Klebsiella O1 and Escherichia coli O19. This HMW-LPS epitope was present in eight other Klebsiella O1 isolates which were examined. Electron microscopy demonstrated that HMW-LPS excluded overlying capsular polysaccharide for a distance of 25 to 40 nm. The distance was reduced to 10 to 18 nm in strains which synthesized only LMW-LPS and to zero in rough LPS strains. The HMW-LPS of Klebsiella O1 was shown to be an important virulence determinant, since this molecule was responsible for the resistance of the bacterium to nonspecific, complement-mediated serum killing. Images

McCallum, K L; Schoenhals, G; Laakso, D; Clarke, B; Whitfield, C

1989-01-01

282

A high-molecular-weight fraction of smooth lipopolysaccharide in Klebsiella serotype O1:K20 contains a unique O-antigen epitope and determines resistance to nonspecific serum killing.  

PubMed

The lipopolysaccharide (LPS) O-antigen side chains of Klebsiella serotype O1 have been studied by using mutants selected by resistance to a Klebsiella bacteriophage designated O1-A. Two classes of LPS mutants were identified. The major group (90%) synthesized rough LPS. The remaining 10% of the mutants produced a novel LPS profile that lacked the highest-molecular-weight O-substituted molecules (HMW-LPS) but still produced lower-molecular-weight O-substituted species (LMW-LPS). By using antisera raised against mutant Klebsiella strains and antiserum specific for Pasteurella haemolytica serotype 4, it was demonstrated that HMW-LPS and LMW-LPS contain shared epitopes. HMW-LPS also contained an epitope absent in LMW-LPS. This unique epitope was recognized by a monoclonal antibody (O1-52.6) and appears to be responsible for the serological cross-reaction between the O antigens of Klebsiella O1 and Escherichia coli O19. This HMW-LPS epitope was present in eight other Klebsiella O1 isolates which were examined. Electron microscopy demonstrated that HMW-LPS excluded overlying capsular polysaccharide for a distance of 25 to 40 nm. The distance was reduced to 10 to 18 nm in strains which synthesized only LMW-LPS and to zero in rough LPS strains. The HMW-LPS of Klebsiella O1 was shown to be an important virulence determinant, since this molecule was responsible for the resistance of the bacterium to nonspecific, complement-mediated serum killing. PMID:2478478

McCallum, K L; Schoenhals, G; Laakso, D; Clarke, B; Whitfield, C

1989-12-01

283

A new link between skeleton, obesity and insulin resistance: relationships between osteocalcin, leptin and insulin resistance in obese children before and after weight loss  

Microsoft Academic Search

Background:The skeleton is regarded recently as an endocrine organ that affects energy metabolism. However, there are very limited data available concerning the relationships between the osteoblast-derived hormone osteocalcin, weight status, adiponectin and leptin in obese humans, especially in children.Methods:We analyzed osteocalcin, adiponectin, leptin and insulin resistance (IR) index homeostasis model assessment (HOMA) in 60 obese and 19 age- and gender-matched

T Reinehr; C L Roth

2010-01-01

284

Interactions of Adiponectin and Lipopolysaccharide from Porphyromonas gingivalis on Human Oral Epithelial Cells  

PubMed Central

Background Periodontitis is an inflammatory disease caused by pathogenic microorganisms, such as Porphyromonas gingivalis, and characterized by the destruction of the periodontium. Obese individuals have an increased risk for periodontitis and show decreased serum levels of adiponectin. This in-vitro study was established to examine whether adiponectin modulates critical effects of lipopolysaccharide (LPS) from P. gingivalis on oral epithelial cells (OECs). Methodology/Principal Findings The presence of adiponectin and its receptors in human gingival tissue samples and OECs was analyzed by immunohistochemistry and PCR. Furthermore, OECs were treated with LPS and/or adiponectin for up to 72 h, and the gene expression and protein synthesis of pro- and anti-inflammatory mediators, matrix metalloproteinases (MMPs) and growth factors were analyzed by real-time PCR and ELISA. Additionally, cell proliferation, differentiation and in-vitro wound healing were studied. The nuclear translocation of NF?B was investigated by immunofluorescence. Gingival tissue sections showed a strong synthesis of adiponectin and its receptors in the epithelial layer. In cell cultures, LPS induced a significant up-regulation of interleukin (IL) 1?, IL6, IL8, MMP1 and MMP3. Adiponectin abrogated significantly the stimulatory effects of LPS on these molecules. Similarly, adiponectin inhibited significantly the LPS-induced decrease in cell viability and increase in cell proliferation and differentiation. Adiponectin led to a time-dependent induction of the anti-inflammatory mediators IL10 and heme oxygenase 1, and blocked the LPS-stimulated NF?B nuclear translocation. Conclusions/Significance Adiponectin may counteract critical actions of P. gingivalis on oral epithelial cells. Low levels of adiponectin, as observed in obese individuals, may increase the risk for periodontal inflammation and destruction.

Kraus, Dominik; Winter, Jochen; Jepsen, S?ren; Jager, Andreas; Meyer, Rainer; Deschner, James

2012-01-01

285

Adiponectin and adiponectin receptor gene variants in relation to resting metabolic rate, respiratory quotient, and adiposity-related phenotypes in the Québec Family Study1-3  

Microsoft Academic Search

Background: Despite adiponectin's presumed role in fatty acid oxidationandenergyhomeostasis,littleisknownabouttheeffectof gene variants on substrate oxidation, energy expenditure, and adiposity-related phenotypes. Objective: We examined the effects of genetic variation in adi- ponectin (ADIPOQ) and adiponectin receptors 1 and 2 (ADIPOR1 andADIPOR2)onrestingmetabolicrate,respiratoryquotient(RQ), and adiposity-related phenotypes. Design: We studied the associations of ADIPOQ, ADIPOR1, and ADIPOR2 polymorphisms with resting metabolic rate, RQ, and bodymassindex,percentagebodyfat,sumof6skinfoldthicknesses,

Ruth JF Loos; Stéphanie Ruchat; Tuomo Rankinen; Angelo Tremblay; Louis Pérusse; Claude Bouchard

286

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

287

Postoperative Plasma Interleukin6 in Patients with Renal Cancer Correlates with C-reactive Protein but Not with Total Fibrinogen or with High Molecular Weight Fibrinogen Fraction  

Microsoft Academic Search

The concentration of fibrinogen (Fb) and its fractions, the levels of interleukin-6 (Il-6), C-reactive protein (CRP), and immunoglobulin G (IgG) were determined in 38 patients operated on because of renal cancer. The increased Fb and Il-6 concentrations were found in approximately one-half of the patients with malignancy. The relations among the high molecular weight (HMW) and two low molecular weight

Grazyna Adler; Wojciech Eichman; Maciej Szczepanski; Izabela Targonska; Alicja Jasinska

1998-01-01

288

Association between adiponectin production in coronary circulation and future cardiovascular events in patients with coronary artery disease.  

PubMed

Adiponectin has antiatherosclerotic properties and is also produced in the local coronary circulation. We previously reported that significantly less adiponectin was produced in the coronary circulation of patients with than without coronary artery disease (CAD). The goal of this study was to determine whether adiponectin production in the coronary circulation could predict future cardiovascular events in patients with CAD.Forty-eight CAD patients whose left anterior descending coronary arteries required percutaneous coronary intervention (PCI) were enrolled. The amount of adiponectin production in the coronary circulation was defi ned as the plasma adiponectin level at the great cardiac vein minus that at the orifice of the left coronary artery. All patients were divided by adiponectin production level in the coronary circulation into the adiponectin-positive production group (> 0 µg/ mL) and adiponectin-negative production group (? 0 µg/mL). Median follow-up period was 66 months (maximum, 108 months). The primary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization due to unstable angina, heart failure, nonfatal myocardial infarction, revascularization with PCI or coronary artery bypass grafting, ischemic stroke, and cardiovascular death.Sixteen MACE occurred. The incidence of MACE was signifi cantly higher in the adiponectin-negative production group than in the adiponectin-positive production group (P = 0.02). In multivariate analysis, adiponectin-negative production was a predictor of MACE (P = 0.03). Kaplan-Meier analysis revealed that the MACE-free rate was signifi cantly lower in the adiponectin-negative production group than in the adiponectin-positive production group.Adiponectin production in the coronary circulation with CAD may be associated with MACE. PMID:24806386

Kawagoe, Junji; Ishikawa, Tetsunori; Iwakiri, Hironao; Date, Haruhiko; Imamura, Takuroh; Kitamura, Kazuo

2014-05-26

289

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

PubMed Central

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

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

2012-01-01

290

Lack of prognostic significance of adiponectin immunohistochemical expression in patients with triple-negative breast cancer  

PubMed Central

Introduction Triple-negative breast cancers (TNBCs) – which lack the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) – have no established markers that can be used for prognostic stratification. As adiponectin has been previously implicated in a more aggressive phenotype of primary breast cancer, we explored the relation between adiponectin immunohistochemical expression and prognosis in TNBCs. Material and methods Immunohistochemical staining for adiponectin was performed in 38 TNBC patients. Disease-free survival (DFS) and overall survival (OS) served as the main outcome measures. Results Of the 38 TNBC patients, 18 (47%) had negative and 20 (53%) positive adiponectin immunohistochemical expression. We did not find any significant association between adiponectin immunohistochemical expression and the baseline characteristics. In addition, there were no associations between adiponectin immunohistochemical expression and prognosis. Conclusions Although our results suggest that adiponectin immunohistochemical expression is not of prognostic significance in TNBCs, further studies are warranted to determine the role of this adipokine in breast cancer biology.

Olmez, Omer Fatih; Kanat, Ozkan; Kabul, Selva; Canhoroz, Mustafa; Avci, Nilufer; Hartavi, Mustafa; Deligonul, Adem; Cubukcu, Sinem; Manavoglu, Osman

2014-01-01

291

Genetic Analysis of Adiponectin Variation and its Association with Type 2 Diabetes in African Americans  

PubMed Central

Objective Adiponectin is an adipocytokine that has been implicated in a variety of metabolic disorders, including T2D and cardiovascular disease. Studies evaluating genetic variants in ADIPOQ have been contradictory when testing association with T2D in different ethnic groups. Design and Methods In this study, 18 SNPs in ADIPOQ were tested for association with plasma adiponectin levels and diabetes status. SNPs were examined in two independent African-American cohorts (nmax=1116) from the Insulin Resistance Atherosclerosis Family Study (IRASFS) and the African American-Diabetes Heart Study (AA-DHS). Results Five polymorphisms were nominally associated with plasma adiponectin levels in the meta-analysis (p=0.035–1.02x10?6) including a low frequency arginine to cysteine mutation (R55C) which reduced plasma adiponectin levels to <15% of the mean. Variants were then tested for association with T2D in a meta-analysis of these and the Wake Forest T2D Case-Control study (n=3233 T2D, 2645 non-T2D). Association with T2D was not observed (p?0.08), suggesting limited influence of ADIPOQ variants on T2D risk. Conclusions Despite identification of variants associated with adiponectin levels, a detailed genetic analysis of ADIPOQ revealed no association with T2D risk. This puts into question the role of adiponectin in T2D pathogenesis: whether low adiponectin levels are truly causal for or rather a consequence.

An, S. Sandy; Palmer, Nicholette D.; Hanley, Anthony J. G.; Ziegler, Julie T.; Brown, W. Mark; Freedman, Barry I.; Register, Thomas C.; Rotter, Jerome I.; Guo, Xiuqing; Chen, Y.-D. Ida; Wagenknecht, Lynne E.; Langefeld, Carl D.; Bowden, Donald W.

2013-01-01

292

The peroxisome proliferator-activated receptor gamma agonist rosiglitazone ameliorates murine lupus by induction of adiponectin.  

PubMed

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease for which current therapy is suboptimal. SLE is characterized by autoantibody production, with renal disease and premature atherosclerosis being common and severe manifestations causing appreciable morbidity and mortality. Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists are widely used in the treatment of diabetes mellitus for their insulin-sensitizing properties, but also have immunomodulatory effects. In this report, we show that the PPARgamma agonist rosiglitazone reduces autoantibody production, renal disease, and atherosclerosis in mouse models of SLE. The beneficial effect of rosiglitazone on SLE manifestations depends on the induction of adiponectin, because rosiglitazone has no effect on autoantibody production or renal disease in lupus mice that lack adiponectin. In addition, lupus mice that lack adiponectin develop more severe disease than adiponectin-sufficient lupus mice, indicating that endogenous adiponectin is involved in regulating disease activity. Furthermore, administration of exogenous adiponectin ameliorates disease. These experiments suggest that PPARgamma agonists may be useful agents for the treatment of SLE. They also demonstrate that induction of adiponectin is a major mechanism underlying the immunomodulatory effects of PPARgamma agonists. PMID:19109165

Aprahamian, Tamar; Bonegio, Ramon G; Richez, Christophe; Yasuda, Kei; Chiang, Lo-Ku; Sato, Kaori; Walsh, Kenneth; Rifkin, Ian R

2009-01-01

293

The Peroxisome Proliferator-Activated Receptor ? Agonist Rosiglitazone Ameliorates Murine Lupus by Induction of Adiponectin1  

PubMed Central

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease for which current therapy is suboptimal. SLE is characterized by autoantibody production, with renal disease and premature atherosclerosis being common and severe manifestations causing appreciable morbidity and mortality. Peroxisome proliferator-activated receptor ? (PPAR?) agonists are widely used in the treatment of diabetes mellitus for their insulin-sensitizing properties, but also have immunomodulatory effects. In this report, we show that the PPAR? agonist rosiglitazone reduces autoantibody production, renal disease, and atherosclerosis in mouse models of SLE. The beneficial effect of rosiglitazone on SLE manifestations depends on the induction of adiponectin, because rosiglitazone has no effect on autoantibody production or renal disease in lupus mice that lack adiponectin. In addition, lupus mice that lack adiponectin develop more severe disease than adiponectin-sufficient lupus mice, indicating that endogenous adiponectin is involved in regulating disease activity. Furthermore, administration of exogenous adiponectin ameliorates disease. These experiments suggest that PPAR? agonists may be useful agents for the treatment of SLE. They also demonstrate that induction of adiponectin is a major mechanism underlying the immunomodulatory effects of PPAR? agonists.

Aprahamian, Tamar; Bonegio, Ramon G.; Richez, Christophe; Yasuda, Kei; Chiang, Lo-Ku; Sato, Kaori; Walsh, Kenneth; Rifkin, Ian R.

2010-01-01

294

Serum adiponectin and resistin levels in patients with polycystic ovarian syndrome and their clinical implications.  

PubMed

In this study, serum adiponectin and resistin levels were determined in 46 patients with polycystic ovarian syndrome (PCOS), and their correlation with serum sexual hormones and insulin resistance (IR) were examined. The subjects included 26 obese patients with body mass index (BMI)>25 and 20 non-obese patients with BMI[Symbol: see text]25, with 25 obese and 25 non-obese healthy volunteers without PCOS serving as controls. Serum adiponectin and resistin levels in all subjects were measured, and endocrinal and metabolic indices were also analysed. Our results showed that the serum adiponectin levels in both obese and non-obese PCOS groups were significantly lower than their controls, while the serum resistin levels in obese and non-obese PCOS group were significantly higher than in their controls (P<0.001). The serum adiponectin level was significantly lower and serum resistin level significantly higher in the non-obese PCOS group as compared with the obese control group (P<0.05). Serum adiponectin level was negatively correlated with FIN, HOMA-IR, LH and LH/FSH (P<0.05), but serum resistin level was positively correlated with FIN, HOMA-IR, LH and LH/FSH (P<0.05). We are led to conclude that PCOS patients have obvious IR, low serum adiponectin and high serum resistin, and adiponectin and resistin might play important roles in the pathogenesis of IR in PCOS patients. PMID:21063848

Wang, Yuxia; Xie, Xingmei; Zhu, Weijie

2010-10-01

295

Associations of adiponectin with individual European ancestry in African Americans: the Jackson Heart Study  

PubMed Central

Background: Compared with European Americans, African Americans (AAs) exhibit lower levels of the cardio-metabolically protective adiponectin even after accounting for adiposity measures. Because few studies have examined in AA the association between adiponectin and genetic admixture, a dense panel of ancestry informative markers (AIMs) was used to estimate the individual proportions of European ancestry (PEA) for the AAs enrolled in a large community-based cohort, the Jackson Heart Study (JHS). We tested the hypothesis that plasma adiponectin and PEA are directly associated and assessed the interaction with a series of cardio-metabolic risk factors. Methods: Plasma specimens from 1439 JHS participants were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the HapMap Consortium, PEA was estimated with a panel of up to 1447 genome-wide preselected AIMs by a maximum likelihood approach. Interaction assessment, stepwise linear and cubic multivariable-adjusted regression models were used to analyze the cross-sectional association between adiponectin and PEA. Results: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. Body mass index (BMI) (p = 0.04) and insulin resistance (p = 0.0001) modified the association between adiponectin and PEA. Adiponectin was directly and linearly associated with PEA (? = 0.62 ± 0.28, p = 0.03) among non-obese (n = 673) and insulin sensitive participants (n = 1141; ? = 0.74 ± 0.23, p = 0.001), but not among those obese or with insulin resistance. No threshold point effect was detected for non-obese participants. Conclusions: In a large AA population, the individual proportion of European ancestry was linearly and directly associated with plasma adiponectin among non-obese and non insulin-resistant participants, pointing to the interaction of genetic and metabolic factors influencing adiponectin levels.

Bidulescu, Aurelian; Choudhry, Shweta; Musani, Solomon K.; Buxbaum, Sarah G.; Liu, Jiankang; Rotimi, Charles N.; Wilson, James G.; Taylor, Herman A.; Gibbons, Gary H.

2014-01-01

296

Associations of adiponectin with individual European ancestry in African Americans: the Jackson Heart Study.  

PubMed

Background: Compared with European Americans, African Americans (AAs) exhibit lower levels of the cardio-metabolically protective adiponectin even after accounting for adiposity measures. Because few studies have examined in AA the association between adiponectin and genetic admixture, a dense panel of ancestry informative markers (AIMs) was used to estimate the individual proportions of European ancestry (PEA) for the AAs enrolled in a large community-based cohort, the Jackson Heart Study (JHS). We tested the hypothesis that plasma adiponectin and PEA are directly associated and assessed the interaction with a series of cardio-metabolic risk factors. Methods: Plasma specimens from 1439 JHS participants were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the HapMap Consortium, PEA was estimated with a panel of up to 1447 genome-wide preselected AIMs by a maximum likelihood approach. Interaction assessment, stepwise linear and cubic multivariable-adjusted regression models were used to analyze the cross-sectional association between adiponectin and PEA. Results: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. Body mass index (BMI) (p = 0.04) and insulin resistance (p = 0.0001) modified the association between adiponectin and PEA. Adiponectin was directly and linearly associated with PEA (? = 0.62 ± 0.28, p = 0.03) among non-obese (n = 673) and insulin sensitive participants (n = 1141; ? = 0.74 ± 0.23, p = 0.001), but not among those obese or with insulin resistance. No threshold point effect was detected for non-obese participants. Conclusions: In a large AA population, the individual proportion of European ancestry was linearly and directly associated with plasma adiponectin among non-obese and non insulin-resistant participants, pointing to the interaction of genetic and metabolic factors influencing adiponectin levels. PMID:24575123

Bidulescu, Aurelian; Choudhry, Shweta; Musani, Solomon K; Buxbaum, Sarah G; Liu, Jiankang; Rotimi, Charles N; Wilson, James G; Taylor, Herman A; Gibbons, Gary H

2014-01-01

297

Adiponectin normalizes LPS-stimulated TNF-? production by rat Kupffer cells after chronic ethanol feeding  

PubMed Central

Chronic ethanol feeding sensitizes Kupffer cells to activation by lipopolysac-charide (LPS), leading to increased production of tumor necrosis factor-? (TNF-?). Adiponectin treatment protects mice from ethanol-induced liver injury. Because adiponectin has anti-inflammatory effects on macrophages, we hypothesized that adiponectin would normalize chronic ethanol-induced sensitization of Kupffer cells to LPS-mediated signals. Serum adiponectin concentrations were decreased by 45% in rats fed an ethanol-containing diet for 4 wk compared with pair-fed rats. Adiponectin dose dependently inhibited LPS-stimulated accumulation of TNF-? mRNA and peptide in Kupffer cells from both pair- and ethanol-fed rats. Kupffer cells from ethanol-fed rats were more sensitive to both globular (gAcrp) and full-length adiponectin (flAcrp) than Kupffer cells from pair-fed controls with suppression at 10 ng/ml adiponectin after chronic ethanol feeding. Kupffer cells expressed both adiponectin receptors 1 and 2; chronic ethanol feeding did not change the expression of adiponectin receptor mRNA or protein. gAcrp suppressed LPS-stimulated ERK1/2 and p38 phosphorylation as well as I?B degradation at 100–1,000 ng/ml in Kupffer cells from both pair- and ethanol-fed rats. However, only LPS-stimulated ERK1/2 phosphorylation was sensitive to 10 ng/ml gAcrp. gAcrp also normalized LPS-stimulated DNA binding activity of early growth response-1 with greater sensitivity in Kupffer cells from rats fed chronic ethanol. In conclusion, these results demonstrate that Kupffer cells from ethanol-fed rats are more sensitive to the anti-inflammatory effects of both gAcrp and flAcrp. Suppression of LPS-stimulated ERK1/2 signaling by low concentrations of gAcrp was associated with normalization of TNF-? production by Kupffer cells after chronic ethanol exposure.

Thakur, Varsha; Pritchard, Michele T.; McMullen, Megan R.; Nagy, Laura E.

2007-01-01

298

The adiponectin gene, ADIPOQ, and genetic susceptibility to colon cancer  

PubMed Central

In order to evaluate the contribution of polymorphisms of the adiponectin gene, ADIPOQ, to the risk of colon cancer, we conducted a case-control study of 60 colon cancer patients and 60 age, gender and ethnicity-matched controls in the Saudi population. We tested the hypothesis by analyzing the genotypes for two single nucleotide polymorphisms (SNPs), rs1501299 (G276T) and rs2241766 (T45G), in the ADIPOQ gene. In addition, the study was also designed to assess whether the two SNPs contribute to circulating adiponectin levels. We observed an increased risk of colon cancer associated with the 276T allele. The odds ratio (OR) was 2.64 [95% confidence interval (CI), 0.49–14.6]. The G allele at the T45G polymorphism was associated with a lower risk of colon cancer (OR=0.41; 95% CI, 0.19–0.86). Our results suggest that the risk of developing colon cancer may be partially explained by genetic polymorphisms in the ADIPOQ gene.

AL-HARITHY, ROWYDA N.; AL-ZAHRANI, MARYAM H.

2012-01-01

299

[Adiponectin and resistin: a role in the reproductive functions?].  

PubMed

Adipokines are hormones mainly produced by the white adipose tissue, an endocrine organ involved in energy homeostasis. They play an important role in the regulation of lipid and glucose metabolisms, in inflammation and immune disorders. New roles for adipokines have recently emerged in the field of fertility and reproduction. Indeed, adipokines such as adiponectin and resistin are able to regulate the functions of male and female gonads and of the hypothalamic-pituitary axis. For example, they modulate steroidogenesis of gonadic somatic cells, germ cell maturation and secretion of gonadotrope hormones in various species. The reproductive system is tightly coupled with energy balance, and thereby metabolic abnormalities can lead to the development of physiopathological situations such as the polycystic ovary syndrome (PCOS). Obesity and overweight are significantly involved in the declining natural fertility and decrease the effectiveness of treatments. Women with obesity and/or PCOS have abnormal plasma adiponectin and resistin profiles. Thus, these adipokines could be a link between reproduction and energy metabolism and could partly explain some infertility related to obesity or PCOS. PMID:23621938

Reverchon, Maxime; Maillard, Virginie; Froment, Pascal; Ramé, Christelle; Dupont, Joëlle

2013-04-01

300

Targeting 11q23 positive acute leukemia cells with high molecular weight-melanoma associated antigen-specific monoclonal antibodies  

Microsoft Academic Search

Background  Acute leukemia with 11q23 aberrations is associated with a poor outcome with therapy. The lack of efficacy of conventional\\u000a therapy has stimulated interest in developing novel strategies. Recent studies have shown that 11q23-positive acute leukemia\\u000a cells express the high molecular weight-melanoma associated antigen (HMW-MAA). This tumor antigen represents a useful target\\u000a to control growth of human melanoma tumors in patients

Allison S. Drake; Michael T. Brady; Xin Hui Wang; Sheila J. N. Sait; Justin C. Earp; Soldano Ferrone; Eunice S. Wang; Meir Wetzler

2009-01-01

301

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

Microsoft Academic Search

The primary aim of this work was to evaluate potential changes in the metabolic network of transgenic wheat grain over-expressing\\u000a the high-molecular-weight (HMW) glutenin Dx5-subunit gene. GC–MS and multivariate analyses were used to compare the metabolite\\u000a profiles of developing caryopses of two independently transformed lines over-expressing Dx5 and another two independently transformed lines expressing only the selectable-marker gene (controls). Developing

Boryana S. Stamova; Ute Roessner; Suganthi Suren; Debbie Laudencia-Chingcuanco; Antony Bacic; Diane M. Beckles

2009-01-01

302

Leptin prevents the metabolic effects of adiponectin in L6 myotubes  

Microsoft Academic Search

Aims\\/hypothesis  Adiponectin and leptin are negatively and positively correlated with human obesity respectively, and have both been shown\\u000a to regulate energy metabolism in skeletal muscle. However, little is known about their signalling and functional crosstalk.\\u000a Here we investigated the effects of leptin on metabolic actions of (1) globular adiponectin (gAd) and (2) full-length adiponectin\\u000a (fAd) in L6 cells.\\u000a \\u000a \\u000a \\u000a Methods  Glucose uptake was

X. Fang; J. Fetros; K. E. Dadson; A. Xu; G. Sweeney

2009-01-01

303

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin  

PubMed Central

The interaction between ghrelin and adiponectin is still controversial. We investigated the effect of cafeteria diet and pioglitazone on body weight, insulin resistance, and adiponectin/ghrelin levels in an experimental study on male Wistar rats. The animals were divided into four groups of 6 rats each, and received balanced chow with saline (CHOW-O) or pioglitazone (CHOW-P), or a cafeteria diet with saline (CAFE-O) or pioglitazone (CAFE-P). The chow/cafeteria diets were administered for 35 days, and saline/pioglitazone (10?mg·kg body weight?1·day?1) was added in the last 14 days prior to euthanasia. CAFE-O animals had a higher mean final weight (372.5 ± 21.01?g) than CHOW-O (317.66 ± 25.11?g, P = 0.017) and CHOW-P (322.66 ± 28.42?g, P = 0.035) animals. Serum adiponectin levels were significantly higher in CHOW-P (55.91 ± 20.62?ng/mL) than in CHOW-O (30.52 ± 6.97?ng/mL, P = 0.014) and CAFE-O (32.54 ± 9.03?ng/mL, P = 0.027) but not in CAFE-P. Higher total serum ghrelin levels were observed in CAFE-P compared to CHOW-P animals (1.65 ± 0.69 vs 0.65 ± 0.36?ng/mL, P = 0.006). Likewise, acylated ghrelin levels were higher in CAFE-P (471.52 ± 195.09?pg/mL) than in CHOW-P (193.01 ± 87.61?pg/mL, P = 0.009) and CAFE-O (259.44 ± 86.36?pg/mL, P = 0.047) animals. In conclusion, a cafeteria diet can lead to a significant weight gain. Although CAFE-P animals exhibited higher ghrelin levels, this was probably related to food deprivation rather than to a direct pharmacological effect, possibly attenuating the increase in adiponectin levels.

Colombo, G.; Bazzo, M.L.; Nogueira, C.L.; Colombo, M.D.H.P.; Schiavon, L.L.; d'Acampora, A.J.

2012-01-01

304

The trans-10, cis-12 isomer of conjugated linoleic acid decreases adiponectin assembly by PPAR -dependent and PPAR -independent mechanisms  

Microsoft Academic Search

Abstract,The adipocyte-derived secretory,protein,adipo- nectin functions as an insulin-sensitizing agent. In plasma, adiponectin exists as low, medium, and high molecular weight oligomers. Treatment with trans-10, cis-12 conju- gated linoleic acid (t-10, c-12 CLA) reduces levels of adipo- nectin,as well as triglyceride,(TG) in mice,and,adipocyte cell culture models. The aim,of this study was to determine whether the effects of t-10, c-12 CLA on

Jessica R. Miller; Pilaiwan Siripurkpong; Jennifer Hawes; Amin Majdalawieh; Hyo-Sung Ro; Roger S. McLeod

2008-01-01

305

Serum Adiponectin in Relation to Race-Ethnicity and Vascular Risk Factors in the Northern Manhattan Study  

PubMed Central

Abstract Background Population-based data on serum adiponectin levels, an adipocytokine secreted from adipose tissue, are lacking, particularly across race–ethnic groups. Studies have suggested an inverse association between adiponectin and vascular risk factors, but data are limited and inconsistent. We examined the cross-sectional association between adiponectin, vascular risk factors and race–ethnicity in the population-based Northern Manhattan Study (NOMAS). Methods Blood samples, anthropomorphics, and vascular risk factors were collected at baseline. Multivariable linear regression analysis was conducted with log-transformed adiponectin as the dependent variable. Results Adiponectin was measured among 2900 participants (age 69±10 years, body mass index (BMI) 28.0±5.6, 37% male, 21% white, 53% Hispanic, 24% black). The mean adiponectin was 11.4±6.2??g/mL (median=9.8, range=2.1–53.3). After multivariable adjustment, adiponectin levels were greatest among whites, followed by Hispanics, and lowest among blacks. Lower adiponectin levels were observed in participants with the following characteristics: Male, former smoking, hypertension, diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), metabolic syndrome, moderate alcohol use, elevated waist circumference, BMI, estimated glomerular filtration rate (eGFR), triglycerides, low-density lipoprotein cholesterol (LDL-C), lower high-density lipoprotein cholesterol (HDL-C), and younger age. Obesity was a stronger risk factor for decreased adiponectin among blacks than among whites or Hispanics. The associations for several vascular risk factors, including hypertension, triglycerides, and low HDL-C, with low adiponectin were stronger among individuals who were not obese than among those who were obese. Conclusions Adiponectin levels were lower among blacks and Hispanics and among those with various vascular risk factors, and greater with older age. The association between BMI and adiponectin varied across race–ethnic groups. Investigation of whether differences in body fat distribution may explain race–ethnic differences in adiponectin is needed.

Crisby, Milita; Sjoberg, Charlotte; Hudson, Barry; Goldberg, Ronald; Mendez, Armando J.; Wright, Clinton B.; Rundek, Tatjana; Elkind, Mitchell S.V.; Sacco, Ralph L.

2013-01-01

306

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

307

First-trimester adiponectin and subsequent development of preeclampsia or fetal growth restriction.  

PubMed

Background/Aims: The evidence regarding the utility of assessing first-trimester adiponectin (ApN) serum levels in early prediction of preeclampsia (PE) and fetal growth restriction (FGR) is contradictory. This study aims to determine the role of maternal serum ApN levels as an early predictor of PE and FGR. Methods: A prospective case-control study among a pregnant population who attended their 11- to 14-week ultrasound scan at the University of Chile's Clinical Hospital's Fetal Medicine Unit. We included patients who developed PE or FGR (10 cases per group) and 35 healthy controls. We determined ApN levels in blood samples from these 55 patients using a commercial ELISA kit and assessed the relationship of ApN levels with variables like development of PE, FGR, weight at birth and maternal BMI. Results: There were no significant differences among first-trimester ApN serum levels in the groups. Average concentrations were 8, 6.8 and 10.8 ng/ml for the control, PE and FGR groups, respectively. Conclusion: In our study, maternal serum ApN levels were not useful in predicting subsequent development of PE and FGR. However, maternal serum ApN concentration adjusted by BMI was significantly higher during the first trimester in women who later developed FGR. PMID:21912074

Valdés, Enrique R; Lattes, Karinna A; Muñoz, Hernán S; Barja, Pilar Y; Papapietro, Karin V

2011-01-01

308

Oral administration of ?-aminobutyric acid and ?-oryzanol prevents stress-induced hypoadiponectinemia.  

PubMed

Metabolic syndrome is a cluster of risk factors including insulin resistance and type 2 diabetes and is found to associate partly with chronic stress at work in human. Adiponectin circulates in mammal blood mainly as a low molecular weight (LMW) trimer, hexamer, and a high molecular weight (HMW) multimers. Low circulating levels of adiponectin are related to metabolic syndrome. We have then investigated the influence of immobilization stress on plasma adiponectin concentrations in mice. Relative LMW and HMW adiponectin levels were markedly reduced by immobilization stress (0.66±0.07 and 0.59±0.06 after 102 h, respectively), significantly different from the control values (p<0.01 and 0.05, respectively). ?-Aminobutyric acid (GABA) and ?-oryzanol abundantly contained in germinated brown rice have some physiological functions. We further investigated the effect of GABA, ?-oryzanol, GABA plus ?-oryzanol on adiponectin levels in mice subjected to immobilization stress. GABA and ?-oryzanol significantly increased the relative LMW and HMW adiponectin levels under immobilization stress (1.10±0.11 and 0.99±0.19 after 102 h, respectively, for GABA; 1.08±0.17 and 1.15±0.17 after 102 h, respectively, for ?-oryzanol). Additionally, the co-administration of GABA and ?-oryzanol also increased both relative LMW and HMW adiponectin levels (1.02±0.07 and 0.99±0.10 after 102 h, respectively) and was effective in an earlier phase from 30 to 54 h. The results indicate that the co-administration of GABA and ?-oryzanol might be effective in preventing stress-induced hypoadiponectinemia in mice and be also a promising tool for improving metabolic syndrome aggravated by chronic stress. PMID:21316207

Ohara, Kazuyuki; Kiyotani, Yuka; Uchida, Asako; Nagasaka, Reiko; Maehara, Hiroyuki; Kanemoto, Shigeharu; Hori, Masatoshi; Ushio, Hideki

2011-06-15

309

Relationship between polymorphism of insulin receptor gene, and adiponectin gene with PCOS  

PubMed Central

Background: Polycystic ovary syndrome (PCOS) is a complex disease having both genetic and environmental components and candidate genes on obesity and insulin metabolism have been hypothesized to be involved in its etiology. Objective: We examined the possible association of adiponectin and insulin receptor gene polymorphisms with PCOS. Materials and Methods: A total of 186 women with PCOS using NIH criteria and 156 healthy women were recruited. Their samples were genotyped for the polymorphism in exon 17 and 8 of the insulin receptor gene or exon and intron 2 of the adiponectin gene. Results: The distributions of genotypes and alleles of both polymorphisms were not different in women with PCOS and controls. There was no significant differences on the anthropometric and hormonal profiles of various adiponectin and insulin receptor genes polymorphisms among both groups. Conclusion: Adiponectin and insulin receptor gene polymorphisms are not associated with PCOS in a sample of Iranian population.

Ramezani Tehrani, Fahimeh; Daneshpour, Maryam; Hashemi, Somayeh; Zarkesh, Maryam; Azizi, Feridoun

2013-01-01

310

Adiponectin concentration in the orbital fat of patients with Graves' ophthalmopathy  

PubMed Central

Background “Graves’ ophthalmopathy” (GO), is an inflammatory disease of the orbit, with extensive adipose tissue involvement. Previous studies of orbital fat derived from such patients have demonstrated overexpression of the adiponectin gene and messenger RNA. Aim The study reported here aimed to measure the protein concentration of orbital adipose tissue adiponectin in GO patients, in comparison to healthy controls. Methods This was a prospective study. Orbital samples from ten healthy controls undergoing blepharoplasty and five patients with GO undergoing orbital fat decompression for proptosis were analyzed by enzyme-linked immunosorbent assay. Results The mean adiponectin concentration in samples from GO patients was 121.9 ± 29.5 ng/mL (mean ± standard deviation), versus 107.9 ± 26.6 ng/mL in the control group (P=0.20). Conclusion This study was unable to demonstrate a statistically significant difference in adiponectin protein concentrations between the two studied groups.

Soiberman, Uri; Levy, Ran; Leibovitch, Igal

2013-01-01

311

Population-specific coding variant underlies genome-wide association with adiponectin level.  

PubMed

Adiponectin is a protein hormone that can affect major metabolic processes including glucose regulation and fat metabolism. Our previous genome-wide association (GWA) study of circulating plasma adiponectin levels in Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) detected a 100 kb two-SNP haplotype at KNG1-ADIPOQ associated with reduced adiponectin (frequency = 0.050, P = 1.8 × 10(-25)). Subsequent genotyping of CLHNS young adult offspring detected an uncommon variant [minor allele frequency (MAF) = 0.025] located ~800 kb from ADIPOQ that showed strong association with lower adiponectin levels (P = 2.7 × 10(-15), n = 1695) and tagged a subset of KNG1-ADIPOQ haplotype carriers with even lower adiponectin levels. Sequencing of the ADIPOQ-coding region detected variant R221S (MAF = 0.015, P = 2.9 × 10(-69)), which explained 17.1% of the variance in adiponectin levels and largely accounted for the initial GWA signal in Filipinos. R221S was not present in 12 514 Europeans with previously sequenced exons. To explore the mechanism of this substitution, we re-measured adiponectin level in 20 R221S offspring carriers and 20 non-carriers using two alternative antibodies and determined that the presence of R221S resulted in artificially low quantification of adiponectin level using the original immunoassay. These data provide an example of an uncommon variant responsible for a GWA signal and demonstrate that genetic associations with phenotypes measured by antibody-based quantification methods can be affected by uncommon coding SNPs residing in the antibody target region. PMID:22010046

Croteau-Chonka, Damien C; Wu, Ying; Li, Yun; Fogarty, Marie P; Lange, Leslie A; Kuzawa, Christopher W; McDade, Thomas W; Borja, Judith B; Luo, Jingchun; AbdelBaky, Omar; Combs, Terry P; Adair, Linda S; Lange, Ethan M; Mohlke, Karen L

2012-01-15

312

Dietary antioxidant capacity and concentration of adiponectin in apparently healthy adults: the ATTICA study  

Microsoft Academic Search

Background\\/Objectives:This study aimed at evaluating the relationship of adiponectin concentration with total dietary antioxidant capacity in free-living, apparently healthy adults from the ATTICA study.Subjects\\/Methods:A random subsample from the ATTICA study, consisting of 310 men (40±11 years) and 222 women (38±12 years), was selected. Adiponectin, along with other inflammatory markers, was measured in fasting participants. Dietary habits were evaluated using a

P Detopoulou; D B Panagiotakos; C Chrysohoou; E Fragopoulou; T Nomikos; S Antonopoulou; C Pitsavos; C Stefanadis

2010-01-01

313

Maternal Serum Adiponectin at 11–13 Weeks of Gestation in Preeclampsia  

Microsoft Academic Search

Objective: To determine whether the maternal serum levels of adiponectin in the first trimester of pregnancy are altered in cases that develop preeclampsia (PE) and whether the levels are related to pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (PI). Methods: Serum adiponectin, PAPP-A and uterine artery PI were measured at 11–13 weeks in 90 cases that developed PE,

Surabhi Nanda; Christina K. H. Yu; Laura Giurcaneanu; Ranjit Akolekar; Kypros H. Nicolaides

2011-01-01

314

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

315

A genome-wide association study reveals variants in ARL15 that influence adiponectin levels  

Microsoft Academic Search

The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their

J. Brent Richards; Dawn Waterworth; Stephen O'Rahilly; Marie-France Hivert; Ruth J. F. Loos; John R. B. Perry; Toshiko Tanaka; Nicholas John Timpson; Robert K. Semple; Nicole Soranzo; Kijoung Song; Nuno Rocha; Elin Grundberg; Josée Dupuis; Jose C. Florez; Claudia Langenberg; Inga Prokopenko; Richa Saxena; Robert Sladek; Yurii Aulchenko; David Evans; Gerard Waeber; Jeanette Erdmann; Mary-Susan Burnett; Naveed Sattar; Joseph Devaney; Christina Willenborg; Aroon Hingorani; Jaquelin C. M. Witteman; Peter Vollenweider; Beate Glaser; Christian Hengstenberg; Luigi Ferrucci; David Melzer; Klaus Stark; John Deanfield; Janina Winogradow; Martina Grassl; Alistair S. Hall; Josephine M. Egan; John R. Thompson; Sally L. Ricketts; Inke R. König; Wibke Reinhard; Scott Grundy; H-Erich Wichmann; Phil Barter; Robert Mahley; Y. Antero Kesaniemi; Daniel J. Rader; Muredach P. Reilly; Stephen E. Epstein; Alexandre F. R. Stewart; P. Tikka-Kleemola; Heribert Schunkert; Keith Burling; Panos Deloukas; Tomi Pastinen; Nilesh J. Samani; Ruth McPherson; George Davey Smith; Timothy M. Frayling; Nicholas J. Wareham; James B. Meigs; Vincent Mooser; Tim D. Spector

2009-01-01

316

Adiponectin and Leptin Molecular Actions and Clinical Significance in Breast Cancer  

PubMed Central

Obesity is an important public health problem and major risk factor for postmenopausal breast cancer. Adipose tissue is the major component involved in the control of the metabolism through energy homeostasis, adipocyte differentiation, insulin sensitivity and the activation of anti-inflammatory metabolic and immune pathways. Leptin and Adiponectin pathways are involved in proliferation process in breast cancer. Current review describes potential relationship between the molecular actions and clinical significance of leptin and adiponectin in breast cancer.

Nalabolu, Mohan Reddy; Palasamudram, Kalyani

2014-01-01

317

Diet-induced insulin resistance in mice lacking adiponectin\\/ACRP30  

Microsoft Academic Search

Here we investigated the biological functions of adiponectin\\/ACRP30, a fat-derived hormone, by disrupting the gene that encodes it in mice. Adiponectin\\/ACRP30-knockout (KO) mice showed delayed clearance of free fatty acid in plasma, low levels of fatty-acid transport protein 1 (FATP-1) mRNA in muscle, high levels of tumor necrosis factor-? (TNF-?) mRNA in adipose tissue and high plasma TNF-? concentrations. The

Norikazu Maeda; Ken Kishida; Hitoshi Nishizawa; Morihiro Matsuda; Hiroyuki Nagaretani; Naoki Furuyama; Hidehiko Kondo; Masahiko Takahashi; Yukio Arita; Ryutaro Komuro; Noriyuki Ouchi; Shinji Kihara; Yoshihiro Tochino; Keiichi Okutomi; Masato Horie; Satoshi Takeda; Toshifumi Aoyama; Tohru Funahashi; Yuji Matsuzawa; Iichiro Shimomura

2002-01-01

318

Population-specific coding variant underlies genome-wide association with adiponectin level  

PubMed Central

Adiponectin is a protein hormone that can affect major metabolic processes including glucose regulation and fat metabolism. Our previous genome-wide association (GWA) study of circulating plasma adiponectin levels in Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) detected a 100 kb two-SNP haplotype at KNG1–ADIPOQ associated with reduced adiponectin (frequency = 0.050, P = 1.8 × 10?25). Subsequent genotyping of CLHNS young adult offspring detected an uncommon variant [minor allele frequency (MAF) = 0.025] located ?800 kb from ADIPOQ that showed strong association with lower adiponectin levels (P = 2.7 × 10?15, n = 1695) and tagged a subset of KNG1–ADIPOQ haplotype carriers with even lower adiponectin levels. Sequencing of the ADIPOQ-coding region detected variant R221S (MAF = 0.015, P = 2.9 × 10?69), which explained 17.1% of the variance in adiponectin levels and largely accounted for the initial GWA signal in Filipinos. R221S was not present in 12 514 Europeans with previously sequenced exons. To explore the mechanism of this substitution, we re-measured adiponectin level in 20 R221S offspring carriers and 20 non-carriers using two alternative antibodies and determined that the presence of R221S resulted in artificially low quantification of adiponectin level using the original immunoassay. These data provide an example of an uncommon variant responsible for a GWA signal and demonstrate that genetic associations with phenotypes measured by antibody-based quantification methods can be affected by uncommon coding SNPs residing in the antibody target region.

Croteau-Chonka, Damien C.; Wu, Ying; Li, Yun; Fogarty, Marie P.; Lange, Leslie A.; Kuzawa, Christopher W.; McDade, Thomas W.; Borja, Judith B.; Luo, Jingchun; AbdelBaky, Omar; Combs, Terry P.; Adair, Linda S.; Lange, Ethan M.; Mohlke, Karen L.

2012-01-01

319

Brown adipocytes are novel sites of expression and regulation of adiponectin and resistin  

Microsoft Academic Search

Adiponectin and resistin, two recently identified adipocyte-specific secretory factors, are able to modulate insulin actions in target tissues. To investigate their expression and hormonal regulation in brown adipocytes, we used the brown adipocyte cell line T37i, which, beside uncoupling protein expression, secretes leptin. Adiponectin and resistin mRNA were detected as a function of cell differentiation. Both transcripts were expressed at

Say Viengchareun; Maria-Christina Zennaro; Laurent Pascual-Le Tallec; Marc Lombes

2002-01-01

320

Role of Adiponectin and Its Receptors in Cancer  

PubMed Central

Adiponectin (APN), a novel hormone/cytokine derived from adipocyte tissue, is involved in various physiological functions. Genetics, nutrition, and adiposity are factors contributing to circulating plasma concentrations of APN. Clinical correlation studies have shown that lower levels of serum APN are associated with increased malignancy of various cancers, such as breast and colon cancers, suggesting that APN has a role in tumorigenesis. APN affects insulin resistance, thus further influencing cancer development. Tumor cells may express receptors for APN. Cellular signaling is the mechanism by which APN exerts its host-protective responses. These factors suggest that serum APN levels and downstream signaling targets of APN may serve as potential diagnostic markers for malignancies. Further research is necessary to clarify the exact role of APN in cancer diagnosis and therapy.

Obeid, Stephanie; Hebbard, Lionel

2012-01-01

321

Effects of leptin and adiponectin on proliferation and protein metabolism of porcine myoblasts.  

PubMed

The aim of this study was to show the abundance of leptin and adiponectin receptors (LEPR, ADIPOR1, ADIPOR2) and to determine the direct effects of leptin and adiponectin on the in vitro growth of porcine skeletal muscle cells. ADIPOR1 and ADIPOR2 were abundant at mRNA and protein level in proliferating and differentiating myoblast cultures derived from semimembranosus and semitendinosus muscles of newborn piglets, whereas LEPR expression was close to the detection limit. Adiponectin (10, 20, 40 ?g/ml) attenuated the proliferation of porcine myoblasts, measured as [(3)H]-thymidine incorporation and real-time monitoring of the cells in response to 24- and 48-h exposure, in a dose-dependent manner. This effect resulted from suppressed basic fibroblast growth factor (bFGF)-mediated stimulation of DNA synthesis in serum-free medium (SFM) containing bFGF. No effects of leptin (5, 10, 20, 40, 80 ng/ml) on myoblast proliferation in SFM were detectable. Neither leptin nor adiponectin altered protein synthesis and degradation in differentiating porcine myoblasts cultured in SFM. The results on receptor abundance suggest that porcine skeletal muscle cells may be sensitive to adiponectin and leptin. However, except via inhibitory interaction of adiponectin with bFGF, these adipokines appear not to affect in vitro proliferation and protein metabolism of porcine muscle cells directly under serum-free culture conditions. PMID:22527694

Will, Katja; Kalbe, Claudia; Kuzinski, Judith; Lösel, Dorothea; Viergutz, Torsten; Palin, Marie-France; Rehfeldt, Charlotte

2012-08-01

322

Rheumatoid Arthritis Impacts on the Independent Relationships between Circulating Adiponectin Concentrations and Cardiovascular Metabolic Risk  

PubMed Central

Adiponectin and leptin are likely involved in the pathophysiology of rheumatoid arthritis (RA) and therefore potential new therapeutic targets. Adiponectin inhibition could be expected to enhance cardiovascular metabolic risk. However, it is unknown whether RA changes the influence of adipokines on cardiovascular metabolic risk. We determined whether RA impacts on the independent relationships of circulating leptin and adiponectin concentrations with cardiovascular risk factors and carotid intima-media thickness (cIMT) in 277 black African subjects from a developing population; 119 had RA. RA impacted on the relationships of adiponectin concentrations with lipid concentrations and blood pressure, independent of confounders including adiposity (interaction P < 0.05). This translated into an association of adiponectin concentrations with more favorable lipid variables including HDL cholesterol (P = 0.0005), non-HDL cholesterol (P = 0.007), and triglyceride (P = 0.005) concentrations, total cholesterol-HDL cholesterol (P = 0.0002) and triglycerides-HDL cholesterol (P = 0.0003) ratios, and higher systolic (P = 0.0006), diastolic (P = 0.0004), and mean blood pressure (P = 0.0007) in RA but not non-RA subjects. Leptin was not associated with metabolic risk after adjustment for adiposity. The cIMT did not differ by RA status, and adipokine concentrations were unrelated to atherosclerosis. This study suggests that leptin and adiponectin inhibition may not alter overall cardiovascular risk and disease in RA.

Dessein, Patrick H.; Norton, Gavin R.; Badenhorst, Margaret; Woodiwiss, Angela J.; Solomon, Ahmed

2013-01-01

323

Serum Adiponectin Level in Diabetic Patients with and without Helicobacter pylori Infection: Is There Any Difference?  

PubMed Central

Background. Increased insulin resistance is an extragastrointestinal manifestation of Helicobacter pylori (HP) infection. HP changes the level of inflammatory markers and cytokines and changes the adipocyte function by altering the adiponectin level. Given the high prevalence of HP and diabetes in our society, we evaluated the association between HP and serum adiponectin level. In this cross-sectional study, 211 diabetic patients under treatment other than insulin were studied. These patients were divided into two groups of HP+ and HP? based on their HP IgG antibody serology and their blood adiponectin levels were measured. Data was analyzed using independent t-test, Chi-square test, and Fisher's exact test. Results. Seventy-two patients with an average age of 51.56 ± 8.34 years were HP? and 139 patients with an average age of 50.35 ± 9.01 years were HP+. The mean serum adiponectin level in HP? and HP+ groups was 4.54 ± 5.43 and 5.64 ± 3.88?ng/mL, respectively. Insulin resistance degree was significantly higher in HP+ group (HP? = 3.160 ± 3.327 versus HP+ = 4.484 ± 3.781, P = 0.013) but no significant difference was found between the mean serum adiponectin level in HP? and HP+ groups (P = 0.140). Conclusions. Although the insulin resistance degree was significantly higher in HP+ diabetic patients, no significant relationship was found between HP infection and serum levels of adiponectin.

Effatpanah, Marzieh

2014-01-01

324

Adiponectin is required for enhancement of CCL2 expression in adipose tissue during Listeria monocytogenes infection.  

PubMed

Obesity is an important background of metabolic syndrome progression. Our previous study demonstrated that chemokine CCL2 expression was suppressed in liver of obese mice that were highly susceptible to Listeria monocytogenes infection. We investigated the role of adiponectin in CCL2 expression in obese mice after L. monocytogenes infection. When leptin-deficient obese ob/ob mice were infected intraperitoneally with L. monocytogenes, the elimination of bacteria from spleen, liver, mesenteric lymph nodes and adipose tissue was inhibited in ob/ob mice compared with their heterozygote littermates, ob/? mice. CCL2 expression in the adipose tissue of ob/? mice was enhanced by L. monocytogenes infection, different from ob/ob mice. Similarly, adiponectin expression was not observed in the adipose tissue of ob/ob mice. When mouse adipocyte 3T3-F442A-derived adipocytes were infected with L. monocytogenes, CCL2 expression was transiently up-regulated, following up-regulation of adiponectin expression. Up-regulation of CCL2 in adipocytes by L. monocytogenes infection was suppressed by knocked-down of adiponectin expression and supplementation of recombinant adiponectin partially recovered CCL2 expression. These results suggest that adiponectin is required for appropriate expression of CCL2 that is important for macrophage recruitment in response to bacterial infection. PMID:20045352

Sashinami, Hiroshi; Nakane, Akio

2010-05-01

325

Impact of a Single Intracoronary Administration of Adiponectin on Myocardial Ischemia/Reperfusion Injury in a Pig Model  

PubMed Central

Background Adiponectin plays a protective role in the development of obesity-linked disorders. We demonstrated that adiponectin exerts beneficial actions on acute ischemic injury in mice hearts. However, the effects of adiponectin treatment in large animals and its feasibility in clinical practice have not been investigated. This study investigated the effects of intracoronary administration of adiponectin on myocardial ischemia-reperfusion (I/R) injury in pigs. Methods and Results The left anterior descending coronary artery was occluded in pigs for 45 minutes and then reperfused for 24 hours. Recombinant adiponectin protein was given as a bolus intracoronary injection during ischemia. Cardiac functional parameters were measured by a manometer-tipped catheter. Apoptosis was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling staining. Tumor necrosis factor-? and interleukin-10 transcripts were analyzed by real-time polymerase chain reaction. Serum levels of derivatives of reactive oxygen metabolites and biological antioxidant potential were measured. Adiponectin protein was determined by immunohistochemical and Western blot analyses. Intracoronary administration of adiponectin protein led to a reduction in myocardial infarct size and improvement of left ventricular function in pigs after I/R. Injected adiponectin protein accumulated in the I/R-injured heart. Adiponectin treatment resulted in decreased tumor necrosis factor-? and increased interleukin-10 mRNA levels in the myocardium after I/R. Adiponectin-treated pigs had reduced apoptotic activity in the I/R-injured heart and showed increased biological antioxidant potential levels and decreased derivatives of reactive oxygen metabolite levels in the blood stream after I/R. Conclusions These data suggest that adiponectin protects against I/R injury in a preclinical pig model through its ability to suppress inflammation, apoptosis, and oxidative stress. Administration of intracoronary adiponectin could be a useful adjunctive therapy for acute myocardial infarction.

Kondo, Kazuhisa; Shibata, Rei; Unno, Kazumasa; Shimano, Masayuki; Ishii, Masakazu; Kito, Tetsutaro; Shintani, Satoshi; Walsh, Kenneth; Ouchi, Noriyuki; Murohara, Toyoaki

2013-01-01

326

Maternal Serum Adiponectin at 11–13 Weeks of Gestation in Pregnancies Delivering Small for Gestation Neonates  

Microsoft Academic Search

Objective: To investigate whether maternal serum levels of adiponectin in the first trimester are altered in pregnancies that subsequently deliver small for gestational age (SGA) neonates. Methods: Maternal serum adiponectin and pregnancy-associated plasma protein A (PAPP-A) were measured at 11–13 weeks’ gestation in 50 singleton normotensive pregnancies that delivered SGA neonates and 300 non-SGA controls. The median adiponectin and PAPP-A

Surabhi Nanda; Ranjit Akolekar; Danielle Sodre; Eirini Vaikousi; Kypros H. Nicolaides

2011-01-01

327

Paradoxically high adiponectin and the healthy obese phenotype in obese black and white 16-year-old girls.  

PubMed

Although adiponectin is correlated inversely with obesity, some obese adults without metabolic complications of obesity have paradoxically high adiponectin. Therefore, we assessed adiponectin risk factor relations in 133 obese 16-year-old school girls from a cohort of 448, focusing on paradoxically high adiponectin-risk in obesity and the healthy obese phenotype. Median adiponectin (11.9 mg/L) in nonobese girls (body mass index [BMI] < 24.6 kg/m²) was selected as a cutpoint to identify high adiponectin in obese girls. Of 90 black and 43 white obese girls (BMI ? 24.6), 25 black (28%) and 13 white (30%) girls had paradoxically high adiponectin (>11.9). The 38 obese girls with adiponectin >11.9 versus the 95 obese girls with adiponectin ?11.9 had higher median high-density lipoprotein (HDL) cholesterol (54 vs 46 mg/dL, P = 0.0007) and apolipoprotein A1 (ApoA1) (181 vs 164 mg/dL, P = 0.011) and had lower insulin (14 vs 20 uU/mL, P = 0.0006). In the 133 obese girls, through stepwise regression, the adiponectin category (>11.9, ? 11.9 mg/L) was a significant independent positive determinant of HDL cholesterol (partial r² = 8.4%, P = 0.001), ApoA1 (partial r² = 4.1%, P = 0.025), and it was associated inversely with fasting serum insulin (partial r² = 5.4%, P = 0.0074). By stepwise logistic regression in the 133 obese girls, the adiponectin category (high vs low) was a significant inverse explanatory variable for metabolic syndrome (odds ratio 0.20, 95% confidence intervals 0.04-0.95, P = 0.043). We conclude that paradoxically high adiponectin is associated with the healthy obese phenotype in obese adolescent black and white girls. PMID:20970753

Morrison, John A; Glueck, Charles J; Daniels, Stephen; Wang, Ping; Horn, Paul; Stroop, Davis

2010-11-01

328

Effects of sulfonylurea drugs on adiponectin production from 3T3-L1 adipocytes: Implication of different mechanism from pioglitazone  

Microsoft Academic Search

Adiponectin is a fat-derived cytokine with anti-diabetic and anti-atherogenic properties. In this study, effects of sulfonylureas (SUs) on adiponectin production and the action mechanism were evaluated using 3T3-L1 adipocytes. The cells were incubated with glimepiride, glibenclamide, gliclazide, pioglitazone, metformin and the medium only as the control. In the control, the adiponectin level evaluated as the production rate per 24h was

Yukiko Kanda; Masafumi Matsuda; Kazuhito Tawaramoto; Fumiko Kawasaki; Mitsuru Hashiramoto; Michihiro Matsuki; Kohei Kaku

2008-01-01

329

Serum adiponectin levels predict the effect of short-term dietary interventions on insulin sensitivity in humans  

Microsoft Academic Search

Aims\\/hypothesis  Fat-rich diets can acutely induce insulin resistance. Data from adiponectin knock-out mice suggest that this effect might be increased in the absence of adiponectin. In the present study we tested whether plasma adiponectin concentrations influence changes in insulin sensitivity induced by a short-term dietary intervention in humans.Methods  We analysed data from 27 healthy, non-obese men with normal glucose tolerance. These men

C. Thamer; M. Haap; O. Bachmann; T. zur Nieden; O. Tschritter; N. Stefan; A. Fritsche; S. Jacob; M. Stumvoll; H. Häring

2004-01-01

330

Structure characterization of the central repetitive domain of high molecular weight gluten proteins. II. Characterization in solution and in the dry state.  

PubMed Central

The structure of the central repetitive domain of high molecular weight HMW) wheat gluten proteins was characterized in solution and in the dry state using HMW proteins Bx6 and Bx7 and a subcloned, bacterially expressed part of the repetitive domain of HMW Dx5. Model studies of the HMW consensus peptides PGQGQQ and GYYPTSPQQ formed the basis for the data analysis (van Dijk AA et al., 1997, Protein Sci 6:637-648). In solution, the repetitive domain contained a continuous nonoverlapping series of both type I and type II II beta-turns at positions predicted from the model studies; type II beta-turns occurred at QPGQ and QQGY sequences and type I beta-turns at YPTS and SPQQ. The subcloned part of the HMW Dx5 repetitive domain sometimes migrated as two bands on SDS-PAGE; we present evidence that this may be caused by a single amino acid insertion that disturbs the regular structure of beta-turns. The type I beta-turns are lost when the protein is dried on a solid surface, probably by conversion to type II beta-turns. The homogeneous type II beta-turn distribution is compatible with the formation of a beta-spiral structure, which provides the protein with elastic properties. The beta-turns and thus the beta-spiral are stabilized by hydrogen bonds within and between turns. Reformation of this hydrogen bonding network after, e.g., mechanical disruption may be important for the elastic properties of gluten proteins.

Van Dijk, A. A.; De Boef, E.; Bekkers, A.; Van Wijk, L. L.; Van Swieten, E.; Hamer, R. J.; Robillard, G. T.

1997-01-01

331

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

332

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.

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

2007-01-01

333

Effects of sulfonylurea drugs on adiponectin production from 3T3-L1 adipocytes: implication of different mechanism from pioglitazone.  

PubMed

Adiponectin is a fat-derived cytokine with anti-diabetic and anti-atherogenic properties. In this study, effects of sulfonylureas (SUs) on adiponectin production and the action mechanism were evaluated using 3T3-L1 adipocytes. The cells were incubated with glimepiride, glibenclamide, gliclazide, pioglitazone, metformin and the medium only as the control. In the control, the adiponectin level evaluated as the production rate per 24 h was not changed, while pioglitazone significantly increased the adiponectin level. SUs also increased the adiponectin level, but metformin failed to show any increase in adiponectin production. SUs induced adiponectin gene expression as well as pioglitazone. Pioglitazone significantly increased adipogenesis, but glimepiride did not. The aP2 gene expression was increased by pioglitazone, but not by glimepiride. Forskolin, a protein kinase A stimulator, reduced the adiponectin production stimulated by glimepiride but not by pioglitazone. These observations strongly suggest that SUs stimulate the adiponectin production through a different mechanism from pioglitazone, namely an interaction with protein kinase A activity. The significance of the extrapancreatic action of SUs observed in this study should be further evaluated in the clinical field. PMID:18455831

Kanda, Yukiko; Matsuda, Masafumi; Tawaramoto, Kazuhito; Kawasaki, Fumiko; Hashiramoto, Mitsuru; Matsuki, Michihiro; Kaku, Kohei

2008-07-01

334

Adiponectin Activates Adenosine Monophosphate-Activated Protein Kinase and Decreases Luteinizing Hormone Secretion in L?T2 Gonadotropes  

PubMed Central

Metabolic dysregulation is associated with reproductive disorders, but the underlying mechanisms are not clearly understood. Adiponectin is an adipocyte-derived secretory factor that improves insulin sensitivity. Results from animal models indicate that overexpression of adiponectin impairs female fertility. We hypothesized that adiponectin regulates reproduction by altering the hypothalamic-pituitary axis. Mouse L?T2 immortalized gonadotrope cells express both adiponectin receptors 1 and 2. Adiponectin increases phosphorylation of AMP-activated protein kinase (AMPK), a downstream target of adiponectin receptors, and reduces basal and GnRH-stimulated LH secretion, acutely. The repression of LH secretion can be mimicked by 5-aminoimidazole-4-carboxamide-1-?-riboside, an AMP analog, suggesting the involvement of AMPK. A dominant-negative AMPK mutant or compound C, a selective AMPK inhibitor, potentiates basal LH secretion and abolishes the inhibitory effect of adiponectin. Chronic activation of AMPK by 5-aminoimidazole-4-carboxamide-1-?-riboside decreases cellular LH levels, and expression of dominant-negative AMPK increases cellular LH levels, suggesting a second effect of AMPK to regulate LH synthesis. Lastly, intravenous injection of an adenovirus expressing adiponectin into male mice reduces serum LH levels without changing FSH levels. In conclusion, our results suggest that adiponectin decreases LH secretion in pituitary gonadotropes in an AMPK-dependent manner.

Lu, Min; Tang, Qingbo; Olefsky, Jerrold M.; Mellon, Pamela L.; Webster, Nicholas J. G.

2008-01-01

335

Association of adiponectin with cardiovascular events in diabetic and non-diabetic hemodialysis patients.  

PubMed

Adiponectin is a novel collagen-like protein synthesized by white adipose tissue. Its levels are decreased in obesity, type-2 diabetes and insulin-resistant states, and are increased in chronic renal failure. It has anti-inflammatory and anti-atherogenic properties. This study was planned to evaluate the levels of adiponectin in uremic patients with and without diabetes and to find any relationship between adiponectin levels and some cardiovascular risk factors, and to determine the possible predictive value of adiponectin for cardiovascular complications (CVC). The study included 100 subjects, 20 of them were healthy subjects and served as the control group (group I), 40 were uremic non-diabetic patients (group II) (half of them were without CVC, group IIA, and the other half were patients with CVC, group IIB) and, lastly, 40 uremic diabetic patients (group III) (half of them were without CVC, group IIIA, and the other half were patients with CVC, group IIIB). All subjects were subjected to complete clinical examination, including determination of mean arterial blood pressure (MABP), body mass index (BMI), waist to hip ratio, routine laboratory investigations, fasting plasma glucose, fasting plasma insulin, lipid profile (cholesterol, TG, LDL, HDL), determination of insulin resistance by homeostasis model assessment index (HOMA-IR) and estimation of serum levels of adiponectin. There was a significant increase in serum adiponectin levels in all the uremic patients (group II and group III) when compared with the control (group I) group, P <0.01; also, serum adiponectin levels were significantly decreased in uremic diabetic patients (group III) when compared with uremic non-diabetic patients (group II), P <0.01; but this was still higher than in the controls. The patients with CVC, whether uremic non-diabetic (group IIB) or uremic diabetic (group IIIB), had a significant decrease in serum adiponectin levels when compared with patients without CVC (group IIA and group IIIA), P <0.01. Serum adiponectin has a significant positive correlation with HDL and a significant negative correlation with MABP, BMI, plasma insulin, HOMA-IR, LDL, TG and cholesterol in all the patients. Therefore, it can be concluded that adiponectin levels in uremic patients, whether diabetic or non-diabetic, may be a good indicator of cardiovascular disease risk. PMID:22805386

Elokely, Amir; Shoukry, Amira; Ghonemy, Tarek A; Atia, Mrwan; Amr, Ghada

2012-07-01

336

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

337

Guava leaf extracts alleviate fatty liver via expression of adiponectin receptors in SHRSP.Z-Leprfa/Izm rats  

PubMed Central

Background In recent years, the number of people with metabolic syndrome has continued to rise because of changing eating habits, and accompanying hepatic steatosis patients have also increased. This study examined the effect of guava leaf extract on liver fat accumulation using SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP/ZF), which are a metabolic syndrome model animal. Method Seven-week-old male SHRSP/ZF rats were divided into two groups, a control group and a guava leaf extract (GLE) group. We gave 2 g/kg/day GLE or water by forced administration for 6 weeks. After the experimental period, the rats were sacrificed and organ weight, hepatic lipids, serum aminotransferase and liver pathology were examined. To search for a possible mechanism, we examined the changes of key enzyme and transcriptional factors involved in hepatic fatty acid beta-oxidation. Results The triglyceride content of the liver significantly decreased in the GLE group in comparison with the control group, and decreased fat-drop formation in the liver tissue graft in the GLE group was observed. In addition, the improvement of liver organization impairments with fat accumulation restriction was suggested because blood AST and ALT in the GLE group significantly decreased. Furthermore, it was supposed that the activity of AMPK and PPAR? significantly increased in the GLE group via the increase of adiponectin receptors. These were thought to be associated with the decrease of the triglyceride content in the liver because AMPK and PPAR? in liver tissue control energy metabolism or lipid composition. On the other hand, insulin resistance was suggested to have improved by the fatty liver improvement in GLE. Conclusion Our results indicate that administration of GLE may have preventive effects of hepatic accumulation and ameliorated hepatic insulin resistance by enhancing the adiponectin beta-oxidation system. Guava leaf may be potentially useful for hepatic steatosis without the side effects of long-term treatments.

2012-01-01

338

Quantitative Determination of High Molecular Weight Glutenin Subunits of Hard Red Spring Wheat by SDS-PAGE. I. Quantitative Effects of Total Amounts on Breadmaking Quality Characteristics 1  

Microsoft Academic Search

Cereal Chem. 74(6):781-785 Thirteen hard red spring wheat genotypes in which seven genotypes had the same high molecular weight (HMW) glutenin subunits (2*, 7+9, 5+10) were compared for their physical-chemical and breadmaking prop- erties. These samples were categorized into three groups based on their dough mixing and baking performances as follows: the strong dough (SD) group (six genotypes), characterized by

Dong Yin Huang; Khalil Khan

1997-01-01

339

Effects of different molecular weight fractions of dissolved organic matter on the growth of bacteria, algae and protozoa from a highly humic lake  

Microsoft Academic Search

Effects of different molecular size fractions (< 1000 MW, < 10 000 MW, < 100 000 MW and <0.1 µm) of dissolved organic matter\\u000a (DOM) on the growth of bacteria, algae and protozoa from a highly humic lake were investigated. DOM from catchment drainage\\u000a water as well as from the lake consisted mostly (59–63%) of high molecular weight (HMW) compounds

T. Tulonen; K. Salonen; L. Arvola

1992-01-01

340

Niacin Increases Adiponectin and Decreases Adipose Tissue Inflammation in High Fat Diet-Fed Mice  

PubMed Central

Aims To determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. Materials and Methods Male C57BL/6 mice were placed on a control or high-fat diet (HFD) and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2?/? (niacin receptor?/?) mice. Results Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2?/? mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPAR? C/EBP? or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription) in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-L?, or DsbA-L (key ER chaperones involved in adiponectin production and secretion). However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1? in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice. Conclusions Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expression in a niacin receptor-dependent manner.

Wanders, Desiree; Graff, Emily C.; White, B. Douglas; Judd, Robert L.

2013-01-01

341

Plasma adiponectin: A contributing factor for cardiac changes in visceral obesity-associated hypertension.  

PubMed

Abstract This study has been designed to evaluate the impact of adiponectin levels on left ventricular geometry and function in visceral obesity-associated hypertension. 94 consecutive subjects, 53 of them were hypertensives and 41 normotensives with age ? 65 years, subgrouped according to the presence or absence of visceral obesity, were studied. Total adiponectin levels were measured by a validated competitive radioimmunoassay. Left ventricular telediastolic internal diameter, interventricular septum, posterior wall thickness, total left ventricular mass (LVM) and normalized for height to the 2.7 power (LVM/h(2.7)), relative wall thickness, left ventricular ejection fraction by echocardiography and isovolumic relaxation time, E/A ratio and deceleration time of E velocity, by pulsed-wave Doppler, were calculated. Plasma adiponectin levels were significantly lower in visceral obesity-associated hypertensives than lean hypertensives (p < 0.001) and in lean normotensives (p < 0.001). LVM and LVM/h(2.7) were significantly (p < 0.05) higher in both hypertensive groups, and in visceral obesity-associated normotensives in comparison with lean normotensives. Adiponectin levels correlated inversely with LVM/h(2.7) but only in normotensives (adjusted R squared 0.77, p < 0.0001) and hypertensives (0.67, p < 0.0001) subjects with visceral obesity. Multiple regression analysis indicated that adiponectin levels remain significantly associated (p < 0.001) to LVM/h(2.7) also when adjusted for age, gender, body mass index, waist to hip ratio and mean blood pressure. Our data suggest an important role of adiponectin in increased LVM/h(2.7) in visceral obesity-associated normotensive and hypertensive subjects. In this last group, adiponectin, more than blood pressure, may be able to explain the development of cardiac damage. PMID:24011171

Di Chiara, Tiziana; Licata, Anna; Argano, Christiano; Duro, Giovanni; Corrao, Salvatore; Scaglione, Rosario

2014-06-01

342

Serum Adiponectin and Type 2 Diabetes: A 6-Year Follow-Up Cohort Study  

PubMed Central

Background Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women. Methods A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used. Results Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders. Conclusion A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.

Ahn, Chul Woo; Park, Jong Suk; Park, Chang Gyu; Kim, Hyon-Suk; Lee, Sang-Hak; Park, Sungha; Lee, Myoungsook; Lee, Chang Beom; Park, Hye Soon; Kimm, Heejin; Choi, Sung Hee; Sung, Jidong; Oh, Seungjoon; Joung, Hyojee; Kim, Sung Rae; Youn, Ho-Joong; Kim, Sun Mi; Lee, Hong Soo; Mok, Yejin; Choi, Eunmi; Yun, Young Duk; Baek, Soo-Jin; Jo, Jaeseong; Huh, Kap Bum

2013-01-01

343

Adiponectin, an Adipocyte-Derived Plasma Protein, Inhibits Endothelial NF-kB Signaling Through a cAMP-Dependent Pathway  

Microsoft Academic Search

Background—Among the many adipocyte-derived endocrine factors, we found an adipocyte-derived plasma protein, adiponectin, that was decreased in obesity. We recently demonstrated that adiponectin inhibited tumor necrosis factor- a (TNF-a)-induced expression of endothelial adhesion molecules and that plasma adiponectin level was reduced in patients with coronary artery disease (Circulation. 1999;100:2473-2476). However, the intracellular signal by which adiponectin suppressed adhesion molecule expression

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

344

Postoperative plasma interleukin-6 in patients with renal cancer correlates with C-reactive protein but not with total fibrinogen or with high molecular weight fibrinogen fraction.  

PubMed

The concentration of fibrinogen (Fb) and its fractions, the levels of interleukin-6 (I1-6), C-reactive protein (CRP), and immunoglobulin G (IgG) were determined in 38 patients operated on because of renal cancer. The increased Fb and I1-6 concentrations were found in approximately one-half of the patients with malignancy. The relations among the high molecular weight (HMW) and two low molecular weight (LMW and LMW') fibrinogen fractions in these patients before surgery did not differ from the corresponding relations in normal subjects. The levels of all (except IgG) compounds studied increased after surgery and the peak of I1-6 was observed on the first postoperative day but that of CRP on the third day. The concentrations of total Fb and of its HMW fraction were the highest also on the third postoperative day and this was in contrast with the decline of low molecular weight fractions at the same time. These variations of estimated variables can be regarded as being relevant to the acute phase response. We have noted a correlation between the maximal concentrations of I1-6 and CRP, but not between the corresponding concentrations of Il-6 and total Fb or HMW Fb; this may suggest that the concentration of Fb is also under the control of a factor other than I1-6. PMID:9645918

Adler, G; Eichman, W; Szczepanski, M; Targonska, I; Jasinska, A

1998-03-01

345

Adiponectin Is Related to Carotid Artery Plaque and a Predictor of Cardiovascular Outcome in a Cohort of Non-Diabetic Peritoneal Dialysis Patients  

Microsoft Academic Search

Aims: Adiponectin is an adipocytokine with antiatherogenic and anti-inflammatory properties. We investigated associations between circulating adiponectin, inflammation and cardiovascular disease in peritoneal dialysis patients. Methods: A prospective study was performed in 59 non-diabetic patients. The concentrations of serum adiponectin, biochemical data and ultrasound of carotid artery were measured at enrollment. The patients were followed up to 39 months mainly for

Zan-zhe Yu; Zhao-hui Ni; Le-yi Gu; Ai-wu Lin; Wei Fang; Qiang Yao; Bengt Lindholm; Jia-qi Qian

2008-01-01

346

Adiponectin and interleukin-6 levels in insulin-treated diabetic rats with experimental periodontitis.  

PubMed

The aim of the study was to compare the serum levels of adiponectin and interleukin-6 (IL-6) in insulin-treated diabetic rats with or without periodontitis. Forty male Wistar rats were randomly divided into 2 groups (20 rats each): a) insulin-treated diabetic group (control, DI) and b) insulin-treated diabetic periodontitis group (test, DIP). Diabetes was induced, and insulin treatment was initiated on day 5. On day 16, periodontitis was induced in the DIP group. All rats were euthanized on day 77. Adiponectin and IL-6 were assessed on days 16 and 77. At the end of the experiment, 14 and 11 rats survived in the DI and DIP groups, respectively. Adiponectin levels were statistically significantly higher at the end of the experiment compared with levels on day 16 in the periodontitis group (p < 0.05), but not in the control group. At the end of the experiment, adiponectin levels were statistically significantly higher in the periodontitis group compared with the control group (p < 0.05). Within-group and between-group comparisons of IL-6 levels showed no statistically significant difference. In conclusion, serum adiponectin was increased in insulin-treated diabetic rats with periodontitis in comparison with insulin-treated diabetic rats, while IL-6 levels did not differ between groups. PMID:22344341

Xynogala, Ioanna; Pepelassi, Eudoxie; Perrea, Despina; Agrogiannis, George; Pantopoulou, Alkistis; Patsouris, Efstratios; Vrotsos, Ioannis

2012-01-01

347

Perivascular adipose tissue-derived adiponectin activates BKCa channels to induce anticontractile responses  

PubMed Central

This study aims to identify the potential mechanisms by which perivascular adipose tissue (PVAT) reduces tone in small arteries. Small mesenteric arteries from wild-type and large-conductance Ca2+-activated K+ (BKCa) channel knockout mice were mounted on a wire myograph in the presence and absence of PVAT, and contractile responses to norepinephrine were assessed. Electrophysiology studies were performed in isolated vessels to measure changes in membrane potential produced by adiponectin. Contractile responses from wild-type mouse small arteries were significantly reduced in the presence of PVAT. This was not observed in the presence of a BKCa channel inhibitor or with nitric oxide synthase (NOS) inhibition or in BKCa or adiponectin knockout mice. Solution transfer experiments demonstrated the presence of an anticontractile factor released from PVAT. Adiponectin-induced vasorelaxation and hyperpolarization in wild-type arteries were not evident in the absence of or after inhibition of BKCa channels. PVAT from BKCa or adiponectin knockout mice failed to elicit an anticontractile response in wild-type arteries. PVAT releases adiponectin, which is an anticontractile factor. Its effect on vascular tone is mediated by activation of BKCa channels on vascular smooth muscle cells and adipocytes and by endothelial mechanisms.

Withers, Sarah B.; Yao, Zhihong; Werner, Matthias E.; Edwards, Gill; Weston, Arthur H.; Heagerty, Anthony M.

2013-01-01

348

An FGF21-Adiponectin-Ceramide Axis Controls Energy Expenditure and Insulin Action in Mice  

PubMed Central

SUMMARY FGF21, a member of the fibroblast growth factor (FGF) superfamily has recently emerged as a novel regulator of metabolism and energy utilization. However, the exact mechanism(s) whereby FGF21 mediates its actions have not been elucidated. There is considerable evidence that insulin resistance may arise from aberrant accumulation of intracellular lipids in insulin responsive tissues due to lipotoxicity. In particular the sphingolipid ceramide has been implicated in this process. Here, we show that FGF21 rapidly and robustly stimulates adiponectin secretion in rodents, while diminishing accumulation of ceramides in obese animals. Importantly, adiponectin knockout mice are refractory to changes in energy expenditure and ceramide-lowering effects evoked by FGF21 administration. Moreover, FGF21 lowers blood glucose levels and enhances insulin sensitivity in diabetic Lepob/ob mice and diet-induced obese (DIO) mice, only when adiponectin is functionally present. Collectively, these data suggest that FGF21 is a potent regulator of adiponectin secretion, and that FGF21 critically depends on adiponectin to exert its glycemic and insulin sensitizing effects.

Holland, William L.; Adams, Andrew C.; Brozinick, Joseph T.; Bui, Hai H.; Miyauchi, Yukiko; Kusminski, Christine M.; Bauer, Steven M.; Wade, Mark; Singhal, Esha; Cheng, Christine C.; Volk, Katherine; Kuo, Ming-Shang; Gordillo, Ruth; Kharitonenkov, Alexei; Scherer, Philipp E.

2013-01-01

349

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.

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

2014-01-01

350

The Association between Adiponectin/Leptin Ratio and Diabetes Type: The SEARCH for Diabetes in Youth Study  

PubMed Central

We tested the association of adiponectin/leptin ratio (ALR) with diabetes type after adjusting for multiple factors in 1,156 youth with newly diagnosed diabetes in the SEARCH study. Although ALR is associated with diabetes type in youth, it is due to differences in adiponectin, but not leptin levels.

Maahs, David M.; Hamman, Richard F.; D'Agostino, Ralph; Dolan, Lawrence M.; Imperatore, Guiseppina; Lawrence, Jean M.; Marcovina, Santica M.; Mayer-Davis, Elizabeth J.; Pihoker, Catherine; Dabelea, Dana

2009-01-01

351

Adiponectin and arterial stiffness in youth with type 1 diabetes: the SEARCH for diabetes in youth study.  

PubMed

Persons with type 1 diabetes are at increased risk of developing vascular disease. Adiponectin concentrations may play an intermediate role in this process. We sought to determine whether adiponectin is correlated with vascular stiffness in adolescents with type 1 diabetes. Plasma adiponectin, pulse wave velocity (PWV), augmentation index (AIx-75), and brachial distensibility (BrachD) were collected in 225 adolescents. Outcomes were evaluated by sex, and regression models were used to determine whether adiponectin was an independent determinant of arterial stiffness. Males had lower adiponectin levels and stiffer vessels (lower BrachD, p < 0.01) than females. Unadjusted correlations revealed that adiponectin was correlated with BrachD (p < 0.01) but not PWV and AIx-75. After adjustment, adiponectin was not a significant predictor of BrachD. The most consistent predictors of increased stiffness were age, male sex, blood pressure, obesity, and total cholesterol (p < 0.05). Adiponectin's contributions to arterial stiffness appear to be masked by other cardiovascular risk factors in persons with type 1 diabetes. PMID:23155699

Shah, Amy S; Dolan, Lawrence M; Lauer, Abigail; Davis, Cralen; Dabelea, Dana; Daniels, Stephen R; Hamman, Richard F; Marcovina, Santica; Wadwa, R Paul; Urbina, Elaine M

2012-01-01

352

Genetic variation in adiponectin (ADIPOQ) and the type 1 receptor (ADIPOR1), obesity and prostate cancer in African Americans  

Microsoft Academic Search

Adiponectin is a protein derived from adipose tissue suspected to have an important role in prostate carcinogenesis. Variants in the adiponectin gene (ADIPOQ) and its type 1 receptor (ADIPOR1) have been recently linked to risk of both breast and colorectal cancer. Therefore, we set out to examine the relationship between polymorphisms in these genes, obesity and prostate cancer in study

J L Beebe-Dimmer; K A Zuhlke; A M Ray; E M Lange; K A Cooney

2010-01-01

353

Adiponectin as novel regulator of cell proliferation in human glioblastoma.  

PubMed

Adiponectin (Acrp30) is an adipocyte-secreted hormone with pleiotropic metabolic effects, whose reduced levels were related to development and progression of several malignancies. We looked at the presence of Acrp30 receptors in human glioblastomas (GBM), hypothesizing a role for Acrp30 also in this untreatable cancer. Here we demonstrate that human GBM express Acrp30 receptors (AdipoR1 and AdipoR2), which are often co-expressed in GBM samples (70% of the analyzed tumors). To investigate the effects of Acrp30 on GBM growth, we used human GBM cell lines U87-MG and U251, expressing both AdipoR1 and AdipoR2 receptors. In these cells, Acrp30 treatment inhibits DNA synthesis and cell proliferation rate, inducing arrest in G1 phase of the cell cycle. These effects were correlated to a sustained activation of ERK1/2 and Akt kinases, upon Acrp30 treatment. Our results suggest that Acrp30 may represent a novel endogenous negative regulator of GBM cell proliferation, to be evaluated for the possible development of novel pharmacological approaches. J. Cell. Physiol. 229: 1444-1454, 2014. © 2014 Wiley Periodicals, Inc. PMID:24648185

Porcile, Carola; Di Zazzo, Erika; Monaco, Maria Ludovica; D'Angelo, Giorgia; Passarella, Daniela; Russo, Claudio; Di Costanzo, Alfonso; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adriana; Zona, Gianluigi; Barbieri, Federica; Oriani, Giovannangelo; Moncharmont, Bruno; Florio, Tullio; Daniele, Aurora

2014-10-01

354

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.

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

355

Adiponectin deficiency exacerbates age-related hearing impairment.  

PubMed

Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI. PMID:24763046

Tanigawa, T; Shibata, R; Ouchi, N; Kondo, K; Ishii, M; Katahira, N; Kambara, T; Inoue, Y; Takahashi, R; Ikeda, N; Kihara, S; Ueda, H; Murohara, T

2014-01-01

356

Adiponectin Deficiency Increases Allergic Airway Inflammation and Pulmonary Vascular Remodeling  

PubMed Central

Obesity is associated with an increased incidence and severity of asthma, as well as other lung disorders, such as pulmonary hypertension. Adiponectin (APN), an antiinf