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Sample records for weight hmw adiponectin

  1. Low-molecular-weight adiponectin is more closely associated with disease activity of rheumatoid arthritis than other adiponectin multimeric forms.

    PubMed

    Li, Ping; Yang, Li; Ma, Cui-Li; Liu, Bo; Zhang, Xin; Ding, Rui; Bi, Li-qi

    2015-06-01

    Adiponectin is divided into high-molecular-weight (HMW), medium-molecular-weight (MMW), and low-molecular-weight (LMW) forms. These forms differ not only in the number of adiponectin molecules but also in their biological activity. There are conflicting findings regarding the role of adiponectin in rheumatoid arthritis (RA). Moreover, few reports have described the relationships between serum adiponectin multimers levels and RA. Therefore, we examined the association of total adiponectin and its multimers with RA. Two study groups were examined: 180 recently diagnosed untreated RA patients with disease duration less than 1 year (RA group) and 160 age- and sex-matched control subjects (control group). RA-related factors, blood pressure, body mass index, glucose, complete lipid profile, and adiponectin multimers were measured. The levels of total adiponectin and each multimer of adiponectin were significantly lower in the RA than in the control (P < 0.01). Serum levels of total, HMW, MMW, and LMW were positively correlated with triglycerides levels and negatively correlated with the Disease Activity Score for 28 joints (DAS28). Multivariate regression analysis showed that total, HMW, and MMW adiponectin were independently associated with serum triglycerides level. LMW adiponectin was independently correlated with serum triglycerides level and DAS28. The decreased LMW adiponectin levels may be associated with disease activity of RA.

  2. Adiponectin induces NF-kappaB activation that leads to suppression of cytokine-induced NF-kappaB activation in vascular endothelial cells: globular adiponectin vs. high molecular weight adiponectin.

    PubMed

    Tomizawa, Atsuko; Hattori, Yoshiyuki; Kasai, Kikuo; Nakano, Yasuko

    2008-06-01

    Adiponectin circulates in plasma as various isoforms. However, the biological activity of each isoform has not been firmly established. High molecular weight (HMW) adiponectin may be the active form of adiponectin, while a proteolytic cleavage product of adiponectin, known as globular adiponectin (gAd), has recently been shown to activate vascular endothelial cells. We compared HMW adiponectin with gAd to investigate whether they could activate nuclear factor kappa B (NF-kappaB) and suppress cytokine-induced NF-kappaB activation in vascular endothelial cells. HMW adiponectin was found to activate NF-kB modestly compared to the activation observed with gAd. HMW adiponectin requires a shorter incubation period to demonstrate inhibition against tumour necrosis factor alpha (TNFalpha)-induced NF-kappaB activation, compared with gAd. gAd strongly activates NF-kappaB, thereby inducing the expression of various pro-inflammatory and adhesion molecule genes, and requires a longer incubation period to show inhibition against cytokine-induced NF-kappaB activation. Thus, HMW adiponectin might function to protect against inflammatory stimuli, while cleavage of adiponectin at inflammatory sites might enhance the inflammatory process.

  3. High-molecular-weight adiponectin does not predict cardiovascular events in patients with type 2 diabetes.

    PubMed

    Krzyzanowska, Katarzyna; Aso, Yoshimasa; Mittermayer, Friedrich; Inukai, Toshihiko; Brix, Johanna; Schernthaner, Guntram

    2009-04-01

    Low circulating high-molecular-weight (HMW) adiponectin might be associated with increased cardiovascular risk. This study aimed to investigate the relationship between HMW adiponectin and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) with an adverse cardiovascular risk profile. The investigation took place in a specialized outpatient clinic for metabolic diseases and included 147 patients with T2DM following a cross-sectional and a prospective study protocol. Ninety patients had macrovascular disease at baseline defined as preexisting coronary artery disease, previous stroke, or peripheral artery disease. HMW adiponectin measured by enzyme-linked immunosorbent assay (Fujirebio, Tokyo, Japan) and routine clinical parameters were determined in all patients at baseline. The occurrence of new cardiovascular events (myocardial infarction, stroke, and all-cause mortality) during the follow-up period was evaluated. No significant correlations between traditional cardiovascular risk markers and HMW adiponectin could be detected. HMW adiponectin did not differ between subjects with and without macrovascular disease at baseline (3.5 [interquartile range [IQR]: 2.2-5.7] mg/L vs 4.0 [IQR: 2.5-7.1] mg/L). During a follow-up of 19.3 (IQR: 16-25) months, 61 endpoints (41 myocardial infarctions, 10 strokes, and 10 deaths) were observed. A 1-standard-deviation increment of log-transformed HMW adiponectin was not significantly associated with the occurrence of cardiovascular events (Adjusted hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.58-1.54; P = 0.835). In conclusion, HMW adiponectin was not related to present macrovascular disease and is not associated with future cardiovascular events in high-risk patients with T2DM. It is unlikely that HMW adiponectin has significant vasoprotective effects in these patients.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25056918

  5. C-reactive protein inhibits high-molecular-weight adiponectin expression in 3T3-L1 adipocytes via PI3K/Akt pathway.

    PubMed

    Liu, Yuanxin; Liu, Cuiping; Jiang, Chao; Wang, Su; Yang, Qichao; Jiang, Dan; Yuan, Guoyue

    2016-03-25

    Adiponectin, an adipose-specific protein hormone, is secreted from white adipose tissue and involved in glucose and lipid metabolism. It is assembled into low-molecular-weight trimer (LMW), middle-molecular-weight hexameric (MMW) and high-molecular-weight (HMW), among which HMW exhibits higher activity. In this study, we proved that C-reactive protein (CRP), an inflammatory marker, inhibited adiponectin expression, especially HMW in time-and dose-dependent manners. Furthermore, CRP decreased the HMW/total adiponectin ration and reduced adiponectin assembly by increasing ERp44, and decreasing Ero1-α and DsbA-L. CRP activated pAkt, the downstream of PI3K. Inhibition of PI3K or pAkt abolished the effect of CRP. Our study suggested that CRP decreased adiponectin expression and multimerization, while CRP-induced decline in adiponectin might be mediated through the PI3K/Akt pathway.

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

    PubMed Central

    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

    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. PMID:20508194

  7. Association of Anthropometric and Bioelectrical Impedance Analysis Measures of Adiposity with High Molecular Weight Adiponectin Concentration

    PubMed Central

    Zeng, Wei-Fang; Li, Yan; Sheng, Chang-Sheng; Huang, Qi-Fang; Kang, Yuan-Yuan; Zhang, Lu; Wang, Shuai; Cheng, Yi-Bang; Li, Fei-Ka; Wang, Ji-Guang

    2016-01-01

    Objective To investigate the relationship between adiposity measures and plasma concentration of high molecular weight (HMW) adiponectin. Methods In a Chinese sample (n = 1081), we performed measurements of anthropometry and bioelectrical impedance analysis (BIA). We defined overweight and obesity as a body mass index between 24 and 27.4 kg/m² and ≥ 27.5 kg/m², respectively, and central obesity as a waist circumference ≥ 90 cm in men and ≥ 80 cm in women. Plasma HMW adiponectin concentration was measured by the ELISA method. Results Plasma HMW adiponectin concentration was significantly (P < 0.0001) higher in women (n = 677, 2.47 μg/mL) than men (n = 404, 1.58 μg/mL) and correlated with advancing age in men (r = 0.28) and women (r = 0.29). In adjusted analyses, it was lower in the presence of overweight (n = 159, 1.26 μg/mL in men and n = 227, 2.15μg/mL in women) and obesity (n = 60, 1.31 μg/mL and n = 82, 2.10 μg/mL, respectively) than normal weight subjects (n = 185, 2.07μg/mL and n = 368, 2.94 μg/mL, respectively) and in the presence of central obesity (n = 106, 1.28 μg/mL and n = 331, 2.12 μg/mL, respectively) than subjects with a normal waist circumference (n = 298, 1.74 μg/mL and n = 346, 2.74 μg/mL, respectively). In multiple regression analyses stratified for gender, adjusted for confounders and considered separately each of the adiposity measures, all adiposity measures were significantly (r -0.18 to -0.31, P < 0.001) associated with plasma HMW adiponectin concentration. However, in further stratified and adjusted regression analyses considered stepwise all adiposity measures, only waist-to-hip ratio was significantly (P < 0.05) associated with plasma HMW adiponectin concentration in men (r = -0.10) and women (r = -0.15). Conclusions Anthropometric measures of obesity, such as waist-to-hip ratio, but not BIA measures, are independently associated with plasma adiponectin concentration. PMID:27227680

  8. Relations of plasma total and high-molecular-weight adiponectin to new-onset heart failure in adults ≥65 years of age (from the Cardiovascular Health study).

    PubMed

    Karas, Maria G; Benkeser, David; Arnold, Alice M; Bartz, Traci M; Djousse, Luc; Mukamal, Kenneth J; Ix, Joachim H; Zieman, Susan J; Siscovick, David S; Tracy, Russell P; Mantzoros, Christos S; Gottdiener, John S; deFilippi, Christopher R; Kizer, Jorge R

    2014-01-15

    Adiponectin exhibits cardioprotective properties in experimental studies, but elevated levels have been linked to increased mortality in older adults and patients with chronic heart failure (HF). The adipokine's association with new-onset HF remains less well defined. The aim of this study was to investigate the associations of total and high-molecular weight (HMW) adiponectin with incident HF (n = 780) and, in a subset, echocardiographic parameters in a community-based cohort of adults aged ≥65 years. Total and HMW adiponectin were measured in 3,228 subjects without prevalent HF, atrial fibrillation or CVD. The relations of total and HMW adiponectin with HF were nonlinear, with significant associations observed only for concentrations greater than the median (12.4 and 6.2 mg/L, respectively). After adjustment for potential confounders, the hazard ratios per SD increment in total adiponectin were 0.93 (95% confidence interval 0.72 to 1.21) for concentrations less than the median and 1.25 (95% confidence interval 1.14 to 1.38) higher than the median. There was a suggestion of effect modification by body mass index, whereby the association appeared strongest in participants with lower body mass indexes. Consistent with the HF findings, higher adiponectin tended to be associated with left ventricular systolic dysfunction and left atrial enlargement. Results were similar for HMW adiponectin. In conclusion, total and HMW adiponectin showed comparable relations with incident HF in this older cohort, with a threshold effect of increasing risk occurring at their median concentrations. High levels of adiponectin may mark or mediate age-related processes that lead to HF in older adults.

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

    PubMed

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

    2012-08-01

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

  10. The influence of FGF2 high molecular weight (HMW) isoforms in the development of cardiac ischemia-reperfusion injury

    PubMed Central

    Liao, Siyun; Bodmer, Janet R.; Azhar, Mohamad; Newman, Gilbert; Coffin, J. Douglas; Doetschman, Thomas; Schultz, Jo El J.

    2010-01-01

    Fibroblast growth factor 2 (FGF2) consists of multiple protein isoforms (low [LMW] and high molecular weight [HMW]), which are localized to different cellular compartments, indicating unique biological activity. We previously showed that the LMW isoform is important in protecting the heart from myocardial dysfunction associated with ischemia-reperfusion (I/R) injury, but the roles of the HMW isoforms remain unknown. To elucidate the role of HMW isoforms in I/R and cardioprotection, hearts from novel mouse models,in which the murine FGF2 HMWs are knocked out (HMWKO) or the human FGF2 24 kDa HMW isoform is overexpressed (HMW Tg) and their wildtype (Wt) or non-transgenic (NTg) cohorts were subjected to an ex vivo work-performing heart model of I/R. There was a significant improvement in post-ischemic recovery of cardiac function in HMWKO hearts (76±5%, p<0.05) compared to Wt hearts (55±5%), with a corresponding decrease in HMW Tg function (line 20: 38±6% and line 28: 33±4%, p<0.05) compared to non-transgenic hearts (68±9%). FGF2 LMW isoform was secreted from Wt and HMWKO hearts during I/R, and a FGF receptor (FGFR) inhibitor, PD173074 caused a decrease in cardiac function when administered in I/R in Wt and FGF2 HMWKO hearts (p<0.05), indicating that FGFR is involved in FGF2 LMW isoform's biological effect in ischemia-reperfusion injury. Moreover, overexpression of HMW isoform reduced FGFR1 phosphorylation/activation with no further decrease in the phosphorylation state in the presence of the FGFR inhibitor. Overall, our data indicate that HMW isoforms have a detrimental role in the development of post-ischemic myocardial dysfunction. PMID:20116383

  11. Adiponectin Dysregulation and Insulin Resistance in Type 1 Diabetes

    PubMed Central

    Snell-Bergeon, Janet K.; Erickson, Christopher; Schauer, Irene E.; Bergman, Bryan C.; Rewers, Marian; Maahs, David M.

    2012-01-01

    Context: Type 1 diabetes (T1D) is associated with insulin resistance despite elevated levels of the insulin-sensitizing protein adiponectin. Whether the expected positive correlation between adiponectin and insulin sensitivity is preserved in a T1D population is unknown. Objective: We measured the correlation between total and high-molecular-weight (HMW) adiponectin and insulin sensitivity in T1D patients and nondiabetic controls and identified determinants of adiponectin levels in patients with T1D. Design and Participants: Fasting total and HMW adiponectin were measured in 86 subjects from the Coronary Artery Calcification in T1D (CACTI) cohort (39 T1D, 47 nondiabetic; age 45 ± 8 yr; 55% female). The association of adiponectin levels with insulin sensitivity was analyzed. Setting: The study was conducted at an academic research institute. Methods: Fasting total and HMW adiponectin were measured by RIA and ELISA, respectively. Insulin sensitivity was measured by a hyperinsulinemic-euglycemic clamp. Multivariate linear regression was used to identify determinants of adiponectin levels. Results: Adiponectin levels positively correlated with insulin sensitivity in both subject groups (total adiponectin, r = 0.33 P < 0.05 for T1D, r = 0.29 P < 0.05 controls), but insulin sensitivity was lower in T1D subjects at any given level of total or HMW adiponectin. Adiponectin levels were independently associated with age, gender, and trunk fat, but these variables did not account for increased adiponectin in patients with T1D. Conclusion: Adiponectin levels are positively correlated with insulin sensitivity in T1D patients. However, T1D patients have decreased insulin sensitivity compared with controls at every level of adiponectin, suggesting an important adaptive change of adiponectin set point. PMID:22278421

  12. Adiponectin Isoforms and Leptin Impact on Rheumatoid Adipose Mesenchymal Stem Cells Function

    PubMed Central

    Skalska, Urszula; Kontny, Ewa

    2016-01-01

    Adiponectin and leptin have recently emerged as potential risk factors in rheumatoid arthritis (RA) pathogenesis. In this study we evaluated the effects of adiponectin and leptin on immunomodulatory function of adipose mesenchymal stem cells (ASCs) derived from infrapatellar fat pad of RA patients. ASCs were stimulated with leptin, low molecular weight (LMW) and high/middle molecular weight (HMW/MMW) adiponectin isoforms. The secretory activity of ASCs and their effect on rheumatoid synovial fibroblasts (RA-FLS) and peripheral blood mononuclear cells (PBMCs) from healthy donors have been analysed. RA-ASCs secreted spontaneously TGFβ, IL-6, IL-1Ra, PGE2, IL-8, and VEGF. Secretion of all these factors was considerably upregulated by HMW/MMW adiponectin, but not by LMW adiponectin and leptin. Stimulation with HMW/MMW adiponectin partially abolished proproliferative effect of ASC-derived soluble factors on RA-FLS but did not affect IL-6 secretion in FLS cultures. ASCs pretreated with HMW/MMW adiponectin maintained their anti-inflammatory function towards PBMCs, which was manifested by moderate PBMCs proliferation inhibition and IL-10 secretion induction. We have proved that HMW/MMW adiponectin stimulates secretory potential of rheumatoid ASCs but does not exert strong impact on ASCs function towards RA-FLS and PBMCs. PMID:26681953

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

    PubMed

    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

    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

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

    PubMed

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

    2014-08-21

    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

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

    PubMed

    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

    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.

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

    PubMed

    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

    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

  17. Differential effects of leptin on adiponectin expression with weight gain versus obesity

    PubMed Central

    Singh, Prachi; Sharma, Pragya; Sahakyan, Karine R.; Davison, Diane E.; Sert-Kuniyoshi, Fatima H; Romero-Corral, Abel; Swain, James M.; Jensen, Michael D.; Lopez-Jimenez, Francisco; Kara, Tomas; Somers, Virend K.

    2015-01-01

    Background/Objective Adiponectin exerts beneficial effects by reducing inflammation, and improving lipid metabolism and insulin-sensitivity. Although adiponectin is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans. Methods/Results Forty four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8-weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8 ± 1.2 kg resulted in increased adiponectin (p=0.03) while weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (p=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, while a leptin-antagonist had opposite effects. To understand the role of leptin in established obesity, we compared adipose tissue samples obtained from normal weight versus obese subjects. We noted, first, that leptin activated cellular signaling pathways and increased adiponectin mRNA in adipose tissue from normal-weight participants, but did not do so in adipose tissue from obese participants; and second, that obese subjects had increased caveolin-1 expression, which attenuates leptin-dependent increases in adiponectin. Conclusions Modest weight gain in healthy individuals is associated with increases in adiponectin, which correlate positively with changes in leptin. In-vitro, leptin induces adiponectin expression which is attenuated by increased caveolin-1 expression. Additionally, adipose tissue from obese subjects shows increased caveolin-1 expression, and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin in obese subjects despite their

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

    PubMed

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

    2011-02-01

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

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

    PubMed

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

    2012-01-01

    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-5α reducible androgen 17β-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

  20. Influence of acute aerobic exercise on adiponectin oligomer concentrations in middle-aged abdominally obese men.

    PubMed

    Numao, Shigeharu; Katayama, Yasutomi; Hayashi, Yoichi; Matsuo, Tomoaki; Tanaka, Kiyoji

    2011-02-01

    Exercise intensity may induce changes in total adiponectin and adiponectin oligomer levels. However, the effects of acute aerobic exercise on total adiponectin and adiponectin oligomers in middle-aged abdominally obese men remain unknown. The purpose of this study was to investigate the influence of aerobic exercise intensity on changes in the concentrations of total adiponectin and adiponectin oligomers (high-molecular weight [HMW] and middle- plus low-molecular weight [MLMW] adiponectin), and the endocrine mechanisms involved in exercise-induced changes in adiponectin oligomer profiles in middle-aged abdominally obese men. Using a crossover design, 9 middle-aged abdominally obese men (age, 54.1 ± 2.4 years; body mass index, 27.9 ± 0.6 kg/m²) underwent 2 trials that consisted of 60 minutes of stationary cycle exercise at either moderate-intensity (ME) or high-intensity (HE) aerobic exercise (50% or 70% of peak oxygen uptake, respectively). Blood samples were collected to measure the concentrations of adiponectin oligomers, hormones (catecholamines, insulin, and growth hormone), metabolites (free fatty acid, glycerol, triglyceride, and glucose), and cytokines (interleukin-6 and tumor necrosis factor-α). After exercise, plasma catecholamine concentrations were higher during HE than during ME (P < .05). Total adiponectin concentration decreased at the end of HE (P < .05), but remained unchanged after ME. The HMW adiponectin concentration did not change at either intensity, whereas the MLMW concentration decreased at the end of HE (P < .05). The ratio of HMW to total adiponectin concentration increased significantly (P < .05), whereas the ratio of MLMW to total adiponectin concentration decreased significantly (P < .05), at the end of HE. The percentage changes in epinephrine concentration from baseline to the end of exercise were correlated with the percentage changes in total adiponectin concentration (r = -0.67, P < .05) and MLMW adiponectin concentration (r

  1. Lower levels of human milk adiponectin predict offspring weight for age: a study in a lean population of Filipinos.

    PubMed

    Anderson, Justine; McKinley, Kassielle; Onugha, Jason; Duazo, Paulita; Chernoff, Meytal; Quinn, Elizabeth A

    2016-10-01

    Prior studies have reported a significant, inverse association between adiponectin in human milk and offspring growth velocity. Less is known about this association in populations characterised by a loss of weight for age z-scores (WAZs) in early life. We investigated the association between maternal body composition and milk adiponectin in a sample of Filipino mothers. We then tested for an association between milk adiponectin and size for age in their infants. A total of 117 Filipino mothers nursing infants from 0 to 24 months were recruited from Cebu, Philippines. Anthropometrics, interviews and milk samples were collected and analysed using standard protocols. Mean milk adiponectin in this sample was 7.47 ± 5.75 ng mL(-1) . Mean infant WAZ and weight for length (WLZ) decreased with age. Maternal body composition was not associated with milk adiponectin content. Milk adiponectin had a significant, positive association with infant WAZ and WLZ. Prior reports have found an inverse association between milk adiponectin and infant WAZ. Here, we report that in lean populations with lower milk adiponectin, there is a positive association with infant WAZ, possibly reflecting pleiotropic biological functions of adiponectin for post-natal growth. This study increases the understanding of normal biological variation in milk adiponectin and the consequences of low levels of milk adiponectin for offspring growth.

  2. Major components of metabolic syndrome and adiponectin levels: a cross-sectional study

    PubMed Central

    2014-01-01

    Background Adiponectin is a major regulator of glucose and lipid homeostasis by its insulin sensitizer properties. Since decreased insulin sensitivity is linked to metabolic syndrome (MS), decreased adiponectin levels may be related to its development. The purpose of the study was to investigate the relationship between adiponectin levels and MS. Methods Firstly, we cross-sectionally examined subjects with or without MS submitted to an oral glucose tolerance test at Hospital de Clínicas de Porto Alegre (n = 172). A replication analysis was performed in subjects (n = 422) undergoing cardiac angiography at Hospital São Paulo. Subchronic inflammation (US-CRP), coagulation marker (fibrinogen), insulin sensitivity and resistance (Matsuda ISI and HOMA-IR) were estimated. Plasma total and high molecular weight (HMW) adiponectin were measured. Results Total and HMW adiponectin levels were lower in MS subjects (P < 0.05). Total adiponectin levels were lower in the presence of high waist circumference, low HDL-cholesterol and elevated triglyceride criteria in both samples and by elevated blood pressure and glucose criteria in Porto Alegre. HMW adiponectin levels were lower in the presence of low HDL-cholesterol, elevated triglycerides, and glucose criteria. Total adiponectin levels were positively related with HDL-cholesterol and ISI Matsuda, negatively related with waist circumference, glucose, triglycerides, HOMA-IR, and US-CRP and not related with blood pressure. While adjusting for sex and age, increased adiponectin levels remained associated with a reduced prevalence ratio for MS in both cohorts (P = 0.001). Conclusions Adiponectin levels decreased with increasing number of MS criteria, and it is in part determined by its relationship with HDL, triglycerides and abdominal adiposity. PMID:24568287

  3. Evaluation of body weight, insulin resistance, leptin and adiponectin levels in premenopausal women with hyperprolactinemia.

    PubMed

    Atmaca, Aysegul; Bilgici, Birsen; Ecemis, Gulcin Cengiz; Tuncel, Ozgur Korhan

    2013-12-01

    The effects of hyperprolactinemia on metabolic parameters are not clear and a few data evaluating adiponectin levels in prolactinoma and idiopathic hyperprolactinemia exist. The aim of this study was to evaluate the effects of hyperprolactinemia on body weight, insulin resistance, beta cell function, and leptin and adiponectin levels in premenopausal women with hyperprolactinemia. Forty premenopausal women with prolactinoma or idiopathic hyperprolactinemia were compared to 41 age-matched healthy premenopausal women with regard to body weight, body mass index, waist and hip circumferences, waist to hip ratio, fasting plasma glucose, insulin levels, insulin resistance measured by homeostasis model assessment (HOMA)-insulin resistance index, beta cell function measured by HOMA-β index, leptin and adiponectin levels. Plasma insulin levels and HOMA indexes (both insulin resistance and beta indexes) were significantly higher in hyperprolactinemic women. The other parameters were similar between both groups. There was a positive correlation between prolactin levels and fasting plasma glucose in hyperprolactinemic women. The results of this study showed that high prolactin levels may be associated with hyperinsulinemia and insulin resistance in premenopausal women. This effect seems to be independent of body weight, leptin and adiponectin levels. High prolactin levels may directly stimulate insulin secretion from pancreas and directly cause hepatic and whole-body insulin resistance.

  4. Total and high molecular weight adiponectin have similar utility for the identification of insulin resistance

    PubMed Central

    2010-01-01

    Background Insulin resistance (IR) and related metabolic disturbances are characterized by low levels of adiponectin. High molecular weight adiponectin (HMWA) is considered the active form of adiponectin and a better marker of IR than total adiponectin. The objective of this study is to compare the utility of total adiponectin, HMWA and the HMWA/total adiponectin index (SA index) for the identification of IR and related metabolic conditions. Methods A cross-sectional analysis was performed in a group of ambulatory subjects, aged 20 to 70 years, in Mexico City. Areas under the receiver operator characteristic (ROC) curve for total, HMWA and the SA index were plotted for the identification of metabolic disturbances. Sensitivity and specificity, positive and negative predictive values, and accuracy for the identification of IR were calculated. Results The study included 101 men and 168 women. The areas under the ROC curve for total and HMWA for the identification of IR (0.664 vs. 0.669, P = 0.74), obesity (0.592 vs. 0.610, P = 0.32), hypertriglyceridemia (0.661 vs. 0.671, P = 0.50) and hypoalphalipoproteinemia (0.624 vs. 0.633, P = 0.58) were similar. A total adiponectin level of 8.03 μg/ml was associated with a sensitivity of 57.6%, a specificity of 65.9%, a positive predictive value of 50.0%, a negative predictive value of 72.4%, and an accuracy of 62.7% for the diagnosis of IR. The corresponding figures for a HMWA value of 4.25 μg/dl were 59.6%, 67.1%, 51.8%, 73.7% and 64.2%. The area under the ROC curve of the SA index for the identification of IR was 0.622 [95% CI 0.554-0.691], obesity 0.613 [95% CI 0.536-0.689], hypertriglyceridemia 0.616 [95% CI 0.549-0.683], and hypoalphalipoproteinemia 0.606 [95% CI 0.535-0.677]. Conclusions Total adiponectin, HMWA and the SA index had similar utility for the identification of IR and metabolic disturbances. PMID:20573249

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

    PubMed

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

    2015-01-01

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

  6. Impact of Weight Loss on Plasma Leptin and Adiponectin in Overweight-to-Obese Post Menopausal Breast Cancer Survivors

    PubMed Central

    Thompson, Henry J.; Sedlacek, Scot M.; Wolfe, Pamela; Paul, Devchand; Lakoski, Susan G.; Playdon, Mary C.; McGinley, John N.; Matthews, Shawna B.

    2015-01-01

    Women who are obese at the time of breast cancer diagnosis have higher overall mortality than normal weight women and some evidence implicates adiponectin and leptin as contributing to prognostic disadvantage. While intentional weight loss is thought to improve prognosis, its impact on these adipokines is unclear. This study compared the pattern of change in plasma leptin and adiponectin in overweight-to-obese post-menopausal breast cancer survivors during weight loss. Given the controversies about what dietary pattern is most appropriate for breast cancer control and regulation of adipokine metabolism, the effect of a low fat versus a low carbohydrate pattern was evaluated using a non-randomized, controlled study design. Anthropometric data and fasted plasma were obtained monthly during the six-month weight loss intervention. While leptin was associated with fat mass, adiponectin was not, and the lack of correlation between leptin and adiponectin concentrations throughout weight loss implies independent mechanisms of regulation. The temporal pattern of change in leptin but not adiponectin was affected by magnitude of weight loss. Dietary pattern was without effect on either adipokine. Mechanisms not directly related to dietary pattern, weight loss, or fat mass appear to play dominant roles in the regulation of circulating levels of these adipokines. PMID:26132992

  7. Impact of Weight Loss on Plasma Leptin and Adiponectin in Overweight-to-Obese Post Menopausal Breast Cancer Survivors.

    PubMed

    Thompson, Henry J; Sedlacek, Scot M; Wolfe, Pamela; Paul, Devchand; Lakoski, Susan G; Playdon, Mary C; McGinley, John N; Matthews, Shawna B

    2015-07-01

    Women who are obese at the time of breast cancer diagnosis have higher overall mortality than normal weight women and some evidence implicates adiponectin and leptin as contributing to prognostic disadvantage. While intentional weight loss is thought to improve prognosis, its impact on these adipokines is unclear. This study compared the pattern of change in plasma leptin and adiponectin in overweight-to-obese post-menopausal breast cancer survivors during weight loss. Given the controversies about what dietary pattern is most appropriate for breast cancer control and regulation of adipokine metabolism, the effect of a low fat versus a low carbohydrate pattern was evaluated using a non-randomized, controlled study design. Anthropometric data and fasted plasma were obtained monthly during the six-month weight loss intervention. While leptin was associated with fat mass, adiponectin was not, and the lack of correlation between leptin and adiponectin concentrations throughout weight loss implies independent mechanisms of regulation. The temporal pattern of change in leptin but not adiponectin was affected by magnitude of weight loss. Dietary pattern was without effect on either adipokine. Mechanisms not directly related to dietary pattern, weight loss, or fat mass appear to play dominant roles in the regulation of circulating levels of these adipokines. PMID:26132992

  8. 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

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

    2013-01-01

    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  < 0.001), but not in cases, which is possibly a reflection of insulin resistance. Although total adiponectin levels were not significantly different, the elevated percent unmodified adiponectin follows a trend similar to

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

    PubMed

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

    2014-01-01

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

  10. Identification of Unprecedented Anticancer Properties of High Molecular Weight Biomacromolecular Complex Containing Bovine Lactoferrin (HMW-bLf)

    PubMed Central

    Kanwar, Jagat R.; Gurudevan, Sneha; Krishnan, Uma Maheswari; Kanwar, Rupinder K.

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  12. Distribution and Diversity of hmw1A Among Invasive Nontypeable Haemophilus influenzae Isolates in Iran

    PubMed Central

    Shahini Shams Abadi, Milad; Siadat, Seyed Davar; Vaziri, Farzam; Davari, Mehdi; Fateh, Abolfazl; Pourazar, Shahin; Abdolrahimi, Farid; Ghazanfari, Morteza

    2016-01-01

    Background: The pathogenesis of nontypeable Haemophilus influenzae (NTHi) begins with adhesion to the rhinopharyngeal mucosa. Almost 38–80% of NTHi clinical isolates produce proteins that belong to the High Molecular Weight (HMW) family of adhesins, which are believed to facilitate colonization. Methods: In the present study, the prevalence of hmwA, which encodes the HMW adhesin, was determined for a collection of 32 NTHi isolates. Restriction Fragment Length Polymorphism (RFLP) was performed to advance our understanding of hmwA binding sequence diversity. Results: The results demonstrated that hmwA was detected in 61% of NTHi isolates. According to RFLP, isolates were divided into three groups. Conclusion: Based on these observations, it is hypothesized that some strains of nontypeable Haemophilus influenzae infect some specific areas more than other parts. PMID:27141269

  13. Fasting and postprandial regulation of the intracellular localization of adiponectin and of adipokines secretion by dietary fat in rats

    PubMed Central

    Olivares-García, V; Torre-Villalvazo, I; Velázquez-Villegas, L; Alemán, G; Lara, N; López-Romero, P; Torres, N; Tovar, A R; Díaz-Villaseñor, A

    2015-01-01

    Background/Objective: Dietary fat sources modulate fasting serum concentration of adipokines, particularly adiponectin. However, previous studies utilized obese animals in which adipose tissue function is severely altered. Thus, the present study aimed to assess the postprandial regulation of adipokine secretion in nonobese rats that consumed high-fat diet (HFD) composed of different types of fat for a short time. Methods: The rats were fed a control diet or a HFD containing coconut, safflower or soybean oil (rich in saturated fatty acid, monounsaturated fatty acid or polyunsaturated fatty acid, respectively) for 21 days. The serum concentrations of adiponectin, leptin, retinol, retinol-binding protein-4 (RBP-4), visfatin and resistin were determined at fasting and after refeeding. Adiponectin multimerization and intracellular localization, as well as the expression of endoplasmic reticulum (ER) chaperones and transcriptional regulators, were evaluated in epididymal white adipose tissue. Results: In HFD-fed rats, serum adiponectin was significantly decreased 30 min after refeeding. With coconut oil, all three multimeric forms were reduced; with safflower oil, only the high-molecular-weight (HMW) and medium-molecular-weight (MMW) forms were decreased; and with soybean oil, only the HMW form was diminished. These reductions were due not to modifications in mRNA abundance or adiponectin multimerization but rather to an increment in intracellular localization at the ER and plasma membrane. Thus, when rats consumed a HFD, the type of dietary fat differentially affected the abundance of endoplasmic reticulum resident protein 44 kDa (ERp44), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ (PPARγ) mRNAs, all of which are involved in the post-translational processing of adiponectin required for its secretion. Leptin, RBP-4, resistin and visfatin serum concentrations did not change during fasting, whereas modest alterations were observed after

  14. Leptin, Adiponectin and Cognition in Middle-aged HIV-infected and Uninfected Women. The Brooklyn Women’s Interagency HIV Study

    PubMed Central

    Gustafson, Deborah R; Mielke, Michelle M; Keating, Sheila A; Holman, Susan; Minkoff, Howard; Crystal, Howard A

    2016-01-01

    Context Case-control study of women with and without HIV infection. Objective To explore the association of cognition and the adipokines, leptin and adiponectin (total; high molecular weight, HMW), in women with (HIV+) and without HIV (HIV−) infection. Design Cross-sectional analyses of adipokines and cognition using linear regression models of log-transformed adipokines, and Trails A, Trails B, Stroop interference time, Stroop word recall, Stroop color naming and reading, and Symbol Digit Modalities Test (SDMT) with consideration for age, HIV infection status, education, CD4 count, diabetes, body mass index (BMI), waist circumference (WC) and race/ethnicity. Setting Brooklyn, NY. Participants 354 participants (247 HIV+, 107 HIV−), in the Brooklyn Women’s Interagency HIV Study (WIHS), average age 38.9 years, with measured levels of leptin and adiponectin (total and high molecular weight, HMW). Main Outcome Measure Cognition Results Higher levels of leptin were positively associated with worse cognition on the basis of Trails A completion time and SDMT score. Among at risk HIV− women, leptin was associated with worse performance on Trails B. No associations were observed for total or HMW adiponectin. Conclusion Blood adipokine levels were measured to provide mechanistic insights regarding the association of adipose with cognitive function. These data suggest that higher levels of leptin, consistent with more adipose tissue, are associated with worse cognitive function in middle age. Monitoring leptin over time and with increasing age in relation to cognition and dementia, may lend insights to the role of adipose tissue in successful body and brain aging among women with HIV infection. PMID:27536467

  15. Adiponectin Fractions Influence the Development of Posttransplant Diabetes Mellitus and Cardiovascular Disease in Japanese Renal Transplant Recipients

    PubMed Central

    Adachi, Hiroki; Nakayama, Kanae; Hayashi, Norifumi; Matsui, Yuki; Fujimoto, Keiji; Yamaya, Hideki; Tonami, Hisao; Yokoyama, Hitoshi

    2016-01-01

    Background A few studies have investigated the role of adiponectin fraction for cardiovascular disease (CVD) in RTx recipients. Subjects and Methods We studied 57 adult subjects (39 males, 18 females; 10 cadaveric donors) with at least three years of allograft survival (median 251 months). We examined clinical backgrounds such as treated drugs, blood pressure (BP, mmHg), body mass index (BMI), and blood chemistry including cholesterol (total, LDL-C, HDL-C), glucose, glycated hemoglobin (HbA1c), and serum high and low-molecular-weight (HMW/LMW) ADPN fractions with regard to the associations of the visceral and subcutaneous fat areas on CT scan. We also analyzed the associations of CVD and post-transplant diabetes (PTDM) with ADPN fractions and the fat areas. Results The visceral fat area was inversely correlated with serum HMW and LMW ADPN levels and HMW ADPN ratio (r = -0.400, p = 0.002 and r = -0.296, p = 0.025 and r = -0.444, p<0.001, respectively). Furthermore, the visceral fat area was positively with the LMW ADPN ratio (r = 0.467, p<0.001), but no significant correlation was noted between the subcutaneous fat area and the ADPN ratio. On multiple regression analysis, eGFR and the visceral fat area were significant reducing factors of HMW ADPN levels, and the alteration of eGFR was identified as an increasing factor of HMW ADPN levels. Patients with CVD had larger visceral fat area (p = 0.004), lower HMW ADPN ratio (p = 0.022) and higher LMW ADPN ratio (p = 0.049). In addition, the higher HMW ADPN ratio and statin treatment were identified as reducing factors of the development of CVD, but the LDL-C level was an aggravating factor. Moreover, the higher LMW ADPN ratio and the visceral fat area were aggravating factors of PTDM. Conclusion Even in Japanese renal transplant recipients, visceral fat area and ADPN fractions were significant factors for the development of both CVD and PTDM. PMID:27706207

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

    PubMed Central

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

    2012-01-01

    Background: We examined the ability of the apolipoprotein AI mimetic peptide L-4F to improve the metabolic state of female and male ob mice and the mechanisms involved. Methods: Female and male lean and obese (ob) mice were administered L-4F or vehicle for 6 weeks. Body weight was measured weekly. Fat distribution, serum cytokines and markers of cardiovascular dysfunction were determined at the end of treatment. Results: L-4F significantly decreased serum interleukin (IL)-6, tumor necrosis factor-α and IL-1β. L-4F improved vascular function, and increased serum adiponectin levels and insulin sensitivity compared with untreated mice. In addition, L-4F treatment increased heme oxygenase (HO)-1, pAKT and pAMPK levels in kidneys of ob animals. pAKT and pAMPK levels were significantly reduced in the presence of an HO inhibitor. Interestingly, L4F did not alter body weight in female mice, but caused a significant reduction in males. Conclusions: L-4F treatments reduced cardiovascular risk factors and improved insulin sensitivity in female ob mice independent of body fat changes. Reduced inflammatory cytokine levels accompanied by increased HO activity, serum adiponectin and improved insulin sensitivity suggest that L-4F may promote the conversion of visceral fat to a healthier phenotype. Therefore, L-4F appears to be a promising therapeutic strategy for treating both cardiovascular risk factors and insulin resistance in obese patients of either gender. PMID:23169576

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

    PubMed

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

    2005-11-01

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

  18. The HMW1 and HMW2 Adhesins Enhance the Ability of Nontypeable Haemophilus influenzae To Colonize the Upper Respiratory Tract of Rhesus Macaques.

    PubMed

    Rempe, Katherine A; Porsch, Eric A; Wilson, Jolaine M; St Geme, Joseph W

    2016-10-01

    Nontypeable Haemophilus influenzae (NTHi) initiates infection by colonizing the upper respiratory tract and is a common cause of localized respiratory tract disease. Previous work has established that the NTHi HMW1 and HMW2 proteins are potent adhesins that mediate efficient in vitro adherence to cultured human respiratory epithelial cells. In this study, we used a rhesus macaque model to assess the contributions of HMW1 and HMW2 to in vivo colonization. In experiments involving inoculation of individual isogenic derivatives of NTHi strain 12, the parent strain expressing both HMW1 and HMW2 and the mutant strains expressing either HMW1 or HMW2 were able to colonize more frequently than the double mutant strain lacking HMW1 and HMW2. In competition experiments, the parent strain efficiently outcompeted the double mutant lacking HMW1 and HMW2. Colonization with strains expressing HMW2 resulted in development of antibody against HMW2 in a number of the animals, demonstrating that colonization can stimulate an antibody response. In conclusion, we have established that the HMW1 and HMW2 adhesins play a major role in facilitating colonization of the upper respiratory tract of rhesus macaques, in some cases associated with stimulation of an immune response.

  19. Isolation and Quantitation of Adiponectin Higher Order Complexes

    PubMed Central

    Rutkowski, Joseph M.; Scherer, Philipp E.

    2014-01-01

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

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

    PubMed

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

    2004-11-01

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

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

    PubMed Central

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

    2010-01-01

    The Haemophilus influenzae HMW1 adhesin is an important virulence exoprotein that is secreted via the two-partner secretion pathway and is glycosylated at multiple asparagine residues in consensus N-linked sequons. Unlike the heavily branched glycans found in eukaryotic N-linked glycoproteins, the modifying glycan structures in HMW1 are mono-hexoses or di-hexoses. Recent work demonstrated that the H. influenzae HMW1C protein is the glycosyltransferase responsible for transferring glucose and galactose to the acceptor sites of HMW1. An Actinobacillus pleuropneumoniae protein designated ApHMW1C shares high-level homology with HMW1C and has been assigned to the GT41 family, which otherwise contains only O-glycosyltransferases. In this study, we demonstrated that ApHMW1C has N-glycosyltransferase activity and is able to transfer glucose and galactose to known asparagine sites in HMW1. In addition, we found that ApHMW1C is able to complement a deficiency of HMW1C and mediate HMW1 glycosylation and adhesive activity in whole bacteria. Initial structure-function studies suggested that ApHMW1C consists of two domains, including a 15-kDa N-terminal domain and a 55-kDa C-terminal domain harboring glycosyltransferase activity. These findings suggest a new subfamily of HMW1C-like glycosyltransferases distinct from other GT41 family O-glycosyltransferases. PMID:21209858

  2. Specific dietary patterns and concentrations of adiponectin

    PubMed Central

    Izadi, Vajihe; Azadbakht, Leila

    2015-01-01

    Background: One of the adipokines mostly secreted from adipose tissue is adiponectin. Adiponectin is well known as the anti-diabetic, anti-obesity and cardio-protective factor. Present study focused on the review the previous studies about relationship between adherence to healthy dietary pattern, independent of one or two special dietary components, and concentration of adiponectin. Materials and Methods: We searched in PubMed search engine from 2003 to July 2014 using the following key words: Healthy dietary pattern, mediterranean dietary pattern, dietary pattern, diet intervention and adiponectin and adipokines. Then, we recruited 10 articles to review in the present study. Results: Cohort studies that are examined this relationship among women showed the strong positive association in this regard. According to cross-sectional studies adherence to healthy dietary pattern like Mediterranian intervention with moderate weight loss had a positive association with concentration of adiponectin. Conclusion: It seems that adherents to the healthy dietary patterns have great levels of circulating adiponectin. However, it is not clear that whether the separate components of healthy dietary patterns like good sources of fats or protein or fibers mostly have important roles in these beneficial effects of such dietary patterns or not. PMID:25983773

  3. Urinary Adiponectin Excretion

    PubMed Central

    von Eynatten, Maximilian; Liu, Dan; Hock, Cornelia; Oikonomou, Dimitrios; Baumann, Marcus; Allolio, Bruno; Korosoglou, Grigorios; Morcos, Michael; Campean, Valentina; Amann, Kerstin; Lutz, Jens; Heemann, Uwe; Nawroth, Peter P.; Bierhaus, Angelika; Humpert, Per M.

    2009-01-01

    OBJECTIVE Markers reliably identifying vascular damage and risk in diabetic patients are rare, and reports on associations of serum adiponectin with macrovascular disease have been inconsistent. In contrast to existing data on serum adiponectin, this study assesses whether urinary adiponectin excretion might represent a more consistent vascular damage marker in type 2 diabetes. RESEARCH DESIGN AND METHODS Adiponectin distribution in human kidney biopsies was assessed by immunohistochemistry, and urinary adiponectin isoforms were characterized by Western blot analysis. Total urinary adiponectin excretion rate was measured in 156 patients with type 2 diabetes who had a history of diabetic nephropathy and 40 healthy control subjects using enzyme-linked immunosorbent assay. Atherosclerotic burden was assessed by common carotid artery intima-media-thickness (IMT). RESULTS A homogenous staining of adiponectin was found on the endothelial surface of glomerular capillaries and intrarenal arterioles in nondiabetic kidneys, whereas staining was decreased in diabetic nephropathy. Low-molecular adiponectin isoforms (∼30–70 kDa) were detected in urine by Western blot analysis. Urinary adiponectin was significantly increased in type 2 diabetes (7.68 ± 14.26 vs. control subjects: 2.91 ± 3.85 μg/g creatinine, P = 0.008). Among type 2 diabetic patients, adiponectinuria was associated with IMT (r = 0.479, P < 0.001) and proved to be a powerful independent predictor of IMT (β = 0.360, P < 0.001) in multivariable regression analyses. In a risk prediction model including variables of the UK Prospective Diabetes Study coronary heart disease risk engine urinary adiponectin, but not the albumin excretion rate, added significant value for the prediction of increased IMT (P = 0.007). CONCLUSIONS Quantification of urinary adiponectin excretion appears to be an independent indicator of vascular damage potentially identifying an increased risk for vascular events. PMID:19509019

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

    PubMed

    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

    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

  5. Effects of body weight reduction on plasma leptin and adiponectin/leptin ratio in obese patients with type 1 diabetes mellitus.

    PubMed

    Musil, F; Blaha, V; Ticha, A; Hyspler, R; Haluzik, M; Lesna, J; Smahelova, A; Sobotka, L

    2015-01-01

    The aim of this study was to explore the changes in the adipokines leptin and adiponectin in obese patients with type 1 diabetes mellitus (T1DM) who underwent seven days of fasting and 21 days of low-calorie diet (LCD). The plasma leptin and adiponectin concentrations were measured in 14 obese patients with T1DM at baseline, immediately after 7 days of fasting, and after 21 days of LCD. 13 non-obese patients with T1DM were studied only after an overnight fasting. Bioimpedance technique was used for determination of body composition. Obese T1DM patients lost 6.0 kg (6.0; 6.8) (median, 25 %; 75 %) and decreased their fat tissue after fasting and LCD. Plasma leptin in obese T1DM was significantly higher than in non-obese T1DM patients: 9.10 (5.06; 25.89) vs. 1.71 (1.12; 7.08) microg . l(-1) and transiently decreased immediately after fasting: 3.45 microg . l(-1) (1.47; 7.00), (P<0.05). Adiponectin/leptin ratio in obese T1DM was significantly lower than in non-obese T1DM patients: 0.67 (0.57; 1.49) vs. 3.50 (2.46; 6.30) . 10(3) and transiently increased immediately after fasting: 2.22 (1.26; 3.24) . 10(3), (P<0.05). We conclude that obese patients with T1DM are characterized by hyperleptinemia that is reduced by prolonged fasting, but only slightly affected by low calorie diet.

  6. Naturally Acquired HMW1- and HMW2-Specific Serum Antibodies in Adults and Children Mediate Opsonophagocytic Killing of Nontypeable Haemophilus influenzae

    PubMed Central

    Winter, Linda E.

    2015-01-01

    The HMW1 and HMW2 proteins are highly immunogenic adhesins expressed by approximately 75% of nontypeable Haemophilus influenzae (NTHi) strains, and HMW1- and HMW2-specific antibodies can mediate opsonophagocytic killing of NTHi. In this study, we assessed the ability of HMW1- and HMW2-specific antibodies in sera from healthy adults and convalescent-phase sera from children with NTHi otitis media to mediate killing of homologous and heterologous NTHi. The serum samples were examined pre- and postadsorption on HMW1 and HMW2 affinity columns, and affinity-purified antibodies were assessed for ability to mediate killing of homologous and heterologous strains. Adult serum samples mediated the killing of six prototype NTHi strains at titers of <1:10 to 1:1,280. HMW1- and HMW2-adsorbed sera demonstrated unchanged to 8-fold decreased opsonophagocytic titers against the homologous strains. Each affinity-purified antibody preparation mediated the killing of the respective homologous strain at titers of <1:10 to 1:320 and of the five heterologous strains at titers of <1:10 to 1:320, with most preparations killing most heterologous strains to some degree. None of the acute-phase serum samples from children mediated killing, but each convalescent-phase serum sample mediated killing of the infecting strain at titers of 1:40 to 1:640. HMW1- and HMW2-adsorbed convalescent-phase serum samples demonstrated ≥4-fold decreases in titer. Three of four affinity-purified antibody preparations mediated killing of the infecting strain at titers of 1:20 to 1:320, but no killing of representative heterologous strains was observed. HMW1- and HMW2-specific antibodies capable of mediating opsonophagocytic killing are present in the serum from normal adults and develop in convalescent-phase sera of children with NTHi otitis media. Continued investigation of the HMW1 and HMW2 proteins as potential vaccine candidates for the prevention of NTHi disease is warranted. PMID:26512048

  7. The wheat HMW-glutenin 1Dy10 gene promoter controls endosperm expression in Brachypodium distachyon

    PubMed Central

    Thilmony, Roger; Guttman, Mara E; Lin, Jeanie W; Blechl, Ann E

    2014-01-01

    The grass species Brachypodium distachyon has emerged as a model system for the study of gene structure and function in temperate cereals. As a first demonstration of the utility of Brachypodium to study wheat gene promoter function, we transformed it with a T-DNA that included the uidA reporter gene under control of a wheat High-Molecular-Weight Glutenin Subunit (HMW-GS) gene promoter and transcription terminator. For comparison, the same expression cassette was introduced into wheat by biolistics. Histochemical staining for β-glucuronidase (GUS) activity showed that the wheat promoter was highly expressed in the endosperms of all the seeds of Brachypodium and wheat homozygous plants. It was not active in any other tissue of transgenic wheat, but showed variable and sporadic activity in a minority of styles of the pistils of four homozygous transgenic Brachypodium lines. The ease of obtaining transgenic Brachypodium plants and the overall faithfulness of expression of the wheat HMW-GS promoter in those plants make it likely that this model system can be used for studies of other promoters from cereal crop species that are difficult to transform. PMID:24322586

  8. Characterization of a novel y-type HMW-GS with eight cysteine residues from Triticum monococcum ssp. monococcum.

    PubMed

    Li, Zenglin; Li, Hongyu; Chen, Gang; Kou, Chunlan; Ning, Shunzong; Yuan, Zhongwei; Jiang, Qi; Zheng, Youliang; Liu, Dengcai; Zhang, Lianquan

    2015-11-15

    The composition and number of high-molecular-weight glutenin subunits (HMW-GSs) play important roles in determining the grain-processing quality of common wheat. The Glu-1Ay allele is silent in common wheat. In this study, an active y-type HMW-GS allele termed 1Ay8.2 (GenBank No. KP137569) was identified from Triticum monococcum L. ssp. monococcum (AmAm, 2n=2x=14), a species with a genome related to the A-genome of common wheat. Compared with previously reported active 1Ay subunits, this novel subunit contained an extra cysteine residue at position 103 of the amino acid sequence in the N-terminal region, in addition to the six cysteines in the N- and C-terminal regions found in most active 1Ay subunits and the one in the repetitive region that appears in only a few 1Ay alleles. This subunit was expressed in an amphiploid (AAAmAmBB, 2n=6x=42) between Triticum turgidum L. ssp. dicoccon and T. monococcum ssp. monococcum. This amphiploid could be used as a bridge to transfer 1Ay8.2 into common wheat cultivars. Replacing the silenced 1Ay in common wheat with the active 1Ay8.2 allele harboring an extra cysteine residue is expected to improve the quality by increasing the number of HMW-GSs and promoting the formation of covalent interactions through disulfide bonds with the extra cysteine residue.

  9. Quality differences between NILs of wheat variety Long 97-586 possessing HMW-GS 7+8 and 7.

    PubMed

    Zhang, LiLi; Zhang, YanBin; Li, JiLin; Zhao, HaiBin; Song, QingJie; Yu, HaiYang; Zhang, ChunLi; Xin, WenLi; Xiao, ZhiMin

    2010-02-01

    The high molecular weight glutenin subunits (HMW-GS) 7+8 were introduced into the Long 97-586 (1, 7, 2+12) wheat variety (Triticum aestivum) by 5 consecutive backcrosses with biochemical marker-assisted selection. Nearly isogenic lines (NILs) of HMW-GS 7 and 7+8 were obtained, and the NILs were planted in the experimental field at the Crop Breeding Institute of Heilongjiang Academy of Agricultural Science in 2004-2006. The field experiments were designed using the two-column contrast arrangement method with six replicates in 2004-2005 and four replicates in 2006. The result of three years experiments showed that the differences between NILs of Long 97-586 with subunit 7 and those with subunits 7+8 in the quality parameters of flour protein content and dry gluten content were negligible (P>0.1). However, the differences in some of the quality parameters were remarkably significant (P<0.01), including wet gluten content, ratio of wet gluten/dry gluten, gluten index, Zeleny sedimentation, ratio of sedimentation/dry gluten, and the farinogram parameters of water absorption, development time, stability, breakdown time and degree of softening. The difference between NILs with subunits 7+8 and subunit 7 was significant (P<0.05) on the alveogram W value and had a critical value (P=0.05) on the alveogram P value in 2006. The results show that HMW-GS 7+8 is far superior to HMW-GS 7 in terms of baking quality. The possibilities of using subunits 7+8 and subunit 7 in breeding strong and weak gluten wheat varieties are discussed in this paper. PMID:20596839

  10. Human brain tumor-associated urinary high molecular weight transforming growth factor: a high molecular weight form of epidermal growth factor.

    PubMed

    Stromberg, K; Hudgins, W R; Dorman, L S; Henderson, L E; Sowder, R C; Sherrell, B J; Mount, C D; Orth, D N

    1987-02-15

    Urinary protein obtained from a patient with a highly malignant brain tumor (astrocytoma, grade IV) was adsorbed to trimethylsilyl controlled-pore glass beads and selectively eluted with acetonitrile to yield a high molecular weight (HMW) human transforming growth factor (hTGF). This HMW hTGF promoted clonogenic cell growth in soft agar and competed for membrane receptors with mouse epidermal growth factor. After surgical resection of the tumor, no HMW hTGF was found in urine. HMW hTGF generated a human EGF (hEGF) radioimmunoassay competitive binding curve similar to that of hEGF and parallel to that of a highly purified HMW form of hEGF previously reported to be present in trace concentrations in normal human urine. Both hEGF and HMW hEGF were clonogenic in soft agar, and their clonogenic activity as well as that of HMW hTGF was inhibited by anti-hEGF serum. Both HMW hTGF and HMW hEGF had 20 to 25% of the radioreceptor binding activity of hEGF. HMW hTGF purified from the pooled urine of several patients with malignant astrocytomas and HMW hEGF purified from normal control urine comigrated at Mr 33,000. Thus, HMW hTGF was indistinguishable from HMW hEGF in terms of apparent molecular size, epidermal growth factor receptor binding activity, epidermal growth factor immunoreactivity, and clonogenic activity. Urinary HMW hEGF/hTGF may be of tumor cell origin or may represent a response of normal host tissues to the tumor or its products.

  11. The complex role of adiponectin in chronic kidney disease.

    PubMed

    Jia, Ting; Carrero, Juan Jesús; Lindholm, Bengt; Stenvinkel, Peter

    2012-10-01

    Although adiponectin, an adipocytokine released from adipose tissue, is thought to have anti-atherogenic, anti-inflammatory, and insulin-sensitizing effects, it appears that high, rather than low, circulating levels of adiponectin predict increased mortality in chronic kidney disease (CKD) patients in whom the circulating levels may rise to about three times higher than the levels in healthy subjects. As it could be hypothesized that in the uremic milieu high adiponectin levels reflect protein-energy wasting, lower residual renal function and/or volume overload, this may explain, at least in part, the observed paradoxical link between hyperadiponectinemia and poor outcome in CKD. To determine the biological consequences of high circulating adiponectin levels on carbohydrate and insulin metabolism as well as relations with cardiovascular function and mortality in the uremic milieu, further studies need to take into account both high-, and low-molecular weight adiponectin moieties as well as the role of adiponectin receptors. This brief review summarizes some of the recent advances in our understanding of the complex and context-sensitive role of this elusive and intriguing adipokine in the uremic milieu.

  12. Role of adiponectin in delayed embryonic development of the short-nosed fruit bat, Cynopterus sphinx.

    PubMed

    Anuradha; Krishna, Amitabh

    2014-12-01

    The aim of this study was to evaluate the role of adiponectin in the delayed embryonic development of Cynopterus sphinx. Adiponectin receptor (ADIPOR1) abundance was first observed to be lower during the delayed versus non-delayed periods of utero-embryonic unit development. The effects of adiponectin treatment on embryonic development were then evaluated during the period of delayed development. Exogenous treatment increased the in vivo rate of embryonic development, as indicated by an increase in weight, ADIPOR1 levels in the utero-embryonic unit, and histological changes in embryonic development. Treatment with adiponectin during embryonic diapause showed a significant increase in circulating progesterone and estradiol concentrations, and in production of their receptors in the utero-embryonic unit. The adiponectin-induced increase in estradiol synthesis was correlated with increased cell survival (BCL2 protein levels) and cell proliferation (PCNA protein levels) in the utero-embryonic unit, suggesting an indirect effect of adiponectin via estradiol synthesis by the ovary. An in vitro study further confirmed the in vivo findings that adiponectin treatment increases PCNA levels together with increased uptake of glucose by increasing the abundance of glucose transporter 8 (GLUT8) in the utero-embryonic unit. The in vitro study also revealed that adiponectin, together with estradiol but not alone, significantly increased ADIPOR1 protein levels. Thus, adiponectin works in concert with estradiol to increase glucose transport to the utero-embryonic unit and promote cell proliferation, which together accelerate embryonic development. PMID:25295970

  13. Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW1 as an Intracellular Invasion Locus in Haemophilus influenza.

    PubMed

    Mell, Joshua Chang; Viadas, Cristina; Moleres, Javier; Sinha, Sunita; Fernández-Calvet, Ariadna; Porsch, Eric A; St Geme, Joseph W; Nislow, Corey; Redfield, Rosemary J; Garmendia, Junkal

    2016-04-01

    Many bacterial species actively take up and recombine homologous DNA into their genomes, called natural competence, a trait that offers a means to identify the genetic basis of naturally occurring phenotypic variation. Here, we describe "transformed recombinant enrichment profiling" (TREP), in which natural transformation is used to generate complex pools of recombinants, phenotypic selection is used to enrich for specific recombinants, and deep sequencing is used to survey for the genetic variation responsible. We applied TREP to investigate the genetic architecture of intracellular invasion by the human pathogen Haemophilus influenzae, a trait implicated in persistence during chronic infection. TREP identified the HMW1 adhesin as a crucial factor. Natural transformation of the hmw1 operon from a clinical isolate (86-028NP) into a laboratory isolate that lacks it (Rd KW20) resulted in ~1,000-fold increased invasion into airway epithelial cells. When a distinct recipient (Hi375, already possessing hmw1 and its paralog hmw2) was transformed by the same donor, allelic replacement of hmw2AHi375 by hmw1A86-028NP resulted in a ~100-fold increased intracellular invasion rate. The specific role of hmw1A86-028NP was confirmed by mutant and western blot analyses. Bacterial self-aggregation and adherence to airway cells were also increased in recombinants, suggesting that the high invasiveness induced by hmw1A86-028NP might be a consequence of these phenotypes. However, immunofluorescence results found that intracellular hmw1A86-028NP bacteria likely invaded as groups, instead of as individual bacterial cells, indicating an emergent invasion-specific consequence of hmw1A-mediated self-aggregation. PMID:27124727

  14. Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW1 as an Intracellular Invasion Locus in Haemophilus influenza

    PubMed Central

    Moleres, Javier; Sinha, Sunita; Fernández-Calvet, Ariadna; Porsch, Eric A.; St. Geme, Joseph W.; Nislow, Corey; Redfield, Rosemary J.; Garmendia, Junkal

    2016-01-01

    Many bacterial species actively take up and recombine homologous DNA into their genomes, called natural competence, a trait that offers a means to identify the genetic basis of naturally occurring phenotypic variation. Here, we describe “transformed recombinant enrichment profiling” (TREP), in which natural transformation is used to generate complex pools of recombinants, phenotypic selection is used to enrich for specific recombinants, and deep sequencing is used to survey for the genetic variation responsible. We applied TREP to investigate the genetic architecture of intracellular invasion by the human pathogen Haemophilus influenzae, a trait implicated in persistence during chronic infection. TREP identified the HMW1 adhesin as a crucial factor. Natural transformation of the hmw1 operon from a clinical isolate (86-028NP) into a laboratory isolate that lacks it (Rd KW20) resulted in ~1,000-fold increased invasion into airway epithelial cells. When a distinct recipient (Hi375, already possessing hmw1 and its paralog hmw2) was transformed by the same donor, allelic replacement of hmw2AHi375 by hmw1A86-028NP resulted in a ~100-fold increased intracellular invasion rate. The specific role of hmw1A86-028NP was confirmed by mutant and western blot analyses. Bacterial self-aggregation and adherence to airway cells were also increased in recombinants, suggesting that the high invasiveness induced by hmw1A86-028NP might be a consequence of these phenotypes. However, immunofluorescence results found that intracellular hmw1A86-028NP bacteria likely invaded as groups, instead of as individual bacterial cells, indicating an emergent invasion-specific consequence of hmw1A-mediated self-aggregation. PMID:27124727

  15. The Effects of Aerobic Exercise on Plasma Adiponectin Level and Adiponectin-related Protein Expression in Myocardial Tissue of ApoE(-/-) Mice.

    PubMed

    Zhu, Xiao-Juan; Chen, Li-Hui; Li, Jiang-Hua

    2015-12-01

    Numerous reports have confirmed the effect of ApoE knockout in the induction of cardiovascular diseases and the protective effect of adiponectin against the progression of cardiovascular diseases. The aim of this study was to reveal the roles of adiponectin signaling in the progression of cardiovascular diseases induced by ApoE knockout and to analyze the healthy effects of aerobic exercise on ApoE knockout mice (ApoE(-/-) mice) through observing the changes of adiponectin signaling caused by ApoE knockout and aerobic exercise. A twelve-week aerobic exercise program was carried out on the male ApoE(-/-) mice and the C57BL / 6J mice (C57 mice) of the same strain. Results show that the body weights, blood lipid level, plasma adiponectin level and adiponectin-related proteins in myocardial tissue were all significantly changed by ApoE knockout. A twelve-week aerobic exercise program exerted only minimal effects on the body weights, blood lipid levels, and plasma adiponectin levels of ApoE(-/-) mice, but increased the expressions of four adiponectin-related proteins, AdipoR1, PPARα, AMPK and P-AMPK, in the myocardial tissue of the ApoE(-/-) mice. In summary, adiponectin signaling may play an import role in the progression of cardiovascular diseases induced by ApoE knockout, and the beneficial health effects of aerobic exercise on ApoE(-/-) mice may be mainly from the increased adiponectin-related protein expression in myocardial tissue. Key pointsA twelve-week aerobic exercise program exerted only limited effects on the body weights and the plasma adiponectin levels of both the normal mice and the ApoE(-/-) mice but did effectively regulate the blood lipid levels of the normal mice (but not the ApoE(-/-) mice).After 12 weeks of aerobic exercise, expression of the adiponectin-related proteins in the myocardial tissue of the ApoE(-/-) and normal mice was increased, but the increased amplitudes of these proteins in the ApoE(-/-) mice were much larger in the Apo

  16. Role of N-terminal domain of HMW 1Dx5 in the functional and structural properties of wheat dough.

    PubMed

    Wang, Jing Jing; Liu, Guang; Huang, Yan-Bo; Zeng, Qiao-Hui; Song, Guo-Sheng; Hou, Yi; Li, Lin; Hu, Song-Qing

    2016-12-15

    Effects of N-terminal domain of high molecular weight glutenin subunit (HMW-GS) 1Dx5 (1Dx5-N) on functional and structural properties of wheat dough were determined by farinographic and rheological analysis, size exclusion chromatography, non-reducing/reducing SDS-PAGE, total free sulfhydryl determination, scanning electron microscopy and Fourier transform infrared spectroscopy. Results showed that 1Dx5-N improved the quality of dough with the increased water absorption, dough stability time, elastic and viscous modulus, and the decreased degree of softening, loss tangent. These improvements could be attributed to the formation of the macro-molecular weight aggregates and massive protein networks, which were favored by 1Dx5-N through disulfide bonds and hydrophobic interactions. Additionally, 1Dx5-N drove the transition of α-helix and random coil conformations to β-sheet and β-turn conformations, further demonstrating the formation of HMW-GS polymers and the enhancement of dough strength. Moreover, all the positive effects of 1Dx5-N were reinforced by edible salt NaCl. PMID:27451235

  17. Structural Determinants of the Interaction between the TpsA and TpsB Proteins in the Haemophilus influenzae HMW1 Two-Partner Secretion System

    PubMed Central

    Grass, Susan; Rempe, Katherine A.

    2015-01-01

    ABSTRACT The two-partner secretion (TPS) pathway in Gram-negative bacteria consists of a TpsA exoprotein and a cognate TpsB outer membrane pore-forming translocator protein. Previous work has demonstrated that the TpsA protein contains an N-terminal TPS domain that plays an important role in targeting the TpsB protein and is required for secretion. The nontypeable Haemophilus influenzae HMW1 and HMW2 adhesins are homologous proteins that are prototype TpsA proteins and are secreted by the HMW1B and HMW2B TpsB proteins. In the present study, we sought to define the structural determinants of HMW1 interaction with HMW1B during the transport process and while anchored to the bacterial surface. Modeling of HMW1B revealed an N-terminal periplasmic region that contains two polypeptide transport-associated (POTRA) domains and a C-terminal membrane-localized region that forms a pore. Biochemical studies demonstrated that HMW1 engages HMW1B via interaction between the HMW1 TPS domain and the HMW1B periplasmic region, specifically, the predicted POTRA1 and POTRA2 domains. Subsequently, HMW1 is shuttled to the HMW1B pore, facilitated by the N-terminal region, the middle region, and the NPNG motif in the HMW1 TPS domain. Additional analysis revealed that the interaction between HMW1 and HMW1B is highly specific and is dependent upon the POTRA domains and the pore-forming domain of HMW1B. Further studies established that tethering of HMW1 to the surface-exposed region of HMW1B is dependent upon the external loops of HMW1B formed by residues 267 to 283 and residues 324 to 330. These observations may have broad relevance to proteins secreted by the TPS pathway. IMPORTANCE Secretion of HMW1 involves a recognition event between the extended form of the HMW1 propiece and the HMW1B POTRA domains. Our results identify specific interactions between the HMW1 propiece and the periplasmic HMW1B POTRA domains. The results also suggest that the process of HMW1 translocation involves at

  18. Melatonin modulates adiponectin expression on murine colitis with sleep deprivation

    PubMed Central

    Kim, Tae Kyun; Park, Young Sook; Baik, Haing-Woon; Jun, Jin Hyun; Kim, Eun Kyung; Sull, Jae Woong; Sung, Ho Joong; Choi, Jin Woo; Chung, Sook Hee; Gye, Myung Chan; Lim, Ju Yeon; Kim, Jun Bong; Kim, Seong Hwan

    2016-01-01

    AIM To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. METHODS The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. RESULTS Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. CONCLUSION This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti-inflammatory effects on colitis with sleep deprivation.

  19. Melatonin modulates adiponectin expression on murine colitis with sleep deprivation

    PubMed Central

    Kim, Tae Kyun; Park, Young Sook; Baik, Haing-Woon; Jun, Jin Hyun; Kim, Eun Kyung; Sull, Jae Woong; Sung, Ho Joong; Choi, Jin Woo; Chung, Sook Hee; Gye, Myung Chan; Lim, Ju Yeon; Kim, Jun Bong; Kim, Seong Hwan

    2016-01-01

    AIM To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. METHODS The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. RESULTS Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. CONCLUSION This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti-inflammatory effects on colitis with sleep deprivation. PMID:27672276

  20. Spelt-specific alleles in HMW glutenin genes from modern and historical European spelt ( Triticum spelta L.).

    PubMed

    Blatter, Robert H. E.; Jacomet, Stefanie; Schlumbaum, Angela

    2002-02-01

    A partial promoter region of the high-molecular weight (HMW) glutenin genes was studied in two wheat specimens, a 300 year-old spelt ( Triticum spelta L.) and an approximately 250 year-old bread wheat ( Triticum aestivum L.) from Switzerland. Sequences were compared to a recent Swiss landrace T. spelta'Oberkulmer.' The alleles from the historical bread wheat were most similar to those of modern T. aestivumcultivars, whereas in the historical and the recent spelt specific alleles were detected. Pairwise genetic distances up to 0.03 within 200 bp from the HMW Glu-A1-2, Glu-B1-1 and Glu-B1-2 alleles in spelt to the most-similar alleles from bread wheat suggest a polyphyletic origin. The spelt Glu-B1-1 allele, which was unlike the corresponding alleles in bread wheat, was closer related to an allele found in tetraploid wheat cultivars. The results are discussed in context of the origin of European spelt.

  1. Adiponectin, leptin, and yoga practice.

    PubMed

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

    2012-12-01

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

  2. The effect of low calorie diet on adiponectin concentration: a systematic review and meta-analysis.

    PubMed

    Salehi-Abargouei, A; Izadi, V; Azadbakht, L

    2015-07-01

    Adiponectin secreted from adipose tissue is proposed to be inversely related to the body fat mass. However, the magnitude of the effect of low calorie diet on adiponectin concentrations remains unknown. The present study was aimed to conduct a systematic review and meta-analysis on clinical trials that access the effect of low calorie diet on adiponectin concentration. We searched PubMed, SCOPUS, ISI web of science, and Google scholar for RCTs until January 2015. Totally, 13 trials were found, which examined the effect of low calorie diet on adiponectin concentration compared control group without low calorie diet.Our meta-analysis showed that weight loss diet can substantially increase the adiponectin concentration in overall (Hedges' g=0.34, 95% CI:0.17-0.50, p<0.001). Subgroup analysis also revealed that the low calorie diet can substantially enhance adiponectin concentrations when prescribed for ≤16 weeks (Hedges' g=0.48, 95% CI: 0.12-0.83, p=0.01) compared to >16 weeks (Hedges' g=0.30, 95% CI: 0.11-0.48, p=0.002). Weight loss diet beneficially affects blood adiponectin concentrations. More clinical trials are recommended to clear this effect among different genders and nationalities, and assess the magnitude of the effect based on changes in fat mass.

  3. Adiponectin in chronic kidney disease has an opposite impact on protein-energy wasting and cardiovascular risk: two sides of the same coin.

    PubMed

    Park, S-H; Carrero, J J; Lindholm, B; Stenvinkel, P

    2009-08-01

    Adiponectin, an anti-inflammatory, anti-atherogenic and insulin sensitizing adipokine exists in several isoforms in the circulation. In patients with chronic kidney disease (CKD), circulating levels of total as well as high-molecular-weight adiponectin are elevated. In contrast to initial studies, several recent and larger studies on outcomes do not support a protective effect of high adiponectin on cardiovascular disease (CVD) and overall mortality in CKD patients. Paradoxically, high adiponectin predicts increased overall and cardiovascular mortality in CKD patients. This effect seems unrelated to a direct effect of adiponectin, but rather due to a process of protein-energy (PEW) wasting. This review summarizes recent conflicting findings on adiponectin in relation to outcomes and discusses the pathophysiologic roles of adiponectin in PEW, insulin resistance and vascular injuries of CKD patients.

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

    PubMed Central

    2014-01-01

    Adiponectin is the most abundant peptide secreted by adipocytes, being a key component in the interrelationship between adiposity, insulin resistance and inflammation. Central obesity accompanied by insulin resistance is a key factor in the development of metabolic syndrome (MS) and future macrovascular complications. Moreover, the remarkable correlation between coronary artery disease (CAD) and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes mellitus (T2DM) may share a common biological background. We summarize here the current knowledge about the influence of adiponectin on insulin sensitivity and endothelial function, discussing its forthcoming prospects and potential role as a therapeutic target for MS, T2DM, and cardiovascular disease. Adiponectin is present in the circulation as a dimer, trimer or protein complex of high molecular weight hexamers, >400 kDa. AdipoR1 and AdipoR2 are its major receptors in vivo mediating the metabolic actions. Adiponectin stimulates phosphorylation and AMP (adenosin mono phosphate) kinase activation, exerting direct effects on vascular endothelium, diminishing the inflammatory response to mechanical injury and enhancing endothelium protection in cases of apolipoprotein E deficiency. Hypoadiponectinemia is consistently associated with obesity, MS, atherosclerosis, CAD, T2DM. Lifestyle correction helps to favorably modify plasma adiponectin levels. Low adiponectinemia in obese patients is raised via continued weight loss programs in both diabetic and nondiabetic individuals and is also accompanied by reductions in pro-inflammatory factors. Diet modifications, like intake of fish, omega-3 supplementation, adherence to a Mediterranean dietary pattern and coffee consumption also increase adiponectin levels. Antidiabetic and cardiovascular pharmacological agents, like glitazones, glimepiride, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are also able to

  5. Succination of thiol groups in adipose tissue proteins in diabetes: succination inhibits polymerization and secretion of adiponectin.

    PubMed

    Frizzell, Norma; Rajesh, Mathur; Jepson, Matthew J; Nagai, Ryoji; Carson, James A; Thorpe, Suzanne R; Baynes, John W

    2009-09-18

    S-(2-Succinyl)cysteine (2SC) is formed by reaction of the Krebs cycle intermediate fumarate with cysteine residues in protein, a process termed succination of protein. Both fumarate and succination of proteins are increased in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik, M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and Frizzell, N. (2007) J. Biol. Chem. 282, 34219-34228). We show here that succination of protein is also increased in epididymal, mesenteric, and subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a major target for succination in both adipocytes and adipose tissue. Cys-39, which is involved in cross-linking of adiponectin monomers to form trimers, was identified as a key site of succination of adiponectin in adipocytes. 2SC was detected on two of seven monomeric forms of adiponectin immunoprecipitated from adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin accounted for approximately 7 and 8% of total intracellular adiponectin in cells and tissue, respectively. 2SC was found only in the intracellular, monomeric forms of adiponectin and was not detectable in polymeric forms of adiponectin in cell culture medium or plasma. We conclude that succination of adiponectin blocks its incorporation into trimeric and higher molecular weight, secreted forms of adiponectin. We propose that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes.

  6. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome

    PubMed Central

    Kadowaki, Takashi; Yamauchi, Toshimasa; Kubota, Naoto; Hara, Kazuo; Ueki, Kohjiro; Tobe, Kazuyuki

    2006-01-01

    Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic metabolic actions of adiponectin, have been cloned and are downregulated in obesity-linked insulin resistance. Upregulation of adiponectin is a partial cause of the insulin-sensitizing and antidiabetic actions of thiazolidinediones. Therefore, adiponectin and adiponectin receptors represent potential versatile therapeutic targets to combat obesity-linked diseases characterized by insulin resistance. This Review describes the pathophysiology of adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. PMID:16823476

  7. Adiponectin Lowers Glucose Production by Increasing SOGA

    PubMed Central

    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

    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. PMID:20813965

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: The effects of fructose and glucose consumption on plasma acylation stimulating protein (ASP), adiponectin, and leptin concentrations relative to energy intake, body weight, adiposity, circulating triglycerides, and insulin sensitivity were determined. DESIGN AND METHODS: Thirty two over...

  9. Effects of specific domains of high-molecular-weight glutenin subunits’ on dough properties by an in vitro assay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An in vitro system for incorporating bacterially produced high-molecular-weight glutenin subunits (HMW-GS) into doughs was used to study the effects of specific domains of the HMW-GS. Synergistic effects of incorporating into doughs both the Dx5 and Dy10 subunits are localized to the N-terminal do...

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

    PubMed

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

    2003-11-01

    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.

  11. Bioaccumulation of HMW PAHs in the roots of wild blackberry from the Bor region (Serbia): Phytoremediation and biomonitoring aspects.

    PubMed

    Alagić, Slađana Č; Jovanović, Vesna P Stankov; Mitić, Violeta D; Cvetković, Jelena S; Petrović, Goran M; Stojanović, Gordana S

    2016-08-15

    In this work, the samples of roots and soils from the rooting zone of wild blackberry were collected from the urban-industrial and rural locations near "The Copper Mining and Smelting Complex Bor" (Serbia); they were analyzed by gas chromatographic-mass spectrometric method to determine the content of high-molecular weight polycyclic aromatic hydrocarbons (HMW PAHs). The obtained results were further processed using bio-concentration factor, Pearson's correlation study and hierarchical cluster analysis with the aim of investigating if they may be in favor of wild blackberry as a suitable plant for biomonitoring or phytoremediation purposes. In spite of the fact that numerous complex factors can affect the assimilation and accumulation of PAHs in plants, the obtained data expressed clearly many interesting specifics related to HMW PAH accumulation in roots of wild blackberry that naturally grows in an area, which is heavily polluted by heavy metals. The accumulation of individual PAH compounds in plant roots was at different level. The most abundant compound in all plant samples was benzo[a]pyrene and based on the results obtained for this environmental indicator of carcinogenic PAHs, it was possible to make several central conclusions: wild blackberry showed an excellent potential for its extraction from the soil and further accumulation in root tissues which indicate that this plant species may be applied in phytoremediation procedures based on mechanisms such as phytoextraction/phytoaccumulation in roots; phytostabilization and rhizodegradation are also possible as remediation mechanisms; utilization of plant roots in soil monitoring is possible but in this case, only the combination with soil data can provide correct information. PMID:27110970

  12. Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

    SciTech Connect

    Kitahara, Kanako; Kusunoki, Natsuko; Kakiuchi, Terutaka; Suguro, Toru; Kawai, Shinichi

    2009-01-09

    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.

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

    PubMed

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

    2012-07-24

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

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

    PubMed

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

    2012-09-01

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

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

    PubMed Central

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

    2012-01-01

    Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte–derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, “anhedonia,” and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic–pituitary–adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressant-like behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders. PMID:22778410

  16. Plasma adiponectin concentrations are associated with dietary glycemic index in Malaysian patients with type 2 diabetes.

    PubMed

    Loh, Beng-In; Sathyasuryan, Daniel Robert; Mohamed, Hamid Jan Jan

    2013-01-01

    Adiponectin, an adipocyte-derived hormone has been implicated in the control of blood glucose and chronic inflammation in type 2 diabetes. However, limited studies have evaluated dietary factors on plasma adiponectin levels, especially among type 2 diabetic patients in Malaysia. The aim of this study was to investigate the influence of dietary glycemic index on plasma adiponectin concentrations in patients with type 2 diabetes. A cross-sectional study was conducted in 305 type 2 diabetic patients aged 19-75 years from the Penang General Hospital, Malaysia. Socio-demographic information was collected using a standard questionnaire while dietary details were determined by using a pre-validated semi-quantitative food frequency questionnaire. Anthropometry measurement included weight, height, BMI and waist circumference. Plasma adiponectin concentrations were measured using a commercial ELISA kit. Data were analyzed using multiple linear regression. After multivariate adjustment, dietary glycemic index was inversely associated with plasma adiponectin concentrations (β =-0.272, 95% CI -0.262, - 0.094; p<0.001). It was found that in individuals who consumed 1 unit of foods containing high dietary glycemic index that plasma adiponectin level reduced by 0.3 μg/mL. Thirty two percent (31.9%) of the variation in adiponectin concentrations was explained by age, sex, race, smoking status, BMI, waist circumference, HDL-C, triglycerides, magnesium, fiber and dietary glycemic index according to the multiple linear regression model (R2=0.319). These results support the hypothesis that dietary glycemic index influences plasma adiponectin concentrations in patients with type 2 diabetes. Controlled clinical trials are required to confirm our findings and to elucidate the underlying mechanism.

  17. Effects of a 6-month infliximab treatment on plasma levels of leptin and adiponectin in patients with rheumatoid arthritis.

    PubMed

    Derdemezis, Christos S; Filippatos, Theodosios D; Voulgari, Paraskevi V; Tselepis, Alexandros D; Drosos, Alexandros A; Kiortsis, Dimitrios N

    2009-10-01

    Patients with rheumatoid arthritis (RA) appear to have increased plasma levels of leptin and adiponectin. These adipokines may be implicated in the pathophysiology of RA. Tumour necrosis factor alpha (TNF-alpha) is a potential modulator of adipokines. The effects of long-term anti-TNF treatment on plasma levels of leptin and adiponectin are not clear. The aim of this study was to assess the effects of 6-month anti-TNF treatment (infliximab) on leptin and adiponectin plasma levels in RA patients. Thirty women with RA were included in the study. Patients with diabetes mellitus, any endocrine disorder or receiving any hypolipidemic or antidiabetic medication were not included. Thirty healthy age- and body mass index-matched women served as controls. Plasma levels of leptin and adiponectin were measured with enzyme immunoassay methods prior to and after the 6-month treatment with infliximab. Mean age and disease duration of patients were 51.8 +/- 14.4 and 12.2 +/- 6.7 years, respectively. Body weight did not change significantly over the 6-month period. Plasma levels of leptin and adiponectin were higher in patients than controls and did not change significantly after 6-month treatment. Interestingly, in the tertile of patients with the highest baseline adiponectin concentrations, adiponectin levels were significantly reduced (P < 0.05). Infliximab treatment did not change plasma levels of leptin and adiponectin after 6-month treatment in the whole study population. However, a reduction of adiponectin levels was observed in patients with higher baseline adiponectin levels. PMID:19563510

  18. Effect of Extended-Release Niacin/Laropiprant Combination on Plasma Adiponectin and Insulin Resistance in Chinese Patients with Dyslipidaemia

    PubMed Central

    Yang, Ya-Ling; Masuda, Daisaku; Yamashita, Shizuya; Tomlinson, Brian

    2015-01-01

    Objectives. This study examined whether the increase of adiponectin associated with extended-release (ER) niacin/laropiprant combination attenuates the adverse effect of niacin on glucose and insulin resistance in Hong Kong Chinese patients with dyslipidaemia. Methods. Patients (N = 121) were treated with ER niacin/laropiprant 1 g/20 mg for 4 weeks and then the dose was doubled for an additional 8 weeks. Measurements of fasting lipids, glucose, insulin, and adiponectin were performed at baseline and during the study. Results. There were significant (P < 0.001) increases in glucose (9.4 ± 13.1%), insulin (70.2 ± 91.0%), HOMA-IR (87.8 ± 103.9%), and adiponectin (169.3 ± 111.6%). The increase in adiponectin was significantly associated with increase in glucose (r = 0.221, P < 0.05), insulin (r = 0.184, P < 0.05), and HOMA-IR (r = 0.237, P < 0.01) and the association remained significant after adjustment for changes in body weight or body fat mass. Conclusion. Treatment with ER niacin/laropiprant led to a significant increase in adiponectin levels but worsening of glucose levels and insulin resistance, and the increase in adiponectin and insulin resistance were correlated suggesting the increase in adiponectin did not ameliorate the deterioration in insulin resistance. Clinical trial is registered with number on WHO-ICTRP: ChiCTR-ONC-10001038. PMID:26063948

  19. Antiadhesion and antibiofilm activities of high molecular weight coffee components against Streptococcus mutans.

    PubMed

    Stauder, Monica; Papetti, Adele; Mascherpa, Dora; Schito, Anna Maria; Gazzani, Gabriella; Pruzzo, Carla; Daglia, Maria

    2010-11-24

    In previous studies we demonstrated that green and roasted coffee contains low molecular weight (LMW) compounds capable of inhibiting the ability of Streptococcus mutans, the major causative agent of human dental caries, to adhere to hydroxyapatite (HA) beads. This study addressed the ability of the whole high molecular weight coffee fraction (cHMW) and of its melanoidin and non-melanoidin components (GFC1-5), applied at concentrations that occur in coffee beverages, to (i) inhibit S. mutans growth; (ii) affect S. mutans sucrose-dependent adhesion to and detachment from saliva-coated HA beads (sHA); and (iii) inhibit biofilm development on microtiter plates. The results indicated that only cHMW is endowed with antimicrobial activity. The cHMW fraction and each of the five GFC components inhibited S. mutans adhesion, the strongest effect being exerted by cHMW (91%) and GFC1 (88%). S. mutans detachment from sHA was four times greater (∼20%) with cHMW and the GFC1 and GFC4 melanoidins than with controls. Finally, biofilm production by S. mutans was completely abolished by cHMW and was reduced by 20% by the melanoidin components GFC2 and GFC4 and by the non-melanoidin component GFC5 compared with controls. Altogether these findings show that coffee beverage contains both LMW compounds and HMW melanoidin and non-melanoidin components with a strong ability to interfere in vitro with the S. mutans traits relevant for cariogenesis. PMID:21038921

  20. Wheat gluten: high molecular weight glutenin subunits--structure, genetics, and relation to dough elasticity.

    PubMed

    Anjum, Faqir Muhammad; Khan, Moazzam Rafiq; Din, Ahmad; Saeed, Muhammad; Pasha, Imran; Arshad, Muhammad Umair

    2007-04-01

    Gluten proteins, representing the major protein fraction of the starchy endosperm, are predominantly responsible for the unique position of wheat amongst cereals. These form a continuous proteinaceous matrix in the cells of the mature dry grain and form a continuous viscoelastic network during the mixing process of dough development. These viscoelastic properties underline the utilization of wheat to prepare bread and other wheat flour based foodstuffs. One group of gluten proteins is glutenin, which consists of high molecular weight (HMW) and low molecular weight (LMW) subunits. The HMW glutenin subunits (HMW-GS) are particularly important for determining dough elasticity. The common wheat possesses 3 to 5 HMW subunits encoded at the Glu-1 loci on the long arms of group 1 chromosomes (1A, 1B, and 1D). The presence of certain HMW subunits is positively correlated with good bread-making quality. Glutamine-rich repetitive sequences that comprise the central part of the HMW subunits are actually responsible for the elastic properties due to extensive arrays of interchain hydrogen bonds. Genetic engineering can be used to manipulate the amount and composition of the HMW subunits, leading to either increased dough strength or more drastic changes in gluten structure and properties.

  1. The interactive effects of transgenically overexpressed 1Ax1 with various HMW-GS combinations on dough quality by introgression of exogenous subunits into an elite Chinese Wheat variety.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. Negative Skeletal Effects of Locally Produced Adiponectin

    PubMed Central

    Abbott, Marcia J.; Roth, Theresa M.; Ho, Linh; Wang, Liping; O’Carroll, Dylan; Nissenson, Robert A.

    2015-01-01

    Epidemiological studies show that high circulating levels of adiponectin are associated with low bone mineral density. The effect of adiponectin on skeletal homeostasis, on osteoblasts in particular, remains controversial. We investigated this issue using mice with adipocyte-specific over-expression of adiponectin (AdTg). MicroCT and histomorphometric analysis revealed decreases (15%) in fractional bone volume in AdTg mice at the proximal tibia with no changes at the distal femur. Cortical bone thickness at mid-shafts of the tibia and at the tibiofibular junction was reduced (3–4%) in AdTg mice. Dynamic histomorphometry at the proximal tibia in AdTg mice revealed inhibition of bone formation. AdTg mice had increased numbers of adipocytes in close proximity to trabecular bone in the tibia, associated with increased adiponectin levels in tibial marrow. Treatment of BMSCs with adiponectin after initiation of osteoblastic differentiation resulted in reduced mineralized colony formation and reduced expression of mRNA of osteoblastic genes, osterix (70%), Runx2 (52%), alkaline phosphatase (72%), Col1 (74%), and osteocalcin (81%). Adiponectin treatment of differentiating osteoblasts increased expression of the osteoblast genes PPARγ (32%) and C/ebpα (55%) and increased adipocyte colony formation. These data suggest a model in which locally produced adiponectin plays a negative role in regulating skeletal homeostasis through inhibition of bone formation and by promoting an adipogenic phenotype. PMID:26230337

  4. Serum Adiponectin and Indices of Cardiovascular Risk in Young Women with Excessive Body Mass

    PubMed Central

    Sypniewska, G.; Rajewski, P.; Gruszka, M.

    2010-01-01

    Adiponectin reduces oxidative stress, the release of C-reactive protein and influences on the process of atherogenesis reducing lipid accumulation in the blood vessels. The findings on the association of adiponectin with cardiovascular risk are contradictory. This study aimed to assess the relationship between adiponectin and indices of cardiovascular risk in women with excessive body mass. Adiponectin, hsCRP and lipids were measured in blood samples obtained from normoglycemic women with excessive body mass (n=52;BMI≥25 kg/m2) aged 25-40 yrs and age-matched healthy controls (n=36; BMI<25kg/m2). All subjects underwent blood pressure examination and anthropometric measurements. Median concentration of adiponectin in the serum in women with excessive body mass was significantly lower than in women with normal weight (10,8 vs 15,5 µg/ml; p<0,01). Similarly, median serum concentration of triglycerides, hsCRP and blood pressure values were significantly higher and HDL-cholesterol significantly lower in women with BMI≥25 kg/m2 in comparison to these with normal BMI, however only HDL-C and hsCRP were found to be beyond widely accepted cut-offs. Hypoadiponectinemia in women with excessive body mass (adiponectin concentration below the 5th percentile in the control group) was associated predominantly with abnormally increased median values of hsCRP and blood pressure. Concentrations of total cholesterol, non-HDL-C and LDL-C were also significantly higher in women with excessive body mass and hypoadiponectinemia, however still within the reference range. Our results suggest that adiponectin may be used as a prognostic marker of cardiovascular risk in women with excessive body mass.

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

    SciTech Connect

    Kuroyanagi, Kayo; Kang, Min-Sook; Goto, Tsuyoshi; Hirai, Shizuka; Ohyama, Kana; Kusudo, Tatsuya; Yu, Rina; Yano, Masamichi; Sasaki, Takao; Takahashi, Nobuyuki; Kawada, Teruo

    2008-02-01

    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.

  6. Changes of Serum Adiponectin and Testosterone Concentrations Following Twelve Weeks Resistance Training in Obese Young Men

    PubMed Central

    Moradi, Fatah

    2015-01-01

    Background: Circulating levels of adiponectin and testosterone decrease in obese men and this increases risks of cardiovascular disease and diabetes. Objectives: The purpose of this study was to survey changes of serum adiponectin and testosterone concentrations following twelve weeks resistance training in obese young men. Patients and Methods: In a semi-experimental study, twenty one obese young men were randomly placed in two groups: resistance training (26.5 ± 2.8 years) and control (27.4 ± 2.9 years). General characteristics of subjects and serum levels of adiponectin and testosterone were assessed before and after training. Resistance training protocol consisted of twelve weeks weight training (3 sessions per week, 10 exercises, 3 sets of 8 - 12 repetitions in each exercise, intensity 60% - 80% of one repetition maximum, rest between sets 1 minute and between exercises 2 minutes, duration of main training 20 - 40 minutes per each session). Results: Resistance training had no significant effect on body weight and body mass index (P > 0.05), whereas it decreased body fat percent (P = 0.017). Also, serum adiponectin (8.1 ± 1.8 vs. 10.5 ± 2.3 μg/mL) and testosterone concentrations (6.9 ± 2.4 vs. 8.2 ± 1.7 ng/mL) were increased after resistance training (P = 0.033, P = 0.018 respectively), while there were no significant changes in serum levels of these hormones in control group (P > 0.05). Conclusions: Twelve weeks of resistance training increased serum concentrations of adiponectin and testosterone in obese young men. With respect to inverse associations between changes of adiponectin and testosterone with BFP and insulin level variations after resistance training, it is recommended that obese young men do resistance training to benefit useful decreasing/preventive effects of this type of training against the risks of cardiovascular diseases and diabetes. PMID:26715965

  7. A common variant in the CLDN7/ELP5 locus predicts adiponectin change with lifestyle intervention and improved fitness in obese individuals with diabetes.

    PubMed

    Belalcazar, L Maria; Papandonatos, George D; McCaffery, Jeanne M; Peter, Inga; Pajewski, Nicholas M; Erar, Bahar; Allred, Nicholette D; Balasubramanyam, Ashok; Bowden, Donald W; Brautbar, Ariel; Pi-Sunyer, F Xavier; Ballantyne, Christie M; Huggins, Gordon S

    2015-06-01

    Overweight/obese individuals with Type 2 diabetes have low adiponectin levels, which may improve with lifestyle changes. We investigated whether genetic variants associated with adiponectin levels in genome-wide association studies (GWAS) would also be related with adiponectin changes in response to an intensive lifestyle intervention (ILI), potentially through mechanisms altering the adipose microenvironment via weight loss and/or improved cardiorespiratory fitness. Look AHEAD was a randomized trial comparing the cardiovascular benefits of ILI-induced weight loss and physical activity compared with diabetes support and education among overweight/obese individuals with Type 2 diabetes. In a subsample of Look AHEAD with adiponectin data and genetic consent (n=1,351), we evaluated the effects of 24 genetic variants, demonstrated by GWAS to be cross-sectionally associated with adiponectin, on adiponectin change 1-yr postintervention. We explored via mediational analyses whether any differential effects by treatment arm were occurring through weight loss and/or improved fitness. A variant, rs222857, in the CLDN7 locus, potentially associated with epithelial barrier integrity and tight junction physiology, and a putative cis expression quantitative trail locus for elongator acetyltransferase complex subunit 5 (ELP5), predicted adiponectin increases within ILI (log-adiponectin in overall sample per copy: β±SE=0.05±0.02, P=0.008; in non-Hispanic whites: 0.06±0.02, P=0.009). The favorable effects of rs222857 (minor allele frequency 45.5%) appeared to be mediated by mechanisms associated with improved fitness, and not weight loss. This is the first study to identify a genetic variant that modifies adiponectin response to lifestyle intervention in overweight/obese diabetic individuals. PMID:25759378

  8. Hawthorn leaf flavonoids alleviate nonalcoholic fatty liver disease by enhancing the adiponectin/AMPK pathway.

    PubMed

    Li, Zhongping; Xu, Jiaoya; Zheng, Peiyong; Xing, Lianjun; Shen, Hongyi; Yang, Lili; Zhang, Li; Ji, Guang

    2015-01-01

    Hawthorn (Crataeguspinnatifida) belongs to the genus Rosaceae family of plants. The hawthorn leaf, Crataeguspinnatifida Bunge, is used for both condiment and medicinal purposes to prevent and treat metabolic dysfunctions, such as hyperlipidemia, hypertension, and cardiovascular disease in traditional Chinese medicine. However, its effects on nonalcoholic fatty liver disease (NAFLD) remain obscure. The purpose of the present study was to investigate the protective effect of hawthorn leaf flavonoids (HLF), the dominant bioactive extracts of hawthorn leaves, on high fat diet (HFD)-induced hepatic steatosis and to elucidate its underlying mechanisms. HLF supplementation significantly lowered body weight, liver weight, liver/body weight ratio, improved serum parameters and liver dysfunction and markedly decreased hepatic lipid accumulation in HFD-fed rats. In addition, HLF intervention dramatically increased circulating adiponectin levels and up-regulated the expression of adiponectin receptors, particularly adiponectin receptor 2 (AdipoR2) in the liver. Moreover, adenosine monophosphate (AMP)-activated protein kinase (AMPK) was also activated, as well as AMPK-mediated alteration of sterol regulatory element binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor α (PPARα) and their downstream targets. Taken together, our data suggest that HLF ameliorates hepatic steatosis by enhancing the adiponectin/AMPK pathway in the liver of HFD-induced NAFLD rats. PMID:26770322

  9. Is adiponectin a risk factor for transient ischaemic attacks?

    PubMed

    Sener, Ufuk; Uludag, Irem Fatma; Kose, Sukran; Ozcelik, Murat; Zorlu, Yasar

    2015-01-01

    Adiponectin is an adipocytokine, and it plays a role in atherosclerosis. The role of adiponectin in the development of ischaemic stroke is controversial. Up to now, adiponectin was not evaluated in transient ischaemic stroke. In this study, we investigated the relationship between adiponectin and transient ischaemic attack. Forty patients with transient ischaemic attack were included into the study. In all patients, traditional risk factors of ischaemic stroke and intima-media thickness of carotid arteries were determined. Also, the relationship between these parameters and adiponectin levels were examined. No difference was found in terms of adiponectin levels between patients and healthy subjects. In addition, there was no association between adiponectin levels and traditional risk factors. Our results suggest that adiponectin may not be a predictive risk factor of transient ischaemic attack.

  10. Adiponectin as a target for the treatment of nonalcoholic steatohepatitis with thiazolidinediones: A systematic review.

    PubMed

    Polyzos, Stergios A; Mantzoros, Christos S

    2016-09-01

    Thiazolidinediones (TZDs; pioglitazone and rosiglitazone) have provided promising results in clinical trials for nonalcoholic steatohepatitis (NASH). The main purpose of this systematic review was to summarize evidence on circulating adiponectin levels in relation to histological changes following TZD treatment in patients with histologically confirmed NASH. We performed a systematic search in PubMed, Scopus and Cochrane Library. We included four studies, published between 2006 and 2012, providing data for 187 histologically confirmed NASH adult patients (105 on TZD and 82 controls) treated for 6-12months. Significant increase in adiponectin (80-178%) after TZD treatment was observed in all included studies. Improvement in steatosis following treatment was observed in all studies. A trend towards improvement in lobular inflammation was observed in all studies after pioglitazone, but not after rosiglitazone. Trends toward improvement in ballooning and fibrosis were observed in the two studies after pioglitazone using either the highest doses or the longest duration of therapy. Overall disease activity score was improved in all studies after pioglitazone, but not after rosiglitazone. Insulin resistance and liver function tests were also improved after treatment. Despite weight gain, circulating leptin was not increased after treatment. In conclusion, parallel increases in circulating adiponectin levels and histological improvement were observed in this systematic review. These results warrant further consideration of TZDs, but even more importantly point to a key role for novel potential treatments for NASH patients such as the newer selective peroxisome proliferator activated receptor-γ modulators, which increase adiponectin without significant weight gain. PMID:27506737

  11. Bioremediation of Mixtures of High Molecular Weight Polycyclic Aromatic Hydrocarbons

    NASA Astrophysics Data System (ADS)

    Xu, H.; Wu, J.; Shi, X.; Sun, Y.

    2014-12-01

    Although bioremediation has been considered as one of the most promising means to remove polycyclic aromatic hydrocarbons (PAHs) from polluted environments, the efficacy of PAHs bioremediation still remains challenged, especially for high molecular weight PAHs (HMW PAHs) and their mixtures. This study was focused on (a) isolation and characterization of pure strain and mixed microbial communities able to degrade HMW PAHs and (b) further evaluation of the ability of the isolated microbes to degrade HMW PAHs mixtures in the absence and presence of indigenous flora. Fluoranthene, benzo[b]fluoranthene and pyrene were selected as the representative HMW PAHs in this study. A pure bacterial strain, identified as Herbaspirillum chlorophenolicum FA1, was isolated from activated sludge. A mixed bacterial community designated as consortium-4 was isolated from petroleum contaminated soils, containing Pseudomonas sp. FbP1、Enterobacter sp. FbP2、Hydrogenophaga sp. FbP3 and Luteolibacter pohnpeiensis. FbP4. To our knowledge, this is the first study to demonstrate that bacterial strains of Herbaspirillum chlorophenolicum FA1 and Luteolibacter pohnpeiensis. FbP4 can also degrade fluoranthene, benzo[b]fluoranthene and pyrene. Experiment results showed that both strain FA1 and consortium-4 could degrade fluoranthene, benzo[b]fluoranthene and pyrene within a wide range of temperature, pH and initial PAHs concentration. Degradation of HMW PAHs mixtures (binary and ternary) demonstrated the interactive effects that can alter the rate and extent of biodegradation within a mixture. The presence of indigenous flora was found to either increase or decrease the degradation of HMW PAHs, suggesting possible synergistic or competition effects. Biodegradation kinetics of HMW PAHs for sole substrates, binary and ternary systems was evaluated, with the purpose to better characterize and compare the biodegradation process of individual HMW PAH and mixtures of HMW PAHs. Results of this study

  12. Adiponectin gene polymorphisms: Association with childhood obesity.

    PubMed

    Fraga, Vanêssa Gomes; Gomes, Karina Braga

    2014-03-01

    The current childhood obesity epidemic represents a particular challenge for public health. Understanding of the etiological mechanisms of obesity remains integral in treating this complex disorder. In recent years, studies have elucidated the influence of hormones secreted by adipose tissue named adipokines. Adiponectin is a adipokine that exhibits important anti-inflammatory, insulin-sensitizing and anti-atherogenic properties and it is strongly associated to obesity development. It is well known that adiponectin levels decrease with obesity. Furthermore, studies show that some single nucleotide polymorphisms in the gene encoding adiponectin, ADIPOQ, may influence the expression of this protein. The objective of this paper is to provide an up-to-date review of ADIPOQ polymorphisms in the context of childhood obesity. PMID:27625863

  13. Adiponectin gene polymorphisms: Association with childhood obesity

    PubMed Central

    Fraga, Vanêssa Gomes; Gomes, Karina Braga

    2014-01-01

    The current childhood obesity epidemic represents a particular challenge for public health. Understanding of the etiological mechanisms of obesity remains integral in treating this complex disorder. In recent years, studies have elucidated the influence of hormones secreted by adipose tissue named adipokines. Adiponectin is a adipokine that exhibits important anti-inflammatory, insulin-sensitizing and anti-atherogenic properties and it is strongly associated to obesity development. It is well known that adiponectin levels decrease with obesity. Furthermore, studies show that some single nucleotide polymorphisms in the gene encoding adiponectin, ADIPOQ, may influence the expression of this protein. The objective of this paper is to provide an up-to-date review of ADIPOQ polymorphisms in the context of childhood obesity. PMID:27625863

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

    PubMed

    Salmanowicz, Boleslaw P

    2010-07-01

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

  15. AdipoR1 and 2 are expressed on warm sensitive neurons of the hypothalamic preoptic area and contribute to central hyperthermic effects of adiponectin

    PubMed Central

    Klein, Izabella; Sanchez-Alavez, Manuel; Tabarean, Iustin; Schaefer, Jean; Holmberg, Kristina H.; Klaus, Joe; Xia, Fengcheng; Marcondes, Maria Cecilia Garibaldi; Dubins, Jeffrey S.; Morrison, Brad; Zhukov, Viktor; Sanchez-Gonzalez, Alejandro; Mitsukawa, Kayo; Hadcock, John R.; Bartfai, Tamas; Conti, Bruno

    2011-01-01

    Adiponectin can act in the brain to increase energy expenditure and reduce body weight by mechanisms not entirely understood. We found that adiponectin type 1 and type 2 receptors (AdipoR1 and AdipoR2) are expressed in warm sensitive neurons of the hypothalamic preoptic area (POA) which play a critical role in the regulation of core body temperature (CBT) and energy balance. Thus, we tested the ability of adiponectin to influence CBT in wild-type mice and in mice deficient for AdipoR1 or AdipoR2. Local injection of adiponectin into the POA induced prolonged elevation of core body temperature and decreased respiratory exchange ratio (RER) indicating that increased energy expenditure is associated with increased oxidation of fat over carbohydrates. In AdipoR1 deficient mice, the ability of adiponectin to raise CBT was significantly blunted and its ability to decrease RER was completely lost. In AdipoR2 deficient mice, adiponectin had only diminished hyperthermic effects but reduced RER similarly to wild type mice. These results indicate that adiponectin can contribute to energy homeostasis by regulating CBT by direct actions on AdipoR1 and R2 in the POA. PMID:22000082

  16. Adiponectin stimulates proliferation and cytokine secretion in colonic epithelial cells.

    PubMed

    Ogunwobi, Olorunseun Olatunji; Beales, Ian L P

    2006-05-15

    Adiponectin is a recently described mediator secreted by adipose tissue. Here we report the growth promoting and pro-inflammatory actions of adiponectin on colonic epithelial cancer cells. Full-length and globular adiponectin produced an identical stimulation of HT-29 cell growth that was blocked by inhibition of adenylate cyclase and protein kinase A and partially inhibited by a pan-specific protein kinase C inhibitor, but was unaffected by specific inhibition of extracellular signal-related kinase (ERK) or p38 MAP kinase. Globular adiponectin but not full-length adiponectin significantly increased the secretion and mRNA levels of IL-8, GM-CSF and MCP-1. Globular adiponectin doubled IL-1beta-stimulated IL-8 and GM-CSF secretion. Adiponectin-stimulated cytokine secretion was blocked by pharmacological inhibitors of NF-kappaB, ERK and p38 MAP kinase. Globular adiponectin increased phosphorylation of both ERK and p38 MAP kinase and increased the nuclear translocation of active NF-kappaB. Adiponectin has pro-proliferative and pro-inflammatory actions on colonic epithelial cells; these appear to be differentially activated by the adiponectin isoforms. Adiponectin may have a role in the regulation of gastrointestinal mucosal function, inflammation and colon carcinogenesis.

  17. Conserved cis-regulatory modules in promoters of genes encoding wheat high-molecular-weight glutenin subunits

    PubMed Central

    Ravel, Catherine; Fiquet, Samuel; Boudet, Julie; Dardevet, Mireille; Vincent, Jonathan; Merlino, Marielle; Michard, Robin; Martre, Pierre

    2014-01-01

    The concentration and composition of the gliadin and glutenin seed storage proteins (SSPs) in wheat flour are the most important determinants of its end-use value. In cereals, the synthesis of SSPs is predominantly regulated at the transcriptional level by a complex network involving at least five cis-elements in gene promoters. The high-molecular-weight glutenin subunits (HMW-GS) are encoded by two tightly linked genes located on the long arms of group 1 chromosomes. Here, we sequenced and annotated the HMW-GS gene promoters of 22 electrophoretic wheat alleles to identify putative cis-regulatory motifs. We focused on 24 motifs known to be involved in SSP gene regulation. Most of them were identified in at least one HMW-GS gene promoter sequence. A common regulatory framework was observed in all the HMW-GS gene promoters, as they shared conserved cis-regulatory modules (CCRMs) including all the five motifs known to regulate the transcription of SSP genes. This common regulatory framework comprises a composite box made of the GATA motifs and GCN4-like Motifs (GLMs) and was shown to be functional as the GLMs are able to bind a bZIP transcriptional factor SPA (Storage Protein Activator). In addition to this regulatory framework, each HMW-GS gene promoter had additional motifs organized differently. The promoters of most highly expressed x-type HMW-GS genes contain an additional box predicted to bind R2R3-MYB transcriptional factors. However, the differences in annotation between promoter alleles could not be related to their level of expression. In summary, we identified a common modular organization of HMW-GS gene promoters but the lack of correlation between the cis-motifs of each HMW-GS gene promoter and their level of expression suggests that other cis-elements or other mechanisms regulate HMW-GS gene expression. PMID:25429295

  18. Adiponectin in eutrophic and obese children as a biomarker to predict metabolic syndrome and each of its components

    PubMed Central

    2013-01-01

    Background Obesity is associated with the rise of noncommunicable diseases worldwide. The pathophysiology behind this disease involves the increase of adipose tissue, being inversely related to adiponectin, but directly related to insulin resistance and metabolic syndrome (MetS). Therefore, this study aimed to determine the relationship between adiponectin levels with each component of MetS in eutrophic and obese Mexican children. Methods A cross sectional study was conducted in 190 school-age children classified as obese and 196 classified as eutrophic. Adiponectin, glucose, insulin, high density lipoprotein cholesterol (HDL-C) and triglycerides were determined from a fasting blood sample. Height, weight, waist circumference, systolic and diastolic blood pressures (BP) were measured; MetS was evaluated with the IDF definition. The study groups were divided according to tertiles of adiponectin, using the higher concentration as a reference. Linear regression analysis was used to assess the association between adiponectin and components of the MetS. Finally, stepwise forward multiple logistic regression analysis controlling for age, gender, basal HOMA-IR values and BMI was performed to determine the odds ratio of developing MetS according to adiponectin tertiles. Results Anthropometric and metabolic measurements were statistically different between eutrophic and obese children with and without MetS (P <0.001). The prevalence of MetS in obese populations was 13%. Adiponectin concentrations were 15.5 ± 6.1, 12.0 ± 4.8, 12.4 ± 4.9 and 9.4 ± 2.8 μg/mL for eutrophic and obese subjects, obese without MetS, and obese with MetS, respectively (P <0.001). Obese children with low values of adiponectin exhibited a higher frequency of MetS components: abdominal obesity, 49%; high systolic BP, 3%; high diastolic BP, 2%; impaired fasting glucose, 17%; hypertriglyceridemia, 31%; and low HDL-C values, 42%. Adjusted odds ratio of presenting MetS according to

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

    PubMed Central

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

    2013-01-01

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

  20. Comparison of Serum Adiponectin in Smoke-induced Pulmonary Emphysema Rats Fed Different Diets

    PubMed Central

    Wang, Rui-Ying; Liu, Hu; Ma, Li-Juan; Xu, Jian-Ying

    2016-01-01

    Background: Smoking and body mass index (BMI) are the key risk factors for chronic obstructive pulmonary disease (COPD). Adiponectin with both anti-inflammatory and pro-inflammatory properties is a vital modulator of inflammatory processes, which is expressed in epithelial cells in the airway in COPD-emphysema. The aim of this study was to examine the effects of adiponectin on tobacco smoke-induced emphysema in rats, which were fed different diets. Methods: Seventy-six adult (6–8 weeks old) male Sprague-Dawley rats (average weight 220 ± 20 g) were exposed to smoke or smoke-free room atmosphere and fed different diets (regular, high-fat, or low-fat diets) for 6 months. The rats were randomly divided into six groups. They are nonsmoke-exposed regular diet (n = 10), nonsmoke-exposed high-fat diet (n = 14), nonsmoke-exposed low-fat diet (n = 14), smoke-exposed regular diet (n = 10), smoke-exposed high-fat diet (n = 14), and smoke-exposed low-fat diet groups (n = 14). A full 23 factorial design was used to evaluate the effect of independent variables on smoke exposure and different rearing methods. Serum adiponectin and inflammatory cytokines were measured by the enzyme-linked immunosorbent assay (ELISA). Results: Serum adiponectin levels in rats fed low-fat and regular diets exposed to smoke exposure were remarkably higher than that of rats exposed to room air while serum adiponectin levels of fat-rich diet rats exposed to tobacco smoke were lower than that of rats exposed to room air. Compared with regular diet or low-fat diet group, serum adiponectin levels in high-fat diet rats exposed to tobacco smoke were lower (t = 6.932, 11.026; all P < 0.001). BMI was inversely correlated with serum adiponectin levels (r = −0.751, P = 0.012). Serum interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and 4-hydroxy 2-nonenal (HNE) levels in rats exposed to low-fat or fat-rich diets were remarkably higher than that of rats exposed to normal diets (IL-6, t = 4.196, 3

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2014-01-01

    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

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

    PubMed

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

    2010-06-01

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

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

    NASA Astrophysics Data System (ADS)

    Kaufman, Darrell S.; Miller, Gifford H.

    1995-07-01

    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 (Σ[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

  5. Relationship between adiponectin and fertility in the female pig.

    PubMed

    Campos, Danila B; Albornoz, Marcelo; Papa, Paula C; Palin, Marie-France; Bordignon, Vilceu; Murphy, Bruce D

    2015-03-01

    Adiponectin isoforms may mediate different aspects of the pleiotropic function of the protein, including the reproductive process. We examined the pattern of circulating adiponectin and adiponectin system expression in fat and ovarian tissues of hyperfertile and subfertile sows. We demonstrated the presence of five different isoforms of adiponectin (90, 158, 180, 250 and >250kDa) in the circulation and identified a subgroup of subfertile females that displayed reduced abundance of all adiponectin isoforms as well as a lack of the 250-kDa adiponectin isoform in both serum and follicular fluid. Subfertility in these animals was associated with fewer large follicles and corpora lutea in the ovaries, as well as lower concentrations of 17β-oestradiol in the follicular fluid of large follicles. In addition, subfertile females showed higher adiponectin mRNA in fat tissue and altered mRNA and protein expression of adiponectin and its receptors in the ovary. Changes in the abundance and pattern of circulating adiponectin isoforms have been associated with reproductive disorders in animals and humans, including polycystic ovarian syndrome (PCOS). Our findings suggest that the adiponectin system may play an important role in controlling ovarian function and influencing porcine fertility.

  6. Maternal adiponectin controls milk composition to prevent neonatal inflammation.

    PubMed

    Jin, Zixue; Du, Yang; Schwaid, Adam G; Asterholm, Ingrid W; Scherer, Philipp E; Saghatelian, Alan; Wan, Yihong

    2015-04-01

    Adiponectin is an important adipokine. Increasing evidence suggests that altered adiponectin levels are linked with metabolic and inflammatory disorders. Here we report an important yet previously unrecognized function of adiponectin in lactation by which maternal adiponectin determines the inflammatory status in the nursing neonates. Surprisingly, both maternal adiponectin overexpression in the transgenic mice and maternal adiponectin deletion in the knockout mice lead to systemic inflammation in the pups, manifested as transient hair loss. However, distinct mechanisms are involved. Adiponectin deficiency triggers leukocyte infiltration and production of inflammatory cytokines in the lactating mammary gland. In contrast, adiponectin overabundance increases lipid accumulation in the lactating mammary gland, resulting in excessive long-chain saturated fatty acids in milk. Interestingly, in both cases, the inflammation and alopecia in the pups can be rescued by Toll-like receptor (TLR)-2/4 deletion because TLR2/4 double-knockout pups are resistant. Mechanistically, long-chain saturated fatty acid activation of inflammatory genes is TLR2/4 dependent and can be potentiated by proinflammatory cytokines, indicating that the inflammatory stimuli in both scenarios functionally converge by activating the TLR2/4 signaling. Therefore, our findings reveal adiponectin as a dosage-dependent regulator of lactation homeostasis and milk quality that critically controls inflammation in the nursing neonates. Furthermore, these results suggest that inflammatory infantile disorders may result from maternal adiponectin dysregulation that can be treated by TLR2/4 inhibition. PMID:25590242

  7. Maternal Overweight Programs Insulin and Adiponectin Signaling in the Offspring

    PubMed Central

    Shankar, Kartik; Kang, Ping; Harrell, Amanda; Zhong, Ying; Marecki, John C.; Ronis, Martin J. J.; Badger, Thomas M.

    2010-01-01

    Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult life. Male offspring from OW dams gain greater body weight and fat mass and develop insulin resistance when fed high-fat diets (45% fat). In this report, we identify molecular targets of maternal OW-induced programming at postnatal d 21 before challenge with the high-fat diet. We conducted global transcriptome profiling, gene/protein expression analyses, and characterization of downstream signaling of insulin and adiponectin pathways in conjunction with endocrine and biochemical characterization. Offspring born to OW dams displayed increased serum insulin, leptin, and resistin levels (P < 0.05) at postnatal d 21 preceding changes in body composition. A lipogenic transcriptome signature in the liver, before development of obesity, was evident in OW-dam offspring. A coordinated locus of 20 sterol regulatory element-binding protein-1-regulated target genes was induced by maternal OW. Increased nuclear levels of sterol regulatory element-binding protein-1 and recruitment to the fatty acid synthase promoter were confirmed via ELISA and chromatin immunoprecipitation analyses, respectively. Higher fatty acid synthase and acetyl coenzyme A carboxylase protein and pAKT (Thr308) and phospho-insulin receptor-β were confirmed via immunoblotting. Maternal OW also attenuated AMP kinase/peroxisome proliferator-activated receptor-α signaling in the offspring liver, including transcriptional down-regulation of several peroxisome proliferator-activated receptor-α-regulated genes. Hepatic mRNA and circulating fibroblast growth factor-21 levels were significantly lower in OW-dam offspring. Furthermore, serum levels of high-molecular-weight adiponectin (P < 0.05) were decreased in OW-dam offspring. Phosphorylation of hepatic AMP-kinase (Thr172) was significantly decreased in OW-dam offspring, along with lower AdipoR1 mRNA. Our results strongly suggest that gestational exposure to maternal

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

    PubMed

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

    2003-09-01

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

  9. Back to the heart: the protective role of adiponectin.

    PubMed

    Caselli, C; D'Amico, A; Cabiati, M; Prescimone, T; Del Ry, S; Giannessi, D

    2014-04-01

    Cardiovascular disease (CVD) is the leading cause of death worldwide and the prevalence of obesity and diabetes are increasing. In obesity, adipose tissue increases the secretion of bioactive mediators (adipokines) that may represent a key mechanism linking obesity to CVD. Adiponectin, extensively studied in metabolic diseases, exerts anti-diabetic, anti-atherogenic and anti-inflammatory activities. Due to these positive actions, the role of adiponectin in cardiovascular protection has been evaluated in recent years. In particular, for its potential therapeutic benefits in humans, adiponectin has become the subject of intense preclinical research. In the cardiovascular context, understanding of the cellular and molecular mechanisms underlying the adiponectin system, throughout its secretion, regulation and signaling, is critical for designing new drugs that target adiponectin system molecules. This review focused on recent advances regarding molecular mechanisms related to protective effects of the adiponectin system on both cardiac and vascular compartments and its potential use as a target for therapeutic intervention of CVD.

  10. [SNPs detection of adiponectin gene and its relationship with carcass and meat quality traits in Qinchuan cattle].

    PubMed

    Yang, Yan-Jie

    2009-10-01

    Four hundred and five Qinchuan cattle at the age of 24 months were used to detect SNPs of adiponectin gene by PCR-SSCP and sequencing technology and to analyze the correlation of SNPs with carcass and meat quality traits using the general linear model (GLM) in SPSS program. Five genotypes (AA, AB, BB, CC, CD) were detected,with one G-->C mutation at 64 bp in exon2 of adiponectin in ABBB genotypes and one C-->T mutation at 50 bp in exon3 of adiponectin in CD genotype. G-->C mutation resulted glutamic acid (GGA) into glutamine (GCA) and C-->T mutation resulted serine (TCA) into leucine (TTA). Statistical analysis revealed that Qinchuan cattle with AA genotype was higher than BB genotype in slaughter weight, back fat thickness, carcass weight, loin muscle area (P < 0.05). The crural girth of AA genotype was significantly higher than AB and BB genotypes (P < 0.01). Qinchuan cattle with CD genotype was higher than CC genotype in slaughter weight, subcutaneous fat thickness, back fat thickness, crural girth, and tenderness (P < 0.05). Adiponectin gene was proved to be closely related to carcass and meat quality traits (P < 0.05), which can be used as a candidate molecular marker for production of high-grade meat in Qinchuan beef cattle.

  11. Serum Adiponectin and Leptin Concentrations in Relation to Body Fat Distribution, Hematological Indices and Lipid Profile in Humans

    PubMed Central

    Lubkowska, Anna; Radecka, Aleksandra; Bryczkowska, Iwona; Rotter, Iwona; Laszczyńska, Maria; Dudzińska, Wioleta

    2015-01-01

    The purpose of the study was to evaluate the relationship between serum adiponectin and leptin concentrations and body composition, hematological indices and lipid profile parameters in adults. The study involved 95 volunteers (BMI from 23.3 to 53 kg/m2). Anthropometric parameters were measured: body weight and height, waist and hip circumference, waist-to-hip ratio, body fat mass (BMF), subcutaneous and visceral fat mass (SFM, VFM), lean body mass (LBM), skeletal muscle mass (SMM). In serum we determined adiponectin and leptin concentrations, extracellular hemoglobin, total bilirubin, as well as lipid metabolism (TCh, HDL-Ch, LDL-Ch, TG). Mean adipokine levels were significantly higher in women (p ≤ 0.01), adiponectin significantly negatively correlated with body height and weight, systolic blood pressure and absolute LBM and SMM values. The same relation was observed for erythroid system indicators and lipid indicators. A positive correlation was exceptionally found between adiponectin and HDL-Ch. LEP negatively correlated with some percentage rates (%LBM, %SMM). Only in women, we observed a positive correlation between LEP and body weight, BMI and WHR. Studies on ADPN and the ADPN/LEP ratio as a valuable complementary diagnostic element in the prediction and prevention of cardiovascular diseases need to be continued. PMID:26389928

  12. Serum Adiponectin and Leptin Concentrations in Relation to Body Fat Distribution, Hematological Indices and Lipid Profile in Humans.

    PubMed

    Lubkowska, Anna; Radecka, Aleksandra; Bryczkowska, Iwona; Rotter, Iwona; Laszczyńska, Maria; Dudzińska, Wioleta

    2015-09-14

    The purpose of the study was to evaluate the relationship between serum adiponectin and leptin concentrations and body composition, hematological indices and lipid profile parameters in adults. The study involved 95 volunteers (BMI from 23.3 to 53 kg/m²). Anthropometric parameters were measured: body weight and height, waist and hip circumference, waist-to-hip ratio, body fat mass (BMF), subcutaneous and visceral fat mass (SFM, VFM), lean body mass (LBM), skeletal muscle mass (SMM). In serum we determined adiponectin and leptin concentrations, extracellular hemoglobin, total bilirubin, as well as lipid metabolism (TCh, HDL-Ch, LDL-Ch, TG). Mean adipokine levels were significantly higher in women (p ≤ 0.01), adiponectin significantly negatively correlated with body height and weight, systolic blood pressure and absolute LBM and SMM values. The same relation was observed for erythroid system indicators and lipid indicators. A positive correlation was exceptionally found between adiponectin and HDL-Ch. LEP negatively correlated with some percentage rates (%LBM, %SMM). Only in women, we observed a positive correlation between LEP and body weight, BMI and WHR. Studies on ADPN and the ADPN/LEP ratio as a valuable complementary diagnostic element in the prediction and prevention of cardiovascular diseases need to be continued.

  13. Association of adiponectin and adiponectin receptor genes with sow productivity estimated breeding values.

    PubMed

    Jafarikia, Moshen; Méthot, Steve; Maignel, Laurence; Fortin, Frédéric; Wyss, Stefanie; Sullivan, Brian; Palin, Marie-France

    2015-09-01

    Our objectives were to estimate frequencies of previously identified single nucleotide polymorphisms (SNPs) in adiponectin (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) in a population of Duroc, Landrace and Yorkshire pigs and evaluate the effect of these alleles on sow productivity estimated breeding values (EBVs). Eight SNPs were genotyped on 446 pigs in the ADIPOQ (c.178G>A, c.*300A>G, c.*1094_1095insC and c.*1779A>C), ADIPOR1 (c.*129A>C) and ADIPOR2 (c.*112G>A, c.*295G>C and c.*1455G>A) genes. Association analyses were performed with sow productivity EBVs based on litter records collected in Canadian breeding farms. There were significant associations between ADIPOQ c.178G>A and c.*1094_1095insC SNPs and studied traits. However, none of these associations remained significant after applying a Bonferroni correction. The ADIPOR2 c.*112G>A SNP was associated with the total number of piglets born (TNB, P < 0.001) and litter weight at weaning (LWW, P < 0.001) EBVs. Associations were also observed between the ADIPOR2 [A;C;G] haplotype and TNB and LWW (P < 0.001). Our results demonstrate that a selection in favor of the c.*112G allele or against the [A;C;G] haplotype may have the potential to increase LWW EBVs. However, the c.*112G allele is also associated with lower TNB EBVs. Some of the alleles of the genes studied showed substantial variability and in general, the results corroborated previously reported findings for an independent sow population. However, careful cost-benefits analyses should be performed before using these markers in selection program as an improvement in TNB may translate into lighter LWW, with its associated negative impact on production traits such as growth performances.

  14. Do Low Molecular Weight Agents Cause More Severe Asthma than High Molecular Weight Agents?

    PubMed Central

    Meca, Olga; Cruz, María-Jesús; Sánchez-Ortiz, Mónica; González-Barcala, Francisco-Javier; Ojanguren, Iñigo; Munoz, Xavier

    2016-01-01

    Introduction The aim of this study was to analyse whether patients with occupational asthma (OA) caused by low molecular weight (LMW) agents differed from patients with OA caused by high molecular weight (HMW) with regard to risk factors, asthma presentation and severity, and response to various diagnostic tests. Methods Seventy-eight patients with OA diagnosed by positive specific inhalation challenge (SIC) were included. Anthropometric characteristics, atopic status, occupation, latency periods, asthma severity according to the Global Initiative for Asthma (GINA) control classification, lung function tests and SIC results were analysed. Results OA was induced by an HMW agent in 23 patients (29%) and by an LMW agent in 55 (71%). A logistic regression analysis confirmed that patients with OA caused by LMW agents had a significantly higher risk of severity according to the GINA classification after adjusting for potential confounders (OR = 3.579, 95% CI 1.136–11.280; p = 0.029). During the SIC, most patients with OA caused by HMW agents presented an early reaction (82%), while in patients with OA caused by LMW agents the response was mainly late (73%) (p = 0.0001). Similarly, patients with OA caused by LMW agents experienced a greater degree of bronchial hyperresponsiveness, measured as the difference in the methacholine dose-response ratio (DRR) before and after SIC (1.77, range 0–16), compared with patients with OA caused by HMW agents (0.87, range 0–72), (p = 0.024). Conclusions OA caused by LMW agents may be more severe than that caused by HMW agents. The severity of the condition may be determined by the different mechanisms of action of these agents. PMID:27280473

  15. Adiponectin as a potential biomarker of vascular disease

    PubMed Central

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

    2015-01-01

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

  16. Crystal structures of the human adiponectin receptors.

    PubMed

    Tanabe, Hiroaki; Fujii, Yoshifumi; Okada-Iwabu, Miki; Iwabu, Masato; Nakamura, Yoshihiro; Hosaka, Toshiaki; Motoyama, Kanna; Ikeda, Mariko; Wakiyama, Motoaki; Terada, Takaho; Ohsawa, Noboru; Hato, Masakatsu; Ogasawara, Satoshi; Hino, Tomoya; Murata, Takeshi; Iwata, So; Hirata, Kunio; Kawano, Yoshiaki; Yamamoto, Masaki; Kimura-Someya, Tomomi; Shirouzu, Mikako; Yamauchi, Toshimasa; Kadowaki, Takashi; Yokoyama, Shigeyuki

    2015-04-16

    Adiponectin stimulation of its receptors, AdipoR1 and AdipoR2, increases the activities of 5' AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR), respectively, thereby contributing to healthy longevity as key anti-diabetic molecules. AdipoR1 and AdipoR2 were predicted to contain seven transmembrane helices with the opposite topology to G-protein-coupled receptors. Here we report the crystal structures of human AdipoR1 and AdipoR2 at 2.9 and 2.4 Å resolution, respectively, which represent a novel class of receptor structure. The seven-transmembrane helices, conformationally distinct from those of G-protein-coupled receptors, enclose a large cavity where three conserved histidine residues coordinate a zinc ion. The zinc-binding structure may have a role in the adiponectin-stimulated AMPK phosphorylation and UCP2 upregulation. Adiponectin may broadly interact with the extracellular face, rather than the carboxy-terminal tail, of the receptors. The present information will facilitate the understanding of novel structure-function relationships and the development and optimization of AdipoR agonists for the treatment of obesity-related diseases, such as type 2 diabetes. PMID:25855295

  17. Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action

    PubMed Central

    Liu, Ying; Sen, Sanjana; Wannaiampikul, Sivaporn; Palanivel, Rengasamy; Hoo, Ruby L. C.; Isserlin, Ruth; Bader, Gary D.; Tungtrongchitr, Rungsunn; Deshaies, Yves; Xu, Aimin; Sweeney, Gary

    2016-01-01

    Adiponectin mediates anti-diabetic effects via increasing hepatic insulin sensitivity and direct metabolic effects. In the present study, we conducted a comprehensive and unbiased metabolomic profiling of liver tissue from AdKO (adiponectin-knockout) mice, with and without adiponectin supplementation, fed on an HFD (high-fat diet) to derive insight into the mechanisms and consequences of insulin resistance. Hepatic lipid accumulation and insulin resistance induced by the HFD were reduced by adiponectin. The HFD significantly altered levels of 147 metabolites, and bioinformatic analysis indicated that one of the most striking changes was the profile of increased lysophospholipids. These changes were largely corrected by adiponectin, at least in part via direct regulation of PLA2 (phospholipase A2) as palmitate-induced PLA2 activation was attenuated by adiponectin in primary hepatocytes. Notable decreases in several glycerolipids after the HFD were reversed by adiponectin, which also corrected elevations in several diacyglycerol and ceramide species. Our data also indicate that stimulation of ω-oxidation of fatty acids by the HFD is enhanced by adiponectin. In conclusion, this metabolomic profiling approach in AdKO mice identified important targets of adiponectin action, including PLA2, to regulate lysophospholipid metabolism and ω-oxidation of fatty acids. PMID:25915851

  18. Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: adiponectin regulates steroidogenesis.

    PubMed

    Li, Ping; Sun, Fei; Cao, Huang-Ming; Ma, Qin-Yun; Pan, Chun-Ming; Ma, Jun-Hua; Zhang, Xiao-Na; Jiang, He; Song, Huai-Dong; Chen, Ming-Dao

    2009-12-25

    Obesity is frequently associated with malfunctions of the hypothalamus-pituitary-adrenal (HPA) axis and hyperaldosteronism, but the mechanism underlying this association remains unclear. Since the adrenal glands are embedded in adipose tissue, direct cross-talk between adipose tissue and the adrenal gland has been proposed. A previous study found that adiponectin receptor mRNA was expressed in human adrenal glands and aldosterone-producing adenoma (APA). However, the expression of adiponectin receptors in adrenal glands has not been confirmed at the protein level or in other species. Furthermore, it is unclear whether adiponectin receptors expressed in adrenal cells are functional. We found, for the first time, that adiponectin receptor (AdipoR1 and AdipoR2) mRNA and protein were expressed in mouse adrenal and adrenocortical Y-1 cells. However, adiponectin itself was not expressed in mouse adrenal or Y-1 cells. Furthermore, adiponectin acutely reduced basal levels of corticosterone and aldosterone secretion. ACTH-induced steroid secretion was also inhibited by adiponectin, and this was accompanied by a parallel change in the expression of the key genes involved in steroidogenesis. These findings indicate that adiponectin may take part in the modulation of steroidogenesis. Thus, adiponectin is likely to have physiological and/or pathophysiological significance as an endocrine regulator of adrenocortical function.

  19. Structural Characterization and Evolutionary Relationship of High-Molecular-Weight Glutenin Subunit Genes in Roegneria nakaii and Roegneria alashanica

    PubMed Central

    Zhang, Lujun; Li, Zhixin; Fan, Renchun; Wei, Bo; Zhang, Xiangqi

    2016-01-01

    The Roegneria of Triticeae is a large genus including about 130 allopolyploid species. Little is known about its high-molecular-weight glutenin subunits (HMW-GSs). Here, we reported six novel HMW-GS genes from R. nakaii and R. alashanica. Sequencing indicated that Rny1, Rny3, and Ray1 possessed intact open reading frames (ORFs), whereas Rny2, Rny4, and Ray2 harbored in-frame stop codons. All of the six genes possessed a similar primary structure to known HMW-GS, while showing some unique characteristics. Their coding regions were significantly shorter than Glu-1 genes in wheat. The amino acid sequences revealed that all of the six genes were intermediate towards the y-type. The phylogenetic analysis showed that the HMW-GSs from species with St, StY, or StH genome(s) clustered in an independent clade, varying from the typical x- and y-type clusters. Thus, the Glu-1 locus in R. nakaii and R. alashanica is a very primitive glutenin locus across evolution. The six genes were phylogenetically split into two groups clustered to different clades, respectively, each of the two clades included the HMW-GSs from species with St (diploid and tetraploid species), StY, and StH genomes. Hence, it is concluded that the six Roegneria HMW-GS genes are from two St genomes undergoing slight differentiation. PMID:27447615

  20. T-cadherin Is Essential for Adiponectin-mediated Revascularization*

    PubMed Central

    Parker-Duffen, Jennifer L.; Nakamura, Kazuto; Silver, Marcy; Kikuchi, Ryosuke; Tigges, Ulrich; Yoshida, Sumiko; Denzel, Martin S.; Ranscht, Barbara; Walsh, Kenneth

    2013-01-01

    Adipose tissue secretes protein factors that have systemic actions on cardiovascular tissues. Previous studies have shown that ablation of the adipocyte-secreted protein adiponectin leads to endothelial dysfunction, whereas its overexpression promotes wound healing. However, the receptor(s) mediating the protective effects of adiponectin on the vasculature is not known. Here we examined the role of membrane protein T-cadherin, which localizes adiponectin to the vascular endothelium, in the revascularization response to chronic ischemia. T-cadherin-deficient mice were analyzed in a model of hind limb ischemia where blood flow is surgically disrupted in one limb and recovery is monitored over 28 days by laser Doppler perfusion imaging. In this model, T-cadherin-deficient mice phenocopy adiponectin-deficient mice such that both strains display an impaired blood flow recovery compared with wild-type controls. Delivery of exogenous adiponectin rescued the impaired revascularization phenotype in adiponectin-deficient mice but not in T-cadherin-deficient mice. In cultured endothelial cells, T-cadherin deficiency by siRNA knockdown prevented the ability of adiponectin to promote cellular migration and proliferation. These data highlight a previously unrecognized role for T-cadherin in limb revascularization and show that it is essential for mediating the vascular actions of adiponectin. PMID:23824191

  1. Linkage analysis of circulating levels of adiponectin in hispanic children

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. About the origin of European spelt ( Triticum spelta L.): allelic differentiation of the HMW Glutenin B1-1 and A1-2 subunit genes.

    PubMed

    Blatter, R H E; Jacomet, S; Schlumbaum, A

    2004-01-01

    To investigate the origin of European spelt ( Triticum spelta L., genome AABBDD) and its relation to bread wheat ( Triticum aestivum L., AABBDD), we analysed an approximately 1-kb sequence, including a part of the promoter and the coding region, of the high-molecular-weight (HMW) glutenin B1-1 and A1-2 subunit genes in 58 accessions of hexa- and tetraploid wheat from different geographical regions. Six Glu-B1-1 and five Glu-A1-2 alleles were identified based on 21 and 19 informative sites, respectively, which suggests a polyphyletic origin of the A- and B-genomes of hexaploid wheat. In both genes, a group of alleles clustered in a distinct, so-called beta subclade. High frequencies of alleles from the Glu-B1-1 and Glu-A1-2 beta subclades differentiated European spelt from Asian spelt and bread wheat. This indicates different origins of European and Asian spelt, and that European spelt does not derive from the hulled progenitors of bread wheat. The conjoint differentiation of alleles of the A- and B-genome in European spelt suggests the introgression of a tetraploid wheat into free-threshing hexaploid wheat as the origin of European spelt.

  3. Localization of high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae by immunoelectron microscopy.

    PubMed Central

    Bakaletz, L O; Barenkamp, S J

    1994-01-01

    A family of high-molecular-weight (HMW) surface-exposed proteins important in the attachment of nontypeable Haemophilus influenzae (NTHi) to human epithelial cells was previously identified (J. W. St. Geme III, S. Falkow, and S. J. Barenkamp, Proc. Natl. Acad. Sci. USA 90:2875-2879, 1993). In the present investigation, indirect immunogold labeling and electron microscopy were used to localize these proteins on three clinical isolates of NTHi, mutants deficient in expression of one or both HMW proteins, and embedded sections of human oropharyngeal cells after incubation with NTHi strain 12. The filamentous material comprising the proteins was labeled with monoclonal antibodies directed against two prototype HMW proteins (HMW1 and HMW2) of prototype NTHi strain 12. Gold labeling was observed as a cap or discrete aggregate off one pole or centrally along one long axis of the bacterial cell. Heavily labeled, non-bacterial-cell-associated, disk-like aggregates of the HMW proteins were frequently noted in both bacterial preparations as well as in association with the oropharyngeal cell surface and intracellularly. Mutants demonstrated diminished labeling or an absence thereof, respectively, which correlated well with their previously demonstrated reduced ability or inability to adhere to Chang conjunctival epithelial cells in vitro. The Haemophilus HMW proteins share antigenic determinants with and demonstrate amino acid sequence similarity to the filamentous hemagglutinin protein of Bordetella pertussis, a critical adhesin of that organism. The studies presented here demonstrate that the Haemophilus proteins and B. pertussis filamentous hemagglutinin show impressive morphologic and perhaps additional functional similarity. Images PMID:7927710

  4. Biofilm and Planktonic Bacterial and Fungal Communities Transforming High-Molecular-Weight Polycyclic Aromatic Hydrocarbons.

    PubMed

    Folwell, Benjamin D; McGenity, Terry J; Whitby, Corinne

    2016-04-01

    High-molecular-weight polycyclic aromatic hydrocarbons (HMW-PAHs) are natural components of fossil fuels that are carcinogenic and persistent in the environment, particularly in oil sands process-affected water (OSPW). Their hydrophobicity and tendency to adsorb to organic matter result in low bioavailability and high recalcitrance to degradation. Despite the importance of microbes for environmental remediation, little is known about those involved in HMW-PAH transformations. Here, we investigated the transformation of HMW-PAHs using samples of OSPW and compared the bacterial and fungal community compositions attached to hydrophobic filters and in suspension. It was anticipated that the hydrophobic filters with sorbed HMW-PAHs would select for microbes that specialize in adhesion. Over 33 days, more pyrene was removed (75% ± 11.7%) than the five-ring PAHs benzo[a]pyrene (44% ± 13.6%) and benzo[b]fluoranthene (41% ± 12.6%). For both bacteria and fungi, the addition of PAHs led to a shift in community composition, but thereafter the major factor determining the fungal community composition was whether it was in the planktonic phase or attached to filters. In contrast, the major determinant of the bacterial community composition was the nature of the PAH serving as the carbon source. The main bacteria enriched by HMW-PAHs were Pseudomonas, Bacillus, and Microbacterium species. This report demonstrates that OSPW harbors microbial communities with the capacity to transform HMW-PAHs. Furthermore, the provision of suitable surfaces that encourage PAH sorption and microbial adhesion select for different fungal and bacterial species with the potential for HMW-PAH degradation. PMID:26850299

  5. Biofilm and Planktonic Bacterial and Fungal Communities Transforming High-Molecular-Weight Polycyclic Aromatic Hydrocarbons

    PubMed Central

    Folwell, Benjamin D.

    2016-01-01

    High-molecular-weight polycyclic aromatic hydrocarbons (HMW-PAHs) are natural components of fossil fuels that are carcinogenic and persistent in the environment, particularly in oil sands process-affected water (OSPW). Their hydrophobicity and tendency to adsorb to organic matter result in low bioavailability and high recalcitrance to degradation. Despite the importance of microbes for environmental remediation, little is known about those involved in HMW-PAH transformations. Here, we investigated the transformation of HMW-PAHs using samples of OSPW and compared the bacterial and fungal community compositions attached to hydrophobic filters and in suspension. It was anticipated that the hydrophobic filters with sorbed HMW-PAHs would select for microbes that specialize in adhesion. Over 33 days, more pyrene was removed (75% ± 11.7%) than the five-ring PAHs benzo[a]pyrene (44% ± 13.6%) and benzo[b]fluoranthene (41% ± 12.6%). For both bacteria and fungi, the addition of PAHs led to a shift in community composition, but thereafter the major factor determining the fungal community composition was whether it was in the planktonic phase or attached to filters. In contrast, the major determinant of the bacterial community composition was the nature of the PAH serving as the carbon source. The main bacteria enriched by HMW-PAHs were Pseudomonas, Bacillus, and Microbacterium species. This report demonstrates that OSPW harbors microbial communities with the capacity to transform HMW-PAHs. Furthermore, the provision of suitable surfaces that encourage PAH sorption and microbial adhesion select for different fungal and bacterial species with the potential for HMW-PAH degradation. PMID:26850299

  6. Niacin stimulates adiponectin secretion through the GPR109A receptor.

    PubMed

    Plaisance, Eric P; Lukasova, Martina; Offermanns, Stefan; Zhang, Youyan; Cao, Guoqing; Judd, Robert L

    2009-03-01

    Niacin (nicotinic acid) has recently been shown to increase serum adiponectin concentrations in men with the metabolic syndrome. However, little is known about the mechanism(s) by which niacin regulates the intracellular trafficking and secretion of adiponectin. Since niacin appears to exert its effects on lipolysis through receptor (GPR109A)-dependent and -independent pathways, the purpose of this investigation was to examine the role of the recently identified GPR109A receptor in adiponectin secretion. Initial in vivo studies in rats demonstrated that niacin (30 mg/kg po) acutely increases serum adiponectin concentrations, whereas it decreases NEFAs. Further in vitro studies demonstrated an increase in adiponectin secretion and a decrease in lipolysis in primary adipocytes following treatment with niacin or beta-hydroxybutyrate (an endogenous ligand of the GPR109A receptor), but these effects were blocked when adipocytes were pretreated with pertussis toxin. Niacin had no effect on adiponectin secretion or lipolysis in 3T3-L1 adipocytes, which have limited cell surface expression of the GPR109A receptor. To further substantiate these in vitro findings, wild-type and GPR109A receptor knockout mice were administered a single dose of niacin or placebo, and serum was obtained for the determination of adiponectin and NEFA concentrations. Serum adiponectin concentrations increased and serum NEFAs decreased in the wild-type mice within 10 min following niacin administration. However, niacin administration had no effect on adiponectin and NEFA concentrations in the GPR109A receptor knockout mice. These results demonstrate that the GPR109A receptor plays an important role in the dual regulation of adiponectin secretion and lipolysis.

  7. Similar Adiponectin Levels in Obese Normotensive and Obese Hypertensive Men and No Vasorelaxant Effect of Adiponectin on Human Arteries.

    PubMed

    Dreier, Rasmus; Asferg, Camilla; Berg, Jais O; Andersen, Ulrik B; Flyvbjerg, Allan; Frystyk, Jan; Linneberg, Allan; Jeppesen, Jørgen L; Edvinsson, Lars; Skovsted, Gry F

    2016-02-01

    Obesity is a strong risk factor for hypertension, but the mechanism linking obesity to hypertension is not fully elucidated. In obesity, circulating concentrations of adiponectin are decreased and hypoadiponectinaemia has in some but not all studies been associated with increased risk of hypertension. Due to this inconsistency, we decided to study adiponectin from two aspects in a cross-sectional in vivo study and in an experimental in vitro study. In the cross-sectional study, 103 men with body mass index (BMI) ≥ 30.0 kg/m(2) were studied; 63 had 24-hr ambulatory blood pressure (ABP) ≥ 130/80 mmHg (ObeseHT) and 40 had 24-hr ABP < 130/80 mmHg (ObeseNT). As controls, we studied 27 men with BMI between 20.0 and 24.9 kg/m(2) and 24-hr ABP < 130/80 mmHg (LeanNT). Serum concentrations of adiponectin and body composition using dual-energy X-ray absorptiometry scanning were determined. In vitro, the direct vasomotor response of adiponectin was tested on subcutaneous resistance arteries from human abdominal adipose tissue. The two obese groups had lower adiponectin concentrations compared with LeanNT (p < 0.01) [median (interquartile range)]: ObeseHT 6.5 (5.1-8.3) mg/L; ObeseNT 6.6 (5.2-7.8) mg/L; and LeanNT 9.4 (6.7-12.4) mg/L, with no significant difference in adiponectin concentrations (or body composition) between ObeseHT and ObeseNT (p = 0.67). In vitro, adiponectin did not have any direct vasodilatory effect and adiponectin did not affect angiotensin II-stimulated vasoconstriction. In conclusion, obese hypertensive men have similar serum concentrations of adiponectin as obese normotensive men. In combination with the in vitro data, these findings question a pathogenic role of adiponectin in human hypertension.

  8. Impact of Adiponectin Overexpression on Allergic Airways Responses in Mice

    PubMed Central

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

    2013-01-01

    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. PMID:23861690

  9. Biomarkers of Adiponectin: Plasma Protein Variation and Genomic DNA Polymorphisms

    PubMed Central

    Gu, Harvest F.

    2009-01-01

    Adiponectin is secreted by white adipose tissue and exists as the most abundant adipokine in the human plasma. Recent research has indicated that plasma adiponectin levels are inversely correlated with body mass index (BMI) and insulin resistance. Reduction of plasma adiponectin levels is commonly observed in the patients with type 2 diabetes (T2D) and/or in those who are obese in comparison with healthy control individuals. The adiponectin (AdipoQ) gene has a moderate linkage disequilibrium (LD), but two small LD blocks are observed, respectively, in the promoter region and the boundary of exon 2-intron 2. Genetic association studies have demonstrated that single nucleotide polymorphisms (SNPs) +45G15G(T/G) in exon 2 and +276G/T in intron 2 of the AdipoQ gene confer the risk susceptibility to the development of T2D, obesity and diabetic nephropathy (DN). The SNPs in the promoter region, including −11426A/G, −11377C/G and −11391G/A, are found to be associated with T2D and DN. Recent research has indicated that the promoter polymorphisms interfere with the AdipoQ promoter activity. The haplotypes constructed by the promoter polymorphisms and SNP +276G/T in intron 2 are associated with circulating adiponectin levels. This review summarises genetic and pathophysiological relevancies of adiponectin and discusses about the biomarkers of adiponectin plasma protein variation and genomic DNA polymorphisms. PMID:20029651

  10. Expression of adiponectin receptors in pancreatic beta cells.

    PubMed

    Kharroubi, Ilham; Rasschaert, Joanne; Eizirik, Décio L; Cnop, Miriam

    2003-12-26

    Pancreatic beta cell dysfunction is an early and crucial pathogenic factor in the development of type 2 diabetes. Free fatty acids (FFA) and adipokines released from adipose tissues lead to both the development of insulin resistance and beta cell dysfunction. Adiponectin is a novel adipokine with antidiabetic properties. Its circulating concentrations are reduced in subjects with increased visceral adiposity, insulin resistance, or type 2 diabetes. Very recently, the cloning of two adiponectin receptors AdipoR1 and AdipoR2 was reported. AdipoR1 is abundantly expressed in muscle, while AdipoR2 is predominantly expressed in liver. Here we report the marked expression of mRNAs for the adiponectin receptors AdipoR1 and AdipoR2 in human and rat pancreatic beta cells, at levels similar to liver and greater than muscle. Adiponectin receptor expression is increased by beta cell exposure to the unsaturated FFA oleate, and treatment of insulin-producing cells with globular adiponectin induces lipoprotein lipase expression. Regulated adiponectin receptor expression on pancreatic beta cells might be a novel mechanism modulating the effects of circulating adiponectin. PMID:14651988

  11. Adiponectin signaling and function in insulin target tissues

    PubMed Central

    Ruan, Hong; Dong, Lily Q.

    2016-01-01

    Obesity-linked type 2 diabetes is one of the paramount causes of morbidity and mortality worldwide, posing a major threat on human health, productivity, and quality of life. Despite great progress made towards a better understanding of the molecular basis of diabetes, the available clinical counter-measures against insulin resistance, a defect that is central to obesity-linked type 2 diabetes, remain inadequate. Adiponectin, an abundant adipocyte-secreted factor with a wide-range of biological activities, improves insulin sensitivity in major insulin target tissues, modulates inflammatory responses, and plays a crucial role in the regulation of energy metabolism. However, adiponectin as a promising therapeutic approach has not been thoroughly explored in the context of pharmacological intervention, and extensive efforts are being devoted to gain mechanistic understanding of adiponectin signaling and its regulation, and reveal therapeutic targets. Here, we discuss tissue- and cell-specific functions of adiponectin, with an emphasis on the regulation of adiponectin signaling pathways, and the potential crosstalk between the adiponectin and other signaling pathways involved in metabolic regulation. Understanding better just why and how adiponectin and its downstream effector molecules work will be essential, together with empirical trials, to guide us to therapies that target the root cause(s) of type 2 diabetes and insulin resistance. PMID:26993044

  12. Role of Adiponectin in Coronary Heart Disease Risk

    PubMed Central

    Lawlor, Debbie A.; de Oliveira, Cesar; White, Jon; Horta, Bernardo Lessa; Barros, Aluísio J.D.

    2016-01-01

    Rationale: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis. Objective: We aimed to investigate the causal effect of adiponectin on CHD risk. Methods and Results: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68–1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84–1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors. Conclusions: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis. PMID:27252388

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

    PubMed Central

    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.

    2010-01-01

    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

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

    PubMed Central

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

    2008-01-01

    OBJECTIVES The aim of this study was to investigate serum leptin, adiponectin and paraoxonase1 levels in adult females receiving pharmacotherapy for various psychiatric disorders. METHODS The study group consisted of 32 obese females (mean age 40.53 ± 11.00 years, mean body mass index 35.44 ± 5.33 kg/m2) who were receiving treatment for psychiatric disorders, and the control group included 22 obese females (mean age 35.95 ± 9.16 years, mean body mass index 30.78 ± 3.33 kg/m2) who were free of psychiatric disorders. Analyses were performed using a bioelectrical impedance device. Fasting blood samples were obtained for complete blood count and various biochemical tests, including determination of leptin, adiponectin and paraoxonase1 activity. RESULTS Body mass index, waist and hip circumference, body fat percentage, fasting blood glucose, insulin, glycosylated hemoglobin, homeostasis model assesment of insulin resistance, alanine transaminase, aspartate tarnsaminase, and leptin levels were significantly higher in the study group than in controls. Although body weight was positively correlated with leptin levels in both groups, body weight was negatively correlated with adiponectin levels in the control group and positively correlated with adiponectin levels in the study group. In the study group, body mass index and hip circumference correlated positively with leptin levels, hip circumference correlated positively with adiponectin levels, and waist to hip ratio correlated positively with paraoxonase levels. In the control group, body mass index as well as waist and hip circumferences were positively correlated with leptin levels. Weight, body mass index, and hip circumference were also negatively correlated with the adiponectin/leptin ratio in the control group. CONCLUSION This study indicates a higher risk for obesity-related disorders, particularly metabolic syndrome, diabetes and cardiovascular disease, in patients treated with psychiatric drugs. PMID:18925326

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

    PubMed

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

    2013-10-01

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

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

    PubMed

    Kovács, Judit K; Felső, Péter; Emődy, Levente; Schneider, György; Kocsis, Béla

    2014-12-01

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

  17. Cord Blood Adiponectin and Visfatin Concentrations in relation to Oxidative Stress Markers in Neonates Exposed and Nonexposed In Utero to Tobacco Smoke

    PubMed Central

    Ambroszkiewicz, Jadwiga; Gajewska, Joanna; Rowicka, Grażyna; Maciejewski, Tomasz M.; Mazur, Joanna

    2016-01-01

    Aims. Maternal smoking is considered as a source of oxidative stress, which has been implicated to disrupted adipokines expression in adipose tissue. We examined the relationship between selected adipokines and markers of oxidative stress/antioxidant defence in the umbilical cord of neonates exposed and nonexposed in utero to tobacco smoke. Methods. Subjects including 85 healthy neonates (born to 41 smokers and 44 nonsmokers) were tested for adiponectin, visfatin, oxidized low density lipoprotein (ox-LDL), total oxidant capacity (TOC), and total antioxidant capacity (TAC). Results. Cord serum visfatin, ox-LDL, and TOC were significantly higher (p < 0.001) but adiponectin and TAC were lower (p < 0.001 and p < 0.05, resp.) in smoking group than in tobacco abstinents. In whole group of children (adjusted for smoking status, gender, and birth weight) adiponectin showed negative and visfatin positive correlations with ox-LDL. In the model estimated separately for smokers ox-LDL explained 36% of adiponectin and 35.5% of visfatin variance, while in the model of nonsmokers it explained 36.8% and 69.4%, respectively. Conclusion. Maternal smoking enhances oxidative status and depletes antioxidant potential in newborns. Lower level of adiponectin and higher visfatin concentration seem to be related with a less beneficial oxidative stress profile and higher level of lipid peroxidation in neonates exposed and nonexposed in utero to tobacco smoke. PMID:27525051

  18. Cord Blood Adiponectin and Visfatin Concentrations in relation to Oxidative Stress Markers in Neonates Exposed and Nonexposed In Utero to Tobacco Smoke.

    PubMed

    Chełchowska, Magdalena; Ambroszkiewicz, Jadwiga; Gajewska, Joanna; Rowicka, Grażyna; Maciejewski, Tomasz M; Mazur, Joanna

    2016-01-01

    Aims. Maternal smoking is considered as a source of oxidative stress, which has been implicated to disrupted adipokines expression in adipose tissue. We examined the relationship between selected adipokines and markers of oxidative stress/antioxidant defence in the umbilical cord of neonates exposed and nonexposed in utero to tobacco smoke. Methods. Subjects including 85 healthy neonates (born to 41 smokers and 44 nonsmokers) were tested for adiponectin, visfatin, oxidized low density lipoprotein (ox-LDL), total oxidant capacity (TOC), and total antioxidant capacity (TAC). Results. Cord serum visfatin, ox-LDL, and TOC were significantly higher (p < 0.001) but adiponectin and TAC were lower (p < 0.001 and p < 0.05, resp.) in smoking group than in tobacco abstinents. In whole group of children (adjusted for smoking status, gender, and birth weight) adiponectin showed negative and visfatin positive correlations with ox-LDL. In the model estimated separately for smokers ox-LDL explained 36% of adiponectin and 35.5% of visfatin variance, while in the model of nonsmokers it explained 36.8% and 69.4%, respectively. Conclusion. Maternal smoking enhances oxidative status and depletes antioxidant potential in newborns. Lower level of adiponectin and higher visfatin concentration seem to be related with a less beneficial oxidative stress profile and higher level of lipid peroxidation in neonates exposed and nonexposed in utero to tobacco smoke. PMID:27525051

  19. Regulation of adiponectin in adipocytes upon exposure to HIV-1

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. Adiponectin: an adipokine with protective features against metabolic syndrome

    PubMed Central

    Esfahani, Maryam; Movahedian, Ahmad; Baranchi, Mostafa; Goodarzi, Mohammad Taghi

    2015-01-01

    Metabolic syndrome (MetS) as a collection of obesity-associated disorders is associated with inflammation, oxidative stress, pro-thrombotic state, elevated risk of developing cardiovascular disease and type 2 diabetes. Adiponectin is one of the most abundant peptide hormones derived from adipose tissue. This protein plays a major role in glucose and lipid metabolism and prevents development of vascular changes. Anti-oxidative and anti-inflammatory effects are the other features of adiponectin. Hypoadiponectinemia is associated with hypertension and pro-thrombotic state. In this review, we discuss the crucial role of adiponectin in prevention of metabolic syndrome considering its effects on the components of this syndrome. Pharmacological interventions and lifestyle modification may increase plasma adiponectin level or tissue sensitivity which seems to be a promising target for prevention and therapeutic approaches of MetS and related diseases. PMID:26124928

  1. Adiponectin-SOGA Dissociation in Type 1 Diabetes

    PubMed Central

    Snell-Bergeon, Janet K.; Maahs, David M.; Bergman, Bryan C.; Lamarche, Marie; Iberkleid, Laura; AbdelBaky, Omar; Tisch, Roland; Scherer, Philipp E.; Marliss, Errol B.

    2015-01-01

    Context: Circulating adiponectin is elevated in human type 1 diabetes (T1D) and nonobese diabetic (NOD) mice without the expected indications of adiponectin action, consistent with tissue resistance. Objective: Adiponectin stimulates hepatocyte production of the suppressor of glucose from autophagy (SOGA), a protein that inhibits glucose production. We postulated that due to tissue resistance, the elevation of adiponectin in T1D should fail to increase the levels of a surrogate marker for liver SOGA, the circulating C-terminal SOGA fragment. Main Outcome Measures: Liver and plasma SOGA were measured in NOD mice (n = 12) by Western blot. Serum adiponectin and SOGA were measured in T1D and control (Ctrl) participants undergoing a three-stage insulin clamp for the Coronary Artery Calcification in T1D study (n = 20). Glucose turnover was measured using 6,6[2H2]glucose (n = 12). Results: In diabetic NOD mice, the 13%–29% decrease of liver SOGA (P = .003) and the 30%–37% reduction of circulating SOGA (P < .001) were correlated (r = 0.826; P = .001). In T1D serum, adiponectin was 50%–60% higher than Ctrl, SOGA was 30%–50% lower and insulin was 3-fold higher (P < .05). At the low insulin infusion rate (4 mU/m2·min), the resulting glucose appearance correlated negatively with adiponectin in T1D (r = −0.985, P = .002) and SOGA in Ctrl and T1D (r = −0.837, P = .001). Glucose disappearance correlated with adiponectin in Ctrl (r = −0.757, P = .049) and SOGA in Ctrl and T1D (r = −0.709, P = .010). At 40 mU/m2·min, the lowered glucose appearance was similar in Ctrl and T1D. Glucose disappearance increased only in Ctrl (P = .005), requiring greater glucose infusion to maintain euglycemia (8.58 ± 1.29 vs 3.09 ± 0.87 mg/kg·min; P = .009). Conclusions: The correlation between liver and plasma SOGA in NOD mice supports the use of the latter as surrogate marker for liver concentration. Reduced SOGA in diabetic NOD mice suggests resistance to adiponectin. The

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

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

    SciTech Connect

    Zappala, Giovanna; Rechler, Matthew M.

    2009-05-15

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

  4. Profile of leptin, adiponectin, and body fat in patients with hyperprolactinemia: Response to treatment with cabergoline

    PubMed Central

    Pala, Nazir Ahmad; Laway, Bashir Ahmad; Misgar, Raiz Ahmad; Shah, Zaffar Amin; Gojwari, Tariq A.; Dar, Tariq A.

    2016-01-01

    Introduction: Though hypoadiponectinemia and leptin resistance have been proposed as potential factors for weight gain in patients with hyperprolactinemia (HPL), the effects of HPL and cabergoline on these adipocyte-derived hormones are not clear. Aims of this study were (i) to assess the alterations of body fat, leptin, and adiponectin in patients with HPL (ii) effect of cabergoline treatment on these parameters. Methods: Nineteen consecutive patients with prolactinoma (median prolactin [PRL] 118.6 (interquartile range: 105.3) μg/L) and 20 controls were studied in a nonrandomized matched prospective design. The controls were age, gender, and body mass index (BMI) matched. Anthropometric data, metabolic variables, leptin, and adiponectin were studied at baseline and 3 and 6 months after cabergoline treatment. Results: Patients with prolactinoma had increased level of fasting plasma glucose (P < 0.001) as compared to age-, gender-, and BMI-matched healthy controls. Estradiol concentration of controls was higher than that of patients (P = 0.018). Patients with prolactinoma had higher levels of leptin (P = 0.027) as compared to healthy controls without a significant difference in adiponectin levels. There was a significant decrease of body weight at 3 months (P = 0.029), with a further decline at 6 months (P < 0.001) of cabergoline therapy. Furthermore, there was a significant decrement of BMI (P < 0.001), waist circumference (P = 0.003), waist-hip ratio (P = 0.03), total body fat (P = 0.003), plasma glucose (P < 0.001), leptin levels (P = 0.013), and an increase in estradiol concentration (P = 0.03) at 6 months of cabergoline treatment. Conclusion: Patients with prolactinoma have adverse metabolic profile compared to matched controls. Normalization of PRL with cabergoline corrects all the metabolic abnormalities. PMID:27042412

  5. Expression of adiponectin and adiponectin receptors 1 and 2 in the porcine uterus, conceptus, and trophoblast during early pregnancy.

    PubMed

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

    2014-10-15

    Adiponectin, one of the several adipocytokines secreted mainly by the adipose tissue, plays an important role in regulating energy homeostasis and controls female fertility. Female reproductive functions are closely associated with nutritional status, and adiponectin seems to be an important factor linking the regulation of metabolic homeostasis with reproductive processes. The biological activity of adiponectin is mediated by two distinct receptors, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). The objective of this study was to determine the presence of and changes in the gene and protein expression pattern of adiponectin and its receptors in the porcine uterus during early pregnancy and on Days 10 to 11 of the estrous cycle and in the conceptus and trophoblast. The highest level of adiponectin transcript was observed on Days 15 to 16 of gestation, Days 10 to 11 of the cycle in the endometrium, and Days 15 to 16 of gestation in the myometrium. The highest expression of AdipoR1 and AdipoR2 genes was detected on Days 10 to 11 of gestation in the endometrium, and Days 12 to 13 in the myometrium. The highest content of adiponectin protein was noted on Days 12 to 13 and 30 to 32 of gestation in the endometrium and Days 10 to 11 of the cycle in the myometrium. The expression of adiponectin protein was higher on Days 27 to 28 and 30 to 32 in the conceptuses. AdipoR1 protein content in the myometrium was highest on Days 12 to 13 and 30 to 32. In contrast, in the endometrium, it was more constant. The highest content of AdipoR2 protein was detected on Days 15 to 16 and 30 to 32 of gestation, Days 10 to 11 of the cycle in the endometrium, and Days 10 to 11 of gestation in the myometrium. In the conceptuses, the highest AdipoR1 protein content was observed on Days 15 to 16, and the highest AdipoR2 protein expression was determined on Days 15 to 16 and 27 to 28. In the trophoblasts, AdipoR1 protein content was higher on Days 27 to 28 than on Days 30

  6. Monoclonal antibodies with equal specificity to D-dimer and high-molecular-weight fibrin degradation products

    PubMed Central

    Kogan, Alexander E.; Mukharyamova, Kadriya S.; Bereznikova, Anastasia V.; Filatov, Vladimir L.; Koshkina, Ekaterina V.; Bloshchitsyna, Marina N.; Katrukha, Alexey G.

    2016-01-01

    Fibrin degradation results in the formation of fibrin degradation products (FDPs) of different molecular weights, which include D-dimer. Commercial D-dimer assays recognize multiple forms of FDP with different specificity. As a result, the absence of an international D-dimer standard and the marked discrepancy in the D-dimer values in the same samples measured by assays from different manufacturers have become the primary problems that clinicians face in the D-dimer determination. We consider that an assay with equal specificity to all FDP forms regardless of their molecular weights could help to solve these problems. We aimed to produce mAbs that could equally recognize high-molecular-weight FDP (HMW FDP) and D-dimer. mAbs against D-dimer were produced. The HMW FDP/D-dimer ratios in plasma samples were analyzed following protein separation by gel filtration using the developed fluoroimmunoassay. A sandwich immunoassay with equal specificity to HMW FDP and D-dimer was developed and applied to determine HMW FDP/D-dimer ratios in patients with different diseases. Although the HMW FDP levels prevailed in thrombotic patients, the FDP and D-dimer levels were comparable in septic patients. Meanwhile, the D-dimer levels often exceeded the HMW FDP levels in patients who had undergone surgery. The ‘D-dimer’ levels that were detected by different assays also varied greatly depending on the assay specificities to FDP and D-dimer. Our findings show that the introduction of assays with equal specificities to FDP and D-dimer in clinical practice is a possible way of standardizing D-dimer measurements. PMID:26656897

  7. SSA 04-3 LEPTIN/ADIPONECTIN IN CARDIOMETABOLIC DISEASE.

    PubMed

    Lopez-Jaramillo, Patricio

    2016-09-01

    Cardiovascular diseases (CVD) are major causes of death and illness worldwide. In recent decades an increased prevalence of CVD mortality has been reported in low-medium income countries, which has been associated with changes in life styles, deficiencies in health systems and the persistence of social inequities.The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with insulin resistance and increased adiposity as its central features. Identifying individuals with metabolic syndrome is important due to its association with an increased risk of coronary heart disease and type 2 diabetes mellitus (DM2). Attention has focused on the visceral adipose tissue production of cytokines (adipokines) in metabolic syndrome and DM2, as the levels of the anti-inflammatory adipokine adiponectin are decreased, while proinflammatory cytokines are elevated, creating a proinflammatory state associated with insulin resistance and endothelial dysfunction. We have give special attention to the role of the leptin/adiponectin ratio and we have demonstrated that in individuals with severe coronary artery disease, abdominal obesity (AO) was uniquely related to decreased plasma concentrations of adiponectin and increased leptin levels. Leptin/adiponectin imbalance was associated with increased waist circumference and a decreased vascular response to acetylcholine and increased vasoconstriction due to angiotensin II. Leptin and adiponectin have opposite effects on subclinical inflammation and insulin resistance. Leptin upregulates proinflammatory cytokines such as tumor necrosis factor-I and interleukin-6; these are associated with insulin resistance, DM2, and CVD. In contrast, adiponectin has anti-inflammatory properties and downregulates the expression and release of a number of proinflammatory immune mediators. Its concentrations are negatively regulated by the accumulation of visceral fat, and clinical studies implicate hypoadiponectinemia in the pathogenesis of DM

  8. Macrophage polarization phenotype regulates adiponectin receptor expression and adiponectin anti-inflammatory response

    PubMed Central

    van Stijn, Caroline M. W.; Kim, Jason; Lusis, Aldons J.; Barish, Grant D.; Tangirala, Rajendra K.

    2015-01-01

    Adiponectin (APN), a pleiotropic adipokine that exerts anti-inflammatory, antidiabetic, and antiatherogenic effects through its receptors (AdipoRs), AdipoR1 and AdipoR2, is an important therapeutic target. Factors regulating AdipoR expression in monocyte/macrophages are poorly understood, and the significance of polarized macrophage activation in controlling AdipoR expression and the APN-mediated inflammatory response has not been investigated. The aim of this study was to investigate whether the macrophage polarization phenotype controls the AdipoR expression and APN-mediated inflammatory response. With the use of mouse bone marrow and peritoneal macrophages, we demonstrate that classical activation (M1) of macrophages suppressed (40–60% of control) AdipoR expression, whereas alternative activation (M2) preserved it. Remarkably, the macrophage polarization phenotypes produced contrasting inflammatory responses to APN (EC50 5 µg/ml). In M1 macrophages, APN induced proinflammatory cytokines, TNF-α, IL-6, and IL-12 (>10-fold of control) and AdipoR levels. In contrast, in M2 macrophages, APN induced the anti-inflammatory cytokine IL-10 without altering AdipoR expression. Furthermore, M1 macrophages adapt to a cytokine environment by reversing AdipoR expression. APN induced AdipoR mRNA and protein expression by up-regulating liver X receptor-α (LXRα) in macrophages. These results provide the first evidence that macrophage polarization is a key determinant regulating AdipoR expression and differential APN-mediated macrophage inflammatory responses, which can profoundly influence their pathogenic role in inflammatory and metabolic disorders.—van Stijn, C. M. W., Kim, J., Lusis, A. J., Barish, G.D., Tangirala, R. K. Macrophage polarization phenotype regulates adiponectin receptor expression and adiponectin anti-inflammatory response. PMID:25392268

  9. [Adipokines: adiponectin, leptin, resistin and coronary heart disease risk].

    PubMed

    Kopff, Barbara; Jegier, Anna

    2005-01-01

    Visceral obesity is among the known risk factors of atherosclerotic cardiovascular diseases. As long as adipose tissue was considered only an inert store of excess energy, accumulated in triglycerides, explanation of the mechanisms causing increased cardiovascular risk in obesity was difficult. Finding that the adipose tissue is an active endocrine organ and that the adipokines secreted in it influence several metabolic processes, allowed better understanding of this correlation. Several disturbances in secretion, function and balance of adipokines occur in the course of obesity. Changes of adiponectin, leptin and resistin concentrations are among the reasons of accelerated atherosclerosis occurring in the visceral adiposity. Adiponectin concentrations are decreased in visceral adiposity. Adiponectin is adipokine possessing antiatherogenic properties. It's effects exerted though the specific receptors in skeletal muscles and liver include decreased insulin resistance and improved plasma lipid profile. Acting directly in the vessel wall adiponectin prevents development of atheromatic lesions by inhibiting production of adhesive molecules and formation of foam cells. It has been found that decreased adiponectin concentrations are connected not only with increased coronary risk but also with progression of atherosclerosis in coronary vessels. Moreover it was found that adiponectin plasma concentration is significantly decreased in acute coronary incidences. Leptin regulates energy metabolism and balance. The concentrations of this adipokine are increased in obesity and correlate with insulin resistance. Hiperleptinemia has been also recognized as cardiovascular diseases risk factor. Resistin is considered to be a substance increasing insulin resistance, however the exact mechanisms are not known. Resistin plasma concentrations are increased in obese subjects and correlate with the inflammatory state that underlies the initiation and progression of atherosclerotic

  10. High Molecular Weight Hyaluronic Acid Inhibits Fibrosis of Endometrium

    PubMed Central

    Zhu, Yi; Hu, Jianguo; Yu, Tinghe; Ren, Yan; Hu, Lina

    2016-01-01

    Background Elevated fibrosis has been found in patients with intrauterine adhesion, which indicates that fibrotic factors may play a critical role in formation of intrauterine adhesion. The aim of this study was to identify the effect of hyaluronic acid (HA) at high and low molecular weight on fibrosis of the endometrium in a mouse model of Asherman’s syndrome. Material/Methods Endometrial fibrosis in a mouse model of Asherman’s syndrome was confirmed. Then HA at high and low molecular weight was injected into the uterine cavity. Endometrial fibrosis was compared among the control group, LMW-HA, and HMW-HA group. The extent of endometrial fibrosis was calculated using Masson stain. The fibrosis markers (TGFβ1, CTGF, collagen I, and collagen III) in endometrial tissue were detected using immunohistochemistry and Western blotting. Results The ratio of the area with endometrial fibrosis to total endometrial area in the HMW-HA group was significantly decreased compared to the control group (P<0.05). The expression of fibrosis markers (TGFβ1, CTGF, collagen I, and collagen III) in the endometrium was attenuated in the HMW-HA group compared to the control group, but the LMW-HA group had no similar effect. Conclusions Hyaluronic acid at high molecular weight may attenuate the degree of endometrial fibrosis after endometrial damage, which may contribute to preventing formation of intrauterine adhesions. PMID:27670361

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

    SciTech Connect

    Dieudonne, Marie-Noelle; Bussiere, Marianne; Dos Santos, Esther; Leneveu, Marie-Christine; Giudicelli, Yves . E-mail: biochip@wanadoo.fr; Pecquery, Rene

    2006-06-23

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

  12. Circadian expression of adiponectin and its receptors in human adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin is one of the most clinically relevant cytokines associated with obesity. However, circadian rhythmicity of adiponectin in human adipose tissue (AT) has not been analyzed. To assess whether the mRNA levels of adiponectin and its receptors (ADIPOR1 and ADIPOR2) might show daily circadian ...

  13. RNA-directed DNA polymerase from human leukemic blood cells and from primate type-C virus-producing cells: high- and low-molecular-weight forms with variant biochemical and immunological properties.

    PubMed Central

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

    1975-01-01

    RNA-directed DNA polymerase (reverse transcriptase) from leukocytes of individual leukemic patients can be grouped by velocity gradient analyses into two distinct classes, a low-molecular-weight (LMW) class of approximately 70,000 and a high-molecular-weight (HMW) class of 130,000 to 140,000. The reverse transcriptases from mammalian type-C viruses have with one exception (see text) been isolated as enzymes with molecular weights of 70,000. In this study, the reverse transcriptase from extracellular gibbon ape leukemia virus was also isolated only as the LMW class. However, the enzyme from gibbon virus-producing cells was isolated partially in the HMW form; this form was converted completely to the LMW form by treatment with 0.5 M KC1 and 0.5% Triton X-100 and could be re-converted to the HMW form by lowering the KC1 and Triton X-100 concentrations. A similar conversion from a HMW form to a LMW form was demonstrated with enzyme from human leukemic cells. The LMW form of the human and gibbon ape cellular enzymes utilized synthetic primer-templates in a similar fashion to viral enzyme, and this form was strongly inhibited by antisera (IgG) to reverse transcriptase from simian (woolly monkey) type-C virus. The HMW form of both enzymes utilized synthetic primer-templates less efficiently than the LMW form, and was resistant to inhibition by antipolymerase IgG of simian type-C virus. The HMW form of the cellular reverse transcriptases transcribed viral 70S RNA in the absence of synthetic primer relatively more efficiently than did the extracellular viral form. These data suggest that the HMW form is due in part to aggregation of the LMW form and in part to a cellular factor(s) which may affect both the form and function of intracellular reverse transciptase. PMID:48250

  14. Development of second generation peptides modulating cellular adiponectin receptor responses

    PubMed Central

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

    2014-01-01

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

  15. Development of second generation peptides modulating cellular adiponectin receptor responses

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  16. Adiponectin and Metabolic Syndrome in Women at Menopause

    PubMed Central

    Mankowska, Aneta; Nowak, Lena; Sypniewska, Grazyna

    2009-01-01

    Obesity is associated with premature atherosclerosis, as well as with many metabolic alterations including insulin resistance, dyslipidemia and hypertension. Visceral fat accumulation, particularly, is closely associated with the development of metabolic syndrome. The menopause transition, as well as the early postmenopausal period, is associated with increase in total and central obesity. Among adipocytokines secreted by the adipose tissue adiponectin is the only one that has a protective role in the development of obesity-related disorders, such as type 2 diabetes and cardiovascular disease. This review aims to present a role that adiponectin may play during the progress of menopause in relation to development of menopausal metabolic syndrome.

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

    PubMed

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

    2013-12-01

    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.

  18. Pathway-Based Genome-wide Association Studies Reveal That the Rac1 Pathway Is Associated with Plasma Adiponectin Levels

    PubMed Central

    Li, Wei-Dong; Jiao, Hongxiao; Wang, Kai; Yang, Fuhua; Grant, Struan F. A.; Hakonarson, Hakon; Ahima, Rexford; Arlen Price, R.

    2015-01-01

    Pathway-based analysis as an alternative and effective approach to identify disease-related genes or loci has been verified. To decipher the genetic background of plasma adiponectin levels, we performed genome wide pathway-based association studies in extremely obese individuals and normal-weight controls. The modified Gene Set Enrichment Algorithm (GSEA) was used to perform the pathway-based analyses (the GenGen Program) in 746 European American females, which were collected from our previous GWAS in extremely obese (BMI > 35 kg/m2) and never-overweight (BMI<25 kg/m2) controls. Rac1 cell motility signaling pathway was associated with plasma adiponectin after false-discovery rate (FDR) correction (empirical P < 0.001, FDR = 0.008, family-wise error rate = 0.008). Other several Rac1-centered pathways, such as cdc42racPathway (empirical P < 0.001), hsa00603 (empirical P = 0.003) were among the top associations. The RAC1 pathway association was replicated by the ICSNPathway method, yielded a FDR = 0.002. Quantitative pathway analyses yielded similar results (empirical P = 0.001) for the Rac1 pathway, although it failed to pass the multiple test correction (FDR = 0.11). We further replicated our pathway associations in the ADIPOGen Consortium data by the GSA-SNP method. Our results suggest that Rac1 and related cell motility pathways might be associated with plasma adiponectin levels and biological functions of adiponectin. PMID:26299439

  19. Effect of six-month lifestyle intervention on adiponectin, resistin and soluble tumor necrosis factor-α receptors in obese adolescents.

    PubMed

    Huang, Fengyang; Del-Río-Navarro, Blanca Estela; Pérez-Ontiveros, José Alfredo; Ruiz-Bedolla, Eliseo; Saucedo-Ramírez, Omar Josué; Villafaña, Santiago; Bravo, Guadalupe; Mailloux-Salinas, Patrick; Hong, Enrique

    2014-01-01

    The aim of this study was to evaluate the effect of a six-month lifestyle intervention on adiponectin, resistin, and two soluble forms of tumor necrosis factor-α receptor (sTNFR) in obese adolescents. A total of 54 obese adolescents aged 10 to 16 years completed the program. Twenty-four adolescents with normal weight at baseline were used as a control group. Our results demonstrated that obese adolescents had abnormal lipid profile, homeostasis model assessment (HOMA) index, adiponectin level (5.6 ± 2.7 vs. 7.6 ± 2.9 μg/mL, p = 0.005) as well as resistin level (31.0 ± 9.0 vs. 24.3 ± 8.5 ng/mL, p = 0.003), whereas levels of both sTNFRs were similar to those in normal weight subjects. After the six-month lifestyle intervention, obese adolescents had a slight but significant drop in standard deviation score-body mass index (SDS-BMI), a significant decrease in waist circumference, total cholesterol, triglycerides, HOMA index, as well as resistin, and a significant increase in adiponectin and high-density lipoprotein-cholesterol. In adolescents without decreased SDS-BMI, no change was observed in adipokines. Changes in adiponectin correlated negatively with changes in waist circumference (r = -0.275, p = 0.044). Changes in resistin correlated positively with changes in triglycerides (r = 0.302, p = 0.027). The study demonstrated the increase of resistin and the decrease of adiponectin in obese adolescents. Lifestyle intervention improved adipokine abnormalities in obese subjects. PMID:25029953

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

    PubMed

    Anuradha; Krishna, Amitabh

    2014-09-01

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

  1. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

    PubMed

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  2. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding

    PubMed Central

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  3. Comparison of orthologous and paralogous DNA flanking the wheat high molecular weight glutenin genes: sequence conservation and divergence, transposon distribution, and matrix-attachment regions.

    PubMed

    Anderson, O D; Larka, L; Christoffers, M J; McCue, K F; Gustafson, J P

    2002-04-01

    Extended flanking DNA sequences were characterized for five members of the wheat high molecular weight (HMW) glutenin gene family to understand more of the structure, control, and evolution of these genes. Analysis revealed more sequence conservation among orthologous regions than between paralogous regions, with differences mainly owing to transposition events involving putative retrotransposons and several miniature inverted transposable elements (MITEs). Both gyspy-like long terminal repeat (LTR) and non-LTR retrotransposon sequences are represented in the flanking DNAs. One of the MITEs is a novel class, but another MITE is related to the maize Stowaway family and is widely represented in Triticeae express sequence tags (ESTs). Flanking DNA of the longest sequence, a 20 425-bp fragment including and surrounding the HMW-glutenin Bx7 gene, showed additional cereal gene-like sequences both immediately 5' and 3' to the HMW-glutenin coding region. The transcriptional activities of sequences related to these flanking putative genes and the retrotransposon-related regions were indicated by matches to wheat and other Triticeae ESTs. Predictive analysis of matrix-attachment regions (MARs) of the HMW glutenin and several alpha-, gamma-, and omega-gliadin flanking DNAs indicate potential MARs immediately flanking each of the genes. Matrix binding activity in the predicted regions was confirmed for two of the HMW-glutenin genes.

  4. Adiponectin-derived active peptide ADP355 exerts anti-inflammatory and anti-fibrotic activities in thioacetamide-induced liver injury

    PubMed Central

    Wang, Huafeng; Zhang, Huan; Zhang, Zimu; Huang, Biao; Cheng, Xixi; Wang, Dan; la Gahu, Zha; Xue, Zhenyi; Da, Yurong; Li, Daiqing; Yao, Zhi; Gao, Fei; Xu, Aimin; Zhang, Rongxin

    2016-01-01

    Adiponectin is an adipocyte-derived circulating protein with beneficial effects on injured livers. Adiponectin-deficient (adipo(−/−)) mice develop enhanced liver fibrosis, suggesting that adiponectin could be a therapeutic target for liver injury. In the present study, we investigated the protective role of ADP355, an adiponectin-based active short peptide, in thioacetamide (TAA)-induced acute injury and chronic liver fibrosis in mice. ADP355 remarkably reduced TAA-induced necroinflammation and liver fibrosis. ADP355 treatment increased liver glycogen, decreased serum alanine transaminase and alkaline phosphatase activity, and promoted body weight gain, hyper-proliferation and hypo-apoptosis. In addition, ADP355 administration suppressed the TAA-induced activation of hepatic stellate cells and macrophages in the liver. These were associated with the inactivation of TGF-β1/SMAD2 signaling and the promotion of AMPK and STAT3 signaling. Sensitivity of adipo(−/−) mice to chronic liver injury was decreased with ADP355. In conclusion, ADP355 could mimic adiponectin’s action and may be suitable for the preclinical or clinical therapy of chronic liver injury. PMID:26777428

  5. Regulation of high molecular weight bovine brain neutral protease by phospholipids in vitro.

    PubMed

    Chauhan, V; Sheikh, A M; Chauhan, A; Spivack, W D; Fenko, M D; Malik, M N

    2005-04-01

    The activity of the heat stable, glycosylated high molecular weight bovine brain neutral protease (HMW protease) is differentially regulated by phospholipids. While phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidic acid (PA) had only marginal stimulatory effect (40-75%) on the activity of HMW protease, lysophoshatidylcholine (lysoPC) and lysophosphatidic acid (lysoPA) activated the enzyme by more than two-fold. Both lysoPC and lysoPA exhibited concentration-dependent saturation kinetics for the activation of HMW protease. Surprisingly, phosphoinositides (phosphatidylinositol, PI; phosphatidylinositol 4-phosphate, PIP; and phosphatidylinositol 4,5-bisphosphate, PIP2) modulated the activity of protease differently: activation of the enzyme was higher with PIP (90%) as compared to PI (21%), whereas PIP2 inhibited the enzyme (16%). The inhibition of the protease by PIP2 was concentration-dependent. During receptor-coupled cell activation, phospholipase A2 (PLA2) converts PC and PA to lysoPC and lysoPA, respectively; PI is converted to PIP2 by successive enzymatic phosphorylation by PI 4-kinase and PIP 5-kinase; and phospholipase C (PLC) degrades PIP2 to diacylglycerol and inositol 1,4,5-trisphosphate. Therefore, the data suggest that HMW protease may be coupled to cell signal transduction where PLA2, PI 4-kinase, PIP 5-kinase and PLC are involved. PMID:16010981

  6. Advances in the field of high‐molecular‐weight polycyclic aromatic hydrocarbon biodegradation by bacteria

    PubMed Central

    Kanaly, Robert A.; Harayama, Shigeaki

    2010-01-01

    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. PMID:21255317

  7. Ingestion of High Molecular Weight Carbohydrate Enhances Subsequent Repeated Maximal Power: A Randomized Controlled Trial.

    PubMed

    Oliver, Jonathan M; Almada, Anthony L; Van Eck, Leighsa E; Shah, Meena; Mitchell, Joel B; Jones, Margaret T; Jagim, Andrew R; Rowlands, David S

    2016-01-01

    Athletes in sports demanding repeat maximal work outputs frequently train concurrently utilizing sequential bouts of intense endurance and resistance training sessions. On a daily basis, maximal work within subsequent bouts may be limited by muscle glycogen availability. Recently, the ingestion of a unique high molecular weight (HMW) carbohydrate was found to increase glycogen re-synthesis rate and enhance work output during subsequent endurance exercise, relative to low molecular weight (LMW) carbohydrate ingestion. The effect of the HMW carbohydrate, however, on the performance of intense resistance exercise following prolonged-intense endurance training is unknown. Sixteen resistance trained men (23±3 years; 176.7±9.8 cm; 88.2±8.6 kg) participated in a double-blind, placebo-controlled, randomized 3-way crossover design comprising a muscle-glycogen depleting cycling exercise followed by ingestion of placebo (PLA), or 1.2 g•kg•bw-1 of LMW or HMW carbohydrate solution (10%) with blood sampling for 2-h post-ingestion. Thereafter, participants performed 5 sets of 10 maximal explosive repetitions of back squat (75% of 1RM). Compared to PLA, ingestion of HMW (4.9%, 90%CI 3.8%, 5.9%) and LMW (1.9%, 90%CI 0.8%, 3.0%) carbohydrate solutions substantially increased power output during resistance exercise, with the 3.1% (90% CI 4.3, 2.0%) almost certain additional gain in power after HMW-LMW ingestion attributed to higher movement velocity after force kinematic analysis (HMW-LMW 2.5%, 90%CI 1.4, 3.7%). Both carbohydrate solutions increased post-exercise plasma glucose, glucoregulatory and gut hormones compared to PLA, but differences between carbohydrates were unclear; thus, the underlying mechanism remains to be elucidated. Ingestion of a HMW carbohydrate following prolonged intense endurance exercise provides superior benefits to movement velocity and power output during subsequent repeated maximal explosive resistance exercise. This study was registered with

  8. Ingestion of High Molecular Weight Carbohydrate Enhances Subsequent Repeated Maximal Power: A Randomized Controlled Trial

    PubMed Central

    Oliver, Jonathan M.; Almada, Anthony L.; Van Eck, Leighsa E.; Shah, Meena; Mitchell, Joel B.; Jones, Margaret T.; Jagim, Andrew R.; Rowlands, David S.

    2016-01-01

    Athletes in sports demanding repeat maximal work outputs frequently train concurrently utilizing sequential bouts of intense endurance and resistance training sessions. On a daily basis, maximal work within subsequent bouts may be limited by muscle glycogen availability. Recently, the ingestion of a unique high molecular weight (HMW) carbohydrate was found to increase glycogen re-synthesis rate and enhance work output during subsequent endurance exercise, relative to low molecular weight (LMW) carbohydrate ingestion. The effect of the HMW carbohydrate, however, on the performance of intense resistance exercise following prolonged-intense endurance training is unknown. Sixteen resistance trained men (23±3 years; 176.7±9.8 cm; 88.2±8.6 kg) participated in a double-blind, placebo-controlled, randomized 3-way crossover design comprising a muscle-glycogen depleting cycling exercise followed by ingestion of placebo (PLA), or 1.2 g•kg•bw-1 of LMW or HMW carbohydrate solution (10%) with blood sampling for 2-h post-ingestion. Thereafter, participants performed 5 sets of 10 maximal explosive repetitions of back squat (75% of 1RM). Compared to PLA, ingestion of HMW (4.9%, 90%CI 3.8%, 5.9%) and LMW (1.9%, 90%CI 0.8%, 3.0%) carbohydrate solutions substantially increased power output during resistance exercise, with the 3.1% (90% CI 4.3, 2.0%) almost certain additional gain in power after HMW-LMW ingestion attributed to higher movement velocity after force kinematic analysis (HMW-LMW 2.5%, 90%CI 1.4, 3.7%). Both carbohydrate solutions increased post-exercise plasma glucose, glucoregulatory and gut hormones compared to PLA, but differences between carbohydrates were unclear; thus, the underlying mechanism remains to be elucidated. Ingestion of a HMW carbohydrate following prolonged intense endurance exercise provides superior benefits to movement velocity and power output during subsequent repeated maximal explosive resistance exercise. This study was registered with

  9. Differential Role of Leptin and Adiponectin in Cardiovascular System

    PubMed Central

    Ghantous, C. M.; Azrak, Z.; Hanache, S.; Abou-Kheir, W.; Zeidan, A.

    2015-01-01

    Leptin and adiponectin are differentially expressed adipokines in obesity and cardiovascular diseases. Leptin levels are directly associated with adipose tissue mass, while adiponectin levels are downregulated in obesity. Although significantly produced by adipocytes, leptin is also produced by vascular smooth muscle cells and cardiomyocytes. Plasma leptin concentrations are elevated in cases of cardiovascular diseases, such as hypertension, congestive heart failure, and myocardial infarction. As for the event of left ventricular hypertrophy, researchers have been stirring controversy about the role of leptin in this form of cardiac remodeling. In this review, we discuss how leptin has been shown to play an antihypertrophic role in the development of left ventricular hypertrophy through in vitro experiments, population-based cross-sectional studies, and longitudinal cohort studies. Conversely, we also examine how leptin may actually promote left ventricular hypertrophy using in vitro analysis and human-based univariate and multiple linear stepwise regression analysis. On the other hand, as opposed to leptin's generally detrimental effects on the cardiovascular system, adiponectin is a cardioprotective hormone that reduces left ventricular and vascular hypertrophy, oxidative stress, and inflammation. In this review, we also highlight adiponectin signaling and its protective actions on the cardiovascular system. PMID:26064110

  10. Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis.

    PubMed

    Yoon, Young Sil; Ryu, Dongryeol; Lee, Min Woo; Hong, Sungpyo; Koo, Seung Hoi

    2009-08-31

    During fasting periods, hepatic glucose production is enhanced by glucagon to provide fuels for other organs. This process is mediated via cAMP-dependent induction of the CREB regulated transcriptional coactivator (CRTC) 2, a critical transcriptional activator for hepatic gluconeogenesis. We have previously shown that CRTC2 activity is regulated by AMP activated protein kinase (AMPK) family members. Here we show that adiponectin and thiazolidinedione directly regulate AMPK to modulate CRTC2 activity in hepatocytes. Adiponectin or thiazolidinedione lowered glucose production from primary hepatocytes. Treatment of both reagents reduced gluconeogenic gene expression as well as cAMP-mediated induction of CRE reporter, suggesting that these reagents directly affect CREB/CRTC2- dependent transcription. Furthermore, adiponectin or thiazolidinedione mediated repression of CRE activity is largely blunted by co-expression of phosphorylation defective mutant CRTC2, underscoring the importance of serine 171 residue of this factor. Taken together, we propose that adiponectin and thiazolidinedione promote the modulation of AMPK-dependent CRTC2 activity to influence hepatic gluconeogenesis.

  11. Adiponectin and noncardiovascular death: a nested case-control study.

    PubMed

    Matsumoto, Masatoshi; Ishikawa, Shizukiyo; Kajii, Eiji

    2008-06-01

    This study is to evaluate the associations between adiponectin level and noncardiovascular death and to test a hypothesis that adiponectin level reflects the degree of systemic wasting that precedes death. A nested case-control study was conducted involving 5243 subjects, drawn from 12490 subjects of the Jichi Medical School Cohort Study, whose blood samples had been drawn between 1992 and 1995. Over an average of 10.8 years of follow-up, 103 cases with noncardiovascular death and 565 controls without history/event/death of any cardiovascular disease were identified. Odds ratios (ORs) were estimated relative to the lowest quintile of adiponectin level. The risks for noncardiovascular death of the second lowest quintile and the highest quintile of adiponectin level were significantly higher than that of the lowest quintile when adjusted for age and sex (model 1) (OR, 2.38 [95% confidence interval (CI), 1.12-5.06] and 2.16 [1.01-4.80]). All the statistical significances disappeared when adjusted further for body mass index and C-reactive protein level (model 2). When excluding cases with cancer death, the odds for death in the highest 2 quintiles were significantly higher than those in the lowest quintile in model 1 (OR, 2.80 [95% CI, 1.04-7.59] and 3.74 [1.38-10.18]). The significant difference between the highest vs the lowest quintile remained significant in model 2 and even after adjusting further for smoking, diabetes, and total cholesterol level (model 3) (OR, 3.28 [95% CI, 1.02-10.51] and 3.98 [1.21-13.13]). Adiponectin levels had linear associations with the risks of noncardiovascular noncancer death in models 1, 2, and 3 (OR per 1 SD increase in log-adiponectin, 1.72 [95% CI, 1.23-2.40], 1.89 [1.23-2.91], and 2.01 [1.29-3.15]). Adiponectin is an independent indicator of noncardiovascular mortality that may relate with systemic wasting.

  12. Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program

    PubMed Central

    Mather, K. J.; Christophi, C. A.; Jablonski, K. A.; Knowler, W. C.; Goldberg, R. B.; Kahn, S. E.; Spector, T.; Dastani, Z.; Waterworth, D.; Richards, J. B.; Funahashi, T.; Pi-Sunyer, F. X.; Pollin, T. I.; Florez, J. C.; Franks, P. W.

    2012-01-01

    Aims Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. Methods Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. Results Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions from rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ~18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. Conclusions ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations. [Clinical

  13. Circulating leptin and adiponectin levels in patients with primary hyperparathyroidism.

    PubMed

    Delfini, Enrica; Petramala, Luigi; Caliumi, Chiara; Cotesta, Darlo; De Toma, Giorgio; Cavallaro, Giuseppe; Panzironi, Giuseppe; Diacinti, Daniele; Minisola, Savatore; D' Erasmo, Emilio; Mazzuoli, Gian Franco; Letizia, Claudio

    2007-01-01

    Primary hyperparathyroidism (PHPT) has been associated with high cardiovascular morbidity and mortality; its pathogenesis is not fully understood. Moreover, many metabolic abnormalities are frequently present in patients with PHPT. Several substances (such as leptin and adiponectin) are secreted from adipocytes, which may contribute to regulate energy homeostasis and the development of cardiovascular diseases. We examined the relationship between leptin and adiponectin levels and metabolic disorders in 67 newly diagnosed never-treated patients with PHPT and in 46 healthy subjects (HS). Twenty (29.8%) patients with PHPT presented a metabolic syndrome (as defined by Adult Treatment Panel III criteria). Serum leptin and adiponectin levels in HS were 6.28 +/- 3.3 ng/mL (range, 1.7-19.2 ng/mL) and 6.65 +/- 1.7 microg/mL (range, 3.72-10.86 microg/mL), respectively. In all patients with PHPT, the mean leptin levels (34.28 +/- 20.4 ng/mL) were significantly higher than those of HS (P < .01) and, in particular, in PHPT patients with metabolic syndrome (52.63 +/- 31.2 ng/mL) and positively correlated with body mass index, waist circumference, and cholesterol. The mean adiponectin level was significantly lower (4.34 +/- 3.5 mug/mL) only in PHPT patients with metabolic syndrome (P < .005) and negatively correlated with waist circumference and fasting glucose. We concluded that increased serum level of leptin and decreased serum level of adiponectin coexist in patients with PHPT and may represent a pathogenetic factor for cardiovascular disease in this condition.

  14. Inflammatory Adipokines Decrease Expression of Two High Molecular Weight Isoforms of Tropomyosin Similar to the Change in Type 2 Diabetic Patients

    PubMed Central

    Leitch, Helen F.; Harvey, John N.; Thomas, Trevor H.

    2016-01-01

    Cardiovascular disease and cancer are increased in Type 2 diabetes. TPM1 and TPM4 genes encode proteins associated with cardiovascular and neoplastic disease. High (HMW) and low (LMW) molecular weight isoforms from TPM1 and TPM4 are altered in several cancer cells and the 3'UTR of TPM1 mRNA is tumour suppressive. Leukocytes influence cardiovascular and neoplastic disease by immunosurveillance for cancer and by chronic inflammation in Type 2 diabetes and cardiovascular disease. The aim was to determine changes in expression of isoforms from TPM1 and TPM4 genes in leukocytes from Type 2 diabetic patients and to use the leukocyte cell line THP1 to identify possible mediators of changes in the patients. Gene expression was determined by RT-qPCR. In diabetes, expression of HMW isoforms from TPM1 were markedly decreased (0.55 v 1.00; p = 0.019) but HMW isoforms from TPM4 were not significantly different (0.76 v 1.00; p = 0.205). Within individual variance in expression of HMW isoforms was very high. The change in expression in HMW isoforms from TPM1 and TPM4 was replicated in THP1 cells treated with 1 ng/ml TNFα (0.10 and 0.12 v 1.00 respectively) or 10 ng/ml IL-1α (0.17 and 0.14 v 1.00 respectively). Increased insulin or glucose concentrations had no substantial effects on TPM1 or TPM4 expression. Decreased TPM1 mRNA resulted in decreases in HMW protein levels. Expression of HMW isoforms from TPM1 is decreased in Type 2 diabetes. This is probably due to increased levels of inflammatory cytokines TNFα and IL-1α in Type 2 diabetes. Lower levels of TPM1 mRNA reduce tumour suppression and could contribute to increased cancer risk in Type 2 diabetes. Decreased HMW tropomyosin isoforms are associated with cancer. Decreased HMW isoforms give rise to cells that are more plastic, motile, invasive and prone to dedifferentiation resulting in leukocytes that are more invasive but less functionally effective. PMID:27649540

  15. Inflammatory Adipokines Decrease Expression of Two High Molecular Weight Isoforms of Tropomyosin Similar to the Change in Type 2 Diabetic Patients.

    PubMed

    Savill, Stuart A; Leitch, Helen F; Harvey, John N; Thomas, Trevor H

    2016-01-01

    Cardiovascular disease and cancer are increased in Type 2 diabetes. TPM1 and TPM4 genes encode proteins associated with cardiovascular and neoplastic disease. High (HMW) and low (LMW) molecular weight isoforms from TPM1 and TPM4 are altered in several cancer cells and the 3'UTR of TPM1 mRNA is tumour suppressive. Leukocytes influence cardiovascular and neoplastic disease by immunosurveillance for cancer and by chronic inflammation in Type 2 diabetes and cardiovascular disease. The aim was to determine changes in expression of isoforms from TPM1 and TPM4 genes in leukocytes from Type 2 diabetic patients and to use the leukocyte cell line THP1 to identify possible mediators of changes in the patients. Gene expression was determined by RT-qPCR. In diabetes, expression of HMW isoforms from TPM1 were markedly decreased (0.55 v 1.00; p = 0.019) but HMW isoforms from TPM4 were not significantly different (0.76 v 1.00; p = 0.205). Within individual variance in expression of HMW isoforms was very high. The change in expression in HMW isoforms from TPM1 and TPM4 was replicated in THP1 cells treated with 1 ng/ml TNFα (0.10 and 0.12 v 1.00 respectively) or 10 ng/ml IL-1α (0.17 and 0.14 v 1.00 respectively). Increased insulin or glucose concentrations had no substantial effects on TPM1 or TPM4 expression. Decreased TPM1 mRNA resulted in decreases in HMW protein levels. Expression of HMW isoforms from TPM1 is decreased in Type 2 diabetes. This is probably due to increased levels of inflammatory cytokines TNFα and IL-1α in Type 2 diabetes. Lower levels of TPM1 mRNA reduce tumour suppression and could contribute to increased cancer risk in Type 2 diabetes. Decreased HMW tropomyosin isoforms are associated with cancer. Decreased HMW isoforms give rise to cells that are more plastic, motile, invasive and prone to dedifferentiation resulting in leukocytes that are more invasive but less functionally effective. PMID:27649540

  16. Effects of polymer molecular weight on relative oral bioavailability of curcumin

    PubMed Central

    Tsai, Yin-Meng; Chang-Liao, Wan-Ling; Chien, Chao-Feng; Lin, Lie-Chwen; Tsai, Tung-Hu

    2012-01-01

    Background Polylactic-co-glycolic acid (PLGA) nanoparticles have been used to increase the relative oral bioavailability of hydrophobic compounds and polyphenols in recent years, but the effects of the molecular weight of PLGA on bioavailability are still unknown. This study investigated the influence of polymer molecular weight on the relative oral bioavailability of curcumin, and explored the possible mechanism accounting for the outcome. Methods Curcumin encapsulated in low (5000–15,000) and high (40,000–75,000) molecular weight PLGA (LMw-NPC and HMw-NPC, respectively) were prepared using an emulsification-solvent evaporation method. Curcumin alone and in the nanoformulations was administered orally to freely mobile rats, and blood samples were collected to evaluate the bioavailability of curcumin, LMw-NPC, and HMw-NPC. An ex vivo experimental gut absorption model was used to investigate the effects of different molecular weights of PLGA formulation on absorption of curcumin. High-performance liquid chromatography with diode array detection was used for quantification of curcumin in biosamples. Results There were no significant differences in particle properties between LMw-NPC and HMw-NPC, but the relative bioavailability of HMw-NPC was 1.67-fold and 40-fold higher than that of LMw-NPC and conventional curcumin, respectively. In addition, the mean peak concentration (Cmax) of conventional curcumin, LMw-NPC, and HMw-NPC was 0.028, 0.042, and 0.057 μg/mL, respectively. The gut absorption study further revealed that the HMw-PLGA formulation markedly increased the absorption rate of curcumin in the duodenum and resulted in excellent bioavailability compared with conventional curcumin and LMw-NPC. Conclusion Our findings demonstrate that different molecular weights of PLGA have varying bioavailability, contributing to changes in the absorption rate at the duodenum. The results of this study provide the rationale for design of a nanomedicine delivery system to

  17. Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis.

    PubMed

    Yuan, Hui-Ping; Sun, Liang; Li, Xing-Hui; Che, Fu-Gang; Zhu, Xiao-Quan; Yang, Fan; Han, Jing; Jia, Chun-Yuan; Yang, Ze

    2016-01-01

    Many previous studies have provided evidence that the ADIPOQ +45T>G polymorphism (rs2241766) might cause metabolic syndrome (MS). As a cardiovascular manifestation of MS, the incidence of stroke is associated with adiponectin; however, the results remain controversial and inconsistent. Systematic searches of relevant studies published up to Dec 2014 and Jan 2016 on the ADIPOQ +45T>G polymorphism and the risk of MS and adiponectin levels and the risk of stroke, respectively, were conducted in MEDLINE and EMBASE. The odds ratio (OR) or risk ratio (RR) and their 95% confidence interval (95% CI) were extracted. Sixteen studies containing 4,113 MS cases and 3,637 healthy controls indicated a weak positive association between ADIPOQ +45 T>G and MS in the dominant genetic model (OR = 1.30, 95% CI = 1.03-1.65), which was also validated by stratified subgroup analyses. Twelve studies including 26,213 participants and 4,246 stroke cases indicated that 5 μg/ml increments in adiponectin level were not relevant to stroke risk (RR = 1.05, 95% CI = 1.00-1.10, P = 0.069). This study suggested a weak positive association of ADIPOQ +45T>G with MS and a strong association with metabolic-related disease. Additionally, adiponectin level was not a causal factor of increasing stroke risk. PMID:27578536

  18. Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis

    PubMed Central

    Yuan, Hui-Ping; Sun, Liang; Li, Xing-Hui; Che, Fu-Gang; Zhu, Xiao-Quan; Yang, Fan; Han, Jing; Jia, Chun-Yuan; Yang, Ze

    2016-01-01

    Many previous studies have provided evidence that the ADIPOQ +45T>G polymorphism (rs2241766) might cause metabolic syndrome (MS). As a cardiovascular manifestation of MS, the incidence of stroke is associated with adiponectin; however, the results remain controversial and inconsistent. Systematic searches of relevant studies published up to Dec 2014 and Jan 2016 on the ADIPOQ +45T>G polymorphism and the risk of MS and adiponectin levels and the risk of stroke, respectively, were conducted in MEDLINE and EMBASE. The odds ratio (OR) or risk ratio (RR) and their 95% confidence interval (95% CI) were extracted. Sixteen studies containing 4,113 MS cases and 3,637 healthy controls indicated a weak positive association between ADIPOQ +45 T>G and MS in the dominant genetic model (OR = 1.30, 95% CI = 1.03–1.65), which was also validated by stratified subgroup analyses. Twelve studies including 26,213 participants and 4,246 stroke cases indicated that 5 μg/ml increments in adiponectin level were not relevant to stroke risk (RR = 1.05, 95% CI = 1.00–1.10, P = 0.069). This study suggested a weak positive association of ADIPOQ +45T>G with MS and a strong association with metabolic-related disease. Additionally, adiponectin level was not a causal factor of increasing stroke risk. PMID:27578536

  19. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    SciTech Connect

    Elias, V.O.; Simoneit, B.R.T. ); Pereira, A.S.; Cardoso, J.N. ); Cabral, J.A. )

    1999-07-15

    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.

  2. Marker-assisted selection for recognizing wheat mutant genotypes carrying HMW glutenin alleles related to baking quality.

    PubMed

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

    2014-01-01

    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).

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

    Luo Xianghang; Guo Lijuan; Yuan Lingqing; Xie Hui; Zhou Houde; Wu Xianping; Liao Eryuan . E-mail: eyliao1207@21cn.com

    2005-09-10

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

  5. Determinants of serum adiponectin in persons with and without type 1 diabetes.

    PubMed

    Maahs, David M; Ogden, Lorraine G; Snell-Bergeon, Janet K; Kinney, Gregory L; Wadwa, R Paul; Hokanson, John E; Dabelea, Dana; Kretowski, Adam; Eckel, Robert H; Rewers, Marian

    2007-09-15

    Low levels of adiponectin have been related to coronary heart disease, but adiponectin is higher in persons with type 1 diabetes who have an increased rate of coronary disease. In the Coronary Artery Calcification in Type 1 Diabetes Study (2000-2002), the authors investigated potential determinants of elevated adiponectin levels in persons with type 1 diabetes and whether a difference exists compared with nondiabetic persons. Serum adiponectin was measured in 1,393 persons (sex: 48% male; age: 38 (standard deviation: 9) years; diabetes duration: 23 (standard deviation: 9) years; 54% nondiabetic and 46% with type 1 diabetes). Determinants of log-transformed adiponectin levels were evaluated by multiple linear regression analysis with interaction terms to determine whether predictors of adiponectin levels differed by diabetes status. Adiponectin levels were higher in type 1 diabetic than nondiabetic persons (13.5 (standard deviation: 1.0) vs. 8.8 (standard deviation: 1.0) microg/ml; p < 0.0001), adjusting for age, gender, body mass index, and glomerular filtration rate. The final regression model explained 67% of the difference in adiponectin levels between type 1 diabetic and nondiabetic persons. The variables explaining this difference included high density lipoprotein cholesterol, albumin excretion rate, plasminogen activator inhibitor-1, and hemoglobin A1c level. Adiponectin is higher in type 1 diabetic than nondiabetic persons. Although some of the difference can be explained, further study is needed to better understand the relation between elevated adiponectin levels and patient outcomes, including coronary heart disease. PMID:17591595

  6. Adiponectin Reduces Hepatic Stellate Cell Migration by Promoting Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Secretion*

    PubMed Central

    Ramezani-Moghadam, Mehdi; Wang, Jianhua; Ho, Vikki; Iseli, Tristan J.; Alzahrani, Badr; Xu, Aimin; Van der Poorten, David; Qiao, Liang; George, Jacob; Hebbard, Lionel

    2015-01-01

    Hepatic stellate cells (HSC) are central players in liver fibrosis that when activated, proliferate, migrate to sites of liver injury, and secrete extracellular matrix. Obesity, a known risk factor for liver fibrosis is associated with reduced levels of adiponectin, a protein that inhibits liver fibrosis in vivo and limits HSC proliferation and migration in vitro. Adiponectin-mediated activation of adenosine monophosphate-activated kinase (AMPK) inhibits HSC proliferation, but the mechanism by which it limits HSC migration to sites of injury is unknown. Here we sought to elucidate how adiponectin regulates HSC motility. Primary rat HSCs were isolated and treated with adiponectin in migration assays. The in vivo actions of adiponectin were examined by treating mice with carbon tetrachloride for 12 weeks and then injecting them with adiponectin. Cell and tissue samples were collected and analyzed for gene expression, signaling, and histology. Serum from patients with liver fibrosis was examined for adiponectin and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein. Adiponectin administration into mice increased TIMP-1 gene and protein expression. In cultured HSCs, adiponectin promoted TIMP-1 expression and through binding of TIMP-1 to the CD63/β1-integrin complex reduced phosphorylation of focal adhesion kinase to limit HSC migration. In mice with liver fibrosis, adiponectin had similar effects and limited focal adhesion kinase phosphorylation. Finally, in patients with advanced fibrosis, there was a positive correlation between serum adiponectin and TIMP-1 levels. In sum, these data show that adiponectin stimulates TIMP-1 secretion by HSCs to retard their migration and contributes to the anti-fibrotic effects of adiponectin. PMID:25575598

  7. Induction of heme-oxygenase-1 (HO-1) does not enhance adiponectin production in human adipocytes: Evidence against a direct HO-1 - Adiponectin axis.

    PubMed

    Yang, Mengliu; Kimura, Masaki; Ng, Choaping; He, Jingjing; Keshvari, Sahar; Rose, Felicity J; Barclay, Johanna L; Whitehead, Jonathan P

    2015-09-15

    Adiponectin is a salutary adipokine and hypoadiponectinemia is implicated in the aetiology of obesity-related inflammation and cardiometabolic disease making therapeutic strategies to increase adiponectin attractive. Emerging evidence, predominantly from preclinical studies, suggests induction of heme-oxygenase-1 (HO-1) increases adiponectin production and reduces inflammatory tone. Here, we aimed to test whether induction of HO-1 enhanced adiponectin production from mature adipocytes. Treatment of human adipocytes with cobalt protoporphyrin (CoPP) or hemin for 24-48 h increased HO-1 expression and activity without affecting adiponectin expression and secretion. Treatment of adipocytes with TNFα reduced adiponectin secretion and increased expression and secretion of additional pro-inflammatory cytokines, IL-6 and MCP-1, as well as expression of sXBP-1, a marker of ER stress. HO-1 induction failed to reverse these effects. These results demonstrate that induction of HO-1 does not directly enhance adiponectin production or ameliorate the pro-inflammatory effects of TNFα and argue against a direct HO-1 - adiponectin axis.

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

    PubMed

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

    2014-04-01

    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.

  9. Inside out: Bone marrow adipose tissue as a source of circulating adiponectin

    PubMed Central

    Scheller, Erica L.; Burr, Aaron A.; MacDougald, Ormond A.; Cawthorn, William P.

    2016-01-01

    ABSTRACT The adipocyte-derived hormone adiponectin mediates beneficial cardiometabolic effects, and hypoadiponectinemia is a biomarker for increased metabolic and cardiovascular risk. Indeed, circulating adiponectin decreases in obesity and insulin-resistance, likely because of impaired production from white adipose tissue (WAT). Conversely, lean states such as caloric restriction (CR) are characterized by hyperadiponectinemia, even without increased adiponectin production from WAT. The reasons underlying this paradox have remained elusive, but our recent research suggests that CR-associated hyperadiponectinemia derives from an unexpected source: bone marrow adipose tissue (MAT). Herein, we elaborate on this surprising discovery, including further discussion of potential mechanisms influencing adiponectin production from MAT; additional evidence both for and against our conclusions; and observations suggesting that the relationship between MAT and adiponectin might extend beyond CR. While many questions remain, the burgeoning study of MAT promises to reveal further key insights into MAT biology, both as a source of adiponectin and beyond. PMID:27617171

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

    PubMed

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

    2013-08-01

    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.

  11. Adiponectin in chronic kidney disease: a complex and context sensitive clinical situation.

    PubMed

    Stenvinkel, Peter

    2011-01-01

    Although hyperadiponectinemia is a common phenomenon in chronic kidney disease and is considered to have similar beneficial effects on metabolic risk in this patient group, many recent studies in general population have unexpectedly shown that high, rather than low, concentrations predict mortality. However, the apparent unfavorable effect of high adiponectin might not necessarily be exclusively or partially related to a direct effect of adiponectin, but rather it could be a consequence of a concurrent process of wasting (or pathogenic pathways linked to the wasting process) which may increase adiponectin levels. It is also possible that elevated circulating adiponectin levels mirror a state of volume and salt overload because natriuretic peptides and high salt intake were recently shown to stimulate secretion of adiponectin. Until nutritional and pharmacological treatment strategies that increase adiponectin in uremic patients can be advocated nephrologists have an important task to unravel the observed paradoxes.

  12. Inside out: Bone marrow adipose tissue as a source of circulating adiponectin.

    PubMed

    Scheller, Erica L; Burr, Aaron A; MacDougald, Ormond A; Cawthorn, William P

    2016-01-01

    The adipocyte-derived hormone adiponectin mediates beneficial cardiometabolic effects, and hypoadiponectinemia is a biomarker for increased metabolic and cardiovascular risk. Indeed, circulating adiponectin decreases in obesity and insulin-resistance, likely because of impaired production from white adipose tissue (WAT). Conversely, lean states such as caloric restriction (CR) are characterized by hyperadiponectinemia, even without increased adiponectin production from WAT. The reasons underlying this paradox have remained elusive, but our recent research suggests that CR-associated hyperadiponectinemia derives from an unexpected source: bone marrow adipose tissue (MAT). Herein, we elaborate on this surprising discovery, including further discussion of potential mechanisms influencing adiponectin production from MAT; additional evidence both for and against our conclusions; and observations suggesting that the relationship between MAT and adiponectin might extend beyond CR. While many questions remain, the burgeoning study of MAT promises to reveal further key insights into MAT biology, both as a source of adiponectin and beyond. PMID:27617171

  13. Sertoli cell processes have axoplasmic features: an ordered microtubule distribution and an abundant high molecular weight microtubule- associated protein (cytoplasmic dynein)

    PubMed Central

    1988-01-01

    Microtubules in the cytoplasm of rat Sertoli cell stage VI-VIII testicular seminiferous epithelium were studied morphometrically by electron microscopy. The Sertoli cell microtubules demonstrated axonal features, being largely parallel in orientation and predominantly spaced one to two microtubule diameters apart, suggesting the presence of microtubule-bound spacer molecules. Testis microtubule-associated proteins (MAPs) were isolated by a taxol, salt elution procedure. Testis MAPs promoted microtubule assembly, but to a lesser degree than brain MAPs. High molecular weight MAPs, similar in electrophoretic mobilities to brain MAP-1 and MAP-2, were prominent components of total testis MAPs, though no shared immunoreactivity was detected between testis and brain high molecular weight MAPs using both polyclonal and monoclonal antibodies. Unlike brain high molecular weight MAPs, testis high molecular weight MAPs were not heat stable. Testis MAP composition, studied on postnatal days 5, 10, 15, and 24 and in the adult, changed dramatically during ontogeny. However, the expression of the major testis high molecular weight MAP, called HMW-2, was constitutive and independent of the development of mature germ cells. The Sertoli cell origin of HMW-2 was confirmed by identifying this protein as the major MAP found in an enriched Sertoli cell preparation and in two rat models of testicular injury characterized by germ cell depletion. HMW-2 was selectively released from testis microtubules by ATP and co-purified by sucrose density gradient centrifugation with MAP- 1C, a neuronal cytoplasmic dynein. The inhibition of the microtubule- activated ATPase activity of HMW-2 by vanadate and erythro-(2-hydroxy-3- nonyl)adenine and its proteolytic breakdown by vanadate-dependent UV photocleavage confirmed the dynein-like nature of HMW-2. As demonstrated by this study, the neuronal and Sertoli cell cytoskeletons share morphological, structural and functional properties. PMID:2972729

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

    PubMed

    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

    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 β2-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, β2-adrenoceptors, and NO release.

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

    PubMed Central

    Correnti, Jason M.; Juskeviciute, Egle; Swarup, Aditi

    2014-01-01

    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 α (PPAR-α) 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-α. 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-α 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-α 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

  16. Adiponectin deficiency promotes tumor growth in mice by reducing macrophage infiltration.

    PubMed

    Sun, Yutong; Lodish, Harvey F

    2010-08-05

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

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

    PubMed

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

    2013-01-01

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

  18. Acute Systemic Inflammation is Unlikely to Affect Adiponectin and Leptin Synthesis in Humans

    PubMed Central

    Ekström, Mattias; Söderberg, Stefan; Tornvall, Per

    2015-01-01

    Adipose tissue (AT), classically thought to be merely an energy store, has been shown to produce inflammatory and metabolically active cytokines. Recently, adiponectin and leptin, adipokines primarily synthesized by adipocytes, have attracted considerable attention because inflammation has been suggested to modulate adipokine levels. However, the regulation of adiponectin and leptin is complex and the knowledge about their synthesis within the early onset of inflammation is poorly understood. The aim of this study was to investigate if the synthesis of adiponectin and leptin is affected during the early phase of an acute systemic inflammation. Eighteen healthy subjects were allocated to vaccination against Salmonella typhi or to a control group, and adiponectin and leptin concentrations measured in plasma during 24 h. Nine patients, without markers of inflammation, undergoing open heart surgery were investigated before and after the operation by analysis of plasma levels and AT gene expression of adiponectin and leptin. Plasma interleukin (IL)-6 concentrations were measured in both cohorts. Plasma levels of IL-6 were doubled after vaccination and increased 30-fold after open heart surgery. Plasma levels of adiponectin and leptin were unchanged after vaccination whereas adiponectin and leptin tended to decrease after surgery. The gene expression of adiponectin and leptin was unaltered in omental and subcutaneous AT after surgery. Despite the use of two models of stimulated in vivo systemic inflammation, we found no evidence of an early regulation of adiponectin and leptin synthesis, indicating that these two adipokines are not key elements in an acute systemic inflammation in humans. PMID:26664879

  19. Adiponectin resides in mouse skin and upregulates hyaluronan synthesis in dermal fibroblasts.

    PubMed

    Akazawa, Yumiko; Sayo, Tetsuya; Sugiyama, Yoshinori; Sato, Takashi; Akimoto, Noriko; Ito, Akira; Inoue, Shintaro

    2011-01-01

    Adipose tissue is a hormonally active tissue that produces adipokines that influence the activity of other tissues. Adiponectin is an adipocyte-specific adipokine involved in systemic metabolism. We detected the expression of adiponectin receptors (AdipoR1 and AdipoR2) mRNA in cultured dermal fibroblasts. The full-length adiponectin (fAd), but not the globular adiponectin (gAd), increased hyaluronan (HA) production and upregulated HA synthase (HAS) 2 mRNA expression. AdipoR1 and AdipoR2 mRNAs were also expressed in keratinocytes, though neither fAd nor gAd had any effect on HA synthesis. In mouse skin, we found that adiponectin was present and decreased markedly with aging. The age-dependent pattern of adiponectin decrease in skin, correlated well with that of HA in skin. Our experiments were also the first to identify adiponectin production in cultured mouse sebocytes, a finding that suggests that skin adiponectin may derive not only from plasma and/or subcutaneous adipose tissue, but also from the sebaceous gland. These results indicated that adiponectin plays an important role in the HA metabolism of skin. PMID:21117904

  20. Quality trait variations in [⁶⁰Co]-irradiated wheat and high-molecular-weight glutenin subunit mutant identification.

    PubMed

    Lai, D-E; Wang, M; Zhang, C-Y

    2014-10-31

    With 300 Gy of [(60)Co] γ-ray radiation of dry wheat seeds of Vortex 9722, the protein content, wet gluten content, sedimentation value, and hardness variation were analyzed in 341 lines in M4. Using over population mean ± 2X standard deviation as the screening standard, 8 lines with higher protein and wet gluten content and 4 lines with lower protein and wet gluten content were selected. In the M5 generation, the quality traits - silty parameters and high molecular weight glutenin subunits (HMW-GS) - were further analyzed in these 12 lines. The results showed that in the M5 generation, the quality traits in some variants were significantly different from those in the parents; the farinograms varied greatly. Eleven variants had significantly different HMW-GS bands compared to their parents. The parents had a HMW-GS composition of 5 + 14 + 15 + 12 + 9, and the variants had HMW-GS of 11 + 5 + 7 + 9 + 12 subunits or 1 + 5 + 7 + 8 + 12 subunits, indicating that the glutenin loci of these lines were mutated.

  1. Adiponectin gene polymorphisms (T45G and G276T), adiponectin levels and risk for metabolic diseases in an Arab population.

    PubMed

    Al-Daghri, Nasser M; Al-Attas, Omar S; Alokail, Majed S; Alkharfy, Khalid M; Hussain, Tajamul; Yakout, Sobhy; Vinodson, Benjamin; Sabico, Shaun

    2012-02-01

    In this study we examined the association of adiponectin gene variants with circulating adiponectin, and known metabolic diseases in 298 healthy controls and 297 Saudi subjects with type 2 diabetes mellitus (T2DM). Anthropometric and biochemical parameters were measured by standard procedures. Genotyping of T45G and G276T single nucleotide polymorphisms of adiponectin gene was carried out by PCR-RFLP analysis. No significant differences in the genotype distribution of T45G and G276T polymorphism were found between control and diabetic subjects. Neither SNP conferred an association with T2DM, obesity, hypertension or dyslipidemia. Despite a marked decrease in patients as opposed to controls, adiponectin levels were not different according to genotypes of T45G and G276T polymorphisms in control and patients. Thus, neither adiponectin SNPs independently conferred increased T2DM risk nor in other metabolic conditions considered such as obesity, hypertension or dyslipidemia. These findings support the existence of population based differences in the association of adiponectin gene variants with metabolic phenotypes and emphasize the importance of studying multiple polymorphisms, sufficient enough to identify the adiponectin gene as a genetic marker for several non-chronic communicable diseases.

  2. Macrophage polarization phenotype regulates adiponectin receptor expression and adiponectin anti-inflammatory response.

    PubMed

    van Stijn, Caroline M W; Kim, Jason; Lusis, Aldons J; Barish, Grant D; Tangirala, Rajendra K

    2015-02-01

    Adiponectin (APN), a pleiotropic adipokine that exerts anti-inflammatory, antidiabetic, and antiatherogenic effects through its receptors (AdipoRs), AdipoR1 and AdipoR2, is an important therapeutic target. Factors regulating AdipoR expression in monocyte/macrophages are poorly understood, and the significance of polarized macrophage activation in controlling AdipoR expression and the APN-mediated inflammatory response has not been investigated. The aim of this study was to investigate whether the macrophage polarization phenotype controls the AdipoR expression and APN-mediated inflammatory response. With the use of mouse bone marrow and peritoneal macrophages, we demonstrate that classical activation (M1) of macrophages suppressed (40-60% of control) AdipoR expression, whereas alternative activation (M2) preserved it. Remarkably, the macrophage polarization phenotypes produced contrasting inflammatory responses to APN (EC50 5 µg/ml). In M1 macrophages, APN induced proinflammatory cytokines, TNF-α, IL-6, and IL-12 (>10-fold of control) and AdipoR levels. In contrast, in M2 macrophages, APN induced the anti-inflammatory cytokine IL-10 without altering AdipoR expression. Furthermore, M1 macrophages adapt to a cytokine environment by reversing AdipoR expression. APN induced AdipoR mRNA and protein expression by up-regulating liver X receptor-α (LXRα) in macrophages. These results provide the first evidence that macrophage polarization is a key determinant regulating AdipoR expression and differential APN-mediated macrophage inflammatory responses, which can profoundly influence their pathogenic role in inflammatory and metabolic disorders.

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

    PubMed

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

    2012-07-10

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

  4. Protective role of adiponectin in a rat model of intestinal ischemia reperfusion injury

    PubMed Central

    Liu, Xu-Hui; Yang, Yue-Wu; Dai, Hai-Tao; Cai, Song-Wang; Chen, Rui-Han; Ye, Zhi-Qiang

    2015-01-01

    AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion (I/R) injury. METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The production of malondialdehyde (MDA) and superoxide dismutase (SOD) and villous injury scores were also measured. RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase (AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1 (HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway. PMID:26715807

  5. Relative hypoadiponectinemia, insulin resistance, and increased visceral fat in euthyroid prepubertal girls with low-normal serum free thyroxine.

    PubMed

    Prats-Puig, Anna; Sitjar, Carme; Ribot, Rosa; Calvo, Mar; Clausell-Pomés, Núria; Soler-Roca, Maria; Soriano-Rodríguez, Pilar; Osiniri, Inés; Ros-Miquel, Montserrat; Bassols, Judit; de Zegher, Francis; Ibáñez, Lourdes; López-Bermejo, Abel

    2012-07-01

    A lower activity of the thyroid axis within the clinical reference range is related to a dysmetabolic phenotype in adult populations. We posited that such an association is already present as early as in prepubertal childhood. Serum thyroid stimulating hormone (TSH) and free T4, body fat (bioelectric impedance), insulin resistance (homeostasis model assessment of insulin resistance (HOMA(IR))), total and high molecular weight (HMW)-adiponectin and serum lipids were assessed in 234 euthyroid prepubertal children (113 boys and 121 girls) attending primary care clinics. Visceral fat (abdominal ultrasound) was measured in a subset of these subjects (n = 147; 74 boys and 73 girls). Explants of visceral adipose tissue from an additional six prepubertal children (three boys and three girls) were used to study the regulation of total and HMW-adiponectin by thyroid hormone. Serum free T4 was in girls independently associated with HMW-adiponectin, HOMA(IR) and visceral fat, so that circulating HMW-adiponectin decreased by 30% (β = 0.305 P < 0.005, R(2) = 0.13) and HOMA(IR) and visceral fat increased, respectively, by 90% (β = -0.255 P < 0.01, R(2) = 0.05) and 30% (β = -0.369, P < 0.005, R(2) = 0.12) from the highest to the lowest tertile of serum free T4. Nonsignificant differences in these parameters were found in boys. Treatment of visceral fat explants with thyroid hormone increased total and HMW-adiponectin by 70% and 53%, respectively, above control values (P < 0.01). In conclusion, a dysmetabolic phenotype, consisting of relative hypoadiponectinemia, insulin resistance and increased visceral fat, is associated with low-normal serum free thyroxine in euthyroid prepubertal girls. These associations may be partly explained by a positive regulation of HMW-adiponectin secretion by thyroid hormone.

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

    PubMed Central

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

    1996-01-01

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

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

    PubMed

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

    1996-10-01

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

  8. Globular adiponectin reduces vascular calcification via inhibition of ER-stress-mediated smooth muscle cell apoptosis

    PubMed Central

    Lu, Yan; Bian, Yunfei; Wang, Yueru; Bai, Rui; Wang, Jiapu; Xiao, Chuanshi

    2015-01-01

    Objective: This study aims to explore the mechanism of globular adiponectin inhibiting vascular calcification. Methods: We established drug-induced rat vascular calcification model, globular adiponectin was given to observe the effect of globular Adiponectin on the degree of calcification. The markers of vascular calcification and apoptosis were also investigated. Meanwhile, the in vitro effect of globular Adiponectin on vascular calcification was also evaluated using primary cultured rat vascular smooth muscle cells. Results: We found that globular adiponectin could inhibit drug-induced rat vascular calcification significantly in vivo. The apoptosis of vascular smooth muscle cells was also reduced. The possible mechanism could be the down-regulation of endoplasmic reticulum stress by globular adiponectin. Experiments in primary cultured vascular smooth muscle cells also confirmed that globular adiponectin could reduce cell apoptosis to suppress vascular calcification via inhibition of endoplasmic reticulum stress. Conclusions: This study confirmed that globular adiponectin could suppress vascular calcification; one of the mechanisms could be inhibition of endoplasmic reticulum stress to reduce cell apoptosis. It could provide an effective method in the therapy of vascular calcification-associated diseases. PMID:26045760

  9. Adiponectin exacerbates collagen-induced arthritis via enhancing Th17 response and prompting RANKL expression.

    PubMed

    Sun, Xiaoxuan; Feng, Xiaoke; Tan, Wenfeng; Lin, Na; Hua, Minhui; Wei, Yu; Wang, Fang; Li, Ningli; Zhang, Miaojia

    2015-01-01

    We previously reported adiponectin (AD) is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in Rheumatoid arthritis (RA) patients. Here, we investigate the role of adiponectin in regulating Th17 response and the expression of receptor activator of nuclear factor-κB ligand (RANKL) in mice with CIA mice by intraarticularly injection of adiponectin into knee joints on day 17, day 20 and day 23 post first collagen immunization. The increased adiponectin expression was found in inflamed joint tissue of collagen-induced arthritis (CIA) mice. Adiponectin injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia, bone erosion and osteoporosis in CIA mice. CD4(+)IL-17(+) Th17 cells, IL-17 mRNA and RANKL mRNA expression were markedly increased in the joint tissue of adiponectin treated CIA mice. Moreover, adiponectin treatment markedly enhanced Th17 cell generation from naive CD4(+) T cells in vitro, which accompanied by the high expression of Th17 transcription factor ROR-γt, and Th17 cytokine genes included IL-22 and IL-23. This study reveals a novel effect of adiponectin in exacerbating CIA progression by enhancing Th17 cell response and RANKL expression. PMID:26063682

  10. Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance

    PubMed Central

    Kim, A. Young; Park, Yoon Jeong; Pan, Xuebo; Shin, Kyung Cheul; Kwak, Soo-Heon; Bassas, Abdulelah F.; Sallam, Reem M.; Park, Kyong Soo; Alfadda, Assim A.; Xu, Aimin; Kim, Jae Bum

    2015-01-01

    Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases. PMID:26139044

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  12. Neurogenesis-independent antidepressant-like effects of enriched environment is dependent on adiponectin.

    PubMed

    Nicolas, Sarah; Veyssière, Julie; Gandin, Carine; Zsürger, Nicole; Pietri, Mariel; Heurteaux, Catherine; Glaichenhaus, Nicolas; Petit-Paitel, Agnès; Chabry, Joëlle

    2015-07-01

    Environmental enrichment (EE) that combines voluntary physical exercise, sensory and social stimuli, causes profound changes in rodent brain at molecular, anatomical and behavioral levels. Here, we show that EE efficiently reduces anxiety and depression-like behaviors in a mouse model of depression induced by long-term administration of corticosterone. Mechanisms underlying EE-related beneficial effects remain largely unexplored; however, our results point toward adiponectin, an adipocyte-secreted protein, as a main contributor. Indeed, adiponectin-deficient (adipo(-/-)) mice did not benefit from all the EE-induced anxiolytic and antidepressant-like effects as evidenced by their differential responses in a series of behavioral tests. Conversely, a single intravenous injection of exogenous adiponectin restored the sensitivity of adipo(-/-) mice to EE-induced behavioral benefits. Interestingly, adiponectin depletion did not prevent the hippocampal neurogenesis induced by EE. Therefore, antidepressant properties of adiponectin are likely to be related to changes in signaling in the hypothalamus rather than through hippocampal-neurogenesis mechanisms. Additionally, EE did not modify the plasma levels of adiponectin but may favor the passage of adiponectin from the blood to the cerebrospinal fluid. Our findings provide advances in the understanding of the anxiolytic and antidepressant-like effects of EE and highlight adiponectin as a pivotal mediator.

  13. The Role of Adiponectin in Cardiometabolic Diseases: Effects of Nutritional Interventions.

    PubMed

    Lopez-Jaramillo, Patricio

    2016-02-01

    Adiponectin is an adipocyte-derived hormone abundantly present in plasma that exerts its effects through the activation of 3 receptors. Its concentrations are negatively regulated by the accumulation of visceral fat, and clinical studies implicate hypoadiponectinemia in the pathogenesis of diabetes mellitus type 2, coronary artery disease, hypertension, and left ventricular hypertrophy. In contrast, high concentrations of adiponectin are associated with a decreased risk of coronary artery disease, with an improvement in the differentiation of preadipocytes into adipocytes, and with increased endothelial nitric oxide production. Therefore, adiponectin appears to be an important molecule involved in limiting the pathogenesis of obesity-linked disorders, and it may have potential benefits in the treatment and prevention of cardiovascular disease. Caloric restriction, moderate alcohol consumption, and consuming a Mediterranean diet increase adiponectin concentrations, and current evidence suggests a positive, dose-dependent relation between ω-3 (n-3) fatty acid intake and circulating concentrations of adiponectin. Recently, it was reported that the administration of aged garlic extract and a single food intervention with pistachios can increase adiponectin concentrations in individuals with metabolic syndrome. Moreover, the Mediterranean diet is associated with higher adiponectin concentrations. Additional studies are needed to evaluate the potential benefits of increasing adiponectin by nutritional interventions in the treatment and prevention of cardiometabolic diseases. PMID:26764331

  14. Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function After Hemorrhagic Shock.

    PubMed

    Deng, Xiyun; Cao, Yanna; Huby, Maria P; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A; Doursout, Marie-Francoise; Holcomb, John B; Wade, Charles E; Ko, Tien C

    2016-01-01

    Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared with normal individuals, plasma adiponectin levels decreased to 49% in HS patients before resuscitation (P < 0.05) and increased to 64% post-resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared with baseline (P < 0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS.

  15. Serum adiponectin levels in diabetes, obesity and gender in Punjabi subjects from Faisalabad, Pakistan.

    PubMed

    Najam, Syeda Sadia; Awan, Fazli Rabbi; Baig, Shahid Mahmood

    2014-10-01

    Adiponectin has been associated with common metabolic disorders. The current study was conducted to measure and compare levels of adiponectin with obesity, type 2 diabetes mellitus (T2DM) and gender in Punjabi subjects from Faisalabad, Pakistan. Serum adiponectin was measured by enzyme-linked immunosorbent assay (ELISA) along with measurements of some clinically important analytes (fasting blood glucose, cholesterol, triglycerides) as well as body mass index (BMI) in 80 subjects. The main results were significantly (p < 0.003) decreased serum adiponectin level in T2DM patients (n = 40) compared to non-diabetic controls (n = 40). In obese subjects, (n = 40) also, there was a decrease, but it was not significant. Adiponectin levels in the subgroups of diabetic and obese patients were also observed, but no significant gender-based differences were found.

  16. Dietary regulation of adiponectin by direct and indirect lipid activators of nuclear hormone receptors.

    PubMed

    Rühl, R; Landrier, J F

    2016-01-01

    Adiponectin is an adipokine mainly secreted by adipocytes that presents antidiabetic, anti-inflammatory, and antiatherogenic functions. Therefore, modulation of adiponectin expression represents a promising target for prevention or treatment of several diseases including insulin resistance and type II diabetes. Pharmacological agents such as the nuclear hormone receptor synthetic agonists like peroxisome proliferator activated receptor γ agonists are of particular interest in therapeutic strategies due to their ability to increase the plasma adiponectin concentration. Nutritional approaches are also of particular interest, especially in primary prevention, since some active compounds of our diet (notably vitamins, carotenoids, or other essential nutrients) are direct or indirect lipid-activators of nuclear hormone receptors and are modifiers of adiponectin expression and secretion. The aim of the present review is to summarize current knowledge about the nutritional regulation of adiponectin by derivatives of active compounds naturally present in the diet acting as indirect or direct activators of nuclear hormone receptors.

  17. Dermal Lipogenesis Inhibits Adiponectin Production in Human Dermal Fibroblasts while Exogenous Adiponectin Administration Prevents against UVA-Induced Dermal Matrix Degradation in Human Skin

    PubMed Central

    Fang, Chien-Liang; Huang, Ling-Hung; Tsai, Hung-Yueh; Chang, Hsin-I

    2016-01-01

    Adiponectin is one of the most abundant adipokines from the subcutaneous fat, and regulates multiple activities through endocrine, paracrine, or autocrine mechanisms. However, its expression in adipogenic induced fibroblasts, and the potential role in photoaging has not been determined. Here, human dermal fibroblasts, Hs68, were presented as a cell model of dermal lipogenesis through stimulation of adipogenic differentiation medium (ADM). Similar to other studies in murine pre-adipocyte models (i.e., 3T3-L1), Hs68 fibroblasts showed a tendency to lipogenesis based on lipid accumulation, triglyceride formation, and the expressions of PPAR-γ, lipoprotein lipase (LPL), and FABP4 mRNA. As expected, ADM-treated fibroblasts displayed a reduction on adiponectin expression. Next, we emphasized the photoprotective effects of adiponectin against UVA-induced damage in Hs68 fibroblasts. UVA radiation can downregulate cell adhesion strength and elastic modulus of Hs68 fibroblasts. Moreover, UVA radiation could induce the mRNA expressions of epidermal growth factor receptor (EGFR), adiponectin receptor 1 (AdipoR1), matrix metalloproteinase-1 (MMP-1), MMP-3, and cyclooxygenase-2 (COX-2), but downregulate the mRNA expressions of type I and type III collagen. On the other hand, post-treatment of adiponectin can partially overcome UVA-induced reduction in the cell adhesion strength of Hs68 fibroblasts through the activation of AdipoR1 and the suppression of EGF-R. In addition, post-treatment of adiponectin indicated the increase of type III collagen and elastin mRNA expression and the decrease of MMP-1 and MMP-3 mRNA expression, but a limited degree of recovery of elastic modulus on UVA-irradiated Hs68 fibroblasts. Overall, these results suggest that dermal lipogenesis may inhibit the expression of adiponectin while exogenous adiponectin administration prevents against UVA-induced dermal matrix degradation in Hs68 fibroblasts. PMID:27428951

  18. Dermal Lipogenesis Inhibits Adiponectin Production in Human Dermal Fibroblasts while Exogenous Adiponectin Administration Prevents against UVA-Induced Dermal Matrix Degradation in Human Skin.

    PubMed

    Fang, Chien-Liang; Huang, Ling-Hung; Tsai, Hung-Yueh; Chang, Hsin-I

    2016-01-01

    Adiponectin is one of the most abundant adipokines from the subcutaneous fat, and regulates multiple activities through endocrine, paracrine, or autocrine mechanisms. However, its expression in adipogenic induced fibroblasts, and the potential role in photoaging has not been determined. Here, human dermal fibroblasts, Hs68, were presented as a cell model of dermal lipogenesis through stimulation of adipogenic differentiation medium (ADM). Similar to other studies in murine pre-adipocyte models (i.e., 3T3-L1), Hs68 fibroblasts showed a tendency to lipogenesis based on lipid accumulation, triglyceride formation, and the expressions of PPAR-γ, lipoprotein lipase (LPL), and FABP4 mRNA. As expected, ADM-treated fibroblasts displayed a reduction on adiponectin expression. Next, we emphasized the photoprotective effects of adiponectin against UVA-induced damage in Hs68 fibroblasts. UVA radiation can downregulate cell adhesion strength and elastic modulus of Hs68 fibroblasts. Moreover, UVA radiation could induce the mRNA expressions of epidermal growth factor receptor (EGFR), adiponectin receptor 1 (AdipoR1), matrix metalloproteinase-1 (MMP-1), MMP-3, and cyclooxygenase-2 (COX-2), but downregulate the mRNA expressions of type I and type III collagen. On the other hand, post-treatment of adiponectin can partially overcome UVA-induced reduction in the cell adhesion strength of Hs68 fibroblasts through the activation of AdipoR1 and the suppression of EGF-R. In addition, post-treatment of adiponectin indicated the increase of type III collagen and elastin mRNA expression and the decrease of MMP-1 and MMP-3 mRNA expression, but a limited degree of recovery of elastic modulus on UVA-irradiated Hs68 fibroblasts. Overall, these results suggest that dermal lipogenesis may inhibit the expression of adiponectin while exogenous adiponectin administration prevents against UVA-induced dermal matrix degradation in Hs68 fibroblasts. PMID:27428951

  19. Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice

    PubMed Central

    Wang, XianFeng; Buechler, Nancy L; Yoza, Barbara K; McCall, Charles E; Vachharajani, Vidula

    2016-01-01

    Background Morbid obesity increases the cost of care in critically ill patients. Sepsis is the leading cause of death in noncoronary intensive care units. Circulating cell–endothelial cell interactions in microcirculation are the rate-determining factors in any inflammation; obesity increases these interactions further. Adiponectin deficiency is implicated in increased cardiovascular risk in obese patients. We have shown that adiponectin deficiency increases microvascular dysfunction in early sepsis. In the present study, we investigated the effect of adiponectin replacement on nutritionally obese mice with early sepsis. Methods We used cecal ligation and puncture model of sepsis in mice with diet-induced obesity (DIO) vs control diet (CTRL), with or without adiponectin treatment. We studied leukocyte/platelet adhesion in the cerebral microcirculation in early sepsis. We also studied the effect of adiponectin on free fatty acid (FFA)-fed and lipopolysaccharide-stimulated bone marrow-derived macrophages (BMDM) for mechanistic studies. Results Leukocyte and platelet adhesion increased in the cerebral microcirculation of DIO and CTRL mice with early sepsis vs. sham; moreover cell adhesion in DIO-sepsis group was significantly higher than in the CTRL-sepsis group. Adiponectin replacement decreased leukocyte/platelet adhesion in CTRL and DIO mice. In FFA-fed BMDM, adiponectin treatment decreased tumor necrosis factor-alpha mRNA expression and increased sirtuin-1 (SIRT1) mRNA expression. Furthermore, using BMDM from SIRT1 knockout mice, we showed that the adiponectin treatment decreased inflammatory response in FFA-fed BMDM via SIRT1-dependent and -independent pathways. Conclusion Adiponectin replacement attenuates microvascular inflammation in DIO-sepsis mice. Mechanistically, adiponectin treatment in FFA-fed mouse macrophages attenuates inflammatory response via SIRT1-dependent and -independent pathways. PMID:27785087

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

    PubMed

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

    2013-08-01

    As endocrinologically active cells, adipocytes are capable of secreting various adipocytokines such as leptin, resistin, and adiponectin to impact metabolic function. Although adipocytes remain to be the primary site of synthesis and secretion, there is now growing evidence that supports the presence of adiponectin and its receptors within the hypothalamic-pituitary-gonadal axis, providing a possible link between obesity and abnormal reproductive physiology. It has been demonstrated that adiponectin may reduce gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus as well as modulate gonadal steroid hormone production. Furthermore, prior data indicate that adiponectin may play a role in decreasing luteinizing hormone secretion from pituitary gonadotropes. We aimed to identify the hormonal regulators of adiponectin and its receptors, AdipoR1 and AdipoR2, in pituitary gonadotropes using immortalized gonadotropic LβT2 cells and primary rat pituitary cells. Our study shows significant alterations in adiponectin expression across the estrous cycle. In addition, we present a novel finding that GnRH suppresses pituitary adiponectin expression via the calcium and protein kinase A intracellular pathways in both cultured rat primary pituitary cells and the LβT2 gonadotrope cell line. The GnRH did not alter expression of the adiponectin receptors, AdipoR1 and AdipoR2, in cultured gonadotropes. Expression of the adiponectin receptors, AdipoR1 and AdipoR2, was not altered by GnRH in cell culture but in vivo or in vitro. Our data suggest that gonadotrope function may be modulated by GnRH-mediated changes in adiponectin expression.

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

    PubMed

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

    2015-02-01

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

  2. The relationship between physical activity level and cardiovascular disease biomarkers in healthy, normal-weight 3- to 6-year-old children and their parents.

    PubMed

    Huang, Carol; Cantell, Marja; Crawford, Susan; Dewey, Deborah; Pacaud, Danièle

    2016-08-01

    To determine if physical activity is linked to cardiovascular biomarkers in preschool children at risk, we need information on these biomarkers in healthy normal-weight children. In this population, multi-level modelling analyses found no correlation between accelerometer recorded physical activity and fasting lipids, adiponectin, or insulin sensitivity. Exploratory analyses found positive correlations between adiponectin and time spent in light physical activity, and between triglyceride and time spent in sedentary behaviour; these findings need to be confirmed in longitudinal prospective studies.

  3. Adiponectin and Adiponectin Receptor Gene Variants in Relation to Type 2 Diabetes and Insulin Resistance-Related Phenotypes

    PubMed Central

    Potapov, Viktor A.; Chistiakov, Dimitry A.; Dubinina, Anna; Shamkhalova, Minara S.; Shestakova, Marina V.; Nosikov, Valery V.

    2008-01-01

    BACKGROUND: Alterations in adiponectin-mediated pathways are known to be associated with glucose intolerance, insulin resistance (IR), obesity, and type 2 diabetes (T2D) mellitus. Genetic variations in adiponectin (ADIPOQ) and adiponectin 1 and 2 receptor (ADIPOR1 and ADIPOR2) could have effects on IR-related phenotypes and T2D. Here we examine whether the polymorphic markers rs2241766 (ADIPOQ), rs22753738 (ADIPOR1), rs11061971 and rs16928751 (both in ADIPOR2) are implicated in susceptibility to T2D in a Russian population. METHODS: The polymorphic markers were genotyped in 129 T2D patients, and 117 non-diabetic controls, by polymerase chain reaction (PCR) restriction fragment length polymorphism approach. In the subjects, biochemical characteristics including serum insulin, plasma glucose and serum lipids/lipoproteins were measured and compared for correlation with the genetic variations studied. RESULTS: Allele T of rs11061971 and allele A of rs16928751 showed association with higher risk of diabetes providing odds ratios (OR) of 2.05 (p = 0.0025) and 1.88 (p = 0.018), respectively. Haplotype A-G consisting of allele A of rs11061971 and allele G of rs16928751 was associated with reduced risk of T2D (OR = 0.59, pc = 0.0224). Compared to other variants, diabetic patients double homozygous for A/A of rs16928751 and G/G of rs16928751 had decreased homeostasis model assessment-insulin resistance (pc = 0.0375) and serum triglycerides (pc = 0.0285). CONCLUSIONS: The variants of ADIPOR2 confer susceptibility to T2D and are associated with some IR-related phenotypes in the Russian study population. PMID:18548168

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

    SciTech Connect

    Moriuchi, Akie ||. E-mail: f1195@cc.nagasaki-u-ac.jp; Shimamura, Mika; Kita, Atsushi; Kuwahara, Hironaga; Satoh, Tsuyoshi; Satoh, Tsuyoshi; Fujishima, Keiichiro; Fukushima, Keiko |; Hayakawa, Takao; Mizuguchi, Hiroyuki; Nagayama, Yuji; Kawasaki, Eiji

    2007-05-18

    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}.

  5. Bone, body weight, and weight reduction: what are the concerns?

    PubMed

    Shapses, Sue A; Riedt, Claudia S

    2006-06-01

    Of the U.S. population, 65% is either overweight or obese, and weight loss is recommended to reduce co-morbid conditions. However, bone mobilization and loss may also occur with weight loss. The risk for bone loss depends on initial body weight, age, gender, physical activity, and conditions of dieting such as the extent of energy restriction and specific levels of nutrient intake. Older populations are more prone to bone loss with weight loss; in women, this is due at least in part to a reduced dietary Ca intake and/or efficiency of absorption. Potential hormonal mechanisms regulating bone loss during weight loss are discussed, including decreases in estrogen, leptin, glucagon-like peptide-2, growth hormone, and insulin-like growth factor-1, or an increase in cortisol. In contrast, the rise in adiponectin and ghrelin with weight reduction should not be detrimental to bone. Combining energy restriction with exercise does not necessarily prevent bone loss, but may attenuate loss as was shown with additional Ca intake or osteoporosis medications. Future controlled weight loss trials should be designed to further address mechanisms influencing the density and quality of bone sites vulnerable to fracture, in the prevention of osteoporosis. PMID:16702302

  6. Influence of the interaction between the adiponectin G276T polymorphism and body mass index on lipid levels in healthy children.

    PubMed

    Riestra, Pía; García-Anguita, Alicia; Lasunción, Miguel A; Mangas, Alipio; de Oya, Manuel; Garcés, Carmen

    2012-04-01

    Adiponectin is an adipose tissue-specific hormone which is inversely associated with metabolic alterations related to atherosclerosis. Polymorphisms in the adiponectin gene (AdipoQ) have been related to low adiponectin levels as well as several cardiovascular risk factors, but this association remains controversial. In our study we investigated the relationship between the AdipoQ T45G (rs: 2241766) and G276T (rs: 1501299) polymorphisms and adiponectin concentrations, blood pressure, and lipid and insulin levels, in a population-based sample of 12- to 16-year-old children. The study included 815 healthy Spanish children (388 boys and 427 girls). Plasma glucose and lipid levels were determined by standard methods. Insulin concentrations were measured by RIA, and serum adiponectin levels were determined by ELISA. The AdipoQ T45G and AdipoQ G276T polymorphisms were determined by TaqMan(®) allelic discrimination assays. ANOVA or t test allowed for comparison of the studied parameters across genotypes or genotype groups, respectively. A linear regression analysis was performed to examine the independent relationships of the lipid variables with BMI (body mass index), AdipoQ G276T polymorphism and the interaction between the two. When independently comparing the effect of these polymorphisms in normal-weight and overweight children, we observed that overweight boys carriers of the minor allele T had significantly lower TC, LDL-C and apo A-I levels than non-carriers, but these differences were not apparent in normal-weight boys. Furthermore, linear regression analysis demonstrated that interaction between the BMI and the AdipoQ G276T polymorphism is a significant factor explaining the variations of TC and LDL-C levels. To our knowledge, this is the first study to report an association between the AdipoQ G276T polymorphism and lipid levels in overweight boys alone, thereby suggesting that the influence of the AdipoQ polymorphisms on cardiovascular risk factors may be

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

    PubMed

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

    2013-04-01

    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.

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

    PubMed

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

    2013-04-01

    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

  9. Adiponectin Receptor Signaling on Dendritic Cells Blunts Antitumor Immunity

    PubMed Central

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

    2015-01-01

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

  10. Globular Adiponectin Enhances Muscle Insulin Action via Microvascular Recruitment and Increased Insulin Delivery

    PubMed Central

    Zhao, Lina; Chai, Weidong; Fu, Zhuo; Dong, Zhenhua; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong; Liu, Zhenqi

    2014-01-01

    Rationale Adiponectin enhances insulin action and induces nitric oxide–dependent vasodilatation. Insulin delivery to muscle microcirculation and transendothelial transport are 2 discrete steps that limit insulin's action. We have shown that expansion of muscle microvascular surface area increases muscle insulin delivery and action. Objective To examine whether adiponectin modulates muscle microvascular recruitment thus insulin delivery and action in vivo. Methods and Results Overnight fasted adult male rats were studied. We determined the effects of adiponectin on muscle microvascular recruitment, using contrast-enhanced ultrasound, on insulin-mediated microvascular recruitment and whole-body glucose disposal, using contrast-enhanced ultrasound and insulin clamp, and on muscle insulin clearance and uptake with 125I-insulin. Globular adiponectin potently increased muscle microvascular blood volume without altering microvascular blood flow velocity, leading to a significantly increased microvascular blood flow. This was paralleled by a ≈30% to 40% increase in muscle insulin uptake and clearance, and ≈30% increase in insulin-stimulated whole-body glucose disposal. Inhibition of endothelial nitric oxide synthase abolished globular adiponectin-mediated muscle microvascular recruitment and insulin uptake. In cultured endothelial cells, globular adiponectin dose-dependently increased endothelial nitric oxide synthase phosphorylation but had no effect on endothelial cell internalization of insulin. Conclusions Globular adiponectin increases muscle insulin uptake by recruiting muscle microvasculature, which contributes to its insulin-sensitizing action. PMID:23459195

  11. Functional expression of the globular domain of human adiponectin in Pichia pastoris.

    PubMed

    Liu, De-Guo; Liu, Hong-Lei; Song, Tan-Jing; Huang, Hai-Yan; Li, Xi; Tang, Qi-Qun

    2007-11-23

    Adiponectin is an adipokine that predominantly synthesized and secreted from adipocytes mainly in the white adipose tissue. Here, we report that we have successfully expressed human gAdiponectin (the globular domain of adiponectin) in the methylotrophic yeast Pichia pastoris after codon optimization and established the purification procedure. The human gAdiponectin gene was designed and synthesized by PCR according to the P. pastoris preferred codons, and then inserted into the P. pastoris pPIC9K expression vector. The plasmid was electroporated into the P. pastoris strain GS115 and only the G418 resistance colonies could produce the gAdiponectin. After fermentation and purification, we could get 1.2g of recombinant gAdiponectin (purity is approximately 95%) from a 24 L culture media. The recombinant gAdiponectin is fully functional as evidenced by induction the phosphorylation of ACC in differentiated C2C12 myotubes, significantly lowering the blood glucose level and accelerating the clearance of free fatty acid in animal models.

  12. Undercarboxylated osteocalcin is associated with insulin resistance, but not adiponectin, during pregnancy.

    PubMed

    Srichomkwun, Panudda; Houngngam, Natnicha; Pasatrat, Sophitsachi; Tharavanij, Thipaporn; Wattanachanya, Lalita; Khovidhunkit, Weerapan

    2016-07-01

    In mice, undercarboxylated osteocalcin (ucOC) improves beta-cell function and insulin sensitivity through adiponectin. In humans, levels of total osteocalcin (OC) and ucOC were negatively correlated with insulin resistance (IR) indices in patients with type 2 diabetes. Whether ucOC plays a role in glucose homeostasis and whether its effect is mediated through adiponectin during pregnancy is unclear. Serum levels of total OC, ucOC, and adiponectin were measured in 130 pregnant women with varying degrees of IR [gestational diabetes mellitus (GDM), n = 74 and non-GDM, n = 56]. In all participants, total OC and ucOC levels were positively correlated with HOMA-IR and HOMA-%B, and negatively correlated with QUICKI. In contrast, adiponectin levels were negatively correlated with HOMA-IR and positively correlated with QUICKI (P < 0.01, both). However, neither total OC nor ucOC was associated with adiponectin. Although none of these markers could help distinguish women with and without GDM, total OC and ucOC levels were significantly higher in non-GDM women who had 1 abnormal OGTT value than those who had all normal OGTT values. Total OC and ucOC levels were significantly correlated with insulin secretion and IR indices, but not adiponectin levels, in pregnant women. Changes in OC might be a sensitive response to increased IR during pregnancy, which was not mediated through adiponectin. PMID:26708046

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

    PubMed Central

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

    2014-01-01

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

  14. A prospective study of serum adiponectin and regression of metabolic syndrome: The ARIRANG study.

    PubMed

    Kim, Jang-Young; Yadav, Dhananjay; Ahn, Song Vogue; Koh, Sang-Baek

    2015-10-16

    Increased serum adiponectin levels may play a protective role in metabolic syndrome. However, few prospective studies have examined the effect of serum adiponectin in the improvement of metabolic components in subjects with metabolic syndrome. We investigated the association of serum adiponectin levels with the regression of metabolic syndrome in a population-based longitudinal study. A total of 1308 adults (575 men and 733 women) with metabolic syndrome at baseline were examined and followed. Baseline serum adiponectin concentrations were measured by radioimmunoassay. During an average of 2.6 years of follow-up, metabolic syndrome had disappeared in 184 men (29.8%) and 235 women (32.1%). In multivariable adjusted models, the odds ratio (95% confidence interval) for regression of metabolic syndrome comparing the highest to the lowest quartiles of adiponectin levels was 0.93 (0.56-1.53) in men and 2.48 (1.54-4.01) in women. Increased serum adiponectin is a predictor for the regression of metabolic syndrome in women. Adiponectin may have potential therapeutic applications in metabolic disease.

  15. Expression of FABP4, adipsin and adiponectin in Paneth cells is modulated by gut Lactobacillus

    PubMed Central

    Su, Xiaomin; Yan, Hui; Huang, Yugang; Yun, Huan; Zeng, Benhua; Wang, Enlin; Liu, Yu; Zhang, Yuan; Liu, Feifei; Che, Yongzhe; Zhang, Zhiqian; Yang, Rongcun

    2015-01-01

    We here found that intestinal epithelial Paneth cells secrete FABP4, adipsin and adiponectin in both mice and human. Deletion of Paneth cell results in the decrease of FABP4, adipsin and adiponectin not only in intestinal crypt cells but also in sera, suggesting that they may influence the state of the whole body. We also demonstrate that expression of FABP4, adipsin and adiponectin may be modulated by specific gut microbiota. In germ-free (GF) mice, the expression of FABP4, adipsin and adiponectin were lower or difficult to be detected. Feces transplantation promoted the expression of FABP4, adipsin and adiponectin in gut epithelial Paneth cells. We have found that Lactobacillus NK6 colony, which has the highest similarity with Lactobacillus taiwanensis strain BCRC 17755, may induce the expression of FABP4, adipsin and adiponectin through TRAF2 and TRAF6 ubiquitination mediated NF-κB signaling. Taken together, our findings set up a novel mechanism for FABP4, adipsin and adiponectin through gut microbiota mediating expression in gut Paneth cells. PMID:26687459

  16. The aporphine alkaloid boldine induces adiponectin expression and regulation in 3T3-L1 cells.

    PubMed

    Yu, Bangning; Cook, Carla; Santanam, Nalini

    2009-10-01

    Adiponectin is an adipokine secreted by differentiated adipocytes. Clinical studies suggest a negative correlation between oxidative stress and adiponectin levels in patients with metabolic syndrome or cardiovascular disease. Natural compounds that can prevent oxidative stress mediated inhibition of adiponectin may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the medicinal plant Peumus boldus, is a powerful antioxidant. The current study demonstrates the effects of boldine on the expression of adiponectin and its regulators, CCAAT/enhancer binding protein-alpha (C/EBPalpha) and peroxisome proliferator-activated receptor (PPAR)-gamma, in 3T3-L1 cells. Differentiated 3T3-L1 adipocytes were exposed to either hydrogen peroxide (H(2)O(2)) (100 microM) or tumor necrosis factor-alpha (TNFalpha) (1 ng/mL) for 24 hours in the presence or absence of increasing concentrations of boldine (5-100 microM). Quantitative polymerase chain reaction showed that both the oxidants decreased the mRNA levels of adiponectin, PPARgamma, and C/EBPalpha to half of the control levels. Boldine, at all concentrations, counteracted the inhibitory effect of H(2)O(2) or TNFalpha and increased the expression of adiponectin and its regulators. The effect of boldine on adiponectin expression was biphasic, with the lower concentrations (5-25 microM) having a larger inductive effect compared to higher concentrations (50-100 microM). Boldine treatment alone in the absence of H(2)O(2) or TNFalpha was also able to induce adiponectin at the inductive phase of adipogenesis. Peroxisome proliferator response element-luciferase promoter transactivity analysis showed that boldine interacts with the PPAR response element and could potentially modulate PPAR responsive genes. Our results indicate that boldine is able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells and has the potential to be beneficial in obesity-related cardiovascular disease. PMID:19857072

  17. The Aporphine Alkaloid Boldine Induces Adiponectin Expression and Regulation in 3T3-L1 Cells

    PubMed Central

    Yu, Bangning; Cook, Carla

    2009-01-01

    Abstract Adiponectin is an adipokine secreted by differentiated adipocytes. Clinical studies suggest a negative correlation between oxidative stress and adiponectin levels in patients with metabolic syndrome or cardiovascular disease. Natural compounds that can prevent oxidative stress mediated inhibition of adiponectin may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the medicinal plant Peumus boldus, is a powerful antioxidant. The current study demonstrates the effects of boldine on the expression of adiponectin and its regulators, CCAAT/enhancer binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor (PPAR)-γ, in 3T3-L1 cells. Differentiated 3T3-L1 adipocytes were exposed to either hydrogen peroxide (H2O2) (100 μM) or tumor necrosis factor-α (TNFα) (1 ng/mL) for 24 hours in the presence or absence of increasing concentrations of boldine (5–100 μM). Quantitative polymerase chain reaction showed that both the oxidants decreased the mRNA levels of adiponectin, PPARγ, and C/EBPα to half of the control levels. Boldine, at all concentrations, counteracted the inhibitory effect of H2O2 or TNFα and increased the expression of adiponectin and its regulators. The effect of boldine on adiponectin expression was biphasic, with the lower concentrations (5–25 μM) having a larger inductive effect compared to higher concentrations (50–100 μM). Boldine treatment alone in the absence of H2O2 or TNFα was also able to induce adiponectin at the inductive phase of adipogenesis. Peroxisome proliferator response element-luciferase promoter transactivity analysis showed that boldine interacts with the PPAR response element and could potentially modulate PPAR responsive genes. Our results indicate that boldine is able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells and has the potential to be beneficial in obesity-related cardiovascular disease. PMID:19857072

  18. Adiponectin and marine n-3 fatty acids in patients referred for coronary angiography.

    PubMed

    Rasmussen, Jeppe Grøndahl; Christensen, Jeppe Hagstrup; Schmidt, Erik Berg

    2009-06-26

    Marine n-3 polyunsaturated fatty acids (n-3 PUFAs) in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce the risk of coronary heart disease (CHD) and have anti-inflammatory effects. We examined whether levels of serum adiponectin were related to the occurrence and extent of CHD, and whether intake of n-3 PUFAs was associated to high levels of adiponectin. Serum adiponectin and the content of n-3 PUFAs in subcutaneous adipose tissue, platelets and granulocytes were measured in 291 patients referred to elective coronary angiography. Significantly lower levels of serum adiponectin were observed in patients with coronary stenoses compared to patients without stenoses (7336+/-3598 ng/ml vs 10,203+/-8396 ng/ml; p=0.003), but no significant correlation was seen between serum adiponectin and the extent of CHD. In men, serum adiponectin correlated to levels of the content of EPA in platelets (r=0.26; p<0.01) and in granulocytes (r=0.23; p<0.01) and to the content of DHA in subcutaneous adipose tissue (r=0.15; p<0.05) and granulocytes (r=0.17; p<0.05). After regression analysis EPA in platelets (p=0.017) and granulocytes (p=0.030) remained an independent correlate of adiponectin levels, while DHA was no longer an independent correlate. In conclusion, serum levels of adiponectin were lower in patients with angiographically documented coronary artery disease. Also, intake of EPA may increase serum adiponectin and through this exert a protective effect on CHD.

  19. Genetic Architecture of Plasma Adiponectin Overlaps With the Genetics of Metabolic Syndrome–Related Traits

    PubMed Central

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

    2010-01-01

    OBJECTIVE Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome–related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs). RESEARCH DESIGN AND METHODS We made use of a family-based population, the Erasmus Rucphen Family study (1,258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model. RESULTS Plasma adiponectin showed a heritability of 55.1%. Genetic correlations between plasma adiponectin HDL cholesterol and plasma insulin ranged from 15 to 24% but were not significant for fasting glucose, triglycerides, blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), and C-reactive protein. A significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. A nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjustment for plasma adiponectin. CONCLUSIONS The significant genetic correlation between plasma adiponectin and HDL cholesterol and plasma insulin should be taken into account in the interpretation of genome-wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR. PMID:20067957

  20. Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease

    PubMed Central

    Persson, Jonas; Strawbridge, Rona J; McLeod, Olga; Gertow, Karl; Silveira, Angela; Baldassarre, Damiano; Van Zuydam, Natalie; Shah, Sonia; Fava, Cristiano; Gustafsson, Stefan; Veglia, Fabrizio; Sennblad, Bengt; Larsson, Malin; Sabater-Lleal, Maria; Leander, Karin; Gigante, Bruna; Tabak, Adam; Kivimaki, Mika; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J; Mannarino, Elmo; Giral, Philippe; Humphries, Steve E; Tremoli, Elena; de Faire, Ulf; Lind, Lars; Ingelsson, Erik; Hedblad, Bo; Melander, Olle; Kumari, Meena; Hingorani, Aroon; Morris, Andrew D; Palmer, Colin N A; Lundman, Pia; Öhrvik, John; Söderberg, Stefan; Hamsten, Anders

    2015-01-01

    Background Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n =1777; men, n =1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (β =−0.018, P<0.001) in men but not in women (β =−0.006, P =0.185; P for interaction =0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (β =−0.0022, P =0.047), whereas no association was seen in women (0.0007, P =0.475; P for interaction =0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82, 95% CI 0.54 to 1.25). A gene score of adiponectin-raising alleles in 6 loci, reported recently in a large multi-ethnic meta-analysis, was inversely associated with baseline mean bifurcation IMT in men (β =−0.0008, P =0.004) but not in women (β =−0.0003, P =0.522; P for interaction =0.007). Conclusions This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted. PMID:26276317

  1. Adiponectin selectively inhibits oxytocin neurons of the paraventricular nucleus of the hypothalamus

    PubMed Central

    Hoyda, Ted D; Fry, Mark; Ahima, Rexford S; Ferguson, Alastair V

    2007-01-01

    Adiponectin is an adipocyte derived hormone which acts in the brain to modulate energy homeostasis and autonomic function. The paraventricular nucleus of the hypothalamus (PVN) which plays a key role in controlling pituitary hormone secretion has been suggested to be a central target for adiponectin actions. A number of hormones produced by PVN neurons have been implicated in the regulation of energy homeostasis including oxytocin, corticotropin releasing hormone and thyrotropin releasing hormone. In the present study we investigated the role of adiponectin in controlling the excitability of magnocellular (MNC – oxytocin or vasopressin secreting) neurons within the PVN. Using RT-PCR techniques we have shown expression of both adiponectin receptors in the PVN. Patch clamp recordings from MNC neurons in hypothalamic slices have also identified mixed (27% hyperpolarization, 42% depolarization) effects of adiponectin in modulating the excitability of the majority of MNC neurons tested. These effects are maintained when cells are placed in synaptic isolation using tetrodotoxin. Additionally we combined electrophysiological recordings with single cell RT-PCR to examine the actions of adiponectin on MNC neurons which expressed oxytocin only, vasopressin only, or both oxytocin and vasopressin mRNA and assess the profile of receptor expression in these subgroups. Adiponectin was found to hyperpolarize 100% of oxytocin neurons tested (n = 6), while vasopressin cells, while all affected (n = 6), showed mixed responses. Further analysis indicates oxytocin neurons express both receptors (6/7) while vasopressin neurons express either both receptors (3/8) or one receptor (5/8). In contrast 6/6 oxytocin/vasopressin neurons were unaffected by adiponectin. Co-expressing oxytocin and vasopressin neurons express neither receptor (4/6). The results presented in this study suggest that adiponectin plays specific roles in controlling the excitability oxytocin secreting neurons, actions

  2. 11β-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes.

    PubMed

    Koh, Eun Hee; Kim, Ah-Ram; Kim, Hyunshik; Kim, Jin Hee; Park, Hye-Sun; Ko, Myoung Seok; Kim, Mi-Ok; Kim, Hyuk-Joong; Kim, Bum Joong; Yoo, Hyun Ju; Kim, Su Jung; Oh, Jin Sun; Woo, Chang-Yun; Jang, Jung Eun; Leem, Jaechan; Cho, Myung Hwan; Lee, Ki-Up

    2015-06-01

    Mitochondrial dysfunction in hypertrophic adipocytes can reduce adiponectin synthesis. We investigated whether 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression is increased in hypertrophic adipocytes and whether this is responsible for mitochondrial dysfunction and reduced adiponectin synthesis. Differentiated 3T3L1 adipocytes were cultured for up to 21 days. The effect of AZD6925, a selective 11β-HSD1 inhibitor, on metabolism was examined. db/db mice were administered 600 mg/kg AZD6925 daily for 4 weeks via gastric lavage. Mitochondrial DNA (mtDNA) content, mRNA expression levels of 11 β -H sd1 and mitochondrial biogenesis factors, adiponectin synthesis, fatty acid oxidation (FAO), oxygen consumption rate and glycolysis were measured. Adipocyte hypertrophy in 3T3L1 cells exposed to a long duration of culture was associated with increased 11 β -Hsd1 mRNA expression and reduced mtDNA content, mitochondrial biogenesis factor expression and adiponectin synthesis. These cells displayed reduced mitochondrial respiration and increased glycolysis. Treatment of these cells with AZD6925 increased adiponectin synthesis and mitochondrial respiration. Inhibition of FAO by etomoxir blocked the AZD6925-induced increase in adiponectin synthesis, indicating that 11β-HSD1-mediated reductions in FAO are responsible for the reduction in adiponectin synthesis. The expression level of 11 β -Hsd1 was higher in adipose tissues of db/db mice. Administration of AZD6925 to db/db mice increased the plasma adiponectin level and adipose tissue FAO. In conclusion, increased 11β-HSD1 expression contributes to reduced mitochondrial respiration and adiponectin synthesis in hypertrophic adipocytes.

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

    PubMed Central

    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

    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 (β = 0.62 ± 0.28, p = 0.03) among non-obese (n = 673) and insulin sensitive participants (n = 1141; β = 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

  4. Effect of the molecular weight of poly(epsilon-caprolactone-co-DL-lactide) on toremifene citrate release from copolymer/silica xerogel composites.

    PubMed

    Rich, J; Kortesuo, P; Ahola, M; Yli-Urpo, A; Kiesvaara, J; Seppälä, J

    2001-01-01

    The purpose of this study was to develop a biodegradable polymeric carrier system for toremifene citrate based on epsilon-caprolactone/DL-lactide copolymers and silica xerogel. The effect of the molecular weight of poly(epsilon-caprolactone-co-DL-lactide) affecting the release rate of toremifene citrate from copolymer/silica xerogel composites was evaluated by in vitro dissolution study. Lower and higher molecular weight copolymers (LMW 60000 g/mol and HMW 300000 g/mol) were used in the devices. Drug release was compared from the (copolymer/drug) matrix device and the (copolymer/drug impregnated silica xerogel) composite device. Hydrolysis of the copolymer devices was evaluated by water absorption, weight loss and change of molecular weight by size exclusion measurements (SEC). Controlled release of toremifene citrate was obtained from both matrix and composite devices and the release rate was most affected by the initial molecular weight of the copolymer. Throughout the study better results were obtained with LMW devices, since drug release was steady for nearly 1 year and no changes in the release rate were observed. The drug release was diffusion controlled from both LMW matrix and composite devices. Incorporation of toremifene citrate into the silica xerogel was found to enhance the drug release rate. The copolymer matrices degraded by random hydrolytic chain scission and, unexpectedly, HMW P(CL/LA) degraded faster than LMW P(CL/LA). The release of toremifene citrate from HMW devices was not complete before the second stage of polymer degradation began.

  5. Biotransformation of petroleum asphaltenes and high molecular weight polycyclic aromatic hydrocarbons by Neosartorya fischeri.

    PubMed

    Hernández-López, E Lorena; Perezgasga, Lucia; Huerta-Saquero, Alejandro; Mouriño-Pérez, Rosa; Vazquez-Duhalt, Rafael

    2016-06-01

    Neosartorya fischeri, an Aspergillaceae fungus, was evaluated in its capacity to transform high molecular weight polycyclic aromatics hydrocarbons (HMW-PAHs) and the recalcitrant fraction of petroleum, the asphaltenes. N. fischeri was able to grow in these compounds as sole carbon source. Coronene, benzo(g,h,i)perylene, and indeno(1,2,3-c,d)pyrene, together with the asphaltenes, were assayed for fungal biotransformation. The transformation of the asphaltenes and HMW-PAHs was confirmed by reverse-phase high-performance liquid chromatography (HPLC), nano-LC mass spectrometry, and IR spectrometry. The formation of hydroxy and ketones groups on the PAH molecules suggest a biotransformation mediated by monooxygenases such as cytochrome P450 system (CYP). A comparative microarray with the complete genome from N. fischeri showed three CYP monooxygenases and one flavin monooxygenase genes upregulated. These findings, together with the internalization of aromatic substrates into fungal cells and the microsomal transformation of HMW-PAHs, strongly support the role of CYPs in the oxidation of these recalcitrant compounds.

  6. Biotransformation of petroleum asphaltenes and high molecular weight polycyclic aromatic hydrocarbons by Neosartorya fischeri.

    PubMed

    Hernández-López, E Lorena; Perezgasga, Lucia; Huerta-Saquero, Alejandro; Mouriño-Pérez, Rosa; Vazquez-Duhalt, Rafael

    2016-06-01

    Neosartorya fischeri, an Aspergillaceae fungus, was evaluated in its capacity to transform high molecular weight polycyclic aromatics hydrocarbons (HMW-PAHs) and the recalcitrant fraction of petroleum, the asphaltenes. N. fischeri was able to grow in these compounds as sole carbon source. Coronene, benzo(g,h,i)perylene, and indeno(1,2,3-c,d)pyrene, together with the asphaltenes, were assayed for fungal biotransformation. The transformation of the asphaltenes and HMW-PAHs was confirmed by reverse-phase high-performance liquid chromatography (HPLC), nano-LC mass spectrometry, and IR spectrometry. The formation of hydroxy and ketones groups on the PAH molecules suggest a biotransformation mediated by monooxygenases such as cytochrome P450 system (CYP). A comparative microarray with the complete genome from N. fischeri showed three CYP monooxygenases and one flavin monooxygenase genes upregulated. These findings, together with the internalization of aromatic substrates into fungal cells and the microsomal transformation of HMW-PAHs, strongly support the role of CYPs in the oxidation of these recalcitrant compounds. PMID:26893177

  7. Globular adiponectin enhances invasion in human breast cancer cells

    PubMed Central

    FALK LIBBY, EMILY; LIU, JIANZHONG; LI, YI; LEWIS, MONICA J.; DEMARK-WAHNEFRIED, WENDY; HURST, DOUGLAS R.

    2016-01-01

    Every year, a large number of women succumb to metastatic breast cancer due to a lack of curative approaches for this disease. Adiponectin (AdipoQ) is the most abundant of the adipocyte-secreted adipokines. In recent years, there has been an interest in the use of AdipoQ and AdipoQ receptor agonists as therapeutic agents for the treatment of breast cancer. However, while multiple epidemiological studies have previously indicated that low levels of circulating plasma AdipoQ portend poor prognosis in patients with breast cancer, recent studies have reported that elevated expression levels of AdipoQ in breast tissue are correlated with advanced stages of the disease. Thus, the aim of the present study was to clarify the mechanism by which AdipoQ in breast tissue acts directly on tumor cells to regulate the early steps of breast cancer metastasis. In the present study, the effects of different AdipoQ isoforms on the metastatic potential of human breast cancer cells were investigated. The results revealed that globular adiponectin (gAd) promoted invasive cell morphology and significantly increased the migration and invasion abilities of breast cancer cells, whereas full-length adiponectin (fAd) had no effect on these cells. Additionally, gAd, but not fAd, increased the expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B)-II and intracellular LC3B puncta, which are indicators of autophagosome formation, thus suggesting autophagic induction by gAd. Furthermore, the inhibition of autophagic function by autophagy-related protein 7 knockdown attenuated the gAd-induced increase in invasiveness in breast cancer cells. Therefore, the results of the present study suggested that a specific AdipoQ isoform may enhance breast cancer invasion, possibly via autophagic induction. Understanding the roles of the different AdipoQ isoforms as microenvironmental regulatory molecules may aid the development of effective AdipoQ-based treatments for breast cancer

  8. Long term intake of 0.1% ethanol decreases serum adiponectin by suppressing PPARγ expression via p38 MAPK pathway.

    PubMed

    Tian, Chong; Jin, Xin; Ye, Xiaolei; Wu, Hongmei; Ren, Weiye; Zhang, Rui; Long, Jia; Ying, Chenjiang

    2014-03-01

    Light alcohol consumption was reported to be negatively associated with insulin resistance and risk of cardiovascular diseases; however, the results were inconsistent. We here investigate whether long term intake of low-concentration ethanol can affect adiponectin levels. Male Wistar rats were exposed to 0.1% ethanol in drinking water for 26weeks. Visceral adipose tissue (VAT) was cultured and treated with ethanol, SB203580, GW9662, or rosiglitazone. Adiponectin in serum and culture supernatant were measured by ELISA, mRNA levels of adiponectin and PPARγ were determined by RT-PCR, and protein expressions of PPARγ, p38 MAPK and phospho-p38 MAPK were determined by Western blot. In vivo, ethanol decreased the mRNA of adiponectin in VAT and serum adiponectin significantly. Decreased PPARγ and increased activation of p38 MAPK were observed in ethanol treated group. In vitro, SB203580 increased the adiponectin and PPARγ levels in normal DMEM cultured VAT and ameliorated ethanol-induced decrease of adiponectin and PPARγ expressions. GW9662 also decreased the adiponectin levels; Both ethanol and GW9662 weakened the rosiglitazone-induced elevation of adiponectin levels in cultured VAT. These data suggest that long term intake of 0.1% ethanol down-regulated adiponectin levels, and the regulation of PPARγ via p38 MAPK pathway plays an important role in the mechanism underneath.

  9. Associations of Adiponectin with Adiposity, Insulin Sensitivity, and Diet in Young, Healthy, Mexican Americans and Non-Latino White Adults.

    PubMed

    Pereira, Rocio I; Low Wang, Cecilia C; Wolfe, Pamela; Havranek, Edward P; Long, Carlin S; Bessesen, Daniel H

    2015-12-22

    Low circulating adiponectin levels may contribute to higher diabetes risk among Mexican Americans (MA) compared to non-Latino whites (NLW). Our objective was to determine if among young healthy adult MAs have lower adiponectin than NLWs, independent of differences in adiposity. In addition, we explored associations between adiponectin and diet. This was an observational, cross-sectional study of healthy MA and NLW adults living in Colorado (U.S.A.). We measured plasma total adiponectin, adiposity (BMI, and visceral adipose tissue), insulin sensitivity (IVGTT), and self-reported dietary intake in 43 MA and NLW adults. Mean adiponectin levels were 40% lower among MA than NLW (5.8 ± 3.3 vs. 10.7 ± 4.2 µg/mL, p = 0.0003), and this difference persisted after controlling for age, sex, BMI, and visceral adiposity. Lower adiponectin in MA was associated with lower insulin sensitivity (R² = 0.42, p < 0.01). Lower adiponectin was also associated with higher dietary glycemic index, lower intake of vegetables, higher intake of trans fat, and higher intake of grains. Our findings confirm that ethnic differences in adiponectin reflect differences in insulin sensitivity, but suggest that these are not due to differences in adiposity. Observed associations between adiponectin and diet support the need for future studies exploring the regulation of adiponectin by diet and other environmental factors.

  10. Effects of genetic variants in the promoter region of the bovine adiponectin (ADIPOQ) gene on marbling of Hanwoo beef cattle.

    PubMed

    Choi, Yoonjeong; Davis, Michael E; Chung, Hoyoung

    2015-07-01

    This study aimed to verify genetic effects of the bovine adiponectin (ADIPOQ) gene on carcass traits of Hanwoo cattle. The measured carcass traits were marbling score (MAR), backfat thickness (BFT), loineye area (LEA), and carcass weight (CAW). Selection of primers was based on the bovine ADIPOQ sequence, and the analysis amplified approximately 267 and 333 bp genomic segments, including 67 bp of insertions in the promoter region. Sequencing analysis confirmed genetic variants (g.81966235C>T, g.81966377T>C, and g.81966364D>I) that showed significant effects on MAR. The present results suggest that the identified SNPs are useful genetic markers for the improvement of carcass traits in Hanwoo cattle.

  11. Adiponectin inhibits insulin function in primary trophoblasts by PPARα-mediated ceramide synthesis.

    PubMed

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

    2014-04-01

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

  12. Effects of febuxostat on platelet-derived microparticles and adiponectin in patients with hyperuricemia.

    PubMed

    Nishizawa, Tohru; Taniura, Takehito; Nomura, Shosaku

    2015-12-01

    Platelet-derived microparticles (PDMPs) and adiponectin play an important role in the development of atherothrombosis. We investigated the effect of febuxostat on circulating PDMP levels and adiponectin in hyperuricemic patients. Levels of PDMP and biomarkers were measured using an ELISA at baseline and after 2 and 6 months of treatment. Plasma levels of PDMPs and biomarkers were higher, while those of adiponectin were lower in hyperuricemic patients than in normouricemic controls. Uric acid and interleukin (IL)-6 levels decreased significantly in hyperuricemic patients after 2 months of febuxostat treatment. However, PDMP and biomarkers decreased significantly in hyperuricemic patients after only 6 months of febuxostat treatment and adiponectin increased significantly. These results suggest that the effects of febuxostat for PDMPs seen may be the effect on xanthine oxidase but not the decrease of uric acid, and febuxostat may be beneficial for primary prevention of atherothrombosis in hyperuricemic patients.

  13. Effects of febuxostat on platelet-derived microparticles and adiponectin in patients with hyperuricema

    PubMed Central

    Nishizawa, Tohru; Taniura, Takehito; Nomura, Shosaku

    2015-01-01

    Platelet-derived microparticles (PDMPs) and adiponectin play an important role in the development of atherothrombosis. We investigated the effect of febuxostat on circulating PDMP levels and adiponectin in hyperuricemic patients. Levels of PDMP and biomarkers were measured using an ELISA at baseline and after 2 and 6 months of treatment. Plasma levels of PDMPs and biomarkers were higher, while those of adiponectin were lower in hyperuricemic patients than in normouricemic controls. Uric acid and interleukin (IL)-6 levels decreased significantly in hyperuricemic patients after 2 months of febuxostat treatment. However, PDMP and biomarkers decreased significantly in hyperuricemic patients after only 6 months of febuxostat treatment and adiponectin increased significantly. These results suggest that the effects of febuxostat for PDMPs seen may be the effect on xanthine oxidase but not the decrease of uric acid, and febuxostat may be beneficial for primary prevention of atherothrombosis in hyperuricemic patients. PMID:26164850

  14. Evolving role of adiponectin in cancer-controversies and update

    PubMed Central

    Katira, Arnav; Tan, Peng H.

    2016-01-01

    Adiponectin (APN), an adipokine produced by adipocytes, has been shown to have a critical role in the pathogenesis of obesity-associated malignancies. Through its receptor interactions, APN may exert its anti-carcinogenic effects including regulating cell survival, apoptosis and metastasis via a plethora of signalling pathways. Despite the strong evidence supporting this notion, some work may indicate otherwise. Our review addresses all controversies critically. On the whole, hypoadiponectinaemia is associated with increased risk of several malignancies and poor prognosis. In addition, various genetic polymorphisms may predispose individuals to increased risk of obesity-associated malignancies. We also provide an updated summary on therapeutic interventions to increase APN levels that are of key interest in this field. To date efforts to manipulate APN levels have been promising, but much work remains to be done. PMID:27144066

  15. Formation of high-molecular-weight compounds via the heterogeneous reactions of gaseous C8-C10 n-aldehydes in the presence of atmospheric aerosol components

    NASA Astrophysics Data System (ADS)

    Han, Yuemei; Kawamura, Kimitaka; Chen, Qingcai; Mochida, Michihiro

    2016-02-01

    A laboratory study on the heterogeneous reactions of straight-chain aldehydes was performed by exposing n-octanal, nonanal, and decanal vapors to ambient aerosol particles. The aerosol and blank filters were extracted using methanol. The extracts were nebulized and the resulting compositions were examined using a high-resolution time-of-flight aerosol mass spectrometer. The mass spectral analysis showed that the exposures of the aldehydes to aerosol samples increased the peak intensities in the high mass range. The peaks in the mass spectra of the aerosol samples after exposure to different aldehydes were characterized by a homologous series of peak shifts due to the addition of multiple CH2 units. This result is explained by the formation of high-molecular-weight (HMW) compounds that contain single or multiple aldehyde moieties. The HMW fragment peaks for the blank filters exposed to n-aldehydes were relatively weak, indicating an important contribution from the ambient aerosol components to the formation of the HMW compounds. Among the factors affecting the overall interaction of aldehydes with atmospheric aerosol components, gas phase diffusion possibly limited the reactions under the studied conditions; therefore, their occurrence to a similar degree in the atmosphere is not ruled out, at least for the reactions involving n-nonanal and decanal. The major formation pathways for the observed HMW products may be the self-reactions of n-aldehydes mediated by atmospheric aerosol components and the reactions of n-aldehydes with organic aerosol components. The observed formation of HMW compounds encourages further investigations into their effects on the aerosol properties as well as the organic aerosol mass in the atmosphere.

  16. Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain.

    PubMed

    Takeda, Shuko; Wegmann, Susanne; Cho, Hansang; DeVos, Sarah L; Commins, Caitlin; Roe, Allyson D; Nicholls, Samantha B; Carlson, George A; Pitstick, Rose; Nobuhara, Chloe K; Costantino, Isabel; Frosch, Matthew P; Müller, Daniel J; Irimia, Daniel; Hyman, Bradley T

    2015-10-13

    Tau pathology is known to spread in a hierarchical pattern in Alzheimer's disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development.

  17. Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain

    PubMed Central

    Takeda, Shuko; Wegmann, Susanne; Cho, Hansang; DeVos, Sarah L.; Commins, Caitlin; Roe, Allyson D.; Nicholls, Samantha B.; Carlson, George A.; Pitstick, Rose; Nobuhara, Chloe K.; Costantino, Isabel; Frosch, Matthew P.; Müller, Daniel J.; Irimia, Daniel; Hyman, Bradley T.

    2015-01-01

    Tau pathology is known to spread in a hierarchical pattern in Alzheimer's disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development. PMID:26458742

  18. Reduced Bone Density and Cortical Bone Indices in Female Adiponectin-Knockout Mice.

    PubMed

    Naot, Dorit; Watson, Maureen; Callon, Karen E; Tuari, Donna; Musson, David S; Choi, Ally J; Sreenivasan, Dharshini; Fernandez, Justin; Tu, Pao Ting; Dickinson, Michelle; Gamble, Greg D; Grey, Andrew; Cornish, Jillian

    2016-09-01

    A positive association between fat and bone mass is maintained through a network of signaling molecules. Clinical studies found that the circulating levels of adiponectin, a peptide secreted from adipocytes, are inversely related to visceral fat mass and bone mineral density, and it has been suggested that adiponectin contributes to the coupling between fat and bone. Our study tested the hypothesis that adiponectin affects bone tissue by comparing the bone phenotype of wild-type and adiponectin-knockout (APN-KO) female mice between the ages of 8-37 weeks. Using a longitudinal study design, we determined body composition and bone density using dual energy x-ray absorptiometry. In parallel, groups of animals were killed at different ages and bone properties were analyzed by microcomputed tomography, dynamic histomorphometry, 3-point bending test, nanoindentation, and computational modelling. APN-KO mice had reduced body fat and decreased whole-skeleton bone mineral density. Microcomputed tomography analysis identified reduced cortical area fraction and average cortical thickness in APN-KO mice in all the age groups and reduced trabecular bone volume fraction only in young APN-KO mice. There were no major differences in bone strength and material properties between the 2 groups. Taken together, our results demonstrate a positive effect of adiponectin on bone geometry and density in our mouse model. Assuming adiponectin has similar effects in humans, the low circulating levels of adiponectin associated with increased fat mass are unlikely to contribute to the parallel increase in bone mass. Therefore, adiponectin does not appear to play a role in the coupling between fat and bone tissue. PMID:27384302

  19. Insulin-independent role of adiponectin receptor signaling in Drosophila germline stem cell maintenance.

    PubMed

    Laws, Kaitlin M; Sampson, Leesa L; Drummond-Barbosa, Daniela

    2015-03-15

    Adipocytes have key endocrine roles, mediated in large part by secreted protein hormones termed adipokines. The adipokine adiponectin is well known for its role in sensitizing peripheral tissues to insulin, and several lines of evidence suggest that adiponectin might also modulate stem cells/precursors. It remains unclear, however, how adiponectin signaling controls stem cells and whether this role is secondary to its insulin-sensitizing effects or distinct. Drosophila adipocytes also function as an endocrine organ and, although no obvious adiponectin homolog has been identified, Drosophila AdipoR encodes a well-conserved homolog of mammalian adiponectin receptors. Here, we generate a null AdipoR allele and use clonal analysis to demonstrate an intrinsic requirement for AdipoR in germline stem cell (GSC) maintenance in the Drosophila ovary. AdipoR null GSCs are not fully responsive to bone morphogenetic protein ligands from the niche and have a slight reduction in E-cadherin levels at the GSC-niche junction. Conversely, germline-specific overexpression of AdipoR inhibits natural GSC loss, suggesting that reduction in adiponectin signaling might contribute to the normal decline in GSC numbers observed over time in wild-type females. Surprisingly, AdipoR is not required for insulin sensitization of the germline, leading us to speculate that insulin sensitization is a more recently acquired function than stem cell regulation in the evolutionary history of adiponectin signaling. Our findings establish Drosophila female GSCs as a new system for future studies addressing the molecular mechanisms whereby adiponectin receptor signaling modulates stem cell fate.

  20. Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

    SciTech Connect

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana; Klegeris, Andis; Little, Jonathan P.

    2014-03-28

    Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.

  1. Relationship of serum adiponectin and resistin to glucose intolerance and fat topography in south-Asians

    PubMed Central

    Wasim, Hanif; Al-Daghri, Nasser M; Chetty, Raja; McTernan, Phillip G; Barnett, A H; Kumar, Sudhesh

    2006-01-01

    Objectives South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels. Methods In this cross-sectional study, 150 South-Asians (80 males, 70 females) were included, 60 had NGT (Control group, Age 51.33 ± 11.5, BMI 27 ± 2.3), 60 had IGT (Age 57.7 ± 12.5, BMI 27.2 ± 2.7), 30 had type 2 DM (Age 49.5 ± 10.9, BMI 28 ± 1.7). Measures of adiposity, adipocytokines and other metabolic parameters were determined. Parameters were measured using the following: a) Plasma glucose by glucose oxidase method b) CRP by immunoturbidimetric method (Roche/Hitachi analyser) c) insulin by Medgenix INS-ELISA immunoenzymetric assay by Biosource (Belgium) d) Leptin, Adiponectin by radioimmunoassay kits by Linco Research (St. Charles MO) e) Resistin by immunoassay kits by Phoenix Pharmaceuticals INC (530 Harbor Boulevard, Belmont CA 94002, USA). Results Adiponectin concentrations were highest in NGT, decreased in IGT and lowest in DMT2, (both p < 0.01). Leptin was significantly higher in DMT2 than IGT and NGT p = 0.02 and 0.04 respectively. There was a significant positive relationships between log adiponectin and 2-hr insulin values, p = 0.028 and history of hypertensions and a ischemic heart disease p = 0.008 with R = 0.65. There was a significant inverse correlation between log adiponectin and resistin, p < 0.01. Conclusion Resistin levels had an inverse correlation with adiponectin levels, indicating an inverse relationship between pro-inflammatory cytokines and adiponectin. Adiponectin levels were related to glucose tolerance. PMID:16669997

  2. Second-generation antipsychotics and adiponectin levels in schizophrenia: A comparative meta-analysis.

    PubMed

    Bartoli, Francesco; Crocamo, Cristina; Clerici, Massimo; Carrà, Giuseppe

    2015-10-01

    People with schizophrenia treated with second-generation antipsychotics (SGAs) have lower plasma adiponectin levels, as compared with general population, that may lead to metabolic abnormalities. However, the contribution of different SGAs on adiponectin dysregulation is still unclear. The objective of this systematic review and meta-analysis was to estimate differences in adiponectin levels among people with schizophrenia treated with different SGAs. We systematically searched for observational studies published up to March 2015 in main electronic databases. Different SGAs were included if data on adiponectin were available from at least three different samples involving as a minimum five participants per treatment arm. Standardized mean differences with relevant 95% confidence intervals were generated. I(2) was used to test heterogeneity among studies. Eight studies were included with data suitable for carrying out four different comparisons: Clozapine vs. Olanzapine (including n=877 individuals with schizophrenia); Clozapine vs. Risperidone (n=660); Olanzapine vs. Risperidone (n=738); Quetiapine vs. Risperidone (n=186). There were no differences on adiponectin levels between people taking Clozapine and those taking Olanzapine (p=0.86), but high heterogeneity was detected (I(2)=82%). Both individuals taking Clozapine (p<0.001; I(2)=0%) and those taking Olanzapine (p=0.02; I(2)=9%), but not subjects treated with Quetiapine (p=0.47; I(2)=0%), had adiponectin levels significantly lower than people taking Risperidone. Our findings are consistent with previous evidence showing greater metabolic abnormalities attributable to Clozapine and Olanzapine, as compared with other SGAs. Although mechanisms whereby both these SGAs influence adiponectin remain unexplained, its reduction might mediate relevant abnormalities. Prospective evaluations of long-term effects of different SGAs on adiponectin are needed. PMID:26164075

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

    PubMed Central

    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

    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

  4. Leptin and Adiponectin Modulate the Self-renewal of Normal Human Breast Epithelial Stem Cells.

    PubMed

    Esper, Raymond M; Dame, Michael; McClintock, Shannon; Holt, Peter R; Dannenberg, Andrew J; Wicha, Max S; Brenner, Dean E

    2015-12-01

    Multiple mechanisms are likely to account for the link between obesity and increased risk of postmenopausal breast cancer. Two adipokines, leptin and adiponectin, are of particular interest due to their opposing biologic functions and associations with breast cancer risk. In the current study, we investigated the effects of leptin and adiponectin on normal breast epithelial stem cells. Levels of leptin in human adipose explant-derived conditioned media positively correlated with the size of the normal breast stem cell pool. In contrast, an inverse relationship was found for adiponectin. Moreover, a strong linear relationship was observed between the leptin/adiponectin ratio in adipose conditioned media and breast stem cell self-renewal. Consistent with these findings, exogenous leptin stimulated whereas adiponectin suppressed breast stem cell self-renewal. In addition to local in-breast effects, circulating factors, including leptin and adiponectin, may contribute to the link between obesity and breast cancer. Increased levels of leptin and reduced amounts of adiponectin were found in serum from obese compared with age-matched lean postmenopausal women. Interestingly, serum from obese women increased stem cell self-renewal by 30% compared with only 7% for lean control serum. Taken together, these data suggest a plausible explanation for the obesity-driven increase in postmenopausal breast cancer risk. Leptin and adiponectin may function as both endocrine and paracrine/juxtacrine factors to modulate the size of the normal stem cell pool. Interventions that disrupt this axis and thereby normalize breast stem cell self-renewal could reduce the risk of breast cancer.

  5. Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling

    PubMed Central

    Antonopoulos, Alexios S.; Margaritis, Marios; Verheule, Sander; Recalde, Alice; Sanna, Fabio; Herdman, Laura; Psarros, Costas; Nasrallah, Hussein; Coutinho, Patricia; Akoumianakis, Ioannis; Brewer, Alison C.; Sayeed, Rana; Krasopoulos, George; Petrou, Mario; Tarun, Akansha; Tousoulis, Dimitris; Shah, Ajay M.; Casadei, Barbara; Channon, Keith M.

    2016-01-01

    Rationale: Adiponectin has anti-inflammatory effects in experimental models, but its role in the regulation of myocardial redox state in humans is unknown. Although adiponectin is released from epicardial adipose tissue (EpAT), it is unclear whether it exerts any paracrine effects on the human myocardium. Objective: To explore the cross talk between EpAT-derived adiponectin and myocardial redox state in the human heart. Methods and Results: EpAT and atrial myocardium were obtained from 306 patients undergoing coronary artery bypass grafting. Functional genetic polymorphisms that increase ADIPOQ expression (encoding adiponectin) led to reduced myocardial nicotinamide adenine dinucleotide phosphate oxidase–derived O2−, whereas circulating adiponectin and ADIPOQ expression in EpAT were associated with elevated myocardial O2−. In human atrial tissue, we demonstrated that adiponectin suppresses myocardial nicotinamide adenine dinucleotide phosphate oxidase activity, by preventing AMP kinase–mediated translocation of Rac1 and p47phox from the cytosol to the membranes. Induction of O2− production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce peroxisome proliferator-activated receptor-γ–mediated upregulation of ADIPOQ expression in cocultured EpAT. Using a NOX2 transgenic mouse and a pig model of rapid atrial pacing, we found that oxidation products (such as 4-hydroxynonenal) released from the heart trigger peroxisome proliferator-activated receptor-γ–mediated upregulation of ADIPOQ in EpAT. Conclusions: We demonstrate for the first time in humans that adiponectin directly decreases myocardial nicotinamide adenine dinucleotide phosphate oxidase activity via endocrine or paracrine effects. Adiponectin expression in EpAT is controlled by paracrine effects of oxidation products released from the heart. These effects constitute a novel defense mechanism of the heart against myocardial oxidative stress. PMID:26838789

  6. Adiponectin and Leptin Molecular Actions and Clinical Significance in Breast Cancer

    PubMed Central

    Nalabolu, Mohan Reddy; Palasamudram, Kalyani

    2014-01-01

    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. PMID:24505549

  7. Association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer

    PubMed Central

    Jin, Jing Hui; Kim, Hyun-Jung; Kim, Chan Young; Kim, Yun Hwan; Ju, Woong

    2016-01-01

    Objective Decreased adiponectin and increased leptin plasma concentrations are believed to be associated with the occurrence and progression of cancers such as endometrial cancer and breast cancer. The aim of this study was to explore the association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer. Methods For patients with ovarian cancer and the control group, adiponectin and leptin levels were measured; anthropometric data were obtained during a chart review. Statistical comparisons between groups were analyzed using the Student's t-test; correlations were confirmed using the Pearson correlation. Results The mean adiponectin and leptin concentrations in patients with ovarian cancer were lower than those of the control group (8.25 vs. 11.44 µg/mL, respectively; P=0.026) (7.09 vs. 15.4 ng/mL, respectively; P=0.001). However, there was no significant difference in adiponectin and leptin levels between early-stage (I/II) and advanced-stage (III/IV) disease (P=0.078). Conclusion Compared with other gynecological cancers, the level of adiponectin and leptin were decreased in ovarian cancer that may have some diagnostic value; additional study to elucidate the function of these two hormones in the development of ovarian carcinogenesis is necessitated. PMID:27462594

  8. An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart

    PubMed Central

    Fang, Xiangping; Palanivel, Rengasamy; Cresser, Justin; Schram, Kristin; Ganguly, Riya; Thong, Farah S. L.; Tuinei, Joseph; Xu, Aimin; Abel, E. Dale

    2010-01-01

    Adiponectin promotes cardioprotection by various mechanisms, and this study used primary cardiomyocytes and the isolated working perfused heart to investigate cardiometabolic effects. We show in adult cardiomyocytes that adiponectin increased CD36 translocation and fatty acid uptake as well as insulin-stimulated glucose transport and Akt phosphorylation. Coimmunoprecipitation showed that adiponectin enhanced association of AdipoR1 with APPL1, subsequent binding of APPL1 with AMPKα2, which led to phosphorylation and inhibition of ACC and increased fatty acid oxidation. Using siRNA to effectively knockdown APPL1 in neonatal cardiomyocytes, we demonstrated an essential role for APPL1 in mediating increased fatty acid uptake and oxidation by adiponectin. Importantly, enhanced fatty acid oxidation in conjunction with AMPK and ACC phosphorylation was also observed in the isolated working heart. Despite increasing fatty acid oxidation and myocardial oxygen consumption, adiponectin increased hydraulic work and maintained cardiac efficiency. In summary, the present study documents several beneficial metabolic effects mediated by adiponectin in the heart and provides novel insight into the mechanisms behind these effects, in particular the importance of APPL1. PMID:20739511

  9. Differential Associations between CDH13 Genotypes, Adiponectin Levels, and Circulating Levels of Cellular Adhesive Molecules

    PubMed Central

    Teng, Ming-Sheng; Wu, Semon; Hsu, Lung-An; Chou, Hsin-Hua; Ko, Yu-Lin

    2015-01-01

    CDH13 gene variants with lower adiponectin levels are paradoxically associated with a more favorable metabolic profile. We investigated the statistical association between CDH13 locus variants and adiponectin levels by examining 12 circulating inflammation marker levels and adiposity status in 530 Han Chinese people in Taiwan. After adjustments for clinical covariates, adiponectin levels were positively associated with soluble vascular cell adhesion molecule-1 (sVCAM1) levels and negatively associated with adiposity status and levels of C-reactive protein (CRP), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM1). In addition, minor alleles of the CDH13 rs12051272 polymorphism were found to have lower adiponectin levels and higher CRP, sE-selectin, sICAM1, and sVCAM1 levels as well as higher body mass indices and waist circumferences in participants (all P < 0.05). In a subgroup analysis stratified by sex, significant associations between CDH13 genotypes and sE-selectin levels occurred only in men (P = 3.9 × 10−4 and interaction P = 0.005). CDH13 locus variants and adiponectin levels are associated with circulating levels of cellular adhesion molecules and adiposity status in a differential manner that interacts with sex. These results provide further evidence for the crucial role of adiponectin levels and CDH13 gene variants in immune-mediated and inflammatory diseases. PMID:26600672

  10. Deficiency in adiponectin exaggerates cigarette smoking exposure-induced cardiac contractile dysfunction: Role of autophagy.

    PubMed

    Hu, Nan; Yang, Lifang; Dong, Maolong; Ren, Jun; Zhang, Yingmei

    2015-10-01

    Second hand smoke is an independent risk factor for cardiovascular disease. Adiponectin (APN), an adipose-derived adipokine, has been shown to offer cardioprotective effect through an AMPK-dependent manner. This study was designed to evaluate the impact of adiponectin deficiency on second hand smoke-induced cardiac pathology and underlying mechanisms using a mouse model of side-stream smoke exposure. Adult wild-type (WT) and adiponectin knockout (APNKO) mice were placed in a chamber exposed to cigarette smoke for 1 hour daily for 40 days. Echocardiographic, cardiomyocyte function, and intracellular Ca2+ handling were evaluated. Autophagy and apoptosis were examined using western blot. 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) staining was used to evaluate reactive oxygen species (ROS) generation. Masson trichrome staining was employed to measure interstitial fibrosis. Our data revealed that adiponectin deficiency provoked smoke exposure-induced cardiomyopathy (compromised fractional shortening, disrupted cardiomyocyte function and intracellular Ca2+ homeostasis, apoptosis and ROS generation). In addition, these detrimental effects of side-stream smoke were accompanied by defective autophagolysosome formation, the effect of which was exacerbated by adiponectin deficiency. Blocking autophagolysosome formation using bafilomycin A1 (BafA1) negated the cardioprotective effect of rapamycin against smoke extract. Induction of autophagy using rapamycin and AMPKα activation using AICAR rescued against smoke extract-induced myopathic anomalies in APNKO mice. Our data suggest that adiponectin serves as an indispensable cardioprotective factor against side-stream smoke exposure-induced myopathic changes possibly through facilitating autophagolysosome formation. PMID:26276084

  11. Adiponectin and bone metabolism markers in female rowers: eumenorrheic and oral contraceptive users.

    PubMed

    Jürimäe, J; Vaiksaar, S; Mäestu, J; Purge, P; Jürimäe, T

    2011-12-01

    This study investigated whether adiponectin, bone formation (osteocalcin) and bone resorption [type I carboxyterminal telopeptide (ICTP)] values are influenced by menstrual cycle phase and oral contraceptive use in female rowers. Twenty-four rowers divided into normally cycling athletes (NOC; no.=15) and athletes taking oral contraceptive pills (OC; no.=9) participated in this study. Fasting blood samples, body composition and aerobic capacity measurements were taken during the follicular (FP) and the luteal (LP) phases of the menstrual cycle. Adiponectin, insulin, glucose, insulin resistance, body composition and aerobic capacity did not fluctuate significantly during menstrual cycle in both groups. Osteocalcin and ICTP were lower (p<0.05) in OC compared with NOC, but did not change significantly across menstrual cycle phases in both groups. Estradiol and progesterone were not related to adiponectin, osteocalcin or ICTP (r<0.147; p>0.05). Adiponectin was correlated (p<0.05) with osteocalcin (r=0.452) and fat free mass (r=0.428), and osteocalcin was related (p<0.05) to insulin (r=-0.413), glucose (r=-0.486) and insulin resistance (r=-0.528). In conclusion, adiponectin was not affected by menstrual cycle phase and OC use in female rowers, while bone metabolism markers were lower in OC compared to NOC groups. Adiponectin and osteocalcin were interrelated and may characterise energy homeostasis in female athletes. PMID:21169728

  12. Serum Adiponectin Level as a Predictor of Subclinical Cushing's Syndrome in Patients with Adrenal Incidentaloma

    PubMed Central

    Ayturk, Semra; Aldemir, Derya; Bascil Tutuncu, Neslihan

    2016-01-01

    Subclinical Cushing's syndrome (SCS) is a condition of slight but chronic cortisol excess in patients with adrenal incidentaloma (AI) without typical signs and symptoms of Cushing's syndrome. Adiponectin has potent roles in modulating energy balance and metabolic homeostasis and acts in opposition to glucocorticoids. This study aimed to evaluate adiponectin level in SCS and nonfunctional AI (NAI) patients and its relation with metabolic parameters. Patients with AI (n = 40) and metabolically healthy controls (n = 30) were included. In AI patients and controls, detailed medical history assessment, physical examinations, anthropometric measurements, and laboratory measurements were performed. Age, body mass index, waist circumference, and lipid profiles were significantly higher and waist-to-hip ratio and adiponectin level were significantly lower in the AI patients than in the controls. The midnight cortisol and urinary free cortisol levels were significantly higher in the SCS patients (n = 8) than in the NAI patients (n = 32). Adiponectin level of the SCS group was significantly lower than those of the NAI and control groups. The sensitivity and specificity for an adiponectin level of ≤13.00 ng/mL in predicting the presence of SCS were 87.5% and 77.4%, respectively. In conclusion, adiponectin is valuable in predicting the presence of SCS in AI patients.

  13. Serum Adiponectin Level as a Predictor of Subclinical Cushing's Syndrome in Patients with Adrenal Incidentaloma

    PubMed Central

    Ayturk, Semra; Aldemir, Derya; Bascil Tutuncu, Neslihan

    2016-01-01

    Subclinical Cushing's syndrome (SCS) is a condition of slight but chronic cortisol excess in patients with adrenal incidentaloma (AI) without typical signs and symptoms of Cushing's syndrome. Adiponectin has potent roles in modulating energy balance and metabolic homeostasis and acts in opposition to glucocorticoids. This study aimed to evaluate adiponectin level in SCS and nonfunctional AI (NAI) patients and its relation with metabolic parameters. Patients with AI (n = 40) and metabolically healthy controls (n = 30) were included. In AI patients and controls, detailed medical history assessment, physical examinations, anthropometric measurements, and laboratory measurements were performed. Age, body mass index, waist circumference, and lipid profiles were significantly higher and waist-to-hip ratio and adiponectin level were significantly lower in the AI patients than in the controls. The midnight cortisol and urinary free cortisol levels were significantly higher in the SCS patients (n = 8) than in the NAI patients (n = 32). Adiponectin level of the SCS group was significantly lower than those of the NAI and control groups. The sensitivity and specificity for an adiponectin level of ≤13.00 ng/mL in predicting the presence of SCS were 87.5% and 77.4%, respectively. In conclusion, adiponectin is valuable in predicting the presence of SCS in AI patients. PMID:27656211

  14. Maternal diet and cord blood leptin and adiponectin concentrations at birth

    PubMed Central

    Mantzoros, Christos S.; Sweeney, Laura; Williams, Catherine J.; Oken, Emily; Kelesidis, Theodoros; Rifas-Shiman, Sheryl L.; Gillman, Matthew W.

    2010-01-01

    Background & Aims The purpose of this study was to determine the effects of total energy intake, macronutrient intake, and maternal adherence to Mediterranean diet or Alternative Healthy Eating Index (AHEI) on cord blood leptin and adiponectin levels, which have been associated with childhood adiposity. Methods We used multivariable linear regression to assess associations of maternal diet, averaged over 1st and 2nd trimesters, with cord blood adipokines of 780 women from the prospective cohort study Project Viva. Results Mean (SD) energy intake during pregnancy was 2135 (596) kcal. Mean (SD) cord blood levels of leptin and adiponectin were 9.0 (6.6) ng/ml and 28.6 (6.7) μg/ml, respectively. Neither closer adherence to a Mediterranean/AHEI pattern diet nor energy intake was associated with either cord blood leptin or adiponectin. Protein intake was associated with both marginally lower leptin (−0.22 ng/ml [95% CI −0.41, −0.02] for each 1% of energy) and adiponectin (−0.25 μg/ml [95% CI −0.48, −0.02]). Conclusions Closer adherence to a Mediterranean/AHEI pattern diet during pregnancy was not associated with cord blood leptin or adiponectin. Maternal protein intake was weakly but significantly associated with lower cord blood leptin and adiponectin. PMID:20363059

  15. Adiponectin Suppresses UVB-Induced Premature Senescence and hBD2 Overexpression in Human Keratinocytes

    PubMed Central

    Kim, MinJeong; Park, Kui Young; Lee, Mi-Kyung; Jin, Taewon; Seo, Seong Jun

    2016-01-01

    Recent studies have revealed that adiponectin can suppress cellular inflammatory signaling pathways. This study aimed to elucidate the effect of adiponectin on the unregulated production of hBD2 in UVB-induced premature senescent keratinocytes. We constructed an in vitro model of premature senescent keratinocytes through repeated exposure to low energy UVB. After repeated low energy UVB exposure, there was significant generation of reactive oxygen species (ROS) and induction of senescence-associated markers, including senescence associated beta-galactosidase activity and expression of p16INK4a and histone H2AX. In addition, the present clinical study showed higher expression of hBD2 in sun-exposed skin of elderly group, and the overexpression of hBD2 was observed by c-Fos activation in vitro. Adiponectin has the ability to scavenge ROS and consequently inhibit MAPKs and SA-markers in UVB-exposed keratinocytes. An inhibitor study demonstrated that adiponectin downregulated hBD2 mRNA expression through suppression of the AP-1 transcription factor components c-Fos via inactivation of p38 MAPK. Collectively, the dysregulated production of hBD2 by the induction of oxidative stress was attenuated by adiponectin through the suppression of p38 and JNK/SAPK MAPK signaling in UVB-mediated premature senescent inducible conditions. These results suggest the feasibility of adiponectin as an anti-photoaging and anti-inflammatory agent in the skin. PMID:27526049

  16. Effects of pasteurization on adiponectin and insulin concentrations in donor human milk.

    PubMed

    Ley, Sylvia H; Hanley, Anthony J; Stone, Debbie; O'Connor, Deborah L

    2011-09-01

    Although pasteurization is recommended before distributing donor human milk in North America, limited data are available on its impact on metabolic hormones in milk. We aimed to investigate the effects of pasteurization on adiponectin and insulin concentrations in donor human milk. The study investigates concentrations of components in donor human milk before and after Holder pasteurization. After the guidelines of the Human Milk Bank Association of North America, human milk samples were pooled to produce 17 distinct batches (4 individuals per batch) and pasteurized at 62.5°C for 30 min. Adiponectin, insulin, energy, fat, total protein, and glucose concentrations were measured pre- and postpasteurization. Pasteurization reduced milk adiponectin and insulin by 32.8 and 46.1%, respectively (both p < 0.0001). Adiponectin and insulin were significantly correlated with energy and fat milk composition (r = 0.36-0.47; all p < 0.05). Pasteurization effects on milk hormone concentrations remained significant after adjusting for fat and energy (beta ± SEE: -4.11 ± 1.27, p = 0.003 for adiponectin; -70.0 ± 15.0, p < 0.0001 for insulin). Holder pasteurization reduced adiponectin and insulin concentrations in donor human milk. In view of emerging knowledge on the importance of milk components, continued work to find the optimal pasteurization process that mitigates risks but promotes retention of bioactive components is needed.

  17. Adiponectin moderates the relationship between adiposity and leptin in adolescents regardless of gender or race

    PubMed Central

    Bundy, Vanessa; Johnson, Maribeth; Gutin, Bernard; Zhu, Haidong; Stallmann-Jorgensen, Inger; Dong, Yanbin

    2013-01-01

    Objectives To determine gender or race differences in associations between adiposity and leptin, and whether adiponectin moderates these relationships. Methods Subjects were 441 adolescents, 14–18 years old (44% black; 50% female). Percent body fat (%BF) from dual-energy x-ray absorptiometry. Leptin and adiponectin were measured using immunoassays. Results Among the four groups (white boys, white girls, black boys and black girls), white girls had the highest adiponectin (p=0.0017) and black girls had the highest leptin (p=0.0164). Percent BF and leptin were positively correlated (p=0.0164). The %BF-leptin relationship was stronger in boys than girls (p<0.0001). Those with lower adiponectin had a stronger %BF-leptin relationship than those with high adiponectin in the entire sample (p=0.0220). Statistical models were adjusted for age, race, gender and the interaction between race and gender. Conclusion Our data suggest a protective metabolic interaction for adiponectin and lend additional support for obesity prevention strategies in adolescents. PMID:21648277

  18. Adiponectin Suppresses UVB-Induced Premature Senescence and hBD2 Overexpression in Human Keratinocytes.

    PubMed

    Kim, MinJeong; Park, Kui Young; Lee, Mi-Kyung; Jin, Taewon; Seo, Seong Jun

    2016-01-01

    Recent studies have revealed that adiponectin can suppress cellular inflammatory signaling pathways. This study aimed to elucidate the effect of adiponectin on the unregulated production of hBD2 in UVB-induced premature senescent keratinocytes. We constructed an in vitro model of premature senescent keratinocytes through repeated exposure to low energy UVB. After repeated low energy UVB exposure, there was significant generation of reactive oxygen species (ROS) and induction of senescence-associated markers, including senescence associated beta-galactosidase activity and expression of p16INK4a and histone H2AX. In addition, the present clinical study showed higher expression of hBD2 in sun-exposed skin of elderly group, and the overexpression of hBD2 was observed by c-Fos activation in vitro. Adiponectin has the ability to scavenge ROS and consequently inhibit MAPKs and SA-markers in UVB-exposed keratinocytes. An inhibitor study demonstrated that adiponectin downregulated hBD2 mRNA expression through suppression of the AP-1 transcription factor components c-Fos via inactivation of p38 MAPK. Collectively, the dysregulated production of hBD2 by the induction of oxidative stress was attenuated by adiponectin through the suppression of p38 and JNK/SAPK MAPK signaling in UVB-mediated premature senescent inducible conditions. These results suggest the feasibility of adiponectin as an anti-photoaging and anti-inflammatory agent in the skin. PMID:27526049

  19. Aldosterone perturbs adiponectin and PAI-1 expression and secretion in 3T3-L1 adipocytes.

    PubMed

    Li, P; Zhang, X-N; Pan, C-M; Sun, F; Zhu, D-L; Song, H-D; Chen, M-D

    2011-06-01

    Aldosterone is considered as a new cardiovascular risk factor that plays an important role in metabolic syndrome; however, the underlying mechanism of these effects is not clear. Hypoadiponectinemia and elevated circulating concentration of plasminogen activator inhibitor-1 (PAI-1) are causally associated with obesity-related insulin resistance and cardiovascular disease. The aim of the present study is to investigate the effect of aldosterone on the production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Northern and Western blot analyses revealed that aldosterone treatment inhibited adiponectin mRNA expression and secretion and simultaneously enhanced PAI-1 mRNA expression and secretion in a time- and dose-dependent manner. Rosiglitazone did not prevent aldosterone's effect on adiponectin or PAI-1 expression. In contrast, tumor necrosis factor (TNF)-α produced dramatic synergistic effects on adiponectin and PAI-1 expression when added together with aldosterone. Furthermore, the effects of aldosterone on adiponectin and PAI-1 expression appear to be mediated through glucocorticoid receptor (GR) but not mineralocorticoid receptor (MR). These results suggest that the effects of aldosterone on adiponectin and PAI-1 production are one of the underlying mechanisms linking it to insulin resistance, metabolic syndrome and cardiovascular disease. PMID:21667402

  20. Serum Adiponectin Level as a Predictor of Subclinical Cushing's Syndrome in Patients with Adrenal Incidentaloma.

    PubMed

    Dogruk Unal, Asli; Ayturk, Semra; Aldemir, Derya; Bascil Tutuncu, Neslihan

    2016-01-01

    Subclinical Cushing's syndrome (SCS) is a condition of slight but chronic cortisol excess in patients with adrenal incidentaloma (AI) without typical signs and symptoms of Cushing's syndrome. Adiponectin has potent roles in modulating energy balance and metabolic homeostasis and acts in opposition to glucocorticoids. This study aimed to evaluate adiponectin level in SCS and nonfunctional AI (NAI) patients and its relation with metabolic parameters. Patients with AI (n = 40) and metabolically healthy controls (n = 30) were included. In AI patients and controls, detailed medical history assessment, physical examinations, anthropometric measurements, and laboratory measurements were performed. Age, body mass index, waist circumference, and lipid profiles were significantly higher and waist-to-hip ratio and adiponectin level were significantly lower in the AI patients than in the controls. The midnight cortisol and urinary free cortisol levels were significantly higher in the SCS patients (n = 8) than in the NAI patients (n = 32). Adiponectin level of the SCS group was significantly lower than those of the NAI and control groups. The sensitivity and specificity for an adiponectin level of ≤13.00 ng/mL in predicting the presence of SCS were 87.5% and 77.4%, respectively. In conclusion, adiponectin is valuable in predicting the presence of SCS in AI patients. PMID:27656211

  1. Circulating adiponectin, leptin and adiponectin-leptin ratio and endometrial cancer risk: Evidence from a meta-analysis of epidemiologic studies.

    PubMed

    Gong, Ting-Ting; Wu, Qi-Jun; Wang, Yong-Lai; Ma, Xiao-Xin

    2015-10-15

    We performed this meta-analysis of epidemiologic studies to investigate the associations between circulating adiponectin, leptin and adiponectin-leptin (A/L) ratio and endometrial cancer risk. Relevant manuscripts were identified by searching PubMed and ISI Web of Science databases as well as by manual searching the references cited in retrieved manuscripts. Random-effects models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned associations. Fourteen manuscripts with 13 studies (five nested case-control and eight case-control studies) cumulatively involving a total of 1,963 endometrial cancer cases and 3,503 noncases were included in the analyses. Overall, comparing persons with circulating concentrations of adiponectin, leptin and A/L ratio in the top tertile with persons with concentrations of these biomarkers in the bottom tertile yielded SORs of 0.47 (95% CI: 0.34-0.65; I(2)  = 63.7%; n = 13), 2.19 (95% CI: 1.44-3.31; I(2)  = 64.2%; n = 7),and 0.45 (95% CI: 0.24-0.86; I(2)  = 90.1%; n = 5), respectively. Notably, there was an 18% reduction in risk for per each 5 μg/mL increment in circulating adiponectin concentrations (SOR = 0.82; 95% CI: 0.74-0.90; I(2)  = 49%; n = 8). Stratifying by study characteristics and whether these studies considered or adjusted for potential confounders, the findings were robust in the analyses of circulating adiponectin and leptin. No evidence of publication bias was detected. In conclusion, the findings from this meta-analysis suggest that increased circulating adiponectin and A/L ratio or decreased leptin concentrations were associated with reduced risk of endometrial cancer. Further prospective designed studies are warranted to confirm our findings.

  2. Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet

    PubMed Central

    2011-01-01

    Background Studies suggest that leucine supplementation (LS) has a therapeutic potential to prevent obesity and to promote glucose homeostasis. Furthermore, regular physical exercise is a widely accepted strategy for body weight maintenance and also for the prevention of obesity. The aim of this study was to determine the effect of chronic LS alone or combined with endurance training (ET) as potential approaches for reversing the insulin resistance and obesity induced by a high-fat diet (HFD) in rats. Methods Forty-seven rats were randomly divided into two groups. Animals were fed a control diet-low fat (n = 10) or HFD (n = 37). After 15 weeks on HFD, all rats received the control diet-low fat and were randomly divided according to treatment: reference (REF), LS, ET, and LS+ET (n = 7-8 rats per group). After 6 weeks of treatment, the animals were sacrificed and body composition, fat cell volume, and serum concentrations of total cholesterol, HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis factor-alpha (TNF-α) were analyzed. Results At the end of the sixth week of treatment, there was no significant difference in body weight between the REF, LS, ET and LS+ET groups. However, ET increased lean body mass in rats (P = 0.019). In addition, ET was more effective than LS in reducing adiposity (P = 0.019), serum insulin (P = 0.022) and TNF-α (P = 0.044). Conversely, LS increased serum adiponectin (P = 0.021) levels and reduced serum total cholesterol concentration (P = 0.042). Conclusions The results showed that LS had no beneficial effects on insulin sensitivity or adiposity in previously obese rats. On the other hand, LS was effective in increasing adiponectin levels and in reducing total cholesterol concentration. PMID:21899736

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

    PubMed Central

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

    2007-01-01

    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-Lα, 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. PMID:17353260

  4. Effects of pioglitazone and/or simvastatin on circulating TNFα and adiponectin levels in insulin resistance.

    PubMed

    Schaalan, Mona F

    2012-01-01

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

  5. End-use quality and agronomic characteristics associated with the Glu-B1al high-molecular-weight glutenin allele in U.S. hard winter wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High molecular weight glutenin subunits (HMW-GS) conferred by alleles at the Glu-B1 and Glu-D1 loci confer unique end-use quality properties for wheat (Triticum aestivum L.). The Glu-B1al allele at the Glu-B1 locus has not been widely used for cultivar development in the U.S. hard winter wheat regio...

  6. Curcumin Inhibits Non-Small Cell Lung Cancer Cells Metastasis through the Adiponectin/NF-κb/MMPs Signaling Pathway.

    PubMed

    Tsai, Jong-Rung; Liu, Po-Len; Chen, Yung-Hsiang; Chou, Shah-Hwa; Cheng, Yu-Jen; Hwang, Jhi-Jhu; Chong, Inn-Wen

    2015-01-01

    Adipose tissue is now considered as an endocrine organ involved in metabolic and inflammatory reactions. Adiponectin, a 244-amino acid peptide hormone, is associated with insulin resistance and carcinogenesis. Curcumin (diferuloylmethane) is the principal curcuminoid of the popular Indian spice, turmeric. Curcumin possesses antitumor effects, including the inhibition of neovascularization and regulation of cell cycle and apoptosis. However, the effects of adiponectin and curcumin on non-small cell lung cancer (NSCLC) remain unclear. In this study, we evaluated the expression of adiponectin in paired tumors and normal lung tissues from 77 patients with NSCLC using real-time polymerase chain reaction, western blotting, and immunohistochemistry. Kaplan-Meier survival analysis showed that patients with low adiponectin expression ratio (<1) had significantly longer survival time than those with high expression ratio (>1) (p = 0.015). Curcumin inhibited the migratory and invasive ability of A549 cells via the inhibition of adiponectin expression by blocking the adiponectin receptor 1. Curcumin treatment also inhibited the in vivo tumor growth of A549 cells and adiponectin expression. These results suggest that adiponectin can be a prognostic indicator of NSCLC. The effect of curcumin in decreasing the migratory and invasive ability of A549 cells by inhibiting adiponectin expression is probably mediated through NF-κB/MMP pathways. Curcumin could be an important potential adjuvant therapeutic agent for lung cancer in the future. PMID:26656720

  7. Curcumin Inhibits Non-Small Cell Lung Cancer Cells Metastasis through the Adiponectin/NF-κb/MMPs Signaling Pathway

    PubMed Central

    Tsai, Jong-Rung; Liu, Po-Len; Chen, Yung-Hsiang; Chou, Shah-Hwa; Cheng, Yu-Jen; Hwang, Jhi-Jhu; Chong, Inn-Wen

    2015-01-01

    Adipose tissue is now considered as an endocrine organ involved in metabolic and inflammatory reactions. Adiponectin, a 244–amino acid peptide hormone, is associated with insulin resistance and carcinogenesis. Curcumin (diferuloylmethane) is the principal curcuminoid of the popular Indian spice, turmeric. Curcumin possesses antitumor effects, including the inhibition of neovascularization and regulation of cell cycle and apoptosis. However, the effects of adiponectin and curcumin on non-small cell lung cancer (NSCLC) remain unclear. In this study, we evaluated the expression of adiponectin in paired tumors and normal lung tissues from 77 patients with NSCLC using real-time polymerase chain reaction, western blotting, and immunohistochemistry. Kaplan–Meier survival analysis showed that patients with low adiponectin expression ratio (<1) had significantly longer survival time than those with high expression ratio (>1) (p = 0.015). Curcumin inhibited the migratory and invasive ability of A549 cells via the inhibition of adiponectin expression by blocking the adiponectin receptor 1. Curcumin treatment also inhibited the in vivo tumor growth of A549 cells and adiponectin expression. These results suggest that adiponectin can be a prognostic indicator of NSCLC. The effect of curcumin in decreasing the migratory and invasive ability of A549 cells by inhibiting adiponectin expression is probably mediated through NF-κB/MMP pathways. Curcumin could be an important potential adjuvant therapeutic agent for lung cancer in the future. PMID:26656720

  8. Effects of Adiponectin Including Reduction of Androstenedione Secretion and Ovarian Oxidative Stress Parameters In Vivo

    PubMed Central

    Comim, Fabio V.; Gutierrez, Karina; Bridi, Alessandra; Bochi, Guilherme; Chemeris, Raisa; Rigo, Melânia L.; Dau, Andressa Minussi P.; Cezar, Alfredo S.; Moresco, Rafael Noal; Gonçalves, Paulo Bayard Dias

    2016-01-01

    Adiponectin is the most abundantly produced human adipokine with anti-inflammatory, anti-oxidative, and insulin-sensitizing properties. Evidence from in vitro studies has indicated that adiponectin has a potential role in reproduction because it reduces the production of androstenedione in bovine theca cells in vitro. However, this effect on androgen production has not yet been observed in vivo. The current study evaluated the effect of adiponectin on androstenedione secretion and oxidative stress parameters in a rodent model. Seven-week-old female Balb/c mice (n = 33), previously treated with equine gonadotropin chorionic, were assigned to one of four different treatments: Group 1, control (phosphate-buffered saline); Group 2, adiponectin 0.1 μg/mL; Group 3, adiponectin 1.0 μg/mL; Group 4, adiponectin 5.0 μg/mL. After 24 h, all animals were euthanized and androstenedione levels were measured in the serum while oxidative stress markers were quantified in whole ovary tissue. Female mice treated with adiponectin exhibited a significant reduction (about 60%) in serum androstenedione levels in comparison to controls. Androstenedione levels decreased from 0.78 ± 0.4 ng/mL (mean ± SD) in controls to 0.28 ± 0.06 ng/mL after adiponectin (5 μg/mL) treatment (P = 0.01). This change in androgen secretion after 24 hours of treatment was associated with a significant reduction in the expression of CYP11A1 and STAR (but not CYP17A1). In addition, ovarian AOPP product levels, a direct product of protein oxidation, decreased significantly in adiponectin-treated mice (5 μg/mL); AOPP (mean ± SD) decreased to 4.3 ± 2.1 μmol/L in comparison with that of the controls (11.5 ± 1.7 μmol/L; P = 0.0003). Our results demonstrated for the first time that acute treatment with adiponectin reduced the levels of a direct oxidative stress marker in the ovary as well as decreased androstenedione serum levels in vivo after 24 h. PMID:27158926

  9. Association between insulin resistance and estrogen in sexual precocity of obese children

    PubMed Central

    Lin, Shixia; Ji, Wei

    2016-01-01

    The aim of the study was to examine the association between sexual precocity and high-molecular weight (HMW)-adiponectin and investigate the correlation of insulin resistance and estrogen levels in obese children. In total, 60 obese children (30 boys and 30 girls) with sexual precocity were included in group A, 60 obese children (30 boys and 30 girls) without sexual precocity were included in group B, and 60 average weight children (30 boys and 30 girls) were included in group C. The levels of HMW adiponectin, fasting blood glucose, fasting insulin, luteinizing hormone (LH) peak, estradiol and testosterone were measured. The results showed that the HMW-adiponectin level of group A was the lowest and that of group C was the highest. The difference was statistically significant (P<0.05). The homeostasis model assessment of insulin resistance (HOMA-IR) and estradiol levels of group A were significantly higher than those of group B, and group B was higher than that of group C. LH peak and testosterone levels of group A were the lowest while those of group C were the highest. The differences were statistically significant (P<0.05). A subgroup analysis showed that the above results were more significant in girls. The Pearson correlation analysis revealed that the level of HMW-adiponectin was negatively correlated with HOMA-IR and estradiol (P<0.05), and positively correlated with the LH peak (P<0.05). In conclusion, sexual precocity of obese children may be associated with insulin resistance, and the link may be HMW-adiponectin. PMID:27703507

  10. Glucose and Inflammatory Cells Decrease Adiponectin in Epicardial Adipose Tissue Cells: Paracrine Consequences on Vascular Endothelium.

    PubMed

    Fernández-Trasancos, Ángel; Guerola-Segura, Raquel; Paradela-Dobarro, Beatriz; Álvarez, Ezequiel; García-Acuña, José María; Fernández, Ángel Luis; González-Juanatey, José Ramón; Eiras, Sonia

    2016-05-01

    Epicardial adipose tissue (EAT) is a source of energy for heart that expresses the insulin-sensitizer, anti-inflammatory and anti-atherogenic protein, adiponectin. But, in coronary artery disease, adiponectin production declines. Our objective was to determine its regulation by glucose and inflammation in stromal cells from EAT and subcutaneous adipose tissue (SAT) and its paracrine effect on endothelial cells. Stromal cells of EAT and SAT were obtained from patients who underwent cardiac surgery. Adipogenesis was induced at 117, 200, or 295 mg/dl glucose, with or without macrophage-conditioned medium (MCM). Expression of adiponectin, GLUT-4 and the insulin receptor was analyzed by real-time PCR. The paracrine effect of stromal cells was determined in co-cultures with endothelial cells, by exposing them to high glucose and/or MCM, and, additionally, to leukocyte-conditioned medium from patients with myocardial infarction. The endothelial response was determined by analyzing vascular adhesion molecule expression. Our results showed a U-shaped dose-response curve of glucose on adiponectin in EAT, but not in SAT stromal cells. Conversely, MCM reduced the adipogenesis-induced adiponectin expression of EAT stromal cells. The presence of EAT stromal increased the inflammatory molecules of endothelial cells. This deleterious effect was emphasized in the presence of inflammatory cell-conditioned medium from patients with myocardial infarction. Thus, high glucose and inflammatory cells reduced adipogenesis-induced adiponectin expression of EAT stromal cells, which induced an inflammatory paracrine process in endothelial cells. This inflammatory effect was lower in presence of mature adipocytes, producers of adiponectin. These results contribute to understanding the role of EAT dysfunction on coronary atherosclerosis progression.

  11. Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women

    PubMed Central

    Darabi, Hossein; Raeisi, Alireza; Kalantarhormozi, Mohammad Reza; Ostovar, Afshin; Assadi, Majid; Asadipooya, Kamyar; Vahdat, Katayoun; Dobaradaran, Sina; Nabipour, Iraj

    2015-01-01

    Abstract Serum adiponectin levels have been suggested to be predictors of type 2 diabetes mellitus in diverse populations. However, the relationship between circulating adiponectin levels and the risk of development of type 2 diabetes in postmenopausal women has not been investigated. A total of 382 healthy postmenopausal women who participated in a prospective cohort study were followed for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA. Of 195 women who did not have diabetes at baseline and who were reexamined in the second phase of the study for diabetic status, 35 subjects (17.9%) developed type 2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2 diabetes had lower adiponectin levels than the healthy postmenopausal women. Multiple regression analysis showed that, after adjustments were made for age, cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin levels were associated with a lower relative risk (RR) of having type 2 (RR = 0.07, confidence interval [CI]: 0.01–0.66, P = 0.021). Higher baseline adiponectin levels functioned as a predictor of a lower risk of developing type 2 diabetes mellitus among postmenopausal women during a 5.8 years follow-up study. Therefore, it is suggested that elevated adiponectin levels may offer protection against the development of type 2 diabetes mellitus after the menopause. PMID:26287420

  12. Low Adiponectin Concentration in Pregnancy Predicts Postpartum Insulin Resistance, Beta-cell Dysfunction, and Fasting Glycaemia

    PubMed Central

    Retnakaran, R; Qi, Y; Connelly, PW; Sermer, M; Hanley, AJ; Zinman, B

    2010-01-01

    Aims/Hypothesis The postpartum following gestational diabetes (GDM) is characterized by subtle metabolic defects, including beta-cell dysfunction that is believed to mediate the increased future risk of type 2 diabetes in this patient population. Recently, low circulating levels of adiponectin and increased leptin and C-reactive protein (CRP) have emerged as novel diabetic risk factors, although their relevance to GDM and subsequent diabetes has not been characterized. Thus, we sought to determine whether adiponectin, leptin and CRP in pregnancy relate to the postpartum metabolic defects linking GDM with type 2 diabetes. Methods 487 women underwent metabolic characterization, including oral glucose tolerance test (OGTT), in pregnancy and at 3-months postpartum. Based on the antepartum OGTT, there were 137 women with GDM, 91 with gestational impaired glucose tolerance, and 259 with normal glucose tolerance. Results Adiponectin levels were lowest (p<0.0001) and CRP levels highest (p=0.0008) in women with GDM. Leptin did not differ between the glucose tolerance groups (p=0.4483). Adiponectin (r=0.41,p<0.0001), leptin (r=−0.36,p<0.0001) and CRP (r=−0.30,p<0.0001) in pregnancy were all associated with postpartum insulin sensitivity (ISOGTT). Intriguingly, adiponectin was also related to postpartum beta-cell function (insulinogenic index/HOMA-IR) (r=0.16,p=0.0009). Indeed, on multiple linear regression analyses, adiponectin in pregnancy independently predicted both postpartum insulin sensitivity (t=3.97,p<0.0001) and beta-cell function (t=2.37,p=0.0181), even after adjustment for GDM. Furthermore, adiponectin emerged as a significant negative independent determinant of postpartum fasting glucose (t=−3.01,p=0.0027). Conclusions Hypoadiponectinemia in pregnancy predicts postpartum insulin resistance, beta-cell dysfunction, and fasting glycaemia, and hence may be relevant to the pathophysiology relating GDM with type 2 diabetes. PMID:19937225

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

    PubMed Central

    Kwak, Su-Jin; Hong, Seung-Hyun; Bajracharya, Rijan; Yang, Se-Yeol; Lee, Kyu-Sun; Yu, Kweon

    2013-01-01

    Adipokines secreted from adipose tissue are key regulators of metabolism in animals. Adiponectin, one of the adipokines, modulates pancreatic beta cell function to maintain energy homeostasis. Recently, significant conservation between Drosophila melanogaster and mammalian metabolism has been discovered. Drosophila insulin like peptides (Dilps) regulate energy metabolism similarly to mammalian insulin. However, in Drosophila, the regulatory mechanism of insulin producing cells (IPCs) by adipokine signaling is largely unknown. Here, we describe the discovery of the Drosophila adiponectin receptor and its function in IPCs. Drosophila adiponectin receptor (dAdipoR) has high homology with the human adiponectin receptor 1. The dAdipoR antibody staining revealed that dAdipoR was expressed in IPCs of larval and adult brains. IPC- specific dAdipoR inhibition (Dilp2>dAdipoR-Ri) showed the increased sugar level in the hemolymph and the elevated triglyceride level in whole body. Dilps mRNA levels in the Dilp2>dAdipoR-Ri flies were similar with those of controls. However, in the Dilp2>dAdipoR-Ri flies, Dilp2 protein was accumulated in IPCs, the level of circulating Dilp2 was decreased, and insulin signaling was reduced in the fat body. In ex vivo fly brain culture with the human adiponectin, Dilp2 was secreted from IPCs. These results indicate that adiponectin receptor in insulin producing cells regulates insulin secretion and controls glucose and lipid metabolism in Drosophila melanogaster. This study demonstrates a new adipokine signaling in Drosophila and provides insights for the mammalian adiponectin receptor function in pancreatic beta cells, which could be useful for therapeutic application. PMID:23874700

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

    PubMed

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

    2014-06-01

    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.

  15. Circulating adiponectin and breast cancer risk: a systematic review and meta-analysis

    PubMed Central

    Macis, Debora; Guerrieri-Gonzaga, Aliana; Gandini, Sara

    2014-01-01

    Background: We conducted a meta-analysis in order to investigate whether circulating adiponectin, an insulin-sensitizing hormone produced by adipocytes, is associated with breast cancer risk. Methods: A systematic literature search was performed in PubMed, Medline, EMBASE, ISI Web of Knowledge and the Cochrane Library. The summary relative risk (SRR) was calculated by pooling the different study-specific estimates using the random effect models. Meta-regression, subgroup and sensitivity analyses were carried out to investigate between-study heterogeneity and to test publication bias. Results: Data from 15 observational studies, published between 2003 and April 2013 for a total of 4249 breast cancer cases, were analysed. The SRR for the ‘highest’ vs ‘lowest’ adiponectin levels indicated a 34% reduction in breast cancer risk [95% confidence interval (CI): 13%–50%]. Between-study heterogeneity was not substantial (I2 = 53%). Ten studies were included in the dose-response analysis: the SRR for an increase of 3 µg/ml of adiponectin corresponded to a 5% risk reduction (95% CI: 1%–9%). The comparison between ‘highest’ and ‘lowest’ levels of adiponectin showed an inverse association in postmenopausal women (SRR = 0.80; 95% CI: 0.63–1.01) and an indication of an inverse relationship in premenopausal women (SRR = 0.72, 95% CI: 0.30–1.72). No evidence of publication bias was found. Conclusions: Low circulating adiponectin levels are associated with an increased breast cancer risk. However, properly designed studies are needed to confirm the role of adiponectin as breast cancer biomarker, and clinical trials should be performed to identify those interventions that may be effective in modulating adiponectin levels and reducing breast cancer risk. PMID:24737805

  16. Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women.

    PubMed

    Darabi, Hossein; Raeisi, Alireza; Kalantarhormozi, Mohammad Reza; Ostovar, Afshin; Assadi, Majid; Asadipooya, Kamyar; Vahdat, Katayoun; Dobaradaran, Sina; Nabipour, Iraj

    2015-08-01

    Serum adiponectin levels have been suggested to be predictors of type 2 diabetes mellitus in diverse populations. However, the relationship between circulating adiponectin levels and the risk of development of type 2 diabetes in postmenopausal women has not been investigated.A total of 382 healthy postmenopausal women who participated in a prospective cohort study were followed for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.Of 195 women who did not have diabetes at baseline and who were reexamined in the second phase of the study for diabetic status, 35 subjects (17.9%) developed type 2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2 diabetes had lower adiponectin levels than the healthy postmenopausal women. Multiple regression analysis showed that, after adjustments were made for age, cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin levels were associated with a lower relative risk (RR) of having type 2 (RR = 0.07, confidence interval [CI]: 0.01-0.66, P = 0.021).Higher baseline adiponectin levels functioned as a predictor of a lower risk of developing type 2 diabetes mellitus among postmenopausal women during a 5.8 years follow-up study. Therefore, it is suggested that elevated adiponectin levels may offer protection against the development of type 2 diabetes mellitus after the menopause.

  17. Triiodothyronine modulates the expression of leptin and adiponectin in 3T3-L1 adipocytes

    PubMed Central

    de Oliveira, Miriane; Síbio, Maria Teresa De; Olimpio, Regiane Marques Castro; Moretto, Fernanda Cristina Fontes; Luvizotto, Renata de Azevedo Melo; Nogueira, Celia Regina

    2015-01-01

    Objective To study the effect of different doses of triiodothyronine on gene expression of the adipokines leptin and adiponectin, at different times, and to evaluate the difference in expression between the two adipokines in each group. Methods 3T3-L1 adipocytes were incubated with triiodothyronine at physiological dose (10nM) and supraphysiological doses (100nM or 1,000nM), or without triiodothyronine (control, C) for 0.5, 6, or 24 hours. Leptin and adiponectin mRNA was detected using real-time polymerase chain reaction (RT-PCR). One-way analyses of variance, Tukey’s test or Student’s t test, were used to analyze data, and significance level was set at 5%. Results Leptin levels decreased in the 1,000nM-dose group after 0.5 hour. Adiponectin levels dropped in the 10nM-dose group, but increased at the 100nM dose. After 6 hours, both genes were suppressed in all hormone concentrations. After 24 hours, leptin levels increased at 10, 100 and 1,000nM groups as compared to the control group; and adiponectin levels increased only in the 100nM group as compared to the control group. Conclusion These results demonstrated fast actions of triiodothyronine on the leptin and adiponectin expression, starting at 0.5 hour, at a dose of 1,000nM for leptin and 100nM for adiponectin. Triiodothyronine stimulated or inhibited the expression of adipokines in adipocytes at different times and doses which may be useful to assist in the treatment of obesity, assuming that leptin is increased and adiponectin is decreased, in obesity cases. PMID:25993072

  18. Association of adiponectin promoter variants with traits and clusters of metabolic syndrome in Arabs: family-based study.

    PubMed

    Zadjali, F; Al-Yahyaee, S; Hassan, M O; Albarwani, S; Bayoumi, R A

    2013-09-25

    Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value=0.001), waist circumference (p-value=0.037), BMI (p-value=0.015) and percentage of total body fat (p-value=0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend.

  19. Oligomeric adiponectin forms and their complexes in the blood of healthy donors and patients with type 2 diabetes mellitus.

    PubMed

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

    2013-01-01

    Adiponectin (Adn) is a protein that circulates in the blood in several oligomeric forms, namely low-, medium-, and high-molecular-weight forms. Adn may serve as a risk factor for type 2 diabetes mellitus (T2DM). The aims of this work were (1) to produce monoclonal antibodies (MAbs) specific to different Adn oligomeric forms, (2) to design immunoassays suitable for measuring the Adn forms present in human blood, and (3) to investigate the changes in Adn forms that occur in patients with T2DM. Gel filtration, fluoroimmunoassays, and Western blotting were utilized as major techniques in this study. MAbs recognizing various oligomeric forms of Adn were obtained. Complexes between Adn and complement component C1q and between the low molecular weight form of Adn and albumin were described in human blood. A decrease in the total Adn and Adn-albumin complex levels in the blood of patients with T2DM and no difference in the levels of the Adn-C1q complex in comparison with healthy volunteers were demonstrated. An Adn94-Adn63 fluoroimmunoassay was selected as the technique that most accurately measured the mass ratio of Adn oligomers in blood samples, and an Adn214-Adn27 assay that measured the low-molecular-weight form of Adn only.

  20. The prevention and treatment of hypoadiponectinemia-associated human diseases by up-regulation of plasma adiponectin.

    PubMed

    Hossain, Md Murad; Mukheem, Abdul; Kamarul, Tunku

    2015-08-15

    Hypoadiponectinemia is characterized by low plasma adiponectin levels that can be caused by genetic factors, such as single nucleotide polymorphisms (SNPs) and mutations in the adiponectin gene or by visceral fat deposition/obesity. Reports have suggested that hypoadiponectinemia is associated with dyslipidemia, hypertension, hyperuricemia, metabolic syndrome, atherosclerosis, type 2 diabetes mellitus and various cardiovascular diseases. Previous studies have highlighted several potential strategies to up-regulate adiponectin secretion and function, including visceral fat reduction through diet therapy and exercise, administration of exogenous adiponectin, treatment with peroxisome proliferator-activating receptor gamma (PPARγ) agonists (e.g., thiazolidinediones (TZDs)) and ligands (e.g., bezafibrate and fenofibrate) or the blocking of the renin-angiotensin system. Likewise, the up-regulation of the expression and stimulation of adiponectin receptors by using adiponectin receptor agonists would be an effective method to treat obesity-related conditions. Notably, adiponectin is an abundantly expressed bioactive protein that also exhibits a wide spectrum of biological properties, such as insulin-sensitizing, anti-diabetic, anti-inflammatory and anti-atherosclerotic activities. Although targeting adiponectin and its receptors has been useful for treating diabetes and other metabolic-related diseases in experimental studies, current drug development based on adiponectin/adiponectin receptors for clinical applications is scarce, and there is a lack of available clinical trial data. This comprehensive review discusses the strategies that are presently being pursued to harness the potential of adiponectin up-regulation. In addition, we examined the current status of drug development and its potential for clinical applications. PMID:25818192

  1. Stripe rust resistance and dough quality of new wheat - Dasypyrum villosum translocation lines T1DL•1V#3S and T1DS•1V#3L and the location of HMW-GS genes.

    PubMed

    Zhao, W C; Gao, X; Dong, J; Zhao, Z J; Chen, Q G; Chen, L G; Shi, Y G; Li, X Y

    2015-07-17

    The transfer of agronomically useful genes from wild wheat species into cultivated wheat is one of the most effective approaches to improvement of wheat varieties. To evaluate the transfer of genes from Dasypyrum villosum into Triticum aestivum, wheat quality and disease resistance was evaluated in two new translocation lines, T1DL•1V#3S and T1DS•1V#3L. We examined the levels of stripe rust resistance and dough quality in the two lines, and identified and located the stripe rust resistant genes and high molecular weight glutenin subunit (HMW-GS) genes Glu-V1 of D. villosum. Compared to the Chinese Spring (CS) variety, T1DL•1V#3S plants showed moderate resistance to moderate susceptibility to the stripe rust races CYR33 and Su11-4. However, T1DS•1V#3L plants showed high resistance or immunity to these stripe rusts. The genes for resistance to stripe rust were located on 1VL of D. villosum. In comparison to CS, the dough from T1DS•1V#3L had a significantly shorter developing time (1.45 min) and stable time (1.0 min), a higher weakness in gluten strength (208.5 FU), and a lower farinograph quality index (18). T1DL•1V#3S had a significantly longer developing time (4.2 min) and stable time (5.25 min), a lower weakness in gluten strength (53 FU) and a higher farinograph quality index (78.5). We also found that T1DS•1V#3L had reduced gluten strength and dough quality compared to CS, but T1DL•1V#3S had increased gluten strength and dough quality. The results of SDS-PAGE analysis indicated that Glu-V1 of D. villosum was located on short arm 1VS and long arm 1VL. These results prove that the new translocation lines, T1DS•1V#3L and T1DS•1V#3L, have valuable stripe rust resistance and dough quality traits that will be important for improving wheat quality and resistance in future wheat breeding programs.

  2. Serum Adiponectin Level May be an Independent Predictor of Clear Cell Renal Cell Carcinoma

    PubMed Central

    Wang, Hongkai; Wu, Junlong; Gu, Weijie; Wang, Beihe; Wan, Fangning; Dai, Bo; Zhang, Hailiang; Shi, Guohai; Shen, Yijun; Zhu, Yiping; Zhu, Yao; Ye, Dingwei

    2016-01-01

    Objectives: To examine whether serum adiponectin or leptin level has the ability to differentiate clear cell renal cell carcinoma (ccRCC) from other subtypes of renal cell carcinoma (RCC) in a Chinese population. Patients and methods: We recruited 198 consecutive patients who were treated with radical or partial nephrectomy in our department from September 2011 to June 2013. Their histological types were all malignant, including clear cell, papillary, chromophobe and unclassified RCC. We also enrolled 86 people with no cancer or cancer-related diseases as normal controls. We measured patients' preoperative blood samples for plasma adiponectin and leptin concentrations using an enzyme-linked immunosorbent assay method. Statistical methods were used to analyze ccRCC and other subtypes as they relate to serum adiponectin/leptin level and other factors such as body mass index or visceral fat area. Results: In our database, normal controls had significantly higher circulating adiponectin (p < 0.001) and leptin levels (p < 0.001) than patients with RCC. Among the 198 RCC patients, 156 patients had ccRCC while 42 patients had other histological types. Serum adiponectin levels were lower in ccRCC patients than in non-clear-cell RCC patients (p = 0.004). However, the plasma leptin level was not differently distributed between ccRCC and non-ccRCC patients (p = 0.940). In multivariate analysis, we found that serum adiponectin level may be an independent predictor for discriminating ccRCC patients from others (p = 0.004). Furthermore, in the ccRCC subgroup, we observed that men with ccRCC had lower leptin (p < 0.001) and adiponectin (p = 0.002) levels, and diabetic patients had lower plasma adiponectin levels (p = 0.001). Conclusions: Lower plasma adiponectin concentration was related to an increased incidence of ccRCC and may act as an independent predictor for ccRCC. Our study may help define the process from obesity to adipose tissue, to cytokines and finally to ccRCC. PMID

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

    PubMed

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

    2015-01-01

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

  4. Adiponectin protects against hyperoxic lung injury and vascular leak

    PubMed Central

    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

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

  5. Haplotypes and Sequence Variation in the Ovine Adiponectin Gene (ADIPOQ).

    PubMed

    An, Qing-Ming; Zhou, Hui-Tong; Hu, Jiang; Luo, Yu-Zhu; Hickford, Jon G H

    2015-01-01

    The adiponectin gene (ADIPOQ) plays an important role in energy homeostasis. In this study five separate regions (regions 1 to 5) of ovine ADIPOQ were analysed using PCR-SSCP. Four different PCR-SSCP patterns (A₁-D₁, A₂-D₂) were detected in region-1 and region-2, respectively, with seven and six SNPs being revealed. In region-3, three different patterns (A₃-C₃) and three SNPs were observed. Two patterns (A₄-B₄, A₅-B₅) and two and one SNPs were observed in region-4 and region-5, respectively. In total, nineteen SNPs were detected, with five of them in the coding region and two (c.46T/C and c.515G/A) putatively resulting in amino acid changes (p.Tyr16His and p.Lys172Arg). In region-1, -2 and -3 of 316 sheep from eight New Zealand breeds, variants A₁, A₂ and A₃ were the most common, although variant frequencies differed in the eight breeds. Across region-1 and region-3, nine haplotypes were identified and haplotypes A₁-A₃, A₁-C₃, B₁-A₃ and B₁-C₃ were most common. These results indicate that the ADIPOQ gene is polymorphic and suggest that further analysis is required to see if the variation in the gene is associated with animal production traits. PMID:26610572

  6. Adiponectin deficiency exacerbates age-related hearing impairment.

    PubMed

    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

    2014-04-24

    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.

  7. Hypoglycemic effects of three Iranian edible plants; jujube, barberry and saffron: Correlation with serum adiponectin level.

    PubMed

    Hemmati, Mina; Asghari, Somaye; Zohoori, Elham; Karamian, Mehdi

    2015-11-01

    One of the most common disorders of the endocrine system is diabetes mellitus. This disease is associated with dyslipidemia. Adiponectin is a protein hormone that secreted by adipocytes and has an important role in regulating of glucose and fatty acid metabolic pathways. This study was designed to investigate the changes in serum level of adiponectin in diabetic rats treated with hydroalcoholic extracts of three medicinal plants; jujube (Ziziphus jujuba), barberry (Berberis vulgaris) and saffron (Crocus sativus) in comparison with quercetin. Streptozotocin -induced diabetic male rats were gavaged with specified doses of the extracts (25 and 100mg/kg) for two weeks. At the end of treatment period, fasting blood specimens were collected. The levels of adiponectin, fasting blood sugar (FBS), total Cholesterol, triglycerides, HDL-C and LDL-C were measured. Statistical analysis showed that serum levels of triglyceride and VLDL decreased significantly (P<0.05) in all treated groups. FBS level in all treated groups, decreased significantly and reach to normoglycemic level (P<0.05). Except Jujube, other plant extracts had no effect on cholesterol. Jujube in two doses (25 and 100mg/kg) could increased significantly HDL-C (P<0.05) with no effect on total cholesterol and LDL-C. Serum adiponectin level increased in all treated groups. These beneficial effects of C. sativus, B. vulgaris and Z. jujube extracts and quercetin in diabetic rats may be associated with increase in adiponectin level.

  8. Association of ADIPOQ gene with obesity and adiponectin levels in Malaysian Malays.

    PubMed

    Apalasamy, Yamunah Devi; Rampal, Sanjay; Salim, Agus; Moy, Foong Ming; Bulgiba, Awang; Mohamed, Zahurin

    2014-05-01

    Studies have shown that single-nucleotide polymorphisms (SNPs) on the ADIPOQ gene have been linked with obesity and with adiponectin levels in various populations. Here, we aimed to investigate the association of ADIPOQ rs17366568 and rs3774261 SNPs with obesity and with adiponectin levels in Malaysian Malays. Obesity parameters and adiponectin levels were measured in 574 subjects. Genotyping was performed using real-time polymerase chain reaction and Sequenom MassARRAY. A significant genotypic association was observed between ADIPOQ rs17366568 and obesity. The frequencies of AG and AA genotypes were significantly higher in the obese group (11%) than in the non-obese group (5%) (P=0.024). The odds of A alleles occurring among the obese group were twice those among the non-obese group (odds ratio 2.15; 95% confidence interval 1.13-4.09). However, no significant association was found between allelic frequencies of ADIPOQ rs17366568 and obesity after Bonferroni correction (P>0.025) or between ADIPOQ rs3774261 and obesity both at allelic and genotypic levels. ADIPOQ SNPs were not significantly associated with log-adiponectin levels. GA, GG, and AG haplotypes of the ADIPOQ gene were not associated with obesity. We confirmed the previously reported association of ADIPOQ rs17366568 with the risk of obesity. ADIPOQ SNPs are not important modulators of adiponectin levels in this population. PMID:24449366

  9. The regulation of adiponectin receptors in human prostate cancer cell lines

    SciTech Connect

    Mistry, T.; Digby, J.E.; Chen, J.; Desai, K.M.; Randeva, H.S. . E-mail: H.Randeva@warwick.ac.uk

    2006-09-29

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

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

    PubMed

    Salmanowicz, Bolesław P; Langner, Monika; Franaszek, Sławomir

    2014-11-01

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

  11. Combined delivery of the adiponectin gene and rosiglitazone using cationic lipid emulsions.

    PubMed

    Davaa, Enkhzaya; Kang, Bong-Seok; Han, Joo-Hui; Lee, Sang-Eun; Ng, Choon Lian; Myung, Chang-Seon; Park, Jeong-Sook

    2015-04-10

    For the combined delivery of an insulin-sensitizing adipokine; i.e., the ADN gene, and the potent PPARγ agonist rosiglitazone, cationic lipid emulsions were formulated using the cationic lipid DOTAP, helper lipid DOPE, castor oil, Tween 20 and Tween 80. The effect of drug loading on the physicochemical characteristics of the cationic emulsion/DNA complexes was investigated. Complex formation between the cationic emulsion and negatively charged plasmid DNA was confirmed and protection from DNase was observed. The in vitro transfection efficiency and cytotoxicity were evaluated in HepG2 cells. The particle sizes of the cationic emulsion/DNA complex were in the range 230-540 nm and those of the rosiglitazone-loaded cationic emulsion/DNA complex were in the range 220-340 nm. Gel retardation of the complexes was observed when the complexation weight ratios of the cationic lipid to plasmid DNA exceeded 4:1 for both the drug-free and rosiglitazone-loaded complexes. Both complexes stabilized plasmid DNA against DNase. The ADN expression level increased dose-dependently when cells were transfected with the cationic emulsion/DNA complexes. The rosiglitazone-loaded cationic emulsion/DNA complexes showed higher cellular uptake in HepG2 cells depending on the rosiglitazone loading, but not depending on the type of plasmid DNA type such as pVAX/ADN, pCAG/ADN, or pVAX. The drug-loaded cationic emulsion/plasmid DNA complexes were less cytotoxic than free rosiglitazone. Therefore, a cationic emulsion could potentially serve as a co-delivery system for rosiglitazone and the adiponectin gene.

  12. Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways

    PubMed Central

    Kubota, Tetsuya; Kubota, Naoto; Sato, Hiroyuki; Inoue, Mariko; Kumagai, Hiroki; Iwamura, Tomokatsu; Takamoto, Iseki; Kobayashi, Tsuneo; Moroi, Masao; Terauchi, Yasuo; Tobe, Kazuyuki; Ueki, Kohjiro; Kadowaki, Takashi

    2016-01-01

    The aim of this study is to elucidate to what degree adiponectin is involved in TZD-mediated amelioration of neointimal formation. We investigated the effect of 3- or 8-weeks’ pioglitazone on cuff-induced neointimal formation in adiponectin-deficient (APN-KO) and wild-type (WT) mice. Pioglitazone for 3 weeks reduced neointimal formation in the WT mice with upregulation of the plasma adiponectin levels, but failed to reduce neointimal formation in the APN-KO mice, suggesting that pioglitazone suppressed neointimal formation by adiponectin-dependent mechanisms. Pioglitazone for 3 weeks suppressed vascular smooth muscle cell (VSMC) proliferation and increased AdipoR2 expression in the WT mice. In vitro, globular adiponectin activated AMPK through both AdipoR1 and AdipoR2, resulting in the inhibition of VSMC proliferation. Interestingly, 8-weeks’ pioglitazone was reduced neointimal formation in APN-KO mice to degree similar to that seen in the WT mice, suggesting that pioglitazone can also suppress neointimal formation via a mechanism independent of adiponectin. Pioglitazone for 8 weeks completely abrogated the increased VSMC proliferation, along with a reduction of cyclin B1 and cyclin D1 expressions and cardiovascular risk profile in the APN-KO mice. In vitro, pioglitazone suppressed these expressions, leading to inhibition of VSMC proliferation. Pioglitazone suppresses neointimal formation via both adiponectin-dependent and adiponectin-independent mechanisms. PMID:27703271

  13. Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration

    PubMed Central

    Ye, Risheng; Holland, William L; Gordillo, Ruth; Wang, Miao; Wang, Qiong A; Shao, Mengle; Morley, Thomas S; Gupta, Rana K; Stahl, Andreas; Scherer, Philipp E

    2014-01-01

    As an adipokine in circulation, adiponectin has been extensively studied for its beneficial metabolic effects. While many important functions have been attributed to adiponectin under high-fat diet conditions, little is known about its essential role under regular chow. Employing a mouse model with inducible, acute β-cell ablation, we uncovered an essential role of adiponectin under insulinopenic conditions to maintain minimal lipid homeostasis. When insulin levels are marginal, adiponectin is critical for insulin signaling, endocytosis, and lipid uptake in subcutaneous white adipose tissue. In the absence of both insulin and adiponectin, severe lipoatrophy and hyperlipidemia lead to lethality. In contrast, elevated adiponectin levels improve systemic lipid metabolism in the near absence of insulin. Moreover, adiponectin is sufficient to mitigate local lipotoxicity in pancreatic islets, and it promotes reconstitution of β-cell mass, eventually reinstating glycemic control. We uncovered an essential new role for adiponectin, with major implications for type 1 diabetes. DOI: http://dx.doi.org/10.7554/eLife.03851.001 PMID:25339419

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    NASA Astrophysics Data System (ADS)

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

    2005-12-01

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

  16. 5-Hydroxytryptamine 2A receptor signaling cascade modulates adiponectin and plasminogen activator inhibitor 1 expression in adipose tissue.

    PubMed

    Uchida-Kitajima, Shoko; Yamauchi, Toshimasa; Takashina, Youko; Okada-Iwabu, Miki; Iwabu, Masato; Ueki, Kohjiro; Kadowaki, Takashi

    2008-09-01

    Knowledge of the regulatory factors associated with down-regulation of adiponectin gene expression and up-regulation of PAI-1 gene expression is crucial to understand the pathophysiological basis of obesity and metabolic diseases, and could establish new treatment strategies for these conditions. We showed that expression of 5-HT(2A) receptors was up-regulated in hypertrophic 3T3-L1 adipocytes, which exhibited decreased expression of adiponectin and increased expression of PAI-1. 5-HT(2A) receptor antagonists and suppression of 5-HT(2A) receptor gene expression enhanced adiponectin expression. Activation of Gq negatively regulated adiponectin expression, and inhibition of mitogen-activated protein kinase reversed the Gq-induced effect. Moreover, the 5-HT(2A) receptor blockade reduced PAI-1 expression. These findings indicate that antagonism of 5-HT(2A) receptors in adipocytes could improve the obesity-linked decreases in adiponectin expression and increases in PAI-1 expression.

  17. Lipopolysaccharide induces a downregulation of adiponectin receptors in-vitro and in-vivo

    PubMed Central

    Hall, Alison; Leuwer, Martin; Trayhurn, Paul

    2015-01-01

    Background. Adipose tissue contributes to the inflammatory response through production of cytokines, recruitment of macrophages and modulation of the adiponectin system. Previous studies have identified a down-regulation of adiponectin in pathologies characterised by acute (sepsis and endotoxaemia) and chronic inflammation (obesity and type-II diabetes mellitus). In this study, we investigated the hypothesis that LPS would reduce adiponectin receptor expression in a murine model of endotoxaemia and in adipoocyte and myocyte cell cultures. Methods. 25 mg/kg LPS was injected intra-peritoneally into C57BL/6J mice, equivalent volumes of normal saline were used in control animals. Mice were killed at 4 or 24 h post injection and tissues harvested. Murine adipocytes (3T3-L1) and myocytes (C2C12) were grown in standard culture, treated with LPS (0.1 µg/ml–10 µg/ml) and harvested at 4 and 24 h. RNA was extracted and qPCR was conducted according to standard protocols and relative expression was calculated. Results. After LPS treatment there was a significant reduction after 4 h in gene expression of adipo R1 in muscle and peri-renal fat and of adipo R2 in liver, peri-renal fat and abdominal wall subcutaneous fat. After 24 h, significant reductions were limited to muscle. Cell culture extracts showed varied changes with reduction in adiponectin and adipo R2 gene expression only in adipocytes. Conclusions. LPS reduced adiponectin receptor gene expression in several tissues including adipocytes. This reflects a down-regulation of this anti-inflammatory and insulin-sensitising pathway in response to LPS. The trend towards base line after 24 h in tissue depots may reflect counter-regulatory mechanisms. Adiponectin receptor regulation differs in the tissues investigated. PMID:26618091

  18. Mechanisms for the anti-inflammatory effects of adiponectin in macrophages.

    PubMed

    Huang, Honglian; Park, Pil-Hoon; McMullen, Megan R; Nagy, Laura E

    2008-03-01

    Adiponectin is an adipokine with potent anti-inflammatory properties. The development of alcoholic liver disease is thought to involve increased pro-inflammatory activity, mediated in part by the activation of hepatic macrophages (Kupffer cells). Chronic ethanol feeding sensitizes hepatic macrophages to activation by lipopolysaccharide (LPS), leading to increased production of reactive oxygen species and tumor necrosis factor-alpha (TNF-alpha). Adiponectin can normalize Toll-like receptor-4 (TLR-4) mediated signaling in hepatic macrophages after ethanol feeding, likely contributing to the hepatoprotective effect of adiponectin in the progression of alcoholic liver disease. However, the mechanisms by which adiponectin suppress TLR-4 mediated responses are not well understood. Using the macrophage-like cell line, RAW264.7, we have investigated the molecular mechanisms by which adiponectin suppresses LPS-stimulated TNF-alpha production. Globular adiponectin (gAcrp)-mediated desensitization of LPS-stimulated responses in RAW264.7 macrophages was dependent on the production of the anti-inflammatory cytokine interleukin (IL)-10. gAcrp initially increased TNF-alpha expression in RAW264.7 macrophages; this TNF-alpha then contributed to increased expression of IL-10. This initial gAcrp-mediated increase in TNF-alpha production by macrophages was mediated via activation of ERK1/2-->Egr-1 and nuclear factor (NF)-kappaB-dependent mechanisms. gAcrp-stimulated IL-10 expression was also dependent on the phosphorylation of cAMP response element-binding protein and the cAMP response element in the IL-10 promoter. In summary, these studies reveal a complex, integrated response of macrophages to gAcrp. gAcrp initially activated signaling pathways considered to be pro-inflammatory, with a subsequent increase in the expression of the potent, anti-inflammatory cytokine, IL-10. Increased IL-10 expression was ultimately required for the suppression of TLR4-mediated signaling by g

  19. Circulating adiponectin concentration and body composition are altered in response to high-intensity interval training.

    PubMed

    Shing, Cecilia M; Webb, Jessica J; Driller, Matthew W; Williams, Andrew D; Fell, James W

    2013-08-01

    Adiponectin influences metabolic adaptations that would prove beneficial to endurance athletes, and yet to date there is little known about the response of adiponectin concentrations to exercise, and, in particular, the response of this hormone to training in an athlete population. This study aimed to determine the response of plasma adiponectin concentrations to acute exercise after 2 different training programs and to determine the influence of the training on body composition. Seven state-level representative rowers (age: 19 ± 1.2 years [mean ± SD], height: 1.77 ± 0.10 m, body mass: 74.0 ± 10.7 kg, VO2peak 62.1 ± 7.0 ml·kg·min) participated in the double-blind, randomized crossover investigation. Rowers performed an incremental graded exercise test before and after completing 4 weeks of high-intensity interval ergometer training and 4 weeks of traditional ergometer rowing training. Rowers' body composition was assessed at baseline and after each training program. Significant increases in plasma adiponectin concentration occurred in response to maximal exercise after completion of the high-intensity interval training (p = 0.016) but not after traditional ergometer rowing training (p = 0.69). The high-intensity interval training also resulted in significant increases in mean 4-minute power output (p = 0.002) and VO2peak (p = 0.05), and a decrease in body fat percentage (p = 0.022). Mean 4-minute power output, VO2peak, and body fat percentage were not significantly different after 4 weeks of traditional ergometer rowing training (p > 0.05). Four weeks of high-intensity interval training is associated with an increase in adiponectin concentration in response to maximal exercise and a reduction in body fat percentage. The potential for changes in adiponectin concentration to reflect positive training adaptations and athlete performance level should be further explored.

  20. Structural and Functional Similarities between Osmotin from Nicotiana Tabacum Seeds and Human Adiponectin

    PubMed Central

    Colonna, Giovanni

    2011-01-01

    Osmotin, a plant protein, specifically binds a seven transmembrane domain receptor-like protein to exert its biological activity via a RAS2/cAMP signaling pathway. The receptor protein is encoded in the gene ORE20/PHO36 and the mammalian homolog of PHO36 is a receptor for the human hormone adiponectin (ADIPOR1). Moreover it is known that the osmotin domain I can be overlapped to the β-barrel domain of adiponectin. Therefore, these observations and some already existing structural and biological data open a window on a possible use of the osmotin or of its derivative as adiponectin agonist. We have modelled the three-dimensional structure of the adiponectin trimer (ADIPOQ), and two ADIPOR1 and PHO36 receptors. Moreover, we have also modelled the following complexes: ADIPOQ/ADIPOR1, osmotin/PHO36 and osmotin/ADIPOR1. We have then shown the structural determinants of these interactions and their physico-chemical features and analyzed the related interaction residues involved in the formation of the complexes. The stability of the modelled structures and their complexes was always evaluated and controlled by molecular dynamics. On the basis of these results a 9 residues osmotin peptide was selected and its interaction with ADIPOR1 and PHO36 was modelled and analysed in term of energetic stability by molecular dynamics. To confirm in vivo the molecular modelling data, osmotin has been purified from nicotiana tabacum seeds and its nine residues peptide synthesized. We have used cultured human synovial fibroblasts that respond to adiponectin by increasing the expression of IL-6, TNF-alpha and IL-1beta via ADIPOR1. The biological effect on fibroblasts of osmotin and its peptide derivative has been found similar to that of adiponectin confirming the results found in silico. PMID:21311758

  1. Adiponectin effects and gene expression in rainbow trout: an in vivo and in vitro approach.

    PubMed

    Sánchez-Gurmaches, Juan; Cruz-Garcia, Lourdes; Gutiérrez, Joaquím; Navarro, Isabel

    2012-04-15

    Here we present the presence of adiponectin and adiponectin receptors [type 1 (adipoR1) and type 2 (adipoR2)] in rainbow trout (Oncorhynchus mykiss) tissues and cell cultures together with the response to different scenarios. In response to fasting, adiponectin expression was up-regulated in adipose tissue, while the expression of its receptors increased in white and red muscle. Insulin injection decreased adipoR1 expression in white and red muscles. We deduce that the adipoRs in trout muscle show opposite responses to increasing insulin plasma levels, which may maintain sensitivity to insulin in this tissue. Adiponectin expression was inhibited by the inflammatory effect of lipopolysaccharide (LPS) in adipose tissue and red muscle. Moreover, results indicate that LPS may lead to mobilization of fat reserves, increasing adipoR1 expression in adipose tissue. The effects of LPS could be mediated through tumour necrosis factor α (TNFα), at least in red muscle. Insulin, growth hormone and TNFα all diminished expression of adipoR2 in adipocytes and adipoR1 in myotubes, while insulin increased the expression of adipoR2 in the muscle cells. Adiponectin activates Akt in rainbow trout myotubes, which may lead to an increase in fatty acid uptake and oxidation. Overall, our results show that the adiponectin system responds differently to various physiological challenges and that it is hormonally controlled in vivo and in vitro. To the best of our knowledge, this is the first time this has been demonstrated in teleosts, and it may be a valuable contribution to our understanding of adipokines in fish.

  2. Disturbed adiponectin – AMPK system in skeletal muscle of patients with metabolic syndrome.

    PubMed

    Van Berendoncks, An M; Stensvold, Dorthe; Garnier, Anne; Fortin, Dominique; Sente, Tahnee; Vrints, Christiaan J; Arild, Slørdahl Stig; Ventura-Clapier, Renee; Wisløff, Ulrik; Conraads, Viviane M

    2015-02-01

    Patients with metabolic syndrome are characterized by low circulating adiponectin levels and reduced adiponectin sensitivity in skeletal muscles. Through binding on its main skeletal muscle receptor AdipoR1, adiponectin activates AMP-activated protein kinase (AMPK), a key player in energy homeostasis. Fourteen metabolic syndrome patients and seven healthy control subjects were included. Blood samples were taken to determine insulin resistance, adiponectin, lipoproteins, and C-reactive protein. Muscle biopsies (m. vastus lateralis) were obtained to assess mRNA expression of AdipoR1 and both AMPKα1 and AMPKα2 subunits, as well as downstream targets in lipid and glucose metabolism. Skeletal muscle mRNA expression of AMPKα1 and AMPKα2 was lower in metabolic syndrome patients (100 ± 6 vs. 122 ± 8 AU, p = 0.030 and 64 ± 4 vs. 85 ± 9 AU, p = 0.044, respectively), whereas the expression of AdipoR1 was upregulated (138 ± 9 vs. 105 ± 7, p = 0.012). AMPKα1 and AdipoR1 correlated positively in both the control (r = 0.964, p < 0.001) and the metabolic syndrome group (r = 0.600, p = 0.023). However, this relation was shifted upwards in metabolic syndrome patients, indicating increased AdipoR1mRNA expression for a similar AMPKα1 expression. Previously, a blunted stimulatory effect of adiponectin on AMPK activation has been shown in metabolic syndrome patients. The present data suggest that the disturbed interaction of adiponectin with AMPK is located downstream of the AdipoR1 receptor.

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

    PubMed Central

    Effatpanah, Marzieh

    2014-01-01

    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. PMID:24523637

  4. Higher Levels of Adiponectin in Vascular Endothelial Cells are Associated with Greater Brachial Artery Flow-mediated Dilation in Older Adults

    PubMed Central

    Yoo, Jeung-Ki; Hwang, Moon-Hyon; Luttrell, Meredith J.; Kim, Han-Kyul; Meade, Thomas H.; English, Mark; Segal, Mark S.; Christou, Demetra D.

    2015-01-01

    Adiponectin, an adipocyte-derived protein, exerts anti-atherosclerotic effects on the vascular endothelium. Recently adiponectin protein has been reported in murine vascular endothelial cells, however, whether adiponectin is present in human vascular endothelial cells remains unexplored. We sought to examine 1) adiponectin protein in vascular endothelial cells collected from older adults free of overt cardiovascular disease; 2) the relation between endothelial cell adiponectin and in vivo vascular endothelial function; and 3) the relation between endothelial cell adiponectin, circulating (plasma) adiponectin and related factors. We measured vascular endothelial function (brachial artery flow-mediated dilation using ultrasonography), vascular endothelial cell adiponectin (biopsy coupled with quantitative immunofluorescence) and circulating adiponectin (Mercodia, ELISA) in older, sedentary, non-smoking, men and women (55 – 79 years). We found that higher endothelial cell adiponectin was related with greater flow-mediated dilation (r=0.43, P<0.05) and greater flow-mediated dilation normalized for shear stress (r=0.56, P<0.01), but was not related with vascular smooth muscle responsiveness to nitric oxide (r=0.04, P=0.9). Vascular endothelial cell adiponectin was not related with circulating adiponectin (r=−0.14, P=0.6). Endothelial cell and circulating adiponectin were differentially associated with adiposity, metabolic and other factors, but both were inversely associated with renal function (r=0.44 to 0.62, P ≤ 0.04). In conclusion, higher endothelial cell adiponectin levels are associated with higher vascular endothelial function, independent of circulating adiponectin levels in older adults. PMID:25572013

  5. Tumor expression of adiponectin receptor 2 and lethal prostate cancer

    PubMed Central

    Fiorentino, Michelangelo; Kelly, Rachel; Gerke, Travis; Jordahl, Kristina; Sinnott, Jennifer A.; Giovannucci, Edward L.; Loda, Massimo; Mucci, Lorelei A.; Finn, Stephen

    2015-01-01

    To investigate the role of adiponectin receptor 2 (AdipoR2) in aggressive prostate cancer we used immunohistochemistry to characterize AdipoR2 protein expression in tumor tissue for 866 men with prostate cancer from the Physicians’ Health Study and the Health Professionals Follow-up Study. AdipoR2 tumor expression was not associated with measures of obesity, pathological tumor stage or prostate-specific antigen (PSA) at diagnosis. However, AdipoR2 expression was positively associated with proliferation as measured by Ki-67 expression quartiles (P-trend < 0.0001), with expression of fatty acid synthase (P-trend = 0.001), and with two measures of angiogenesis (P-trend < 0.1). An inverse association was observed with apoptosis as assessed by the TUNEL assay (P-trend = 0.006). Using Cox proportional hazards regression and controlling for age at diagnosis, Gleason score, year of diagnosis category, cohort and baseline BMI, we identified a statistically significant trend for the association between quartile of AdipoR2 expression and lethal prostate cancer (P-trend = 0.02). The hazard ratio for lethal prostate cancer for the two highest quartiles, as compared to the two lowest quartiles, of AdipoR2 expression was 1.9 (95% confidence interval [CI]: 1.2–3.0). Results were similar when additionally controlling for categories of PSA at diagnosis and Ki-67 expression quartiles. These results strengthen the evidence for the role of AdipoR2 in prostate cancer progression. PMID:25863129

  6. Novel immunomodulatory effects of adiponectin on dendritic cell functions.

    PubMed

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

    2011-05-01

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

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

    PubMed

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

    2014-01-28

    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.

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

    PubMed

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

    2014-01-01

    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

  9. Function of Succinoglycan Polysaccharide in Sinorhizobium meliloti Host Plant Invasion Depends on Succinylation, Not Molecular Weight

    PubMed Central

    Mendis, Hajeewaka C.; Madzima, Thelma F.; Queiroux, Clothilde

    2016-01-01

    ABSTRACT The acidic polysaccharide succinoglycan produced by the rhizobial symbiont Sinorhizobium meliloti 1021 is required for this bacterium to invade the host plant Medicago truncatula and establish a nitrogen-fixing symbiosis. S. meliloti mutants that cannot make succinoglycan cannot initiate invasion structures called infection threads in plant root hairs. S. meliloti exoH mutants that cannot succinylate succinoglycan are also unable to form infection threads, despite the fact that they make large quantities of succinoglycan. Succinoglycan produced by exoH mutants is refractory to cleavage by the glycanases encoded by exoK and exsH, and thus succinoglycan produced by exoH mutants is made only in the high-molecular-weight (HMW) form. One interpretation of the symbiotic defect of exoH mutants is that the low-molecular-weight (LMW) form of succinoglycan is required for infection thread formation. However, our data demonstrate that production of the HMW form of succinoglycan by S. meliloti 1021 is sufficient for invasion of the host M. truncatula and that the LMW form is not required. Here, we show that S. meliloti strains deficient in the exoK- and exsH-encoded glycanases invade M. truncatula and form a productive symbiosis, although they do this with somewhat less efficiency than the wild type. We have also characterized the polysaccharides produced by these double glycanase mutants and determined that they consist of only HMW succinoglycan and no detectable LMW succinoglycan. This demonstrates that LMW succinoglycan is not required for host invasion. These results suggest succinoglycan function is not dependent upon the presence of a small, readily diffusible form. PMID:27329751

  10. Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic mice.

    PubMed

    Goto, Tsuyoshi; Teraminami, Aki; Lee, Joo-Young; Ohyama, Kana; Funakoshi, Kozue; Kim, Young-Il; Hirai, Shizuka; Uemura, Taku; Yu, Rina; Takahashi, Nobuyuki; Kawada, Teruo

    2012-07-01

    Tiliroside contained in several dietary plants, such as rose hips, strawberry and raspberry, is a glycosidic flavonoid and possesses anti-inflammatory, antioxidant, anticarcinogenic and hepatoprotective activities. Recently, it has been reported that the administration of tiliroside significantly inhibited body weight gain and visceral fat accumulation in normal mice. In this study, we evaluated the effects of tiliroside on obesity-induced metabolic disorders in obese-diabetic KK-A(y) mice. In KK-A(y) mice, the administration of tiliroside (100 mg/kg body weight/day) for 21 days failed to suppress body weight gain and visceral fat accumulation. Although tiliroside did not affect oxygen consumption, respiratory exchange ratio was significantly decreased in mice treated with tiliroside. In the analysis of metabolic characteristics, it was shown that plasma insulin, free fatty acid and triglyceride levels were decreased, and plasma adiponectin levels were increased in mice administered tiliroside. The messenger RNA expression levels of hepatic adiponectin receptor (AdipoR)-1 and AdipoR2 and skeletal muscular AdipoR1 were up-regulated by tiliroside treatment. Furthermore, it was indicated that tiliroside treatment activated AMP-activated protein kinase in both the liver and skeletal muscle and peroxisome proliferator-activated receptor α in the liver. Finally, tiliroside inhibited obesity-induced hepatic and muscular triglyceride accumulation. These findings suggest that tiliroside enhances fatty acid oxidation via the enhancement adiponectin signaling associated with the activation of both AMP-activated protein kinase and peroxisome proliferator-activated receptor α and ameliorates obesity-induced metabolic disorders, such as hyperinsulinemia and hyperlipidemia, although it does not suppress body weight gain and visceral fat accumulation in obese-diabetic model mice.

  11. Gene expression levels of Casein kinase 1 (CK1) isoforms are correlated to adiponectin levels in adipose tissue of morbid obese patients and site-specific phosphorylation mediated by CK1 influences multimerization of adiponectin.

    PubMed

    Xu, Pengfei; Fischer-Posovszky, Pamela; Bischof, Joachim; Radermacher, Peter; Wabitsch, Martin; Henne-Bruns, Doris; Wolf, Anna-Maria; Hillenbrand, Andreas; Knippschild, Uwe

    2015-05-01

    White adipose tissue has now been recognized as an important endocrine organ secreting bioactive molecules termed adipocytokines. In obesity, anti-inflammatory adipocytokines like adiponectin are decreased while pro-inflammatory factors are over-produced. These changes contribute to the development of insulin resistance and obesity-associated diseases. Since members of the casein kinase 1 (CK1) family are involved in the regulation of various signaling pathways we ask here whether they are able to modulate the functions of adiponectin. We show that CK1δ and ε are expressed in adipose tissue and that the expression of CK1 isoforms correlates with that of adiponectin. Furthermore, adiponectin co-immunoprecipitates with CK1δ and CK1ε and is phosphorylated by CK1δ at serine 174 and threonine 235, thereby influencing the formation of adiponectin oligomeric complexes. Furthermore, inhibition of CK1δ in human adipocytes by IC261 leads to an increase in basal and insulin-stimulated glucose uptake. In summary, our data indicate that site-specific phosphorylation of adiponectin, especially at sites targeted by CK1δ in vitro, provides an additional regulatory mechanism for modulating adiponectin complex formation and function. PMID:25724478

  12. Adiponectin ameliorates hyperglycemia-induced cardiac hypertrophy and dysfunction by concomitantly activating Nrf2 and Brg1.

    PubMed

    Li, Haobo; Yao, Weifeng; Irwin, Michael G; Wang, Tingting; Wang, Shuang; Zhang, Liangqing; Xia, Zhengyuan

    2015-07-01

    Hyperglycemia-induced oxidative stress is implicated in the development of cardiomyopathy in diabetes that is associated with reduced adiponectin (APN) and heme oxygenase-1 (HO-1). Brahma-related gene 1 (Brg1) assists nuclear factor-erythroid-2-related factor-2 (Nrf2) to activate HO-1 to increase myocardial antioxidant capacity in response to oxidative stress. We hypothesized that reduced adiponectin (APN) impairs HO-1 induction which contributes to the development of diabetic cardiomyopathy, and that supplementation of APN may ameliorate diabetic cardiomyopathy by activating HO-1 through Nrf2 and Brg1 in diabetes. Control (C) and streptozotocin-induced diabetic (D) rats were untreated or treated with APN adenovirus (1×10(9) pfu) 3 weeks after diabetes induction and examined and terminated 1 week afterward. Rat left ventricular functions were assessed by a pressure-volume conductance system, before the rat hearts were removed to perform histological and biochemical assays. Four weeks after diabetes induction, D rats developed cardiac hypertrophy evidenced as increased ratio of heart weight to body weight, elevated myocardial collagen I content, and larger cardiomyocyte cross-sectional area (all P<0.05 vs C). Diabetes elevated cardiac oxidative stress (increased 15-F2t-isoprostane, 4-hydroxynonenal generation, 8-hydroxy-2'-deoxyguanosine, and superoxide anion generation), increased myocardial apoptosis, and impaired cardiac function (all P<0.05 vs C). In D rats, myocardial HO-1 mRNA and protein expression were reduced which was associated with reduced Brg1 and nuclear Nrf2 protein expression. All these changes were either attenuated or prevented by APN. In primarily cultured cardiomyocytes (CMs) isolated from D rats or in the embryonic rat cardiomyocytes cell line H9C2 cells incubated with high glucose (HG, 25 mM), supplementation of recombined globular APN (gAd, 2μg/mL) reversed HG-induced reductions of HO-1, Brg1, and nuclear Nrf2 protein expression and

  13. The Light Curve of V713 Per (HMW 15): Evidence for Gravitational Sculpting by an Object Embedded in the Circumstellar Disk

    NASA Astrophysics Data System (ADS)

    Herbst, William; Yau, A.; Semkov, E.

    2010-01-01

    HMW 15 (V713 Per, H 187, TJ 108, LRLL 35) is a G-type weak-line T Tauri star (WTTS) in the extremely young cluster IC 348. It has an age of about 3 My, a mass of about 1.5 solar mass and a distance of 300 pc. What distinguishes it from other WTTS is a cyclic variation in optical brightness with an amplitude of about 0.8 mag and a period of 1717 d or 4.7 yr (Nordhagen et al. 2006, ApJ 646, 151). The star shows no detectable radial velocity variations to stringent limits (Grinin et al. 2008, A&A 489,1233) indicating that the periodicity is not caused by a stellar companion. Two complete cycles of this variation have now been observed and we present and discuss its form and features. We suggest that the main cause of the periodic variation is a massive embedded planet or protoplanet orbiting at a distance of 3.3 AU from the central (single) star. Other features in the light curve can be seen at the Lagrangian points (L3, L4 and L5) of this system, where we suppose that gravitational sculpting by the planet has been active. Continued monitoring of this unique and potentially important system is obviously warranted and is needed to test our hypothesis. We thank the NASA-Origins program for its support of this work through a grant to WH and the NSF/REU program for supporting the participation of one us (AY).

  14. Adiponectin upregulates ABCA1 expression through liver X receptor alpha signaling pathway in RAW 264.7 macrophages

    PubMed Central

    Liang, Bin; Wang, Xin; Guo, Xiaohong; Yang, Zhiming; Bai, Rui; Liu, Ming; Xiao, Chuanshi; Bian, Yunfei

    2015-01-01

    ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in reverse cholesterol transport and anti-atherosclerosis. Liver X receptor alpha (LXRα) can stimulate cholesterol efflux through ABCA1. It has been well known that adiponectin has cardiovascular protection. In this study, we attempted to clarify the effect of adiponectin on expression of ABCA1, and explored the role of LXRα in the regulation of ABCA1 in RAW 264.7 macrophages. Our results showed that adiponectin increased ABCA1 expression at both the mRNA and protein levels in a dose-dependent and time-dependent manner. Consequently, adiponectin promoted cholesterol efflux and decreased cholesterol content in RAW 264.7 macrophages. Moreover, adiponectin up-regulated the expression of LXRα in a dose-dependent and time-dependent manner in RAW 264.7 macrophages. LXRα small interfering RNA completely abolished the promotion effects of adiponectin. In summary, adiponectin up-regulates ABCA1 expression via the LXRα pathway in RAW 264.7 macrophages. This novel insight could prove useful for developing new treatment strategies for cardiovascular diseases. PMID:25755733

  15. Low plasma level of adiponectin is associated with stavudine treatment and lipodystrophy in HIV-infected patients.

    PubMed

    Lindegaard, B; Keller, P; Bruunsgaard, H; Gerstoft, J; Pedersen, B K

    2004-02-01

    This study tested the hypothesis that in patients with HIV-associated lipodystrophy, adiponectin levels were related to insulin resistance, TNF-alpha and IL-6 and treatment with nucleoside analogues. HIV seropositive men undergoing highly active antiretroviral treatment were enrolled into three predetermined clinical groups: lipodystrophy with central fat accumulation (n = 12); lipodystrophy without central fat accumulation (n = 15); no lipodystrophy (n = 15). HIV-negative healthy men served as controls (n = 12). Both lipodystrophic groups had a low percentage of limb fat compared to the two control groups. Patients with lipodystrophy with fat accumulation had increased truncal fat compared with controls. Levels of adiponectin did not correlate with either TNF-alpha or IL-6. Low levels of adiponectin were found in both lipodystrophic groups and were associated with current or previous treatment with stavudine. Furthermore, the adiponectin level correlated with the percentage of limb fat. Patients with lipodystrophy with fat accumulation were more insulin resistant, measured by HOMA-IR, compared with controls. However, HOMA-IR did no correlate to adiponectin or other cytokines. In conclusion, the finding of no difference between the two lipodystrophic groups with regard to adiponectin, indicates that low levels of adiponectin reflects fat atrophy, whereas the insulin resistance was best explained by increased truncal fat mass.

  16. Adiponectin and arterial stiffness in youth with type 1 diabetes: the SEARCH for Diabetes in Youth Study

    PubMed Central

    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.

    2015-01-01

    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

  17. High serum adiponectin levels predict incident falls among middle-aged and older adults: a prospective cohort study

    PubMed Central

    Huang, Cong; Momma, Haruki; Niu, Kaijun; Chujo, Masahiko; Otomo, Atsushi; Cui, Yufei; Nagatomi, Ryoichi

    2016-01-01

    Background and objective: adiponectin is an adipocyte-derived hormone with anti-obesity and anti-diabetic properties. However, higher circulating adiponectin levels are related to poor muscle function and physical disability, which suggests a potential link between adiponectin and risk of falls. Nevertheless, no direct association between circulating adiponectin levels and incident fall risk has been reported. Therefore, this study aimed to investigate the relationship between serum adiponectin levels and incident falls in a population of middle-aged and older adults. Design: a prospective cohort study. Setting: Oroshisho Center in Sendai City, Japan. Subjects: Japanese adults who were ≥45 years old (n = 430). Measurements: serum adiponectin levels were measured at baseline, and the subjects were divided into sex-specific tertiles. Data regarding a history of falls were collected via participant recall using a self-reported questionnaire. Incident falls were defined as falls that were experienced by people without a history of falls at baseline. Results: during the 2-year follow-up, 15.6% (67/430) of the subjects experienced an incident fall. In the univariate logistic regression analysis, incident falls were significantly more frequent across the increasing sex-specific serum adiponectin tertiles (P for trend = 0.008). Adjusted odds ratios (95% confidence interval) for incident falls were 2.31 (1.07–4.98) in the middle tertile and 3.61 (1.63–7.99) in the highest tertile; this risk was significantly higher than that for the lowest adiponectin tertile (P for trend = 0.002). Conclusions: the findings of this prospective cohort study indicate that higher serum adiponectin levels may be a predictor of incident falls. PMID:27013505

  18. Cross-Talk between Adiponectin and IGF-IR in Breast Cancer

    PubMed Central

    Mauro, Loredana; Naimo, Giuseppina Daniela; Ricchio, Emilia; Panno, Maria Luisa; Andò, Sebastiano

    2015-01-01

    Obesity is a chronic and multifactorial disorder that is reaching epidemic proportions. It is characterized by an enlarged mass of adipose tissue caused by a combination of size increase of preexisting adipocytes (hypertrophy) and de novo adipocyte differentiation (hyperplasia). Obesity is related to many metabolic disorders like hypertension, type 2 diabetes, metabolic syndrome, and cardiovascular disease, and it is associated with an increased risk of cancer development in different tissues including breast. Adipose tissue is now regarded as not just a storage reservoir for excess energy, but rather as an endocrine organ, secreting a large number of bioactive molecules called adipokines. Among these, adiponectin represents the most abundant adipose tissue-excreted protein, which exhibits insulin sensitizing, anti-inflammatory, and antiatherogenic properties. The serum concentrations of adiponectin are inversely correlated with body mass index. Recently, low levels of plasma adiponectin have been associated with an increased risk for obesity-related cancers and development of more aggressive phenotype, concomitantly with alterations in the bioavailability of insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR) signaling pathways. In this review, we discuss the cross-talk between adiponectin/AdipoR1 and IGF-I/IGF-IR in breast cancer. PMID:26236690

  19. Osmotin: a plant sentinel and a possible agonist of mammalian adiponectin

    PubMed Central

    Anil Kumar, S.; Hima Kumari, P.; Shravan Kumar, G.; Mohanalatha, C.; Kavi Kishor, P. B.

    2015-01-01

    Osmotin is a stress responsive antifungal protein belonging to the pathogenesis-related (PR)-5 family that confers tolerance to both biotic and abiotic stresses in plants. Protective efforts of osmotin in plants range from high temperature to cold and salt to drought. It lyses the plasma membrane of the pathogens. It is widely distributed in fruits and vegetables. It is a differentially expressed and developmentally regulated protein that protects the cells from osmotic stress and invading pathogens as well, by structural or metabolic alterations. During stress conditions, osmotin helps in the accumulation of the osmolyte proline, which quenches reactive oxygen species and free radicals. Osmotin expression results in the accumulation of storage reserves and increases the shelf-life of fruits. It binds to a seven-transmembrane-domain receptor-like protein and induces programmed cell death in Saccharomyces cerevisiae through RAS2/cAMP signaling pathway. Adiponectin, produced in adipose tissues of mammals, is an insulin-sensitizing hormone. Strangely, osmotin acts like the mammalian hormone adiponectin in various in vitro and in vivo models. Adiponectin and osmotin, the two receptor binding proteins do not share sequence similarity at the amino acid level, but interestingly they have a similar structural and functional properties. In experimental mice, adiponectin inhibits endothelial cell proliferation and migration, primary tumor growth, and reduces atherosclerosis. This retrospective work examines the vital role of osmotin in plant defense and as a potential targeted therapeutic drug for humans. PMID:25852715

  20. Does Dietary Iodine Regulate Oxidative Stress and Adiponectin Levels in Human Breast Milk?

    PubMed Central

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

    2014-01-01

    Abstract Little is known about the association between iodine and human milk composition. In this study, we investigated the association between iodine and different markers of oxidative stress and obesity-related hormones in human breast milk. This work is composed of two cross-sectional studies (in lactating women and in the general population), one prospective and one in vitro. In the cross-sectional study in lactating women, the breast milk iodine correlated negatively with superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities, and with adiponectin levels. An in vitro culture of human adipocytes with 1 μM potassium iodide (KI, dose similar to the human breast milk iodine concentration) produced a significant decrease in adiponectin, GSH-Px, SOD1, and SOD2 mRNA expression. However, after 2 months of treatment with KI in the prospective study, a positive correlation was found between 24-h urinary iodine and serum adiponectin. Our observations lead to the hypothesis that iodine may be a factor directly involved in the regulation of oxidative stress and adiponectin levels in human breast milk. Antioxid. Redox Signal. 20, 847–853. PMID:24001137

  1. Weight Control

    MedlinePlus

    ... obese. Achieving a healthy weight can help you control your cholesterol, blood pressure and blood sugar. It ... use more calories than you eat. A weight-control strategy might include Choosing low-fat, low-calorie ...

  2. Body Weight

    MedlinePlus

    ... sign of a medical problem. Causes for sudden weight loss can include Thyroid problems Cancer Infectious diseases Digestive diseases Certain medicines Sudden weight gain can be due to medicines, thyroid problems, ...

  3. Maternal overweight programs offspring insulin and adiponectin signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maternal overweight (OW) was induced in rats by overfeeding via total enteral nutrition. Male offspring from OW dams gained greater (p < 0.005) body weight and %fat mass assessed by NMR, X-ray CT and adipose tissue weights when fed high fat diet (45% fat). Hepatic microarray analyses at postnatal da...

  4. High Molecular Weight Barley β-Glucan Alters Gut Microbiota Toward Reduced Cardiovascular Disease Risk

    PubMed Central

    Wang, Yanan; Ames, Nancy P.; Tun, Hein M.; Tosh, Susan M.; Jones, Peter J.; Khafipour, Ehsan

    2016-01-01

    The physiological cholesterol-lowering benefits of β-glucan have been well documented, however, whether modulation of gut microbiota by β-glucan is associated with these physiological effects remains unknown. The objectives of this study were therefore to determine the impact of β-glucan on the composition of gut microbiota in mildly hypercholesterolemic individuals and to identify if the altered microbiota are associated with bioactivity of β-glucan in improving risk factors of cardiovascular disease (CVD). Using a randomized, controlled crossover study design, individuals received for 5-week either a treatment breakfast containing 3 g high molecular weight (HMW), 3 g low molecular weight (LMW), 5 g LMW barley β-glucan, or wheat and rice. The American Heart Association (AHA) diet served as the background diet for all treatment groups. Phases were separated by 4-week washout periods. Fecal samples were collected at the end of each intervention phase and subjected to Illumina sequencing of 16S rRNA genes. Results revealed that at the phylum level, supplementation of 3 g/d HMW β-glucan increased Bacteroidetes and decreased Firmicutes abundances compared to control (P < 0.001). At the genus level, consumption of 3 g/d HMW β-glucan increased Bacteroides (P < 0.003), tended to increase Prevotella (P < 0.1) but decreased Dorea (P < 0.1), whereas diets containing 5 g LMW β-glucan and 3 g LMW β-glucan failed to alter the gut microbiota composition. Bacteroides, Prevotella, and Dorea composition correlated (P < 0.05) with shifts of CVD risk factors, including body mass index, waist circumference, blood pressure, as well as triglyceride levels. Our data suggest that consumption of HMW β-glucan favorably alters the composition of gut microbiota and this altered microbiota profile associates with a reduction of CVD risk markers. Together, our study suggests that β-glucan induced shifts in gut microbiota in a MW-dependent manner and that might be one of the

  5. Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review

    PubMed Central

    Kawwass, Jennifer F.; Summer, Ross; Kallen, Caleb B.

    2015-01-01

    Obesity is a risk factor for infertility and adverse reproductive outcomes. Adipose tissue is an important endocrine gland that secretes a host of endocrine factors, called adipokines, which modulate diverse physiologic processes including appetite, metabolism, cardiovascular function, immunity and reproduction. Altered adipokine expression in obese individuals has been implicated in the pathogenesis of a host of health disorders including diabetes and cardiovascular disease. It remains unclear whether adipokines play a significant role in the pathogenesis of adverse reproductive outcomes in obese individuals and, if so, whether the adipokines are acting directly or indirectly on the peripheral reproductive tissues. Many groups have demonstrated that receptors for the adipokines leptin and adiponectin are expressed in peripheral reproductive tissues and that these adipokines are likely, therefore, to exert direct effects on these tissues. Many groups have tested for direct effects of leptin and adiponectin on reproductive tissues including the testis, ovary, uterus, placenta and egg/embryo. The hypothesis that decreased fertility potential or adverse reproductive outcomes may result, at least in part, from defects in adipokine signaling within reproductive tissues has also been tested. Here, we present a critical analysis of published studies with respect to two adipokines, leptin and adiponectin, for which significant data have been generated. Our evaluation reveals significant inconsistencies and methodological limitations regarding the direct effects of these adipokines on peripheral reproductive tissues. We also observe a pervasive failure to account for in vivo data that challenge observations made in vitro. Overall, while leptin and adiponectin may directly modulate peripheral reproductive tissues, existing data suggest that these effects are minor and non-essential to human or mouse reproductive function. Current evidence suggests that direct effects of

  6. Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review.

    PubMed

    Kawwass, Jennifer F; Summer, Ross; Kallen, Caleb B

    2015-08-01

    Obesity is a risk factor for infertility and adverse reproductive outcomes. Adipose tissue is an important endocrine gland that secretes a host of endocrine factors, called adipokines, which modulate diverse physiologic processes including appetite, metabolism, cardiovascular function, immunity and reproduction. Altered adipokine expression in obese individuals has been implicated in the pathogenesis of a host of health disorders including diabetes and cardiovascular disease. It remains unclear whether adipokines play a significant role in the pathogenesis of adverse reproductive outcomes in obese individuals and, if so, whether the adipokines are acting directly or indirectly on the peripheral reproductive tissues. Many groups have demonstrated that receptors for the adipokines leptin and adiponectin are expressed in peripheral reproductive tissues and that these adipokines are likely, therefore, to exert direct effects on these tissues. Many groups have tested for direct effects of leptin and adiponectin on reproductive tissues including the testis, ovary, uterus, placenta and egg/embryo. The hypothesis that decreased fertility potential or adverse reproductive outcomes may result, at least in part, from defects in adipokine signaling within reproductive tissues has also been tested. Here, we present a critical analysis of published studies with respect to two adipokines, leptin and adiponectin, for which significant data have been generated. Our evaluation reveals significant inconsistencies and methodological limitations regarding the direct effects of these adipokines on peripheral reproductive tissues. We also observe a pervasive failure to account for in vivo data that challenge observations made in vitro. Overall, while leptin and adiponectin may directly modulate peripheral reproductive tissues, existing data suggest that these effects are minor and non-essential to human or mouse reproductive function. Current evidence suggests that direct effects of

  7. Phycocyanin prevents hypertension and low serum adiponectin level in a rat model of metabolic syndrome.

    PubMed

    Ichimura, Mayuko; Kato, Shigeko; Tsuneyama, Koichi; Matsutake, Sachiko; Kamogawa, Mai; Hirao, Eri; Miyata, Ayako; Mori, Sawako; Yamaguchi, Noriaki; Suruga, Kazuhito; Omagari, Katsuhisa

    2013-05-01

    Endothelial dysfunction is associated with hypertension, atherosclerosis, and metabolic syndrome. Phycocyanin is a pigment found in the blue-green algae, Spirulina, which possesses antihypertensive effect. In this study, we hypothesized that phycocyanin derived from Spirulina exerts antihypertensive actions by improving endothelial dysfunction in metabolic syndrome. Spontaneously hypertensive/NIH-corpulent (SHR/NDmcr-cp) rats were divided into 4 groups then fed a normal diet with or without phycocyanin (2500-, 5000-, or 10,000-mg/kg diet) for 25 weeks. At 34 weeks of age, although systolic blood pressure was not significantly different among groups, phycocyanin-fed groups exhibited a dose-dependent decrease in blood pressure. Serum levels of adiponectin and messenger RNA levels of adiponectin and CCAAT/enhancer-binding protein α in the adipose tissue of rats fed diets containing phycocyanin tended to be higher than those of rats fed a normal diet, but the differences were not statistically significant. Immunohistochemistry analysis showed a significant and positive correlation between aortic endothelial nitric oxide synthase (eNOS) expression levels, a downstream target of the adiponectin receptor, and serum adiponectin levels, although there were no significant differences in eNOS expression among groups. There was also no significant correlation between eNOS expression levels and systolic blood pressure. These results suggest that long-term administration of phycocyanin may ameliorate systemic blood pressure by enhancing eNOS expression in aorta that is stimulated by adiponectin. Phycocyanin may be beneficial for preventing endothelial dysfunction-related diseases in metabolic syndrome.

  8. Phycocyanin prevents hypertension and low serum adiponectin level in a rat model of metabolic syndrome.

    PubMed

    Ichimura, Mayuko; Kato, Shigeko; Tsuneyama, Koichi; Matsutake, Sachiko; Kamogawa, Mai; Hirao, Eri; Miyata, Ayako; Mori, Sawako; Yamaguchi, Noriaki; Suruga, Kazuhito; Omagari, Katsuhisa

    2013-05-01

    Endothelial dysfunction is associated with hypertension, atherosclerosis, and metabolic syndrome. Phycocyanin is a pigment found in the blue-green algae, Spirulina, which possesses antihypertensive effect. In this study, we hypothesized that phycocyanin derived from Spirulina exerts antihypertensive actions by improving endothelial dysfunction in metabolic syndrome. Spontaneously hypertensive/NIH-corpulent (SHR/NDmcr-cp) rats were divided into 4 groups then fed a normal diet with or without phycocyanin (2500-, 5000-, or 10,000-mg/kg diet) for 25 weeks. At 34 weeks of age, although systolic blood pressure was not significantly different among groups, phycocyanin-fed groups exhibited a dose-dependent decrease in blood pressure. Serum levels of adiponectin and messenger RNA levels of adiponectin and CCAAT/enhancer-binding protein α in the adipose tissue of rats fed diets containing phycocyanin tended to be higher than those of rats fed a normal diet, but the differences were not statistically significant. Immunohistochemistry analysis showed a significant and positive correlation between aortic endothelial nitric oxide synthase (eNOS) expression levels, a downstream target of the adiponectin receptor, and serum adiponectin levels, although there were no significant differences in eNOS expression among groups. There was also no significant correlation between eNOS expression levels and systolic blood pressure. These results suggest that long-term administration of phycocyanin may ameliorate systemic blood pressure by enhancing eNOS expression in aorta that is stimulated by adiponectin. Phycocyanin may be beneficial for preventing endothelial dysfunction-related diseases in metabolic syndrome. PMID:23684441

  9. Development of isohomoeoallelic lines within the wheat cv. Courtot for high molecular weight glutenin subunits: transfer of the Glu-D1 locus to chromosome 1A.

    PubMed

    Dumur, J; Branlard, G; Tanguy, A-M; Dardevet, M; Coriton, O; Huteau, V; Lemoine, J; Jahier, Joseph

    2009-08-01

    Wheat quality depends on protein composition and grain protein content. High molecular weight glutenin subunits (HMW-GS) play an important role in determining the viscoelastic properties of gluten. In an attempt to improve the bread-making quality of hexaploid wheat by elaborating novel HMW-GS combinations, a fragment of wheat chromosome 1D containing the Glu-D1 locus encoding the Dx2+Dy12 subunits was translocated to the long arm of chromosome 1A using the ph1b mutation. The partially isohomoeoallelic line selected was characterized using cytogenetical and molecular approaches to assess the amount of chromatin introgressed in the translocated 1A chromosome. Triple-target genomic in situ hybridization indicated that the translocated 1A chromosome had a terminal 1D segment representing 25% of the length of the recombinant long arm. The translocation was also identified on the long arm using molecular markers, and its length was estimated with a minimum of 91 cM. Proteome analysis was performed on total endosperm proteins. Out of the 152 major spots detected, 9 spots were up-regulated and 4 spots were down-regulated. Most of these proteins were identified as alpha-, beta-, gamma-gliadins assigned to the chromosomes of homoeologous groups 1 and 6. Quantitative variations in the HMW-GS were only observed in subunit Dy12 in response to duplication of the Glu-D1 locus.

  10. Improved yield of high molecular weight DNA coincides with increased microbial diversity access from iron oxide cemented sub-surface clay environments.

    PubMed

    Hurt, Richard A; Robeson, Michael S; Shakya, Migun; Moberly, James G; Vishnivetskaya, Tatiana A; Gu, Baohua; Elias, Dwayne A

    2014-01-01

    Despite over three decades of progress, extraction of high molecular weight (HMW) DNA from high clay soils or iron oxide cemented clay has remained challenging. HMW DNA is desirable for next generation sequencing as it yields the most comprehensive coverage. Several DNA extraction procedures were compared from samples that exhibit strong nucleic acid adsorption. pH manipulation or use of alternative ion solutions offered no improvement in nucleic acid recovery. Lysis by liquid N2 grinding in concentrated guanidine followed by concentrated sodium phosphate extraction supported HMW DNA recovery from clays high in iron oxides. DNA recovered using 1 M sodium phosphate buffer (PB) as a competitive desorptive wash was 15.22±2.33 µg DNA/g clay, with most DNA consisting of >20 Kb fragments, compared to 2.46±0.25 µg DNA/g clay with the Powerlyzer system (MoBio). Increasing PB concentration in the lysis reagent coincided with increasing DNA fragment length during initial extraction. Rarefaction plots of 16S rRNA (V1-V3 region) pyrosequencing from A-horizon and clay soils showed an ∼80% and ∼400% larger accessed diversity compared to the Powerlyzer soil DNA system, respectively. The observed diversity from the Firmicutes showed the strongest increase with >3-fold more operational taxonomic units (OTU) recovered.

  11. Supercharging Reagent for Enhanced Liquid Chromatographic Separation and Charging of Sialylated and High-Molecular-Weight Glycopeptides for NanoHPLC-ESI-MS/MS Analysis.

    PubMed

    Lin, Chia-Wei; Haeuptle, Micha A; Aebi, Markus

    2016-09-01

    Recent developments in proteomic techniques have led to the development of mass spectrometry (MS)-based methods to characterize site-specific glycosylation of proteins. However, appropriate analytical tools to characterize acidic and high-molecular-weight (hMW) glycopeptides are still lacking. In this study, we demonstrate that the addition of supercharging reagent, m-nitrobenzyl alcohol (m-NBA), into mobile phases greatly facilitates the analysis of acidic and hMW glycopeptides. Using commercial glycoproteins, we demonstrated that in the presence of m-NBA the charge state of sialylated glycopeptides increased and the chromatographic separation of neutral and acidic glycopeptides revealed a remarkable improvement. Next, we applied this system to the characterization of a glycoconjugate vaccine candidate consisting of a genetically detoxified exotoxin A of Pseudomonas aeruginosa covalently linked to Shigella flexneri type 2a O-antigen (Sf2E) produced by engineered Escherichia coli. The addition of m-NBA, allowed us to identify peptides with glycan chains of unprecedented size, up to 20 repeat units (98 monosaccharides). Our results indicated that incorporation of m-NBA into reversed-phase liquid chromatography (LC) solvents improves sensitivity, charging, and chromatographic resolution for acidic and hMW glycopeptides. PMID:27487254

  12. Supercharging Reagent for Enhanced Liquid Chromatographic Separation and Charging of Sialylated and High-Molecular-Weight Glycopeptides for NanoHPLC-ESI-MS/MS Analysis.

    PubMed

    Lin, Chia-Wei; Haeuptle, Micha A; Aebi, Markus

    2016-09-01

    Recent developments in proteomic techniques have led to the development of mass spectrometry (MS)-based methods to characterize site-specific glycosylation of proteins. However, appropriate analytical tools to characterize acidic and high-molecular-weight (hMW) glycopeptides are still lacking. In this study, we demonstrate that the addition of supercharging reagent, m-nitrobenzyl alcohol (m-NBA), into mobile phases greatly facilitates the analysis of acidic and hMW glycopeptides. Using commercial glycoproteins, we demonstrated that in the presence of m-NBA the charge state of sialylated glycopeptides increased and the chromatographic separation of neutral and acidic glycopeptides revealed a remarkable improvement. Next, we applied this system to the characterization of a glycoconjugate vaccine candidate consisting of a genetically detoxified exotoxin A of Pseudomonas aeruginosa covalently linked to Shigella flexneri type 2a O-antigen (Sf2E) produced by engineered Escherichia coli. The addition of m-NBA, allowed us to identify peptides with glycan chains of unprecedented size, up to 20 repeat units (98 monosaccharides). Our results indicated that incorporation of m-NBA into reversed-phase liquid chromatography (LC) solvents improves sensitivity, charging, and chromatographic resolution for acidic and hMW glycopeptides.

  13. Circulating omentin concentration increases after weight loss

    PubMed Central

    2010-01-01

    Background Omentin-1 is a novel adipokine expressed in visceral adipose tissue and negatively associated with insulin resistance and obesity. We aimed to study the effects of weight loss-induced improved insulin sensitivity on circulating omentin concentrations. Methods Circulating omentin-1 (ELISA) concentration in association with metabolic variables was measured in 35 obese subjects (18 men, 17 women) before and after hypocaloric weight loss. Results Baseline circulating omentin-1 concentrations correlated negatively with BMI (r = -0.58, p < 0.001), body weight (r = -0.35, p = 0.045), fat mass (r = -0.67, p < 0.001), circulating leptin (r = -0.7, p < 0.001) and fasting insulin (r = -0.37, p = 0.03). Circulating omentin-1 concentration increased significantly after weight loss (from 44.9 ± 9.02 to 53.41 ± 8.8 ng/ml, p < 0.001). This increase in circulating omentin after weight loss was associated with improved insulin sensitivity (negatively associated with HOMA value and fasting insulin, r = -0.42, p = 0.02 and r = -0.45, p = 0.01, respectively) and decreased BMI (r = -0.54, p = 0.001). Conclusion As previously described with adiponectin, circulating omentin-1 concentrations increase after weight loss-induced improvement of insulin sensitivity. PMID:20380714

  14. Transformations of the chemical compositions of high molecular weight DOM along a salinity transect: Using two dimensional correlation spectroscopy and principal component analysis approaches

    NASA Astrophysics Data System (ADS)

    Abdulla, Hussain A. N.; Minor, Elizabeth C.; Dias, Robert F.; Hatcher, Patrick G.

    2013-10-01

    In a study of chemical transformations of estuarine high-molecular-weight (HMW, >1000 Da) dissolved organic matter (DOM) collected over a period of two years along a transect through the Elizabeth River/Chesapeake Bay system to the coastal Atlantic Ocean off Virginia, USA, δ13C values, N/C ratios, and principal component analysis (PCA) of the solid-state 13C NMR (nuclear magnetic resonance) spectra of HMW-DOM show an abrupt change in both its sources and chemical structural composition occurring around salinity 20. HMW-DOM in the lower salinity region had lighter isotopic values, higher aromatic and lower carbohydrate contents relative to that in the higher salinity region. These changes around a salinity of 20 are possibly due to introduction of a significant amount of new carbon (autotrophic DOM) to the transect. PC-1 loadings plot shows that spatially differing DOM components are similar to previously reported 13C NMR spectra of heteropolysaccharides (HPS) and carboxyl-rich alicyclic molecules (CRAM). Applying two dimensional correlation spectroscopy techniques to 1H NMR spectra from the same samples reveals increases in the contribution of N-acetyl amino sugars, 6-deoxy sugars, and sulfated polysaccharides to HPS components along the salinity transect, which suggests a transition from plant derived carbohydrates to marine produced carbohydrates within the HMW-DOM pool. In contrast to what has been suggested previously, our combined results from 13C NMR, 1H NMR, and FTIR indicate that CRAM consists of at least two different classes of compounds (aliphatic polycarboxyl compounds and lignin-like compounds).

  15. High molecular weight dissolved organic matter enrichment selects for methylotrophs in dilution to extinction cultures.

    PubMed

    Sosa, Oscar A; Gifford, Scott M; Repeta, Daniel J; DeLong, Edward F

    2015-12-01

    The role of bacterioplankton in the cycling of marine dissolved organic matter (DOM) is central to the carbon and energy balance in the ocean, yet there are few model organisms available to investigate the genes, metabolic pathways, and biochemical mechanisms involved in the degradation of this globally important carbon pool. To obtain microbial isolates capable of degrading semi-labile DOM for growth, we conducted dilution to extinction cultivation experiments using seawater enriched with high molecular weight (HMW) DOM. In total, 93 isolates were obtained. Amendments using HMW DOM to increase the dissolved organic carbon concentration 4x (280 μM) or 10x (700 μM) the ocean surface water concentrations yielded positive growth in 4-6% of replicate dilutions, whereas <1% scored positive for growth in non-DOM-amended controls. The majority (71%) of isolates displayed a distinct increase in cell yields when grown in increasing concentrations of HMW DOM. Whole-genome sequencing was used to screen the culture collection for purity and to determine the phylogenetic identity of the isolates. Eleven percent of the isolates belonged to the gammaproteobacteria including Alteromonadales (the SAR92 clade) and Vibrio. Surprisingly, 85% of isolates belonged to the methylotrophic OM43 clade of betaproteobacteria, bacteria thought to metabolically specialize in degrading C1 compounds. Growth of these isolates on methanol confirmed their methylotrophic phenotype. Our results indicate that dilution to extinction cultivation enriched with natural sources of organic substrates has a potential to reveal the previously unsuspected relationships between naturally occurring organic nutrients and the microorganisms that consume them.

  16. High molecular weight dissolved organic matter enrichment selects for methylotrophs in dilution to extinction cultures

    PubMed Central

    Sosa, Oscar A; Gifford, Scott M; Repeta, Daniel J; DeLong, Edward F

    2015-01-01

    The role of bacterioplankton in the cycling of marine dissolved organic matter (DOM) is central to the carbon and energy balance in the ocean, yet there are few model organisms available to investigate the genes, metabolic pathways, and biochemical mechanisms involved in the degradation of this globally important carbon pool. To obtain microbial isolates capable of degrading semi-labile DOM for growth, we conducted dilution to extinction cultivation experiments using seawater enriched with high molecular weight (HMW) DOM. In total, 93 isolates were obtained. Amendments using HMW DOM to increase the dissolved organic carbon concentration 4x (280 μM) or 10x (700 μM) the ocean surface water concentrations yielded positive growth in 4–6% of replicate dilutions, whereas <1% scored positive for growth in non-DOM-amended controls. The majority (71%) of isolates displayed a distinct increase in cell yields when grown in increasing concentrations of HMW DOM. Whole-genome sequencing was used to screen the culture collection for purity and to determine the phylogenetic identity of the isolates. Eleven percent of the isolates belonged to the gammaproteobacteria including Alteromonadales (the SAR92 clade) and Vibrio. Surprisingly, 85% of isolates belonged to the methylotrophic OM43 clade of betaproteobacteria, bacteria thought to metabolically specialize in degrading C1 compounds. Growth of these isolates on methanol confirmed their methylotrophic phenotype. Our results indicate that dilution to extinction cultivation enriched with natural sources of organic substrates has a potential to reveal the previously unsuspected relationships between naturally occurring organic nutrients and the microorganisms that consume them. PMID:25978545

  17. High molecular weight dissolved organic matter enrichment selects for methylotrophs in dilution to extinction cultures.

    PubMed

    Sosa, Oscar A; Gifford, Scott M; Repeta, Daniel J; DeLong, Edward F

    2015-12-01

    The role of bacterioplankton in the cycling of marine dissolved organic matter (DOM) is central to the carbon and energy balance in the ocean, yet there are few model organisms available to investigate the genes, metabolic pathways, and biochemical mechanisms involved in the degradation of this globally important carbon pool. To obtain microbial isolates capable of degrading semi-labile DOM for growth, we conducted dilution to extinction cultivation experiments using seawater enriched with high molecular weight (HMW) DOM. In total, 93 isolates were obtained. Amendments using HMW DOM to increase the dissolved organic carbon concentration 4x (280 μM) or 10x (700 μM) the ocean surface water concentrations yielded positive growth in 4-6% of replicate dilutions, whereas <1% scored positive for growth in non-DOM-amended controls. The majority (71%) of isolates displayed a distinct increase in cell yields when grown in increasing concentrations of HMW DOM. Whole-genome sequencing was used to screen the culture collection for purity and to determine the phylogenetic identity of the isolates. Eleven percent of the isolates belonged to the gammaproteobacteria including Alteromonadales (the SAR92 clade) and Vibrio. Surprisingly, 85% of isolates belonged to the methylotrophic OM43 clade of betaproteobacteria, bacteria thought to metabolically specialize in degrading C1 compounds. Growth of these isolates on methanol confirmed their methylotrophic phenotype. Our results indicate that dilution to extinction cultivation enriched with natural sources of organic substrates has a potential to reveal the previously unsuspected relationships between naturally occurring organic nutrients and the microorganisms that consume them. PMID:25978545

  18. Elevated Adiponectin Levels Suppress Perivascular and Aortic Inflammation and Prevent AngII-induced Advanced Abdominal Aortic Aneurysms

    PubMed Central

    Wågsäter, Dick; Vorkapic, Emina; van Stijn, Caroline M. W.; Kim, Jason; Lusis, Aldons J.; Eriksson, Per; Tangirala, Rajendra K.

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by aortic dilation and rupture leading to sudden death. Currently, no non-surgical treatments are available and novel therapeutic targets are needed to prevent AAA. We investigated whether increasing plasma levels of adiponectin (APN), a pleiotropic adipokine, provides therapeutic benefit to prevent AngII-induced advanced AAA in a well-established preclinical model. In the AngII-infused hyperlipidemic low-density lipoprotein receptor-deficient mouse (LDLR−/−) model, we induced plasma APN levels using a recombinant adenovirus expressing mouse APN (AdAPN) and as control, adenovirus expressing green florescent protein (AdGFP). APN expression produced sustained and significant elevation of total and high-molecular weight APN levels and enhanced APN localization in the artery wall. AngII infusion for 8 weeks induced advanced AAA development in AdGFP mice. Remarkably, APN inhibited the AAA development in AdAPN mice by suppressing aortic inflammatory cell infiltration, medial degeneration and elastin fragmentation. APN inhibited the angiotensin type-1 receptor (AT1R), inflammatory cytokine and mast cell protease expression, and induced lysyl oxidase (LOX) in the aortic wall, improved systemic cytokine profile and attenuated adipose inflammation. These studies strongly support APN therapeutic actions through multiple mechanisms inhibiting AngII-induced AAA and increasing plasma APN levels as a strategy to prevent advanced AAA. PMID:27659201

  19. Positive correlation between serum taurine and adiponectin levels in high-fat diet-induced obesity rats.

    PubMed

    You, Jeong Soon; Zhao, Xu; Kim, Sung Hoon; Chang, Kyung Ja

    2013-01-01

    The purpose of this study was to investigate the relationship between serum taurine level and serum adiponectin or leptin levels in high-fat diet-induced obesity rats. Five-week-old male Sprague-Dawley rats were randomly divided into three groups for a period of 8 weeks (normal diet, N group; high-fat diet, HF group; high-fat diet + taurine, HFT group). Taurine was supplemented by dissolving in feed water (3% w/v), and the same amount of distilled water was orally administrated to N and HF groups. In serum, adiponectin level was higher in HFT group compared to HF group. The serum taurine level was negatively correlated with serum total cholesterol (TC) level and positively correlated with serum adiponectin level. These results suggest that dietary taurine supplementation has beneficial effects on total cholesterol and adiponectin levels in high-fat diet-induced obesity rats.

  20. Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients

    PubMed Central

    Ayvaz, Havva Hilal; Ozturk, Gulfer; Ergin, Can; Akıs, Havva Kaya; Gonul, Muzeyyen; Arzuhal, Ercan

    2016-01-01

    Introduction Isotretinoin has been successfully used for the treatment of acne vulgaris. Aim To investigate the effects of isotretinoin on body mass index (BMI), to determine whether isotretinoin causes any changes in serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients, and to correlate variables. Material and methods Thirty-two patients were included in this study. Oral isotretinoin was begun at a dose of 0.5–0.6 mg/kg and raised to 0.6–0.75 mg/kg. Pretreatment and posttreatment third-month BMI and adiponectin, leptin, and ghrelin serum levels were measured. Results The pre- and posttreatment BMI values were not significantly different. In addition, serum adiponectin and leptin levels were significantly increased following isotretinoin therapy while serum ghrelin levels were not different. Conclusions Isotretinoin may exert its anti-inflammatory activity by increasing leptin and adiponectin levels.

  1. Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients

    PubMed Central

    Ayvaz, Havva Hilal; Ozturk, Gulfer; Ergin, Can; Akıs, Havva Kaya; Gonul, Muzeyyen; Arzuhal, Ercan

    2016-01-01

    Introduction Isotretinoin has been successfully used for the treatment of acne vulgaris. Aim To investigate the effects of isotretinoin on body mass index (BMI), to determine whether isotretinoin causes any changes in serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients, and to correlate variables. Material and methods Thirty-two patients were included in this study. Oral isotretinoin was begun at a dose of 0.5–0.6 mg/kg and raised to 0.6–0.75 mg/kg. Pretreatment and posttreatment third-month BMI and adiponectin, leptin, and ghrelin serum levels were measured. Results The pre- and posttreatment BMI values were not significantly different. In addition, serum adiponectin and leptin levels were significantly increased following isotretinoin therapy while serum ghrelin levels were not different. Conclusions Isotretinoin may exert its anti-inflammatory activity by increasing leptin and adiponectin levels. PMID:27605902

  2. Recurrent solitary fibrous tumor of the pleura with malignant transformation and non-islet cell tumor-induced hypoglycemia due to paraneoplastic overexpression and secretion of high-molecular-weight insulin-like growth factor II.

    PubMed

    Tominaga, Naoto; Kawarasaki, Chiaki; Kanemoto, Keiko; Yokochi, Akio; Sugino, Keishi; Hatanaka, Kazuhito; Uekusa, Toshimasa; Fukuda, Izumi; Aiba, Motohiko; Hizuka, Naomi; Uda, Susumu

    2012-01-01

    A 41-year-old man was diagnosed with a solitary fibrous tumor (SFT) of the pleura in the posterior mediastinum. Despite two surgeries for excision, the SFT recurred and progressed with direct invasion of the chest wall and bone metastases. He was hospitalized because of cerebral infarction and presented with recurrent severe hypoglycemia fourteen years later. High-molecular-weight (HMW) insulin-like growth factor II (IGF-II) was identified in the serum and tumor using Western blotting and immunohistochemistry. These findings suggested that the cause of the recurrent severe hypoglycemia was SFT production of HMW IGF-II, a mediator of non-islet cell tumor-induced hypoglycemia (NICTH).

  3. Adiponectin levels predict prediabetes risk: the Pathobiology of Prediabetes in A Biracial Cohort (POP-ABC) study

    PubMed Central

    Jiang, Yunna; Owei, Ibiye; Wan, Jim; Ebenibo, Sotonte; Dagogo-Jack, Samuel

    2016-01-01

    Background Adiponectin levels display ethnic disparities, and are inversely associated with the risk of type 2 diabetes (T2DM). However, the association of adiponectin with prediabetes risk in diverse populations has not been well-studied. Here, we assessed baseline adiponectin levels in relation to incident prediabetes in a longitudinal biracial cohort. Research design and methods The Pathobiology of Prediabetes in A Biracial Cohort study followed non-diabetic offspring of parents with T2DM for the occurrence of prediabetes, defined as impaired fasting glucose and/or impaired glucose tolerance. Assessments at enrollment and during follow-up included a 75 g oral glucose tolerance test, anthropometry, biochemistries (including fasting insulin and adiponectin levels), insulin sensitivity and insulin secretion. Logistic regression was used to evaluate the contribution of adiponectin to risk of progression to prediabetes. Results Among the 333 study participants (mean (SD) age 44.2 (10.6) year), 151(45.3%) were white and 182 (54.8%) were black. During approximately 5.5 (mean 2.62) years of follow-up, 110 participants (33%) progressed to prediabetes (N=100) or T2DM (N=10), and 223 participants (67%) were non-progressors. The mean cohort adiponectin level was 9.41+5.30 μg/mL (range 3.1–45.8 μg/mL); values were higher in women than men (10.3+5.67 μg/mL vs 7.27+3.41 μg/mL, p<0.0001) and in white than black offspring (10.7+5.44 μg/mL vs 8.34+4.95 μg/mL, p<0.0001). Adiponectin levels correlated inversely with adiposity and glycemia, and positively with insulin sensitivity and high-density lipoprotein cholesterol levels. Baseline adiponectin strongly predicted incident prediabetes: the HR for prediabetes per 1 SD (approximately 5 μg/mL) higher baseline adiponectin was 0.48 (95% CI 0.27 to 0.86, p=0.013). Conclusions Among healthy white and black adults with parental history of T2DM, adiponectin level is a powerful risk marker of incident prediabetes

  4. Correlation of Adiponectin mRNA Abundance and Its Receptors with Quantitative Parameters of Sperm Motility in Rams

    PubMed Central

    Kadivar, Ali; Heidari Khoei, Heidar; Hassanpour, Hossein; Golestanfar, Arefe; Ghanaei, Hamid

    2016-01-01

    Background Adiponectin and its receptors (AdipoR1 and AdipoR2), known as adiponectin system, have some proven roles in the fat and glucose metabolisms. Several studies have shown that adiponectin can be considered as a candidate in linking metabolism to testicular function. In this regard, we evaluated the correlation between sperm mRNA abundance of adiponectin and its receptors, with sperm motility indices in the present study. Materials and Methods In this completely randomized design study, semen samples from 6 adult rams were fractionated on a two layer discontinuous percoll gradient into high and low motile sperm cells, then quantitative parameters of sperm motility were determined by computer-assisted sperm analyzer (CASA). The mRNA abundance levels of Adiponectin, AdipoR1 and AdipoR2 were measured quantitatively using real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in the high and low motile groups. Results Firstly, we showed that adiponectin and its receptors (AdipoR1 and AdipoR2) were transcriptionally expressed in the ram sperm cells. Using Pfaff based method qRT- PCR, these levels of transcription were significantly higher in the high motile rather than low motile samples. This increase was 3.5, 3.6 and 2.5 fold change rate for Adiponectin, AdipoR1 and AdipoR2, respectively. Some of sperm motility indices [curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), linearity (LIN), wobble (WOB) and straightness (STR)] were also significantly correlated with Adiponectin and AdipoR1 relative expression. The correlation of AdipoR2 was also significant with the mentioned parameters, although this correlation was not comparable with adiponectin and AdipoR1. Conclusion This study revealed the novel association of adiponectin system with sperm motility. The results of our study suggested that adiponectin is one of the possible factors which can be evaluated and studied in male infertility disorders. PMID:27123210

  5. The relationship between physical activity level and cardiovascular disease biomarkers in healthy, normal-weight 3- to 6-year-old children and their parents.

    PubMed

    Huang, Carol; Cantell, Marja; Crawford, Susan; Dewey, Deborah; Pacaud, Danièle

    2016-08-01

    To determine if physical activity is linked to cardiovascular biomarkers in preschool children at risk, we need information on these biomarkers in healthy normal-weight children. In this population, multi-level modelling analyses found no correlation between accelerometer recorded physical activity and fasting lipids, adiponectin, or insulin sensitivity. Exploratory analyses found positive correlations between adiponectin and time spent in light physical activity, and between triglyceride and time spent in sedentary behaviour; these findings need to be confirmed in longitudinal prospective studies. PMID:27458687

  6. Salivary adiponectin levels are associated with training intensity but not with bone mass or reproductive function in elite Rhythmic Gymnasts.

    PubMed

    Roupas, Nikolaos D; Maïmoun, Laurent; Mamali, Irene; Coste, Olivier; Tsouka, Alexandra; Mahadea, Krishna Kunal; Mura, Thibault; Philibert, Pascal; Gaspari, Laura; Mariano-Goulart, Denis; Leglise, Michel; Sultan, Charles; Georgopoulos, Neoklis A

    2014-01-01

    Elite Rhythmic Gymnasts (RGs) constitute a unique metabolic model and they are prone to developing Anorexia Athletica. The aim of the present study was to evaluate the effect of training intensity on salivary adiponectin levels and assess a possible role of salivary adiponectin levels as a predictive factor of reproductive dysfunction and bone mass acquisition in elite RGs. The study included 80 elite female RGs participating in the World Rhythmic Gymnastics Championship tournament held in Montpellier, France on September 2011. Anthropometric values were assessed, training data and menstrual pattern were recorded, bone mass was measured with Broadband ultrasound attenuation (dB/Mhz) and baseline salivary adiponectin levels were determined. The athletes were classified as intensely and very intensely trained, considering the mean training intensity (40.84h/week). Moreover, considering their reproductive status, they were divided into RG's with normal menstruation, primary amenorrhea and oligomenorrhea. All comparisons were adjusted to age, BMI and body fat percentage differences. Very intensely trained RGs showed higher salivary adiponectin levels (p=0.05). Moreover, salivary adiponectin levels showed significant correlation with training intensity (r=0.409, p=0.003). On the other hand, no association of salivary adiponectin levels was documented with either reproductive function or bone mass acquisition. The results of the present study suggest that, in elite RGs, salivary adiponectin levels are associated with the intensity of training, possibly reflecting the deterioration of energy balance rather than the training stress. On the other hand, a predictive role of salivary adiponectin levels in reproductive dysfunction or bone mass acquisition could not be supported.

  7. Salivary adiponectin levels are associated with training intensity but not with bone mass or reproductive function in elite Rhythmic Gymnasts.

    PubMed

    Roupas, Nikolaos D; Maïmoun, Laurent; Mamali, Irene; Coste, Olivier; Tsouka, Alexandra; Mahadea, Krishna Kunal; Mura, Thibault; Philibert, Pascal; Gaspari, Laura; Mariano-Goulart, Denis; Leglise, Michel; Sultan, Charles; Georgopoulos, Neoklis A

    2014-01-01

    Elite Rhythmic Gymnasts (RGs) constitute a unique metabolic model and they are prone to developing Anorexia Athletica. The aim of the present study was to evaluate the effect of training intensity on salivary adiponectin levels and assess a possible role of salivary adiponectin levels as a predictive factor of reproductive dysfunction and bone mass acquisition in elite RGs. The study included 80 elite female RGs participating in the World Rhythmic Gymnastics Championship tournament held in Montpellier, France on September 2011. Anthropometric values were assessed, training data and menstrual pattern were recorded, bone mass was measured with Broadband ultrasound attenuation (dB/Mhz) and baseline salivary adiponectin levels were determined. The athletes were classified as intensely and very intensely trained, considering the mean training intensity (40.84h/week). Moreover, considering their reproductive status, they were divided into RG's with normal menstruation, primary amenorrhea and oligomenorrhea. All comparisons were adjusted to age, BMI and body fat percentage differences. Very intensely trained RGs showed higher salivary adiponectin levels (p=0.05). Moreover, salivary adiponectin levels showed significant correlation with training intensity (r=0.409, p=0.003). On the other hand, no association of salivary adiponectin levels was documented with either reproductive function or bone mass acquisition. The results of the present study suggest that, in elite RGs, salivary adiponectin levels are associated with the intensity of training, possibly reflecting the deterioration of energy balance rather than the training stress. On the other hand, a predictive role of salivary adiponectin levels in reproductive dysfunction or bone mass acquisition could not be supported. PMID:24240086

  8. Adiponectin enhances bone marrow mesenchymal stem cell resistance to flow shear stress through AMP-activated protein kinase signaling.

    PubMed

    Zhao, Lin; Fan, Chongxi; Zhang, Yu; Yang, Yang; Wang, Dongjin; Deng, Chao; Hu, Wei; Ma, Zhiqiang; Jiang, Shuai; Di, Shouyi; Qin, Zhigang; Lv, Jianjun; Sun, Yang; Yi, Wei

    2016-01-01

    Adiponectin has been demonstrated to protect the cardiovascular system and bone marrow mesenchymal stem cells (BMSCs). However, it is unclear whether adiponectin can protect BMSCs against flow shear stress (FSS). In this study, our aim was to explore the effects of adiponectin on BMSCs and to explore the role of AMP-activated protein kinase (AMPK) signaling in this process. Shear stress significantly inhibits the survival and increases the apoptosis of BMSCs in an intensity-dependent manner. The expression levels of TGF-β, bFGF, VEGF, PDGF, and Bcl2 are simultaneously reduced, and the phosphorylation levels of AMPK and ACC, as well as the expression level of Bax, are increased. Supplementation with adiponectin promotes the survival of BMSCs; reverses the changes in the expression levels of TGF-β, bFGF, VEGF, PDGF, Bcl2, and Bax; and further amplifies the phosphorylation of AMPK and ACC. Furthermore, the protective effects of adiponectin can be partially neutralized by AMPK siRNA. In summary, we have demonstrated for the first time that adiponectin can effectively protect BMSCs from FSS and that this effect depends, at least in part, on the activation of AMPK signaling. PMID:27418435

  9. Plasma adiponectin concentration is associated with ambulatory daytime systolic blood pressure but not with the dipping status.

    PubMed

    Vasunta, R L; Kesäniemi, Y A; Ukkola, O

    2010-08-01

    The objective of this study was to analyse the relationship between the ambulatory blood pressure (ABP) measurement and plasma adiponectin levels in a population-based cohort. Non-hypertensive, non-diabetics from the Oulu Project Elucidating Risk of Atherosclerosis cohort aged 40-60 years with ABP measurement available in 226 men and 236 women were analysed. ABP was recorded using the fully automatic SpaceLabs 90207 oscillometric unit. Plasma adiponectin concentrations were assayed using the enzyme-linked immunosorbent assay method. Without adjustment the highest plasma adiponectin tertile was associated with the lowest ABP and office BP measurements (P from 0.025 to P<0.001, respectively). Only the association of plasma adiponectin concentration with systolic ABP was independent of other conventional risk factors (age, body mass index (BMI), waist, gender, insulin sensitivity index, smoking and alcohol consumption) for hypertension (P=0.017). No association was observed between systolic dipping pattern and adiponectin level. The plasma high adiponectin concentration is independently associated with low daytime systolic ABP value. The mechanisms may include effects on endothelial function and the sympathetic nervous system. PMID:20010617

  10. Effects of L-thyroxine therapy on circulating leptin and adiponectin levels in subclinical hypothyroidism: a prospective study.

    PubMed

    Yildiz, Bulent Okan; Aksoy, Duygu Yazgan; Harmanci, Ayla; Unluturk, Ugur; Cinar, Nese; Isildak, Mehlika; Usman, Aydan; Bayraktar, Miyase

    2013-05-01

    Subclinical hypothyroidism (SCH) is defined by increased thyrotropin (TSH) and normal free thyroxine (fT4) levels. Controversial data are available regarding the effects of SCH on adipose tissue. Adiponectin and leptin are two major adipokines secreted from adipose tissue. We aimed to determine the levels of adiponectin and leptin in women with SCH and potential effects of L-thyroxine therapy on those levels. Forty three women with SCH and 53 age- and BMI-matched healthy euthyroid control women were included. Adiponectin and leptin levels, total cholesterol (TC), triglycerides (TG), HDL-, and LDL cholesterol, fat mass (FM) and fat-free mass (FFM) were determined in all participants. Patients received L-thyroxine treatment for 6 months after which all measurements were repeated. Patients with SCH and controls had similar baseline values for adiponectin, leptin, lipids, FM and FFM. All patients reached euthyroid status after 6 months of replacement therapy. Treatment resulted in an increase in adiponectin (p <0.01) and a decrease in leptin levels (p <0.05). Lipid levels, FM and FFM did not show a significant change. Achievement of euthyroid status by replacement therapy increases adiponectin and decreases leptin levels in women with SCH in this prospective study independent of a change in body fat mass.

  11. Adiponectin enhances bone marrow mesenchymal stem cell resistance to flow shear stress through AMP-activated protein kinase signaling

    PubMed Central

    Zhao, Lin; Fan, Chongxi; Zhang, Yu; Yang, Yang; Wang, Dongjin; Deng, Chao; Hu, Wei; Ma, Zhiqiang; Jiang, Shuai; Di, Shouyi; Qin, Zhigang; Lv, Jianjun; Sun, Yang; Yi, Wei

    2016-01-01

    Adiponectin has been demonstrated to protect the cardiovascular system and bone marrow mesenchymal stem cells (BMSCs). However, it is unclear whether adiponectin can protect BMSCs against flow shear stress (FSS). In this study, our aim was to explore the effects of adiponectin on BMSCs and to explore the role of AMP-activated protein kinase (AMPK) signaling in this process. Shear stress significantly inhibits the survival and increases the apoptosis of BMSCs in an intensity-dependent manner. The expression levels of TGF-β, bFGF, VEGF, PDGF, and Bcl2 are simultaneously reduced, and the phosphorylation levels of AMPK and ACC, as well as the expression level of Bax, are increased. Supplementation with adiponectin promotes the survival of BMSCs; reverses the changes in the expression levels of TGF-β, bFGF, VEGF, PDGF, Bcl2, and Bax; and further amplifies the phosphorylation of AMPK and ACC. Furthermore, the protective effects of adiponectin can be partially neutralized by AMPK siRNA. In summary, we have demonstrated for the first time that adiponectin can effectively protect BMSCs from FSS and that this effect depends, at least in part, on the activation of AMPK signaling. PMID:27418435

  12. Weight Management

    MedlinePlus

    ... Quit Smoking Benefits of Quitting Health Effects of Smoking Secondhand Smoke Withdrawal Ways to Quit QuitGuide Pregnancy & Motherhood Pregnancy & Motherhood Before Your Baby is Born From Birth to 2 Years Quitting for Two SmokefreeMom Healthy Kids Parenting & ... Weight Management Weight Management ...

  13. Weight Watcher!

    ERIC Educational Resources Information Center

    Clarke, Doug

    1990-01-01

    The author, using a weight machine in an airport lounge, varies the machine's input parameters of height and gender to generate data sets of ideal weight. These data are later used at in-service workshops and in both primary and secondary classrooms to explore patterns and make predictions. (JJK)

  14. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    PubMed

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

  15. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

    PubMed Central

    Aye, Irving L. M. H.; Rosario, Fredrick J.; Powell, Theresa L.; Jansson, Thomas

    2015-01-01

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

  16. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    PubMed

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

  17. Associations of Testosterone and Sex Hormone Binding Globulin with Adipose Tissue Hormones in Midlife Women

    PubMed Central

    Wildman, Rachel P.; Wang, Dan; Fernandez, Ivonne; Mancuso, Peter; Santoro, Nanette; Scherer, Philipp E.; Sowers, MaryFran R.

    2014-01-01

    Objective Regulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascular disorders, understanding their regulation in midlife women is of clinical importance. Therefore, we assessed the associations between testosterone (T) and sex hormone binding globulin (SHBG) with leptin, high molecular weight (HMW) adiponectin, and the soluble form of the leptin receptor (sOB-R) in healthy midlife women. Design and Methods Cross-sectional analyses were performed using data from 1,881 midlife women (average age 52.6 (±2.7) years) attending the sixth Annual follow-up visit of the multiethnic Study of Women’s Health Across the Nation. Results T was weakly negatively associated with both HMW adiponectin and sOB-R (r = −0.12 and r = −0.10, respectively; P < 0.001 for both), and positively associated with leptin (r = 0.17; P < 0.001). SHBG was more strongly and positively associated with both HMW adiponectin and sOB-R (r = 0.29 and r = 0.24, respectively; P < 0.001 for both), and more strongly and negatively associated with leptin (r = −0.27; P < 0.001). Adjustment for fat mass, insulin resistance, or waist circumference only partially diminished associations with HMW adiponectin and sOB-R, but attenuated associations with leptin. In conclusion, in these midlife women, lower SHBG values, and to a lesser extent, higher T levels, were associated with lower, or less favorable, levels of adiponectin and sOB-R, independent of fat mass. Conclusions These data suggest that variation in these adipose hormones resulting from lower SHBG levels, and possibly, though less likely, greater androgenicity, may contribute to susceptibility for metabolic and cardiovascular outcomes during midlife in women. PMID:23592672

  18. Maternal overweight programs insulin and adiponectin signaling in the offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult-life. Male offspring from OW dams gain greater body weight, fat mass and develop insulin resistance when fed high fat diets (45 percent fat). In this report we identify molecular targets of maternal OW-induced p...

  19. Establishment of a concept of visceral fat syndrome and discovery of adiponectin

    PubMed Central

    Matsuzawa, Yuji

    2010-01-01

    Although obesity is a major background of life style-related diseases such as diabetes mellitus, lipid disorder, hypertension and cardiovascular disease, the extent of whole body fat accumulation does not necessarily the determinant for the occurrence of these diseases. We developed the method for body fat analysis using CT scan and established the concept of visceral fat obesity, in other word metabolic syndrome in which intra-abdominal visceral fat accumulation has an important role in the development of diabetes, lipid disorder, hypertension and atherosclerosis. In order to clarify the mechanism that visceral fat accumulation causes metabolic and cardiovascular diseases, we have analyzed gene expression profile in subcutaneous adipose tissue and visceral adipose tissue. From the analysis, we found that adipose tissue, especially visceral adipose tissue expressed abundantly the genes encoding bioactive substances such as cytokines, growth factors and complements. In addition to known bioactive substances, we found a novel collagen-like protein which we named adiponectin. Adiponectin is present in plasma at a very high concentration and is inversely associated with visceral fat accumulation. Adiponectin has anti-diabetic, anti-hypertensive and anti-atherogenic properties and recent studies revealed that this protein has an anti-inflammatory and anti-oncogenic function. Therefore hypoadiponectinemia induced by visceral fat accumulation should become a strong risk factor for metabolic and cardiovascular diseases and also some kinds of cancers. In this review article, I would like to discuss the mechanism of life style-related diseases by focusing on the dysregulation of adiponectin related to obesity, especially visceral obesity. PMID:20154470

  20. Retinol Binding Protein-4 and Adiponectin Levels in Thyroid Overt and Subclinical Dysfunction.

    PubMed

    Kokkinos, S; Papazoglou, D; Zisimopoulos, A; Papanas, N; Tiaka, E; Antonoglou, C; Maltezos, E

    2016-02-01

    Thyroid dysfunction is accompanied by numerous changes in intermediary metabolism. Retinol binding protein-4 (RBP-4) and adiponectin are 2 adipocytokines that have multiple metabolic functions. The aim of our study was to examine serum RBP4 and adiponectin levels in clinical (before and after therapy) and subclinical hyperthyroid and hypothyroid subjects as compared to controls.150 patients with thyroid dysfunction were recruited (65 hyperthyroid and 85 hypothyroid) while 28 euthyroid subjects served as a control group. We measured anthropometric, biochemical and hormonal (free T4, free T3, TSH, insulin) parameters in all participants. RBP-4 and adiponectin were measured using commercial ELISA kits.Mean baseline levels of RBP-4 were higher in patients with clinical hypothyroidism (29.0±10.2 ng/ml, 25.1±12.6 ng/ml, 38.8±16.5 ng/ml, 31.9±13.2 ng/ml, 20.4±8.2 ng/ml in patients with hyperthyroidism, subclinical hyperthryrodism, hypothyroidism, subclinical hypothyroidism and controls respectively, F=4.86, P<0.001) and decreased significantly in patients with clinical hyperthyroidism and hypothyroidism after normalization of thyroid hormones' levels (from 29.0±10.2 to 24.9±8.4 ng/ml, p=0.003 and from 38.8±16.5 to 29.0±10.8 ng/ml, p=0.001 respectively). We did not observe analogous changes in adiponectin levels in any of the studied groups.RBP-4 levels are higher in patients with clinical hypothyroidism and exhibit a marked decrease after normalization of thyroid function in both hyper and hypothyroid patients. We suggest that RBP-4 may play a role in the metabolic disturbances which accompany thyroid dysfunction. PMID:26575118

  1. Feeding a Modified Fish Diet to Bottlenose Dolphins Leads to an Increase in Serum Adiponectin and Sphingolipids.

    PubMed

    Sobolesky, Philip M; Harrell, Tyler S; Parry, Celeste; Venn-Watson, Stephanie; Janech, Michael G

    2016-01-01

    Feeding a modified fish diet has been suggested to improve insulin sensitivity in bottlenose dolphins; however, insulin sensitivity was not directly measured. Since demonstrating an improvement in insulin sensitivity is technically difficult in dolphins, we postulated that directional changes in the hormone axis: fibroblast growth factor 21 (FGF21)/Adiponectin/Ceramide (Cer), could provide further support to this hypothesis. We measured 2-h post-prandial serum FGF21, total adiponectin, percent unmodified adiponectin, ceramide, and sphingosine levels from dolphins fed a diet rich in heptadecanoic acid (C17:0) over 24 weeks. Serum FGF21 was quantified by ELISA with an observed range of 129-1599 pg/ml, but did not significantly change over the 24-week study period. Total adiponectin levels (mean ± SD) significantly increased from 776 ± 400 pmol/ml at week 0 to 1196 ± 467 pmol/ml at week 24. The percent unmodified adiponectin levels (mean ± SD) decreased from 23.8 ± 6.0% at week 0 to 15.2 ± 5.2% at week 24. Interestingly, although FGF21 levels did not change, there was a good correlation between FGF21 and total adiponectin (ρ = 0.788, P < 0.001). We quantified the abundances of serum ceramides and sphingosines (SPH) because adiponectin has a defined role in sphingolipid metabolism through adiponectin receptor-mediated activation of ceramidases. The most abundant ceramide in dolphin sera was Cer 24:1 comprising 49% of the ceramides measured. Significant reductions were observed in the unsaturated Cer 18:1, Cer 20:1, and Cer 24:1, whereas significant increases were observed in saturated Cer 22:0, Cer 24:0, and Cer 26:0. However, total serum ceramides did not change. Significant elevations were detected for total sphingosine, dihydrosphingosine, sphingosine-1-phosphate, and dihydrosphingosine-1-phosphate. Proteomic analysis of the serum proteins revealed few changes in serum proteins over the study period. In conclusion

  2. Feeding a Modified Fish Diet to Bottlenose Dolphins Leads to an Increase in Serum Adiponectin and Sphingolipids.

    PubMed

    Sobolesky, Philip M; Harrell, Tyler S; Parry, Celeste; Venn-Watson, Stephanie; Janech, Michael G

    2016-01-01

    Feeding a modified fish diet has been suggested to improve insulin sensitivity in bottlenose dolphins; however, insulin sensitivity was not directly measured. Since demonstrating an improvement in insulin sensitivity is technically difficult in dolphins, we postulated that directional changes in the hormone axis: fibroblast growth factor 21 (FGF21)/Adiponectin/Ceramide (Cer), could provide further support to this hypothesis. We measured 2-h post-prandial serum FGF21, total adiponectin, percent unmodified adiponectin, ceramide, and sphingosine levels from dolphins fed a diet rich in heptadecanoic acid (C17:0) over 24 weeks. Serum FGF21 was quantified by ELISA with an observed range of 129-1599 pg/ml, but did not significantly change over the 24-week study period. Total adiponectin levels (mean ± SD) significantly increased from 776 ± 400 pmol/ml at week 0 to 1196 ± 467 pmol/ml at week 24. The percent unmodified adiponectin levels (mean ± SD) decreased from 23.8 ± 6.0% at week 0 to 15.2 ± 5.2% at week 24. Interestingly, although FGF21 levels did not change, there was a good correlation between FGF21 and total adiponectin (ρ = 0.788, P < 0.001). We quantified the abundances of serum ceramides and sphingosines (SPH) because adiponectin has a defined role in sphingolipid metabolism through adiponectin receptor-mediated activation of ceramidases. The most abundant ceramide in dolphin sera was Cer 24:1 comprising 49% of the ceramides measured. Significant reductions were observed in the unsaturated Cer 18:1, Cer 20:1, and Cer 24:1, whereas significant increases were observed in saturated Cer 22:0, Cer 24:0, and Cer 26:0. However, total serum ceramides did not change. Significant elevations were detected for total sphingosine, dihydrosphingosine, sphingosine-1-phosphate, and dihydrosphingosine-1-phosphate. Proteomic analysis of the serum proteins revealed few changes in serum proteins over the study period. In conclusion

  3. Feeding a Modified Fish Diet to Bottlenose Dolphins Leads to an Increase in Serum Adiponectin and Sphingolipids

    PubMed Central

    Sobolesky, Philip M.; Harrell, Tyler S.; Parry, Celeste; Venn-Watson, Stephanie; Janech, Michael G.

    2016-01-01

    Feeding a modified fish diet has been suggested to improve insulin sensitivity in bottlenose dolphins; however, insulin sensitivity was not directly measured. Since demonstrating an improvement in insulin sensitivity is technically difficult in dolphins, we postulated that directional changes in the hormone axis: fibroblast growth factor 21 (FGF21)/Adiponectin/Ceramide (Cer), could provide further support to this hypothesis. We measured 2-h post-prandial serum FGF21, total adiponectin, percent unmodified adiponectin, ceramide, and sphingosine levels from dolphins fed a diet rich in heptadecanoic acid (C17:0) over 24 weeks. Serum FGF21 was quantified by ELISA with an observed range of 129–1599 pg/ml, but did not significantly change over the 24-week study period. Total adiponectin levels (mean ± SD) significantly increased from 776 ± 400 pmol/ml at week 0 to 1196 ± 467 pmol/ml at week 24. The percent unmodified adiponectin levels (mean ± SD) decreased from 23.8 ± 6.0% at week 0 to 15.2 ± 5.2% at week 24. Interestingly, although FGF21 levels did not change, there was a good correlation between FGF21 and total adiponectin (ρ = 0.788, P < 0.001). We quantified the abundances of serum ceramides and sphingosines (SPH) because adiponectin has a defined role in sphingolipid metabolism through adiponectin receptor-mediated activation of ceramidases. The most abundant ceramide in dolphin sera was Cer 24:1 comprising 49% of the ceramides measured. Significant reductions were observed in the unsaturated Cer 18:1, Cer 20:1, and Cer 24:1, whereas significant increases were observed in saturated Cer 22:0, Cer 24:0, and Cer 26:0. However, total serum ceramides did not change. Significant elevations were detected for total sphingosine, dihydrosphingosine, sphingosine-1-phosphate, and dihydrosphingosine-1-phosphate. Proteomic analysis of the serum proteins revealed few changes in serum proteins over the study period. In conclusion

  4. Associations of adiponectin gene polymorphisms with polycystic ovary syndrome: a meta-analysis.

    PubMed

    Jia, Hongxia; Yu, Lili; Guo, Xuxiao; Gao, Wei; Jiang, Zhaoshun

    2012-10-01

    Adiponectin gene polymorphisms have been implicated in polycystic ovary syndrome (PCOS) development. However, results from previous studies were inconsistent and inconclusive. To shed some light on the relationship of two adiponectin gene polymorphisms, T45G and G276T, with PCOS, we conducted the current meta-analysis. PubMed was used for searching all eligible studies up to September 30, 2011. Odds ratio (OR) with the corresponding 95% confidence interval (CI) was adopted to evaluate the strength of the associations. In total, ten case-control studies involving 2,821 participants were included in the meta-analysis. Results showed that the T45G polymorphism was not associated with PCOS for allelic contrast (OR = 1.10, 95%CI: 0.83-1.44, P = 0.514), with evidence of large heterogeneity (P(heterogeneity) = 0.002). Concerning G276T polymorphism, the results showed that the T allele was related to a reduced risk of PCOS compared with the G allele under allelic genetic model (OR = 0.81, 95%CI: 0.70-0.93, P = 0.003), and no significant heterogeneity (P(heterogeneity) = 0.268) was revealed. Similar results were observed under additive, dominant and recessive genetic models for both of these two polymorphisms. No publication bias was detected. Our results suggested that the T45G polymorphism of adiponectin gene was not significantly associated with PCOS, while the G276T polymorphism was related to a decreased risk of PCOS.

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

    PubMed

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

    2014-11-01

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

  6. Birth Weight

    MedlinePlus

    ... with the placenta and substance abuse by the mother. Some low birth weight babies may be more at risk for certain health problems. Some may become sick in the first days of life or develop infections. Others may suffer ...

  7. Weight simulator

    NASA Technical Reports Server (NTRS)

    Howard, W. H.; Young, D. R.

    1972-01-01

    Device applies compressive force to bone to minimize loss of bone calcium during weightlessness or bedrest. Force is applied through weights, or hydraulic, pneumatic or electrically actuated devices. Device is lightweight and easy to maintain and operate.

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

    PubMed Central

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

    2007-01-01

    Background Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation. Adiponectin and its receptors are known to be expressed in osteoblasts, but their actions with regard to bone metabolism are still unclear. In this study, we investigated the effects of adiponectin on the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. Results Adiponectin receptor type 1 (AdipoR1) mRNA was detected in the cells by RT-PCR. The adenosine monophosphate-activated protein kinase (AMP kinase) was phosphorylated by both adiponectin and a pharmacological AMP kinase activator, 5-amino-imidazole-4-carboxamide-riboside (AICAR), in the cells. AdipoR1 small interfering RNA (siRNA) transfection potently knocked down the receptor mRNA, and the effect of this knockdown persisted for as long as 10 days after the transfection. The transfected cells showed decreased expressions of type I collagen and osteocalcin mRNA, as determined by real-time PCR, and reduced ALP activity and mineralization, as determined by von Kossa and Alizarin red stainings. In contrast, AMP kinase activation by AICAR (0.01–0.5 mM) in wild-type MC3T3-E1 cells augmented their proliferation, differentiation, and mineralization. BrdU assay showed that the addition of adiponectin (0.01–1.0 μg/ml) also promoted their proliferation. Osterix, but not Runx-2, appeared to be involved in these processes because AdipoR1 siRNA transfection and AICAR treatments suppressed and enhanced osterix mRNA expression, respectively. Conclusion Taken together, this study suggests that adiponectin stimulates the proliferation, differentiation, and mineralization of osteoblasts via the AdipoR1 and AMP kinase signaling pathways in autocrine and/or paracrine fashions. PMID:18047638

  9. Chlorogenic Acid Improves Late Diabetes through Adiponectin Receptor Signaling Pathways in db/db Mice

    PubMed Central

    Jin, Shasha; Chang, Cuiqing; Zhang, Lantao; Liu, Yang; Huang, Xianren; Chen, Zhimin

    2015-01-01

    The aim of this study was to examine the effects of chlorogenic acid (CGA) on glucose and lipid metabolism in late diabetic db/db mice, as well as on adiponectin receptors and their signaling molecules, to provide evidence for CGA in the prevention of type 2 diabetes. We randomly divided 16 female db/db mice into db/db-CGA and db/db-control (CON) groups equally; db/m mice were used as control mice. The mice in both the db/db-CGA and db/m-CGA groups were administered 80 mg/kg/d CGA by lavage for 12 weeks, whereas the mice in both CON groups were given equal volumes of phosphate-buffered saline (PBS) by lavage. At the end of the intervention, we assessed body fat and the parameters of glucose and lipid metabolism in the plasma, liver and skeletal muscle tissues as well as the levels of aldose reductase (AR) and transforming growth factor-β1 (TGF-β1) in the kidneys and measured adiponectin receptors and the protein expression of their signaling molecules in liver and muscle tissues. After 12 weeks of intervention, compared with the db/db-CON group, the percentage of body fat, fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) in the db/db-CGA group were all significantly decreased; TGF-β1 protein expression and AR activity in the kidney were both decreased; and the adiponectin level in visceral adipose was increased. The protein expression of adiponectin receptors (ADPNRs), the phosphorylation of AMP-activated protein kinase (AMPK) in the liver and muscle, and the mRNA and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) in the liver were all significantly greater. CGA could lower the levels of fasting plasma glucose and HbA1c during late diabetes and improve kidney fibrosis to some extent through the modulation of adiponectin receptor signaling pathways in db/db mice. PMID:25849026

  10. ADIPOQ, ADIPOR1, and ADIPOR2 Polymorphisms in Relation to Serum Adiponectin Levels and Body Mass Index in Black and White Women

    PubMed Central

    Cohen, Sarah S.; Gammon, Marilie D.; North, Kari E.; Millikan, Robert C.; Lange, Ethan M.; Williams, Scott M.; Zheng, Wei; Cai, Qiuyin; Long, Jirong; Smith, Jeffrey R.; Signorello, Lisa B.; Blot, William J.; Matthews, Charles E.

    2012-01-01

    Adiponectin is an adipose-secreted protein with influence on several physiologic pathways including those related to insulin sensitivity, inflammation, and atherogenesis. Adiponectin levels are highly heritable and several single nucleotide polymorphisms (SNPs) in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined in relation to circulating adiponectin levels and obesity phenotypes, but despite differences in adiponectin levels and obesity prevalence by race, few studies have included black participants. Using cross-sectional interview data and blood samples collected from 990 black and 977 white women enrolled in the Southern Community Cohort Study from 2002 to 2006, we examined 25 SNPs in ADIPOQ, 19 in ADIPOR1, and 27 in ADIPOR2 in relation to serum adiponectin levels and body mass index (BMI) using race-stratified linear regression models adjusted for age and percentage African ancestry. SNP rs17366568 in ADIPOQ was significantly associated with serum adiponectin levels in white women only (adjusted mean adiponectin levels = 15.9 for G/G genotype, 13.7 for A/G, and 9.3 for A/A, p=0.00036). No other SNPs were associated with adiponectin or BMI among blacks or whites. Because adiponectin levels as well as obesity are highly heritable and vary by race but associations with polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes have been few in this and other studies, future work including large populations from diverse racial groups is needed to detect additional genetic variants that influence adiponectin and BMI. PMID:21273992

  11. Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells.

    PubMed

    Huang, Chun-Yin; Chang, An-Chen; Chen, Hsien-Te; Wang, Shih-Wei; Lo, Yuan-Shun; Tang, Chih-Hsin

    2016-09-01

    Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.

  12. Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells.

    PubMed

    Huang, Chun-Yin; Chang, An-Chen; Chen, Hsien-Te; Wang, Shih-Wei; Lo, Yuan-Shun; Tang, Chih-Hsin

    2016-09-01

    Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis. PMID:27252405

  13. Biodegradation of high molecular weight PAHs using isolated yeast mixtures: application of meta-genomic methods for community structure analyses.

    PubMed

    Hesham, Abd El-Latif; Khan, Sardar; Tao, Yu; Li, Dong; Zhang, Yu; Yang, Min

    2012-09-01

    Bioaugmentation for the removal of polyaromatic hydrocarbons (PAHs) from wastewater using bacteria and yeasts is considered environment-friendly and a cost-effective technique. The effectiveness of this biodegradation system depends on the stability of inoculated microorganisms and the availability of nutrients. This study is aimed to investigate the removal of high molecular weight (HMW)-PAHs from biologically treated produced water using different biological systems. Three systems, inoculated with activated sludge (AS), the mixture of five yeast strains (MY), and the mixture of AS and the five yeast strains (SY), respectively, were constructed, and their performance for the removal of HMW-PAHs was compared over 10 weeks. The effluent of the biologically treated produced water from an oilfield was used as the influent after chrysene and benzo(a)pyrene were spiked as HMW-PAHs. Polymerase chain reaction-based denaturing gradient gel electrophoresis (PCR-DGGE) and fluorescent in situ hybridization (FISH) techniques were used to examine the changes in the structures and abundances of the bacterial and yeast communities in these three systems. Only SY and MY systems were capable to remove chrysene (90.7 % and 98.5 %, respectively) and benzo(a)pyrene (80.7 % and 95.2 %, respectively). PCR-DGGE analysis confirmed that all of the five yeast strains inoculated remained in the SY and MY systems, while FISH results showed that the relative abundance of yeast in the SY and MY systems (10.6 % to 21.9 %, respectively) were significantly higher than AS system (2.3 % to 7.8 %, respectively). The relative abundances of the catechol 2,3-dioxygenase (C23O) indicated that the copy number ratios of benzene ring cleavage gene C23O in the yeast amended systems were much higher than that in the AS system. In this study, all of the three systems were effective in removing the low molecular weight (LMW)-PAHs, while HMW-PAHs including chrysene and benzo(a)pyrene were efficiently removed by

  14. Proteogenomic Characterization of Novel x-Type High Molecular Weight Glutenin Subunit 1Ax1.1

    PubMed Central

    Ribeiro, Miguel; Bancel, Emmanuelle; Faye, Annie; Dardevet, Mireille; Ravel, Catherine; Branlard, Gérard; Igrejas, Gilberto

    2013-01-01

    Analysis of Portuguese wheat (Triticum aestivum L.) landrace ‘Barbela’ revealed the existence of a new x-type high molecular weight-glutenin subunit (HMW-GS) encoded at the Glu-A1 locus, which we named 1Ax1.1. Using one-dimensional and two-dimensional electrophoresis and mass spectrometry, we compared subunit 1Ax1.1 with other subunits encoded at the Glu-A1 locus. Subunit 1Ax1.1 has a theoretical molecular weight of 93,648 Da (or 91,508 Da for the mature protein) and an isoelectric point (pI) of about 5.7, making it the largest and most acidic HMW-GS known to be encoded at Glu-A1. Specific primers were designed to amplify and sequence 2601 bp of the Glu-A1 locus from the ‘Barbela 28’ wheat genome. A very high level of identity was found between the sequence encoding 1Ax1.1 and those encoding other alleles of the locus. The major difference found was an insertion of 36 amino acids in the central repetitive domain. PMID:23478438

  15. A Delicate Balance When Substituting a Small Hydrophobe onto Low Molecular Weight Polyethylenimine to Improve Its Nucleic Acid Delivery Efficiency.

    PubMed

    Meneksedag-Erol, Deniz; KC, Remant Bahadur; Tang, Tian; Uludağ, Hasan

    2015-11-11

    High molecular weight (HMW) polyethylenimine (PEI) is one of the most versatile nonviral gene vectors that was extensively investigated over the past two decades. The cytotoxic profile of HMW PEI, however, encouraged a search for safer alternatives. Because of lack of cytotoxicity of low molecular weight (LMW) PEI, enhancing its performance via hydrophobic modifications has been pursued to this end. Since the performance of modified PEIs depends on the nature and extent of substituents, we systematically investigated the effect of hydrophobic modification of LMW (1.2 kDa) PEI with a short propionic acid (PrA). Moderate enhancements in PEI hydrophobicity resulted in enhanced cellular uptake of polyplexes and siRNA-induced silencing efficacy, whereas further increase in PrA substitution abolished the uptake as well as the silencing. We performed all-atom molecular dynamics simulations to elucidate the mechanistic details behind these observations. A new assembly mechanism was observed by the presence of hydrophobic PrA moieties, where PrA migrated to core of the polyplex. This phenomenon caused higher surface hydrophobicity and surface charge density at low substitutions, and it caused deleterious effects on surface hydrophobicity and cationic charge at higher substitutions. It is evident that an optimal balance of hydrophobicity/hydrophilicity is needed to achieve the desired polyplex properties for an efficient siRNA delivery, and our mechanistic findings should provide valuable insights for the design of improved substituents on nonviral carriers.

  16. Adiponectin is a candidate biomarker of lower extremity bone density in men with chronic spinal cord injury.

    PubMed

    Doherty, Ashley L; Battaglino, Ricardo A; Donovan, Jayne; Gagnon, David; Lazzari, Antonio A; Garshick, Eric; Zafonte, Ross; Morse, Leslie R

    2014-01-01

    Adipose tissue is a major regulator of bone metabolism and in the general population obesity is associated with greater bone mineral density (BMD). However, bone-fat interactions are multifactorial, and may involve pathways that influence both bone formation and resorption with competing effects on the skeleton. One such pathway involves adipocyte production of adipokines that regulate bone metabolism. In this study we determined the association between BMD, walking status, and circulating adipokines (adiponectin and leptin) in 149 men with chronic spinal cord injury (SCI). Although adipokine levels did not vary significantly based on walking status, there was a significant inverse association between adiponectin and BMD in wheelchair users independent of body composition. We found no association between adiponectin and BMD in the walkers and no association between leptin and BMD in either group. These findings suggest that for subjects with chronic SCI, walking may mitigate the effect of adiponectin mediated bone loss. For wheelchair users, adipose-derived adiponectin may contribute to SCI-induced osteoporosis because the osteoprotective benefits of obesity appear to require mechanical loading during ambulation.

  17. Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

    PubMed Central

    Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

    2015-01-01

    Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy. PMID:26640716

  18. The effects of acute exercise on serum adiponectin and resistin levels and their relation to insulin sensitivity in overweight males.

    PubMed

    Jamurtas, A Z; Theocharis, V; Koukoulis, G; Stakias, N; Fatouros, I G; Kouretas, D; Koutedakis, Y

    2006-05-01

    The purpose of this study was to investigate the effects of a submaximal aerobic exercise bout on adiponectin and resistin levels as well as insulin sensitivity, until 48 h post-exercise in healthy overweight males. Nine subjects performed an exercise bout at an intensity corresponding to approximately 65% of their maximal oxygen consumption for 45 min. Adiponectin, resistin, cortisol, insulin, glucose and insulin sensitivity were measured prior to exercise, immediately after exercise as well as 24 and 48 h after exercise. Data were analyzed using repeated measures ANOVA while Pearson's correlations were performed to identify possible relationship among the assessed variables. There were no significant differences for adiponectin (microg ml(-1)) [pre, 3.61(0.73); post, 3.15(0.43); 24 h, 3.15(0.81); 48 h, 3.37(0.76)] or resistin (ng ml(-1)) [pre, 0.19(0.03); post, 0.13(0.03); 24 h, 0.23(0.04); 48 h, 0.23(0.03)] across time. Insulin sensitivity increased and insulin concentration decreased significantly only immediately after exercise. Furthermore, no significant correlations were observed among the variables assessed except for the expected between insulin level and insulin sensitivity. These results indicate that a submaximal aerobic workout does not result in significant changes in adiponectin and resistin up to 48 h post-exercise. Furthermore, it appears that adiponectin or resistin is not associated with insulin sensitivity.

  19. (-)-Catechin suppresses expression of Kruppel-like factor 7 and increases expression and secretion of adiponectin protein in 3T3-L1 cells.

    PubMed

    Cho, Si Young; Park, Pil Joon; Shin, Hyun Jung; Kim, Young-Kyung; Shin, Dong Wook; Shin, Eui Seok; Lee, Hyoung Ho; Lee, Byeong Gon; Baik, Joo-Hyun; Lee, Tae Ryong

    2007-04-01

    Adiponectin is an adipocyte-specific secretory hormone that can increase insulin sensitivity and promote adipocyte differentiation. Administration of adiponectin to obese or diabetic mice reduces plasma glucose and free fatty acid levels. Green tea polyphenols possess many pharmacological activities such as antioxidant, anti-inflammatory, antiobesity, and antidiabetic activities. To investigate whether green tea polyphenols have an effect on the regulation of adiponectin, we measured expression and secretion levels of adiponectin protein after treatment of each green tea polyphenols in 3T3-L1 adipocytes. We found that (-)-catechin enhanced the expression and secretion of adiponectin protein in a dose- and time-dependent manner. Furthermore, treatment of (-)-catechin increased insulin-dependent glucose uptake in differentiated adipocytes and augmented the expression of adipogenic marker genes, including PPARgamma, CEBPalpha, FAS, and SCD-1, when (-)-catechin was treated during adipocyte differentiation. In search of the molecular mechanism responsible for inducible effect of (-)-catechin on adiponectin expression, we found that (-)-catechin markedly suppresses the expression of Kruppel-like factor 7 (KLF7) protein, which has recently been reported to inhibit the expression of adiponectin and other adipogenesis related genes, including leptin, PPARgamma, C/EBPalpha, and aP2 in adipocytes. KLF7 is a transcription factor in adipocyte and plays an important role in the pathogenesis of type 2 diabetes. Taken together, these data suggest that the upregulation of adiponectin protein by (-)-catechin may involve, at least in part, suppression of KLF7 in 3T3-L1 cells.

  20. Adiponectin levels in south Indian children with type 1 diabetes mellitus and nondiabetic children and its correlation with anthropometry and glycemic control.

    PubMed

    Solomon, J Ritchie Sharon; Varadarajan, Poovazhagi; Varadarajan, V Poovazhagi

    2013-09-01

    Studies have reported high adiponectin levels in children with type 1 diabetes mellitus (T1DM). Adiponectin has been found to have anti-atherogenic action and other protective functions. We wanted to estimate adiponectin level in south Indian T1DM children and compare it with that of non-diabetic children and study its correlation with anthropometry and glycemic status. Sixty children with T1DM and forty non-diabetic children of age less than 15 years were analysed. Mean adiponectin level was higher in T1DM group than in non diabetic group (p < 0.001) irrespective of the age group or sex. Negative correlation was observed between SFT- triceps and adiponectin in diabetic and control group. Multiple regression coefficient analysis of various parameters showed SFT- triceps as a statistically significant predictor of adiponectin level (p = 0.001). We conclude that, children with T1DM had higher adiponectin level than non-diabetic children. Low SFT- triceps measuremet may be a predictor of higher adiponectin level.

  1. Adiponectin promotes VEGF-A-dependent angiogenesis in human chondrosarcoma through PI3K, Akt, mTOR, and HIF-α pathway

    PubMed Central

    Shih, Jhao-Sheng; Fong, Yi-Chin; Wang, Shih-Wei; Li, Te-Mao; Tang, Chih-Hsin

    2015-01-01

    Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. On the other hand, angiogenesis is a critical step in tumor growth and metastasis. However, the relationship of adiponectin with vascular endothelial growth factor-A (VEGF-A) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study we first demonstrated that the expression of adiponectin was correlated with tumor stage of human chondrosarcoma tissues. In addition, we also found that adiponectin increased VEGF-A expression in human chondrosarcoma cells and subsequently induced migration and tube formation in human endothelial progenitor cells (EPCs). Adiponectin promoted VEGF-A expression through adiponectin receptor (AdipoR), phosphoinositide 3 kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF)-1α signaling cascades. Knockdown of adiponectin decreased VEGF-A expression and also abolished chondrosarcoma conditional medium-mediated tube formation in EPCs in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. Therefore, adiponectin is crucial for tumor angiogenesis and growth, which may represent a novel target for anti-angiogenic therapy in human chondrosarcoma. PMID:26468982

  2. Circulating Interferon-Gamma Levels Are Associated with Low Body Weight in Newly Diagnosed Kenyan Non-Substance Using Tuberculosis Individuals

    PubMed Central

    Shaviya, Nathan; Budambula, Valentine; Webale, Mark K.; Were, Tom

    2016-01-01

    Although interferon-gamma, interleukin-10, and adiponectin are key immunopathogenesis mediators of tuberculosis, their association with clinical manifestations of early stage disease is inconclusive. We determined interferon-gamma, interleukin-10, and adiponectin levels in clinically and phenotypically well-characterised non-substance using new pulmonary tuberculosis patients (n = 13) and controls (n = 14) from Kenya. Interferon-gamma levels (P < 0.0001) and interferon-gamma to interleukin-10 (P < 0.001) and interferon-gamma to adiponectin (P = 0.027) ratios were elevated in tuberculosis cases. Correlation analyses in tuberculosis cases showed associations of interferon-gamma levels with body weight (ρ = −0.849; P < 0.0001), body mass index (ρ = 0.664; P = 0.013), hip girth (ρ = −0.579; P = 0.038), and plateletcrit (ρ = 0.605; P = 0.028); interferon-gamma to interleukin-10 ratio with diastolic pressure (ρ = −0.729; P = 0.005); and interferon-gamma to adiponectin ratio with body weight (ρ = −0.560; P = 0.047), body mass index (ρ = −0.604; P = 0.029), and plateletcrit (ρ = 0.793; P = 0.001). Taken together, our results suggest mild-inflammation in early stage infection characterised by upregulation of circulating interferon-gamma production in newly infected TB patients. PMID:26880909

  3. Autocrine and paracrine modulation of microRNA-155 expression by globular adiponectin in RAW 264.7 macrophages: involvement of MAPK/NF-κB pathway.

    PubMed

    Subedi, Amit; Park, Pil-Hoon

    2013-12-01

    Adiponectin, a hormone produced from adipose tissue, regulates various biological responses, including inflammation and many metabolic processes. MicroRNAs control expression of diverse target genes and various physiological responses. Many of these responses are commonly regulated by adiponectin. However, effects of adiponectin on microRNAs regulation are largely unknown. Herein we demonstrated that globular adiponectin induces increase in miR-155 expression, which plays an important role in inflammatory response, in RAW 264.7 macrophages. We further showed that this effect was modulated by and MAPK/NF-κB dependent mechanisms. These results suggest that miR-155 would be a novel promising target mediating adiponectin-induced various biological responses. PMID:24084329

  4. Autocrine and paracrine modulation of microRNA-155 expression by globular adiponectin in RAW 264.7 macrophages: involvement of MAPK/NF-κB pathway.

    PubMed

    Subedi, Amit; Park, Pil-Hoon

    2013-12-01

    Adiponectin, a hormone produced from adipose tissue, regulates various biological responses, including inflammation and many metabolic processes. MicroRNAs control expression of diverse target genes and various physiological responses. Many of these responses are commonly regulated by adiponectin. However, effects of adiponectin on microRNAs regulation are largely unknown. Herein we demonstrated that globular adiponectin induces increase in miR-155 expression, which plays an important role in inflammatory response, in RAW 264.7 macrophages. We further showed that this effect was modulated by and MAPK/NF-κB dependent mechanisms. These results suggest that miR-155 would be a novel promising target mediating adiponectin-induced various biological responses.

  5. [Considerations about study on the underlying mechanism of acu-moxibustion in the treatment of obesity type polycystic ovary syndrome by regulating adiponectin].

    PubMed

    Liao, Yan-Jun; Shi, Yin; Yu, Li-Qing; Fang, Jian-Qiao

    2012-02-01

    Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age, and the obesity and insulin resistance are considered to be the key link in the pathophysiological process of PCOS of obesity type. Adiponectin, a protein hormone, is closely related to insulin resistance and obesity, which has been being researched extensively in recent years. The authors of the present article review the pathogenesis of PCOS of obesity type from the relationship between adiponectin and obesity, and between adiponectin and insulin resistance, separately. In particular, the authors review studies on the underlying mechanism of acupuncture and moxibustion interventions in regulating adiponectin level briefly. The authors think of that acupuncture and moxibustion interventions induced increase of adiponectin level is possibly to improve insulin resistance in obesity and/or PCOS patients, hoping to provide a new target for clinical treatment of PCOS. PMID:22574574

  6. [Leptin to adiponectin ratio, as an index of insulin resistance and atherosclerosis development].

    PubMed

    Kieć-Klimczak, Małgorzata; Malczewska-Malec, Małgorzata; Huszno, Bohdan

    2008-01-01

    Obesity is an effect of interaction of genetic and environmental factors. It leads to development of serious complications, like insulin resistance, diabetes type 2, arterial hypertension and atherosclerosis. The adipose tissue is a place where many adipokines, mainly leptin and adiponectin, are produced and released. Adiponectin, which blood level is decreased in obesity is considered to have antidiabetic and antiatherogenic effect. While leptin, which blood level is increased in obesity, is associated with regulation of appetite, energy expenditure, lipids and carbohydrates metabolism, cellular differentiation and puberty. The aim of this research was estimation of leptin to adiponectin ratio (Lep/AdipoR) in the blood of patients who came from obese families. The study was carried out on 80 patients (43 female and 37 male). The antropometric examination with proportional contents of adipose tissue, oral glucose tolerance test (OGTT) and oral postprandial lipaemia test (OPLT) were performed. The fasting level of leptin (Elisa), adiponectin (Elisa) and von Willebrand factor (Elisa) lipidogram were performed. During OGTT blood was sampled in intervals of 30 minutes up to 2 hours, to measure glucose and insulin concentration. In fasting state and then every 2 hours after consumption of a high-fat meal (OPLT), (0, 2 hours, 4 hours, 6 hours, and 8 hours) blood was sampled for: trigliceride, glucose, free fatty acids and insulin concentration. The insulin resistance ratio (HOMA-IR) was calculated for each patient according to the formula: [insulin (mU/ml) x glucose (mmol/l)]/22.5. Adiponectin blood level was higher in the examined women than in men. It (regardless to the sex) was decreased with decrease of body mass index (BMI). Blood level of leptin (also higher in women) was positively corelated with BMI. In the group of patients with low level of adiponectin in serum (below 5mg/ml in men and 10 mg/ml in women) the highest con- centration of glucose and insulin in

  7. Additive Regulation of Adiponectin Expression by the Mediterranean Diet Olive Oil Components Oleic Acid and Hydroxytyrosol in Human Adipocytes

    PubMed Central

    Scoditti, Egeria; Massaro, Marika; Carluccio, Maria Annunziata; Pellegrino, Mariangela; Wabitsch, Martin; Calabriso, Nadia; Storelli, Carlo; De Caterina, Raffaele

    2015-01-01

    Adiponectin, an adipocyte-derived insulin-sensitizing and anti-inflammatory hormone, is suppressed in obesity through mechanisms involving chronic inflammation and oxidative stress. Olive oil consumption is associated with beneficial cardiometabolic actions, with possible contributions from the antioxidant phenol hydroxytyrosol (HT) and the monounsaturated fatty acid oleic acid (OA, 18:1n-9 cis), both possessing anti-inflammatory and vasculo-protective properties. We determined the effects of HT and OA, alone and in combination, on adiponectin expression in human and murine adipocytes under pro-inflammatory conditions induced by the cytokine tumor necrosis factor(TNF)-α. We used human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes and murine 3T3-L1 adipocytes as cell model systems, and pretreated them with 1-100 μmol/L OA, 0.1-20 μmol/L HT or OA plus HT combination before stimulation with 10 ng/mL TNF-α. OA or HT significantly (P<0.05) prevented TNF-α-induced suppression of total adiponectin secretion (by 42% compared with TNF-α alone) as well as mRNA levels (by 30% compared with TNF-α alone). HT and OA also prevented—by 35%—TNF-α-induced downregulation of peroxisome proliferator-activated receptor PPARγ. Co-treatment with HT and OA restored adiponectin and PPARγ expression in an additive manner compared with single treatments. Exploring the activation of JNK, which is crucial for both adiponectin and PPARγ suppression by TNF-α, we found that HT and OA additively attenuated TNF-α-stimulated JNK phosphorylation (up to 55% inhibition). In conclusion, the virgin olive oil components OA and HT, at nutritionally relevant concentrations, have additive effects in preventing adiponectin downregulation in inflamed adipocytes through an attenuation of JNK-mediated PPARγ suppression. PMID:26030149

  8. The effect of cumulative endurance exercise on leptin and adiponectin and their role as markers to monitor training load.

    PubMed

    Voss, S C; Nikolovski, Z; Bourdon, P C; Alsayrafi, M; Schumacher, Y O

    2016-03-01

    Leptin and adiponectin play an essential role in energy metabolism. Leptin has also been proposed as a marker for monitoring training load. So far, no studies have investigated the variability of these hormones in athletes and how they are regulated during cumulative exercise. This study monitored leptin and adiponectin in 15 endurance athletes twice daily in the days before, during and after a 9-day simulated cycling stage race. Adiponectin significantly increased during the race (p = 0.001) and recovery periods (p = 0.002) when compared to the baseline, while leptin decreased significantly during the race (p < 0.0001) and returned to baseline levels during the recovery period. Intra-individual variability was substantially lower than inter-individual variability for both hormones (leptin 34.1 vs. 53.5%, adiponectin 19% vs. 37.2%). With regards to exercise, this study demonstrated that with sufficient, sustained energy expenditure, leptin concentrations can decrease within the first 24 hours. Under the investigated conditions there also appears to be an optimal leptin concentration which ensures stable energy homeostasis, as there was no significant decrease over the subsequent race days. In healthy endurance athletes the recovery of leptin takes 48-72 hours and may even show a supercompensation-like effect. For adiponectin, significant increases were observed within 5 days of commencing racing, with these elevated values failing to return to baseline levels after 3 days of recovery. Additionally, when using leptin and adiponectin to monitor training loads, establishing individual threshold values improves their sensitivity. PMID:26985130

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

    PubMed Central

    2012-01-01

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

  10. The effect of cumulative endurance exercise on leptin and adiponectin and their role as markers to monitor training load

    PubMed Central

    Nikolovski, Z; Bourdon, PC; Alsayrafi, M; Schumacher, YO

    2015-01-01

    Leptin and adiponectin play an essential role in energy metabolism. Leptin has also been proposed as a marker for monitoring training load. So far, no studies have investigated the variability of these hormones in athletes and how they are regulated during cumulative exercise. This study monitored leptin and adiponectin in 15 endurance athletes twice daily in the days before, during and after a 9-day simulated cycling stage race. Adiponectin significantly increased during the race (p = 0.001) and recovery periods (p = 0.002) when compared to the baseline, while leptin decreased significantly during the race (p < 0.0001) and returned to baseline levels during the recovery period. Intra-individual variability was substantially lower than inter-individual variability for both hormones (leptin 34.1 vs. 53.5%, adiponectin 19% vs. 37.2%). With regards to exercise, this study demonstrated that with sufficient, sustained energy expenditure, leptin concentrations can decrease within the first 24 hours. Under the investigated conditions there also appears to be an optimal leptin concentration which ensures stable energy homeostasis, as there was no significant decrease over the subsequent race days. In healthy endurance athletes the recovery of leptin takes 48-72 hours and may even show a supercompensation-like effect. For adiponectin, significant increases were observed within 5 days of commencing racing, with these elevated values failing to return to baseline levels after 3 days of recovery. Additionally, when using leptin and adiponectin to monitor training loads, establishing individual threshold values improves their sensitivity. PMID:26985130

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

    SciTech Connect

    Chen Baoying; Lam, Karen S.L.; Wang Yu; Wu Donghai; Lam, Michael C.; Shen Jiangang; Wong Laiching; Hoo, Ruby L.C.; Zhang Jialiang; Xu Aimin . E-mail: amxu@hkucc.hku.hk

    2006-03-10

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

  12. The relationship between dietary lipids and serum visfatin and adiponectin levels in postmenopausal women.

    PubMed

    Rahbar, Ali R; Nabipour, Iraj

    2014-01-01

    Cardiovascular diseases (CVD) are the leading cause of death in humans, particularly in postmenopausal women. Inflammation has been shown to play a basic role in the development of CVD. In light of the involvement of adipocytokines and dietary lipids in the induction of inflammation in CVD, this study was conducted to investigate the potential relationship between dietary lipids and two well-known adipocytokines, visfatin and adiponectin. A total of 374 postmenopausal women were randomly selected from 13 geographical clusters in Bushehr port. Serum visfatin and adiponectin were determined with an enzyme-linked immunosorbant assay technique and current dietary intake was recorded with a food frequency questionnaire and a 3-day recall. Each food and beverage was analyzed for macro- and micronutrient content. Bivariate correlation analysis showed a correlation between serum visfatin level and dietary SFA, n-6 PUFA and cholesterol intake. In multiple regression analyses, serum visfatin levels showed a significant positive correlation with dietary SFA (β=0.06, p=0.01), PUFA (β=0.02, p=0.02) and cholesterol (β=0.005, p=0.002) after controlling for age, diabetes, total energy intake and BMI. There was no significant relationship between dietary MUFA intake and serum visfatin level. No significant correlations were found between age- and BMI-adjusted adiponectin and dietary SFA, MUFA or n-6 PUFA intake (p>0.05). We found a positive relationship between dietary SFA, PUFA and cholesterol with serum visfatin level in postmenopausal women, and conclude that the postmenopause-induced inflammatory responses may be modulated at least in part by dietary modification.

  13. Effects of Tai Chi on adiponectin and glucose homeostasis in individuals with cardiovascular risk factors.

    PubMed

    Chang, Rei-Yeuh; Koo, Malcolm; Ho, Meng-Ying; Lin, Zi-Zi; Yu, Zer-Ran; Lin, Yen-Fen; Wang, Be-Jen

    2011-01-01

    The aim of this study was to evaluate the acute effect of a single bout of Tai Chi (TC) exercise on adiponectin and glucose homeostasis in individuals with cardiovascular risk factors. Twenty-six individuals (mean age 60.2 years) with at least one cardiovascular risk factor who had been practicing Yang's style TC exercise for at least 3 months were recruited from a regional hospital in Taiwan. A one-group repeated measured quasi-experimental design was used. Participants completed a 60-min Yang's style TC exercise routine including warm up, stretching exercises, and TC followed by a 30-min resting period. After a 1-week washout period, the same group of participants underwent a control condition in which they were instructed to remain seated for 90 min at the study location. Blood samples were collected both before and after the TC intervention or the sitting condition. The difference between pre-post measurements for adiponectin was 0.58 ± 1.42 μg/ml in the TC trial and -0.46 ± 0.99 μg/ml in the sitting trial. The differences between the two trials were statistically significant (P = 0.004). The changes from pretrial to posttrial were significantly greater for glycerol (P < 0.001), cholesterol (P = 0.046), and LDL-C (P = 0.038) in the TC trial compared with those in the sitting trial. Conversely, the changes were significantly lesser for HOMA-IR (P = 0.004), log (HOMA-IR) (P = 0.001), and glucose (P = 0.003) in TC trial compared with those in the sitting trial. In conclusion, a single bout of TC exercise had a significant positive effect on blood adiponectin concentrations in individuals with cardiovascular risk factors. PMID:20809228

  14. FGF21 attenuates pathological myocardial remodeling following myocardial infarction through the adiponectin-dependent mechanism.

    PubMed

    Joki, Yusuke; Ohashi, Koji; Yuasa, Daisuke; Shibata, Rei; Ito, Masanori; Matsuo, Kazuhiro; Kambara, Takahiro; Uemura, Yusuke; Hayakawa, Satoko; Hiramatsu-Ito, Mizuho; Kanemura, Noriyoshi; Ogawa, Hayato; Daida, Hiroyuki; Murohara, Toyoaki; Ouchi, Noriyuki

    2015-03-27

    Ischemic heart disease is one of the leading causes of death. Fibroblast growth factor 21 (FGF21) is a circulating factor with an anti-diabetic property. Skeletal muscle is an important source of FGF21 production. Here, we investigated whether skeletal muscle-derived FGF21 modulates cardiac remodeling in a murine model of myocardial infarction. Myocardial infarction was produced in C57BL/6J wild-type (WT) mice by the permanent ligation of the left anterior descending coronary artery (LAD). Adenoviral vectors expressing FGF21 (Ad-FGF21) or control β-galactosidase were intramuscularly injected into mice at 3 days before permanent LAD ligation. Intramuscular injection of Ad-FGF21 increased plasma FGF21 levels in WT mice compared with control. Treatment of WT mice with Ad-FGF21 led to improvement of left ventricular systolic dysfunction and dilatation at 2 weeks after LAD ligation. Ad-FGF21 administration to WT mice also led to enhancement of capillary density in the infarct border zone, and reduction of myocyte apoptosis in the remote zone, which were accompanied by decreased expression of pro-inflammatory cytokines. Furthermore, treatment of WT mice with Ad-FGF21 increased plasma levels of adiponectin, which is a cardioprotective adipokine. The beneficial effects of Ad-FGF21 on cardiac dysfunction and inflammatory response after myocardial infarction were diminished in adiponectin-knockout mice. These data suggest that muscle-derived FGF21 ameliorates adverse cardiac remodeling after myocardial infarction, at least in part, through an adiponectin-dependent mechanism.

  15. Relationship among serum taurine, serum adipokines, and body composition during 8-week human body weight control program.

    PubMed

    You, Jeong Soon; Park, Ji Yeon; Zhao, Xu; Jeong, Jin Seok; Choi, Mi Ja; Chang, Kyung Ja

    2013-01-01

    Human adipose tissue is not only a storage organ but also an active endocrine organ to release adipokines. This study was conducted to investigate the relationship among serum taurine and adipokine levels, and body composition during 8-week human body weight control program in obese female college students. The program consisted of diet therapy, exercise, and behavior modification. After the program, body weight, body fat mass, percent body fat, and body mass index (BMI) were significantly decreased. Serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased. Also serum adiponectin level was significantly increased and serum leptin level was significantly decreased. There were no differences in serum taurine and homocysteine levels. The change of serum adiponectin level was positively correlated with change of body fat mass and percent body fat. These results may suggest that body fat loss by human body weight control program is associated with an increase in serum adiponectin in obese female college students. Therefore, further study such as taurine intervention study is needed to know more exact correlation between dietary taurine intake and serum adipokines or body composition.

  16. Two Novel Y-Type High Molecular Weight Glutenin Genes in Chinese Wheat Landraces of the Yangtze-River Region.

    PubMed

    Peng, Yanchun; Yu, Kan; Zhang, Yujuan; Islam, Shahidul; Sun, Dongfa; Ma, Wujun

    2015-01-01

    High molecular weight glutenin subunits (HMW-GSs) are key determinants for the end-use quality of wheat. Chinese wheat landraces are an important resource for exploring novel HMW-GS genes to improve the wheat baking quality. Two novel Glu-1Dy HMW-GSs (designated as 1Dy12.6 and 1Dy12.7) were identified and cloned from two Chinese wheat landraces Huazhong830 and Luosimai. The 1Dy12.6 and 1Dy12.7 subunits were deposited as the NCBInr Acc. No KR262518, and KR262519, respectively. The full open reading frames (ORFs) of 1Dy12.6 and 1Dy12.7 were 2022 bp and 1977 bp, encoding for proteins of 673 and 658 amino acid residues, respectively. Each contains four typical primary regions of HMW-GSs (a signal peptide, N- and C-terminal regions, and a central repetitive region). Their deduced molecular masses (70,165 Da and 68,400 Da) were strikingly consistent with those identified by MALDI-TOF-MS (69,985Da and 68,407 Da). The 1Dy12.6 is the largest 1Dy glutenin subunits cloned in common wheat up to date, containing longer repetitive central domains than other 1Dy encoded proteins. In comparison with the most similar active 1Dy alleles previously reported, the newly discovered alleles contained a total of 20 SNPs and 3 indels. The secondary structure prediction indicated that 1Dy12.6 and 1Dy12.7 have similar proportion of α-helix, β-turn, and β-bend to those of 1Dy10 (X12929). The phylogenetic analysis illustrated that the x- and y-type subunits of glutenins were well separated, but both 1Dy12.6 and 1Dy12.7 were clustered with the other Glu-1Dy alleles. Our results revealed that the 1Dy12.6 and 1Dy12.7 subunit have potential to strengthen gluten polymer interactions, and are valuable genetic resources for wheat quality improvement.

  17. Nitric Oxide Bioavailability and Adiponectin Production in Chronic Systolic Heart Failure: Relation to Severity of Cardiac Dysfunction

    PubMed Central

    Tang, W.H. Wilson; Shrestha, Kevin; Tong, Wilson; Wang, Zeneng; Troughton, Richard W.; Borowski, Allen G.; Klein, Allan L.; Hazen, Stanley L.

    2013-01-01

    Adiponectin is an anti-inflammatory, anti-atherogenic adipokine elevated in heart failure (HF) that may protect against endothelial dysfunction by influencing underlying nitric oxide bioavailablity. In this study, we examine the relationship between plasma adiponectin levels and measures of nitric oxide bioavailability and myocardial performance in patients with chronic systolic HF. In 139 ambulatory patients with stable, chronic systolic HF (left ventricular [LV] ejection fraction ≤40%, New York Heart Association [NYHA] class I to IV), we measured plasma levels of adiponectin, asymmetric dimethylarginine (ADMA) and global arginine bioavailability (GABR), and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse events (all-cause mortality or cardiac transplantation) were prospectively tracked for a median of 39 months. Plasma adiponectin levels directly correlated with plasma ADMA levels (Spearman’s r=0.41, p<0.001) and NT-proBNP levels (r=0.55, p<0.001), inversely correlated with GABR (r= −0.39, p<0.001), and were not associated with hsCRP (p=0.81) or MPO (p=0.07). Interestingly, increased plasma adiponectin levels remained positively correlated with plasma ADMA levels only in patients with elevated NT-proBNP levels (r= 0.33, p=0.009). Higher plasma adiponectin levels were associated with worse LV diastolic dysfunction (rank sums p=0.002), RV systolic dysfunction (rank sums p=0.002), and RV diastolic dysfunction (rank sums p=0.011), but not after adjustment for plasma ADMA and NT-proBNP levels. Plasma adiponectin levels predicted increased risk of adverse clinical events (HR [95% CI]: 1.45 [1.02–2.07], p=0.038) but not after adjustment for plasma ADMA and NT-proBNP levels, or echocardiographic indices of diastolic or RV systolic dysfunction. In patients with chronic systolic HF, adiponectin production is more closely linked with nitric oxide bioavailability than inflammation, and appears to be more robust

  18. Scuba Weights

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The Attitude Adjuster is a system for weight repositioning corresponding to a SCUBA diver's changing positions. Compact tubes on the diver's air tank permit controlled movement of lead balls within the Adjuster, automatically repositioning when the diver changes position. Manufactured by Think Tank Technologies, the system is light and small, reducing drag and energy requirements and contributing to lower air consumption. The Mid-Continent Technology Transfer Center helped the company with both technical and business information and arranged for the testing at Marshall Space Flight Center's Weightlessness Environmental Training Facility for astronauts.

  19. Investigate the relation between Adiponectin gene variants and cardiovascular comorbidities and diabetes

    PubMed Central

    Eissa, AT.

    2016-01-01

    Objectives This study aimed to study the relationship between the adiponectin gene and coronary artery disease as well as myocardial infarction, hypertension and diabetes in the Saudi population in Riyadh. Methods This was a cohort study of Saudi patients from the Coronary Artery Disease (CAD) registry maintained at King Faisal Specialist Hospital and Research Centre. Samples were genotyped for target Single Nucleotide Polymorphisms (SNPs) by real time polymerase chain reaction (PCR). Furthermore, Chi Square test was used for comparing the variables. Results Out of 860 CAD patients compared with 467 non-CAD. The prevalence of the minor G allele of +45T>G in CAD patients was 934 compared to 786 in controls, and it shows no significant difference (p=0.598) between the two groups. The possibility tested that this variant might be associated with one or more of the CAD risk factors, such as hypertension, myocardial infarction, hypertension and diabetes mellitus. Nevertheless, the study did not show any significance between the two groups in CAD, gender and hypertension. On the other hand, the difference in MI was borderline and significant in diabetes mellitus. Conclusions This study showed a relationship between adiponectin and diabetes only as compared to results from other countries which also showed relationship with coronary artery disease, myocardial infarction and hypertension. PMID:27103900

  20. A Microfluidic Interface for the Culture and Sampling of Adiponectin from Primary Adipocytes

    PubMed Central

    Godwin, Leah A.; Brooks, Jessica C.; Hoepfner, Lauren D.; Wanders, Desiree; Judd, Robert L.; Easley, Christopher J.

    2014-01-01

    Secreted from adipose tissue, adiponectin is a vital endocrine hormone that acts in glucose metabolism, thereby establishing its crucial role in diabetes, obesity, and other metabolic disease states. Insulin exposure to primary adipocytes cultured in static conditions has been shown to stimulate adiponectin secretion. However, conventional, static methodology for culturing and stimulating adipocytes falls short of truly mimicking physiological environments. Along with decreases in experimental costs and sample volume, and increased temporal resolution, microfluidic platforms permit small-volume flowing cell culture systems, which more accurately represent the constant flow conditions through vasculature in vivo. Here, we have integrated a customized primary tissue culture reservoir into a passively operated microfluidic device made of polydimethylsiloxane (PDMS). Fabrication of the reservoir was accomplished through unique PDMS “landscaping” above sampling channels, with a design strategy targeted to primary adipocytes to overcome issues of positive cell buoyancy. This reservoir allowed three-dimensional culture of primary murine adipocytes, accurate control over stimulants via constant perfusion, and sampling of adipokine secretion during various treatments. As the first report of primary adipocyte culture and sampling within microfluidic systems, this work sets the stage for future studies in adipokine secretion dynamics. PMID:25423362

  1. Inter-relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity.

    PubMed

    Szewczyk-Golec, Karolina; Woźniak, Alina; Reiter, Russel J

    2015-10-01

    Obesity and its medical complications represent a significant problem throughout the world. In recent decades, mechanisms underlying the progression of obesity have been intensively examined. The involvement of both the behavioral aspects, such as calorie-rich diet, low physical activity and sleep deprivation, and the intrinsic factors, including adipose tissue deregulation, chronic inflammation, oxidative stress, and chronodisruption, has been identified. The circadian disturbances of the adipose tissue endocrine function have been correlated with obesity. Leptin and adiponectin are adipokines strongly associated with glucose and lipid metabolism and with energy balance. Their synthesis and secretion display circadian rhythms that are disturbed in the obese state. Hyperleptinemia resulting in leptin resistance, and hypo-adiponectinemia have been linked to the pathophysiology of the obesity-related disorders. A deficiency of melatonin, one of the consequences of sleep deprivation, has also been demonstrated to correlate with obesity. Melatonin is a pineal secretory product involved in numerous actions, such as regulation of internal biological clocks and energy metabolism, and it functions as an antioxidant and as an anti-inflammatory agent. There exists a substantial amount of evidence supporting the beneficial effects of melatonin supplementation on obesity and its complications. In the current review, the results of studies related to the interactions between melatonin, and both leptin and adiponectin are discussed. Despite the existence of some inconsistencies, melatonin has been found to normalize the expression and secretion patterns of both adipokines. These results support the concept of melatonin as a potential therapeutic agent for obesity and related disorders.

  2. Relationship Between Plasma Adiponectin Level With Inflammatory and Metabolic Markers in Patients With Chronic Kidney Disease

    PubMed Central

    Sedighi, Omid; Abediankenari, Saeid

    2013-01-01

    Background: Adiponectin (ADPN) is an important anti-inflammatory marker with anti-atherogenic effects. However, its role in patients with chronic kidney disease (CKD) should be determined. Objectives: The aim of this study was to determine the relationship between plasma adiponectin level with some inflammatory and metabolic markers in CKD patients. Patients and Methods: In this case-control study, we measured plasma ADPN level in 42 CKD patients and 46 healthy persons with the same age and sex as control group. Then, we investigated the association between plasma ADPN level with some inflammatory and metabolic determinants in CKD patients. Results: Plasma ADPN level was significantly higher in CKD patients than control group (P = 0.04). It was directly correlated with HDL-cholesterol (r = 0.599, P < 0.001) and serum creatinine levels (r = 0.675, P < 0.001) and inversely correlated with glomerular filtration rate (GFR) (r = -0.570, P < 0.001), body mass index (BMI) (r = -0.318, P = 0.04), C-reactive protein (CRP) (r = -0.548, P < 0.001) and fasting blood sugar (FBS) (r = -0.640, P < 0.001) in CKD patients. Conclusions: These findings suggested that plasma ADPN level is inversely associated with GFR and directly correlate with HDL-cholesterol and inversely with some, but not all metabolic factors of CKD patients who were not undergone dialysis. PMID:24719803

  3. An improved method for extracting bacteria from soil for high molecular weight DNA recovery and BAC library construction.

    PubMed

    Liu, Juan; Li, Jingquan; Feng, Li; Cao, Hui; Cui, Zhongli

    2010-12-01

    Separation of bacterial cells from soil is a key step in the construction of metagenomic BAC libraries with large DNA inserts. Our results showed that when combined with sodium pyro-phosphate and homogenization for soil dispersion, sucrose density gradient centrifugation (SDGC) was more effective at separating bacteria from soil than was low speed centrifugation (LSC). More than 70% of the cells, along with some soil colloids, were recovered with one round of centrifugation. A solution of 0.8% NaCl was used to resuspend these cell and soil pellets for purification with nycodenz density gradient centrifugation (NDGC). After purification, more than 30% of the bacterial cells in the primary soil were extracted. This procedure effectively removed soil contamination and yielded sufficient cells for high molecular weight (HMW) DNA isolation. Ribosomal intergenic spacer analysis (RISA) showed that the microbial community structure of the extracted cells was similar to that of the primary soil, suggesting that this extraction procedure did not significantly change the the soil bacteria community structure. HMW DNA was isolated from bacterial cells extracted from red soil for metagenomic BAC library construction. This library contained DNA inserts of more than 200 Mb with an average size of 75 kb.

  4. Adiponectin and Insulin in Gray Seals during Suckling and Fasting: Relationship with Nutritional State and Body Mass during Nursing in Mothers and Pups.

    PubMed

    Bennett, K A; Hughes, J; Stamatas, S; Brand, S; Foster, N L; Moss, S E W; Pomeroy, P P

    2015-01-01

    Animals that fast during breeding and/or development, such as phocids, must regulate energy balance carefully to maximize reproductive fitness and survival probability. Adiponectin, produced by adipose tissue, contributes to metabolic regulation by modulating sensitivity to insulin, increasing fatty acid oxidation by liver and muscle, and promoting adipogenesis and lipid storage in fat tissue. We tested the hypotheses that (1) circulating adiponectin, insulin, or relative adiponectin gene expression is related to nutritional state, body mass, and mass gain in wild gray seal pups; (2) plasma adiponectin or insulin is related to maternal lactation duration, body mass, percentage milk fat, or free fatty acid (FFA) concentration; and (3) plasma adiponectin and insulin are correlated with circulating FFA in females and pups. In pups, plasma adiponectin decreased during suckling (linear mixed-effects model [LME]: T = 4.49; P < 0.001) and the early postweaning fast (LME: T = 3.39; P = 0.004). In contrast, their blubber adiponectin gene expression was higher during the early postweaning fast than early in suckling (LME: T = 2.11; P = 0.046). Insulin levels were significantly higher in early (LME: T = 3.52; P = 0.004) and late (LME: T = 6.99; P < 0.001) suckling than in fasting and, given the effect of nutritional state, were also positively related to body mass (LME: T = 3.58; P = 0.004). Adiponectin and insulin levels did not change during lactation and were unrelated to milk FFA or percentage milk fat in adult females. Our data suggest that adiponectin, in conjunction with insulin, may facilitate fat storage in seals and is likely to be particularly important in the development of blubber reserves in pups.

  5. Leptin and adiponectin levels in middle-aged postmenopausal women: associations with lifestyle habits, hormones, and inflammatory markers--a cross-sectional study.

    PubMed

    Rolland, Yves M; Perry, Horace M; Patrick, Ping; Banks, William A; Morley, John E

    2006-12-01

    To investigate the relationships between blood levels of leptin or adiponectin and lifestyle habits, hormones, and inflammatory markers, we measured parameters of alcohol intake, smoking, physical activity, and blood levels of leptin, adiponectin, testosterone, estrone, estradiol, cortisol, dihydroepiandrostenedione, luteinizing hormone, thyroxin, C-reactive protein (CRP), and interleukin 6 and interleukin 2 receptor in 76 healthy middle-aged postmenopausal women. Anthropometric measures and body composition (evaluated by dual-energy x-ray absorptiometry) and lipid profiles were also assessed. By simple regression, leptin correlated positively with fat and lean masses, glucose, triglycerides, low-density lipoprotein cholesterol, and total cholesterol, and negatively with high-density lipoprotein cholesterol. Adioponectin correlated negatively with fat and lean masses and low-density lipoprotein cholesterol, and positively with high-density lipoprotein cholesterol. Leptin concentration was correlated inversely with adiponectin (r = -0.26, P < .05) and positively with CRP (r = 0.56, P < .01). Adiponectin concentration was negatively correlated with time since last alcoholic drink (r = -0.24, P < .05) and CRP (r = -0.27, P < .05) and positively with testosterone level (r = 0.23, P < .05). By multiple regression analysis, leptin concentration was predicted by age (P < .05), testosterone (P < .05), adiponectin (P < .05), CRP (P < .01), and interleukin 6 receptor (P < .01). Adiponectin concentration was predicted by the time since last alcoholic drink (P < .05), testosterone (P < .05), leptin (P < .05), and C-reactive protein (P = .05). Similar results were found when leptin or adiponectin concentration was adjusted for fat mass. These results suggested that levels of leptin and adiponectin in middle-aged postmenopausal women are partially determined by sexual hormones and inflammatory marker levels, and both predicted one another. Moreover, adiponectin level may be

  6. Effect of L-arginine supplementation on insulin resistance and serum adiponectin concentration in rats with fat diet

    PubMed Central

    Miczke, Anna; Suliburska, Joanna; Pupek-Musialik, Danuta; Ostrowska, Lucyna; Jabłecka, Anna; Krejpcio, Zbigniew; Skrypnik, Damian; Bogdański, Paweł

    2015-01-01

    Object: The purpose of this study was to determine whether supplementation with L-arginine, a substrate used in the production of nitric oxide, had an effect on adiponectin concentration in rats fed a high-fat diet. The influence of L-arginine on insulin resistance was also evaluated. Materials and methods: The experiment was performed using 36 Wistar rats divided into three groups: group 1 was fed a standard diet, group 2 a high-fat (HF) diet, group 3 a HF diet supplemented with L-arginine. After 42 days, serum levels of lipids, glucose, insulin, NO, and adiponectin were measured. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment (HOMA). Results: Body mass was equal in all 3 groups, at the beginning as well as at the end of the study, however, in group 2 the amount of visceral fat was greater after 42 days. In group 3, there was a tendency for visceral fat to decrease. An increase in cholesterol, triglycerides, insulin and HOMA-IR, as well as a decrease in NO and adiponectin were seen in group 2, while in group 3, L-arginine supplementation ameliorated these disturbances. Conclusions: Our study shows that L-arginine supplementation in rats fed a HF diet is associated with an increase in insulin sensitivity. Our findings suggest that the underlying mechanism could be at least partially related to an increase in adiponectin concentration. PMID:26379826

  7. Perinatal BPA exposure induces hyperglycemia, oxidative stress and decreased adiponectin production in later life of male rat offspring.

    PubMed

    Song, Shunzhe; Zhang, Ling; Zhang, Hongyuan; Wei, Wei; Jia, Lihong

    2014-04-01

    The main object of the present study was to explore the effect of perinatal bisphenol A (BPA) exposure on glucose metabolism in early and later life of male rat offspring, and to establish the potential mechanism of BPA-induced dysglycemia. Pregnant rats were treated with either vehicle or BPA by drinking water at concentrations of 1 and 10 µg/mL BPA from gestation day 6 through the end of lactation. We measured the levels of fasting serum glucose, insulin, adiponectin and parameters of oxidative stress on postnatal day (PND) 50 and PND100 in male offspring, and adiponectin mRNA and protein expression in adipose tissue were also examined. Our results showed that perinatal exposure to 1 or 10 µg/mL BPA induced hyperglycemia with insulin resistance on PND100, but only 10 µg/mL BPA exposure had similar effects as early as PND50. In addition, increased oxidative stress and decreased adiponectin production were also observed in BPA exposed male offspring. Our findings indicated that perinatal exposure to BPA resulted in abnormal glucose metabolism in later life of male offspring, with an earlier and more exacerbated effect at higher doses. Down-regulated expression of adiponectin gene and increased oxidative stress induced by BPA may be associated with insulin resistance.

  8. The Effect of Vegan Protein-Based Diets on Metabolic Parameters, Expressions of Adiponectin and Its Receptors in Wistar Rats

    PubMed Central

    Chen, Jie-Hua; Song, Jia; Chen, Yan; Ding, Qiang; Peng, Anfang; Mao, Limei

    2016-01-01

    Vegan protein-based diet has attracted increasing interest in the prevention of metabolic syndrome (MetS). Meanwhile, adiponectin has become a highly potential molecular target in the prevention of MetS. Our study will identify a potential vegan protein diet for the prevention of MetS using rat models. Thirty-six Wistar rats were randomly assigned into three groups and given diets containing one of the following proteins for 12 weeks: casein (CAS, control diet), soy protein (SOY), and gluten-soy mixed protein (GSM). Changes in metabolic parameters as well as the expressions of adiponectin and its receptors were identified. Compared to CAS diet, both SOY and GSM diets led to decreases in blood total cholesterol and triglycerides, but only GSM diet led to an increase in HDL-cholesterol; no marked difference was observed in blood glucose in all three groups; HOMA-IR was found lower only in SOY group. Among groups, the order of serum adiponectin level was found as GSM > SOY > CAS. Similar order pattern was also observed in expression of adiponectin in adipose tissue and AdipoR1 mRNA in skeletal muscle. Our results suggested for the first time that, besides SOY diet, GSM diet could also be a possible substitute of animal protein to prevent MetS. PMID:27763537

  9. Adiponectin, a downstream target gene of peroxisome proliferator-activated receptor {gamma}, controls hepatitis B virus replication

    SciTech Connect

    Yoon, Sarah; Jung, Jaesung; Kim, Taeyeung; Park, Sun; Chwae, Yong-Joon; Shin, Ho-Joon; Kim, Kyongmin

    2011-01-20

    In this study, HepG2-hepatitis B virus (HBV)-stable cells that did not overexpress HBx and HBx-deficient mutant-transfected cells were analyzed for their expression of HBV-induced, upregulated adipogenic and lipogenic genes. The mRNAs of CCAAT enhancer binding protein {alpha} (C/EBP{alpha}), peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), adiponectin, liver X receptor {alpha} (LXR{alpha}), sterol regulatory element binding protein 1c (SREBP1c), and fatty acid synthase (FAS) were expressed at higher levels in HepG2-HBV and lamivudine-treated stable cells and HBx-deficient mutant-transfected cells than in the HepG2 cells. Lamivudine treatment reduced the mRNA levels of PPAR{gamma} and C/EBP{alpha}. Conversely, HBV replication was upregulated by adiponectin and PPAR{gamma} agonist rosiglitazone treatments and was downregulated by adiponectin siRNAs. Collectively, our results demonstrate that HBV replication and/or protein expression, even in the absence of HBx, upregulated adipogenic or lipogenic genes, and that the control of adiponectin might prove useful as a therapeutic modality for the treatment of chronic hepatitis B.

  10. Lipidomic analysis of the liver identifies changes of major and minor lipid species in adiponectin deficient mice

    PubMed Central

    Wanninger, Josef; Liebisch, Gerhard; Schmitz, Gerd; Bauer, Sabrina; Eisinger, Kristina; Neumeier, Markus; Ouchi, Noriyuki; Walsh, Kenneth; Buechler, Christa

    2014-01-01

    Adiponectin protects from hepatic fat storage but adiponectin deficient mice (APN−/−) fed a standard chow do not develop liver steatosis. This indicates that other pathways might be activated to compensate for adiponectin deficiency. An unbiased and comprehensive screen was performed to identify hepatic alterations of lipid classes in these mice. APN−/− mice had decreased hepatic cholesteryl esters while active SREBP2 and systemic total cholesterol were not altered. Upregulation of cytochromes for bile acid synthesis suggests enhanced biliary cholesterol excretion. Analysis of 37 individual fatty acid species showed reduced stearate whereas total fatty acids were not altered. Total amount of triglycerides and phospholipids were equally abundant. A selective increase of monounsaturated phosphatidylcholine and phosphatidylethanolamine which positively correlate with hepatic and systemic triglycerides with the latter being elevated in APN−/− mice, was identified. Stearoyl-CoA desaturase 1 (SCD1) is involved in the synthesis of monounsaturated fatty acids and despite higher mRNA expression enzyme activity was not enhanced. Glucosylceramide postulated to contribute to liver damage was decreased. This study demonstrates that adiponectin deficiency is associated with hepatic changes in lipid classes in mice fed a standard chow which may protect from liver steatosis. PMID:22465357

  11. Endocrine Determinants of Changes in Insulin Sensitivity and Insulin Secretion during a Weight Cycle in Healthy Men

    PubMed Central

    Karschin, Judith; Lagerpusch, Merit; Enderle, Janna; Eggeling, Ben; Müller, Manfred J.; Bosy-Westphal, Anja

    2015-01-01

    Objective Changes in insulin sensitivity (IS) and insulin secretion occur with perturbations in energy balance and glycemic load (GL) of the diet that may precede the development of insulin resistance and hyperinsulinemia. Determinants of changes in IS and insulin secretion with weight cycling in non-obese healthy subjects remain unclear. Methods In a 6wk controlled 2-stage randomized dietary intervention 32 healthy men (26±4y, BMI: 24±2kg/m2) followed 1wk of overfeeding (OF), 3wks of caloric restriction (CR) containing either 50% or 65% carbohydrate (CHO) and 2wks of refeeding (RF) with the same amount of CHO but either low or high glycaemic index at ±50% energy requirement. Measures of IS (basal: HOMA-index, postprandial: Matsuda-ISI), insulin secretion (early: Stumvoll-index, total: tAUC-insulin/tAUC-glucose) and potential endocrine determinants (ghrelin, leptin, adiponectin, thyroid hormone levels, 24h-urinary catecholamine excretion) were assessed. Results IS improved and insulin secretion decreased due to CR and normalized upon RF. Weight loss-induced improvements in basal and postprandial IS were associated with decreases in leptin and increases in ghrelin levels, respectively (r = 0.36 and r = 0.62, p<0.05). Weight regain-induced decrease in postprandial IS correlated with increases in adiponectin, fT3, TSH, GL of the diet and a decrease in ghrelin levels (r-values between -0.40 and 0.83, p<0.05) whereas increases in early and total insulin secretion were associated with a decrease in leptin/adiponectin-ratio (r = -0.52 and r = -0.46, p<0.05) and a decrease in fT4 (r = -0.38, p<0.05 for total insulin secretion only). After controlling for GL associations between RF-induced decrease in postprandial IS and increases in fT3 and TSH levels were no longer significant. Conclusion Weight cycling induced changes in IS and insulin secretion were associated with changes in all measured hormones, except for catecholamine excretion. While leptin, adiponectin and

  12. The Adipokine Profile of Metabolically Benign Obese and At-Risk Normal Weight Postmenopausal Women: The Women’s Health Initiative Observational Study

    PubMed Central

    Khan