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Sample records for adiponectin resistin visfatin

  1. Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy in patients with bilateral knee osteoarthritis

    NASA Astrophysics Data System (ADS)

    Fioravanti, Antonella; Giannitti, Chiara; Cheleschi, Sara; Simpatico, Antonella; Pascarelli, Nicola Antonio; Galeazzi, Mauro

    2015-11-01

    Adipocytokines, including adiponectin, resistin, and visfatin may play an important role in the pathophysiology of osteoarthritis (OA). Spa therapy is one of the most commonly used non-pharmacological approaches for OA, but its mechanisms of action are not completely known. The aim of the present study was to assess whether a cycle of mud-bath therapy (MBT) influences the serum levels of adiponectin, resistin, and visfatin in patients with knee OA. As part of a prospective randomized, single blind-controlled trial evaluating the efficacy of MBT in knee OA, we included in this study 95 outpatients. One group ( n = 49) received a cycle of MBT at the spa center of Chianciano Terme (Italy) in addition to the usual treatment, and one group (control group; n = 46) continued their regular care routine alone. Patients were assessed at basal time and at the end of the study (15 days) for clinical and biochemical parameters. Clinical assessments included spontaneous pain on a visual analog scale (VAS) score and the Western Ontario and McMaster Universities index (WOMAC) subscores for knee OA evaluated as total pain score (W-TPS), total stiffness score (W-TSS), and total physical function score (W-TPFS). Adiponectin, resistin and visfatin serum levels were assessed by enzyme immunoassay methods. At the end of the mud-bath therapy, serum adiponectin levels showed a significant decrease ( p < 0.001), while no significant modifications were found in the control group at day 15. Serum resistin showed a significant decrease ( p < 0.0001) in the MBT group at the end of the study and a significant increase in the control patients ( p < 0.001). No significant modifications of visfatin were found in MBT. Furthermore, we tested the relationships between demographic and clinical parameters and adipocytokine concentrations measured in the MBT group at basal and at the end of the study. In conclusion, the present study shows that a cycle of MBT can modify serum levels of adiponectin and

  2. Resistin and Visfatin Expression in HCT-116 Colorectal Cancer Cell Line

    PubMed Central

    Ghaemmaghami, Sara; Mohaddes, Seyed Mojtaba; Hedayati, Mehdi; Gorgian Mohammadi, Masumeh; Dehbashi, Golnoosh

    2013-01-01

    Adipocytokines, hormones secreted from adipose tissue, have been shown to be associated with many cancers such as breast, prostate and colorectal cancer. Recent studies have indicated that resistin and visfatin, two of these adipokines have high level plasma concentrations in colorectal cancer patients and may be promising biomarkers for colorectal cancer. The aim of this study was to identify whether the colorectal cancer cell line, HCT-116, itself is the source of these two adipokines secretion. Resistin and visfatin expression were investigated in HCT-116 by RT – PCR at mRNA level and confirmed by ELISA at protein level. Visfatin showed a high expression at both mRNA and protein levels in HCT-116. Conversely, resistin was not expressed in either cell lysate or supernatant. These results showed that HCT-116 colorectal cancer cells secrete and express visfatin endogenously. However, they are not the main source of resistin and the high level of resistin in colorectal cancer may be due to monocytes and other inflammatory cells which increase in proinflammation status of cancer. Taken together, visfatin may act on colorectal cancer cell in an autocrine manner while resistin may act in a paracrine manner. PMID:24551805

  3. Adiponectin and visfatin concentrations in children treated with valproic acid.

    PubMed

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

    2008-02-01

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

  4. Adiponectin and resistin: a role in the hypothalamo-pituitary gonadal axis ?

    PubMed

    Rak, Agnieszka; Mellouk, Namya; Froment, Pascal; Dupont, Joëlle

    2017-03-22

    Adipokines, including adiponectin and resistin, are cytokines produced mainly by adipose tissue. They play a significant role in the metabolic functions that regulate insulin sensitivity and inflammation. Alteration of adiponectin and resistin plasma levels, or their expression in metabolic and gonadal tissue, are observed in some metabolic pathologies, such as obesity. Several studies have shown that these two hormones and the receptors for adiponectin, AdipoR1 and AdipoR2, are present in various reproductive tissues in both sexes of different species. Thus, these adipokines could be metabolic signals that partially explain infertility related to obesity, such as polycystic ovary syndrome (PCOS). Species and gender differences in plasma levels, tissue or cell distribution and hormonal regulation have been reported for resistin and adiponectin. Furthermore, until now, it has been unclear whether adiponectin and resistin act directly or indirectly on the hypothalamo-pituitary-gonadal axis. The objective of this review was to summarize the latest findings and particularly the species and gender differences known to date of adiponectin and resistin on female and male reproduction, based on the hypothalamo-pituitary-gonadal axis.

  5. Cord blood resistin and adiponectin in term newborns of diabetic mothers

    PubMed Central

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

    2010-01-01

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

  6. Increased Serum Levels of Tumor Necrosis Factor-Alpha, Resistin, and Visfatin in the Children with Autism Spectrum Disorders: A Case-Control Study

    PubMed Central

    Ghaffari, Mohammad Ali; Riahi, Forough; Mousavinejad, Masoumeh; Afsharmanesh, Mohammad Reza

    2016-01-01

    Background. Autism spectrum disorders (ASDs) are complex disorders where the pathogenesis is not fully understood. Several proinflammatory and immunoinflammatory disturbances have been observed in the etiology of ASD. There is, however, limited knowledge on variations of adipokines in ASD. The present study aimed to analyze the serum levels of resistin, visfatin, and tumor necrosis factor-alpha (TNF-α) in children with ASD in relation to body weight, gender, and ASD severity level. Method. In total, 30 children with ASD (mean age: 7.72 ± 2.65 y; range; 4–12 y) and 30 healthy children (mean age: 8.4 ± 2.66 y; range: 4–12 y), including males and females, were matched for age, gender, and body mass index (BMI). Serum samples were collected, and visfatin, resistin, and TNF-α serum levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Result. Serum visfatin, resistin, and TNF-α levels in children with ASD were significantly higher than that in the healthy patients (p < 0.05). Two significant correlations were found: a correlation between resistin and visfatin with TNF-α in children with ASD (R = 0.8 and R = 0.62, resp.) and a correlation between resistin and visfatin in children with ASD (R = 0.66). Conclusion. Higher TNF-α, resistin, and visfatin levels were found in children with ASD in comparison with controls, suggesting that elevated levels of serum proinflammatory agents may be implicated in the pathophysiology of ASD. PMID:28018676

  7. Increased Serum Levels of Tumor Necrosis Factor-Alpha, Resistin, and Visfatin in the Children with Autism Spectrum Disorders: A Case-Control Study.

    PubMed

    Ghaffari, Mohammad Ali; Mousavinejad, Elham; Riahi, Forough; Mousavinejad, Masoumeh; Afsharmanesh, Mohammad Reza

    2016-01-01

    Background. Autism spectrum disorders (ASDs) are complex disorders where the pathogenesis is not fully understood. Several proinflammatory and immunoinflammatory disturbances have been observed in the etiology of ASD. There is, however, limited knowledge on variations of adipokines in ASD. The present study aimed to analyze the serum levels of resistin, visfatin, and tumor necrosis factor-alpha (TNF-α) in children with ASD in relation to body weight, gender, and ASD severity level. Method. In total, 30 children with ASD (mean age: 7.72 ± 2.65 y; range; 4-12 y) and 30 healthy children (mean age: 8.4 ± 2.66 y; range: 4-12 y), including males and females, were matched for age, gender, and body mass index (BMI). Serum samples were collected, and visfatin, resistin, and TNF-α serum levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Result. Serum visfatin, resistin, and TNF-α levels in children with ASD were significantly higher than that in the healthy patients (p < 0.05). Two significant correlations were found: a correlation between resistin and visfatin with TNF-α in children with ASD (R = 0.8 and R = 0.62, resp.) and a correlation between resistin and visfatin in children with ASD (R = 0.66). Conclusion. Higher TNF-α, resistin, and visfatin levels were found in children with ASD in comparison with controls, suggesting that elevated levels of serum proinflammatory agents may be implicated in the pathophysiology of ASD.

  8. Molecular cloning of feline resistin and the expression of resistin, leptin and adiponectin in the adipose tissue of normal and obese cats.

    PubMed

    Takashima, Satoshi; Nishii, Naohito; Kato, Akiko; Matsubara, Tatsuya; Shibata, Sanae; Kitagawa, Hitoshi

    2016-01-01

    Resistin, one of the adipokines that has a cycteine-rich C-terminus, is considered to relate to the development of insulin resistance in rats. However, in cats, there is little knowledge regarding resistin. In this study, we cloned the feline resistin cDNA from adipose tissue by RT-PCR. The feline resistin clone contained an entire open reading frame encoding 107 amino acids that had 72.8%, 75.4%, 50.9% and 51.8% homology with bovine, human, mouse and rat homologues, respectively. In both subcutaneous and visceral adipose tissues, the transcription levels of feline resistin mRNA were significantly higher in obese cats than normal cats, and those of feline adiponectin mRNA were significantly lower in obese cats than normal cats. However, there was no difference in the expression of feline leptin between normal and obese cats. On the other hand, in both normal and obese cats, there were no significant differences in resistin, leptin and adiponectin mRNA levels between subcutaneous and visceral adipose tissues. In cats, the altered expression of resistin and adiponectin mRNA with obesity may contribute to the pathogenesis of insulin resistance and subsequent diabetes mellitus. In addition to feline adiponectin, the feline resistin cDNA clone obtained in this study will be useful for further investigation of the pathogenesis of obesity in cats.

  9. Leptin, resistin and visfatin: the missing link between endocrine metabolic disorders and immunity

    PubMed Central

    2013-01-01

    Adipose tissue is still regarded as a principle site for lipid storage and mobilizing tissue with an important role in the control of energy homeostasis. Additionally, adipose tissue-secreted hormones such as leptin, visfatin, resistin, apelin, omentin, sex steroids, and various growth factors are now regarded as a functional part of the endocrine system. These hormones also play an important role in the immune system. Several in vitro and in vivo studies have suggested the complex role of adipocyte-derived hormones in immune system and inflammation. Adipokines mediate beneficial and detrimental effects in immunity and inflammation. Many of these adipocytokines have a physiological role in metabolism. The uncontrolled secretions of several adipocytokines were associated with the stimulation of inflammatory processes leading to metabolic disorders including obesity, atherosclerosis, insulin resistance and type 2 diabetes. Obesity leads to the dysfunction of adipocytes andcorrelated with the imbalance of adipokines levels. In obese and diabetic conditions, leptin deficiency inhibited the Jak/Stat3/PI3K and insulin pathways. In this review, ample evidence exists to support the recognition of the adipocyte’s role in various tissues and pathologies. New integral insights may add dimensions to translate any potential agents into the future clinical armamentarium of chronic endocrine metabolic and inflammatory diseases. Functional balance of both adipocytes and immune cells is important to exert their effects on endocrine metabolic disorders; furthermore, adipose tissue should be renamed not only as a functional part of the endocrine system but also as a new part of the immune system. PMID:23634778

  10. 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

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

    PubMed Central

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

    2010-01-01

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

  12. Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin.

    PubMed

    Gonciarz, Maciej; Bielański, Wladyslaw; Partyka, Robert; Brzozowski, Tomasz; Konturek, Piotr C; Eszyk, Jerzy; Celiński, Krzysztof; Reiter, Russel J; Konturek, Stanislaw J

    2013-03-01

    Insulin resistance, oxidative stress, and an abnormal production of adipokines and cytokines are implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently, we reported a significant improvement in plasma liver enzymes among patients with NASH treated with melatonin. In this study, we investigated the effect of melatonin, administered at a dose of 10 mg/day for 28 days to 16 patients with histologically proven NASH on insulin resistance (HOMA-IR), on the plasma levels of adiponectin, leptin, ghrelin, and resistin. Additionally, plasma levels of aminotransferases and gamma glutamyltranspeptidase as well as plasma concentrations of melatonin were evaluated. Median baseline values of HOMA-IR, leptin (ng/mL), and resistin (pg/mL) in patients with NASH were significantly higher in comparison with controls: 4.90 versus 1.60, 10.70 versus 4.30, and 152 versus 91, respectively. Median adiponectin level (μg/mL) was decreased in patients compared to controls: 6.40 versus 16.25; no significant difference in ghrelin levels between patients and controls was found. After melatonin treatment, the median value of HOMA-IR was significantly reduced by 60% as compared to baseline values, whereas adiponectin, leptin, and ghrelin plasma levels rose significantly by 119%, 33%, and 20%, respectively; the difference between pre-/posttreatment in plasma resistin levels was not significant. These findings make melatonin a suitable candidate for testing in patients with NASH in the large controlled clinical trials.

  13. Visfatin -948G/T and resistin -420C/G polymorphisms in Egyptian type 2 diabetic patients with and without cardiovascular diseases.

    PubMed

    Motawi, Tarek M K; Shaker, Olfat G; El-Sawalhi, Maha M; Abdel-Nasser, Zeinab M

    2014-05-01

    Diabetes mellitus is one of the main threats to human health in the 21st century. Visfatin/Nampt and resistin are novel adipokines that have been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) complication. Several genetic studies have shown inconsistent results regarding association of visfatin/Nampt gene (NAMPT) and resistin gene (RETN) polymorphisms with T2DM and CVD complications. Here, we investigate whether NAMPT -948G/T and RETN -420C/G polymorphisms are associated with T2DM, its CVD complications, and serum adipokines levels in 90 Egyptian diabetic patients (44 without CVD and 46 with CVD) along with 60 healthy control subjects. Higher frequencies of NAMPT -948G/G and RETN -420G/G were observed among T2DM patients compared with controls. Furthermore, the frequencies of these genotypes were significantly higher in T2DM patients with CVD than those without CVD. Both NAMPT -948G/G and RETN -420G/G genotypes and G alleles were significantly associated with T2DM and CVD in Egyptian diabetic patients. Moreover, serum visfatin/Nampt and resistin levels were markedly elevated in T2DM patients, with the highest values observed in G/G genotypes among T2DM patients with CVD. In addition, positive correlations were observed between plasma adipokines levels and CVD risk factors. In conclusion, our data suggests that genetic variations in NAMPT -948G/T and RETN -420C/G may contribute to the disposition for T2DM and its CVD complications in Egyptian patients. However, further studies with greater sample size should be performed to verify these results.

  14. 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

  15. 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.

  16. Effect of Omega-3 Supplementation on Visfatin, Adiponectin, and Anthropometric Indices in Women with Polycystic Ovarian Syndrome

    PubMed Central

    Nadjarzadeh, Azadeh; Dehghani-Firouzabadi, Razieh; Daneshbodi, Hoorieh; Lotfi, Mohammad Hassan; Vaziri, Niloofar; Mozaffari-Khosravi, Hassan

    2015-01-01

    Background: Polycystic ovary syndrome (PCOS) is a multifactorial, metabolic disorder. Characteristics are chronic anovulation, polycystic ovaries and hyperandrogenism. The aim of this study was to determine the effect of omega-3 supplementation on visfatin, adiponectin, and anthropometric indices in PCOS women. Methods: The study was a randomized double blind placebo-controlled clinical trial. It was conducted on 84 women with polycystic ovary syndrome (26.92±5.05 years, BMI=31.69 Kg/m2) who referred to the fertility and infertility research center and Shahid Sadoughi hospital in Yazd. After the examination, evaluation and para-medical assessment by obstetrician, they were recruited. They took 3 capsules of omega-3 (each one contained 180 mg EPA and 120 mg DHA) or placebo (each contained 1 g paraffin) daily for 8 weeks. Statistical analysis was paired T-test and student T-test, and a p<0.05 was considered statistically significant. Results: After the intervention, visfatin concentration did not change in neither groups. But, at the end of the study, the mean of adiponectin concentration increased (p<0.001) in omega-3 group. Moreover, the mean of changes in this factor was significantly different between groups (p<0.005). FSH did not change in two groups of the study. However, the mean of LH decreased about 1.74 mlU/ml in omega-3 group (p<0.005). The mean of change of LH/FSH ratio between groups was significant (p<0.05). After the intervention, prolactin did not meaningfully change in both groups. Conclusion: Our results showed that 8 weeks of supplementation of omega-3 may have some beneficial effects on PCOS biochemical characteristics such as LH, LH/FSH, and adiponectin. PMID:27110520

  17. Study of the correlation between growth hormone deficiency and serum leptin, adiponectin, and visfatin levels in adults.

    PubMed

    Li, Z-P; Zhang, M; Gao, J; Zhou, G-Y; Li, S-Q; An, Z-M

    2014-02-14

    We aimed to determine the significance and changes in leptin, adiponectin (ADP), and visfatin levels in adults with growth hormone deficiency (GHD). Forty adults (19 men, 21 women) who had been diagnosed with GHD comprised the observation group, while 36 healthy adults (18 men, 18 women) were used as the control group. Fasting venous blood was collected to detect leptin, ADP, and visfatin levels. There was no statistically significant difference (P > 0.05) between the GHD group and the control group in terms of gender ratio, age, and body mass index. The waist-to-hip ratio (0.894 ± 0.061 vs 0.830 ± 0.481), cholesterol (4.99 ± 1.046 vs 4.18 ± 0.683), triglyceride (1.97 ± 1.428 vs 1.08 ± 0.403), LDL (2.91 ± 0.980 vs 2.29 ± 0.540), leptin (3.00 ± 1.233 vs 1.89 ± 1.554), ADP (15.26 ± 6.449 vs 10.24 ± 7.608), and visfatin levels (10.42 ± 3.715 vs 5.87 ± 3.90) in the GHD group were significantly higher than those in the control group (all P < 0.05). The levels of growth hormone (1.68 ± 1.67 vs 15.53 ± 6.23), insulin-like growth factor-1 (IGF-1, 22.64 ± 16.41 vs 61.85 ± 28.48), IGF-binding protein-3 (4889 ± 2962 vs 6866 ± 3823), and dehydroepiandrosterone sulfate (1.466 ± 1.804 vs 6.000 ± 2.767) in the GHD group were significantly lower than those in the control group (all P < 0.05). Correlation analysis demonstrated that leptin level was positively correlated to ADP and visfatin in both the GHD and control groups and negatively correlated to IGF-1 (r = 0.332, P < 0.05). Logistic regression analysis demonstrated that leptin, ADP, and visfatin were independent risk factors for adults with GHD.

  18. Adiponectin, resistin and IL-6 plasma levels in subjects with diabetic foot and possible correlations with clinical variables and cardiovascular co-morbidity

    PubMed Central

    2010-01-01

    Introduction It is very suggestive that diabetic foot is characterized by a pronounced inflammatory reaction and the pathogenic significance of this inflammation has received little attention. On this basis the aim of our study was to evaluate plasma levels of adiponectin, resistin and IL-6 in subjects with diabetic foot in comparison with subjects without foot complications. Materials and methods We recruited 34 subjects with type 2 diabetes mellitus and foot ulceration hospitalized for every condition related to diabetic disease, but not for new vascular events (group A). As controls we recruited 37 patients with type 2 diabetes mellitus without foot ulceration (group B) hospitalized for every condition related to diabetic disease, but not for new vascular events. Adiponectin, Resistin and IL-6 serum levels were evaluated. Results Subjects of group A showed lower median plasma levels of adiponectin [7.7450 (4.47-12.17) μg/ml vs 8.480 (5.15-12.87) μg/ml], higher median plasma levels of IL-6 [3.21 (1.23-5.34) pg/ml vs 2.73 (1.24-3.97 pg/ml)] and of resistin [3.860 (2.96-6.29 ng/ml) vs 3.690 (2.,37-6.5 ng/ml)]. Conclusion Our study demonstrated that diabetic subjects with diabetic foot showed in comparison with diabetics without diabetic foot higher IL-6 and resistin plasma levels, lower adiponectin plasma levels. PMID:20836881

  19. The Association of Chlamydia pneumonia and Helicobacter pylori IgG Seropositivity With Omentin-1, Visfatin and Adiponectin Levels in Postmenopausal Women.

    PubMed

    Ranjbar, Reza; Bolkheir, Alireza; Vahdat, Katayoun; Assadi, Majid; Darabi, Hossein; Nabipour, Iraj

    2016-12-01

    Some adipocytokines are cardioprotective or pro-inflammatory for cardiovascular system. Chronic infection with Chlamydia pneumoniae and Helicobacter pylori has been also considered as novel risk factors for atherosclerosis. The main aim of the current population-based study is to investigate the potential link between circulating adipocytokines and Chlamydia pneumoniae or Helicobacter pylori IgG seropositivities. A total of 250 healthy postmenopausal women who participated in a prospective cohort study were evaluated for IgG antibodies directed against C.pneumoniae and H. pylori. Omentin-1, visfatin, adiponectin, and high sensitivity C-reactive protein were measured by highly specific enzyme-linked immunosorbent assay methods. The prevalence of IgG antibodies against C. pneumoniae and H. pylori among the studied population was 20.4% (51 women) and 57.2% (143 women), respectively. There were no significant differences in adipocytokine levels between H. pylori IgG seropositive and H. pylori seronegative subjects. Similar results for visfatin and omentin-1 were found when C. pneumoniae IgG seropositive were compared with C. pneumoniae IgG seronegative subjects. However, in general linear model adjusted for age, body mass index and hs-CRP levels revealed significant difference between C. pneumoniae seropositive and C. pneumoniae seronegative subjects for circulating adiponectin. In conclusion, Chlamydia pneumoniae IgG seropositivity was associated with higher adiponectin levels in postmenopausal women. The elucidation of interaction mechanism of Chlamydia pneumoniae and a cardioprotective adipocytokine (adiponectin) will be useful in future therapeutic strategies.

  20. Effect of peripheral kisspeptin administration on adiponectin, leptin, and resistin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta).

    PubMed

    Wahab, F; Bano, R; Jabeen, S; Irfan, S; Shahab, M

    2010-07-01

    In the last few years, kisspeptin-KISS1R signaling has appeared as a major regulator of the reproductive function in several vertebrate species. However, KISS1(encoding kisspeptin) and its putative receptor, KISS1R, are expressed in several other tissues. Adipose tissue, which secretes many peptides with diverse functions in normal physiology, expresses KISS1, which is modulated by gonadal steroids as well as by body nutritional status. Similarly, KISS1Rexpression is also found in adipose tissue, but the local role of kisspeptin in adipocyte function is currently unknown. Therefore, in the present study the effects of exogenous human kisspeptin-10 (KP10) were studied on three important adipokines, namely, adiponectin, leptin, and resistin in a set of four chair-restraint habituated intact adult male rhesus monkeys under; 1) normal fed conditions, 2) 24-h fasting conditions, and 3) 48-h fasting conditions. Plasma resistin and leptin levels decreased (p<0.01), whereas adiponectin levels increased (p<0.05) in fasted monkeys. Kisspeptin administration significantly increased (p<0.05) mean plasma adiponectin levels under fed and 24-h fasting conditions as compared to pretreatment or vehicle-treatment levels. A stimulatory effect was also observed on the 48-h fasting stimulated plasma adiponectin levels, but it lacked statistical significance. In contrast, no effect of kisspeptin was observed on mean plasma leptin and resistin levels. Thus, the present study demonstrated a stimulatory effect of peripheral kisspeptin administration on the plasma adiponectin levels under fed and 24-h fasting conditions in the adult male rhesus monkey. These findings, therefore, assign a novel role to kisspeptin, a regulator of adipocyte function in higher primate.

  1. Adipokine adiponectin is a potential protector to human bronchial epithelial cell for regulating proliferation, wound repair and apoptosis: comparison with leptin and resistin.

    PubMed

    Zhu, Xiao Lin; Qin, Xiao Qun; Xiang, Yang; Tan, Yu Rong; Qu, Xiang Pin; Liu, Hui Jun

    2013-02-01

    Epidemiological data indicate an increasing incidence of asthma in the obese individuals recent decades, while very little is known about the possible association between them. Here, we compared the roles of adipocyte-derived factors, including leptin, adiponectin and resistin on proliferation, wound repair and apoptosis in human bronchial epithelial cells (HBECs) which play an important role in the pathogenesis of asthma. The results showed that exogenous globular adiponectin (gAd) promoted proliferation, cell-cycle and wound repair of HBECs. This effect may be relevant to Ca(2+)/calmodulin signal pathway. Besides, gAd inhibited apoptosis induced by ozone and release of lactate dehydrogenase (LDH) of HBECs via regulated adipoR1 and reactive oxygen species. No effects of leptin or resistin on proliferation, wound repair and apoptosis of HBECs were detectable. These data indicate that airway epithelium is the direct target of gAd which plays an important role in protecting HBECs from mechanical or oxidant injuries and may have therapeutic implications in the treatment of asthma.

  2. N-3 Polyunsaturated fatty acid therapy improves endothelial function and affects adiponectin and resistin balance in the first month after myocardial infarction

    PubMed Central

    Mizia-Stec, Katarzyna; Haberka, Maciej; Mizia, Magdalena; Chmiel, Artur; Gieszczyk, Klaudia; Lasota, Bartosz; Janowska, Joanna; Zahorska-Markiewicz, Barbara; Gąsior, Zbigniew

    2011-01-01

    Introduction N-3 Polyunsaturated fatty acids (n-3 PUFA) exert clinical beneficial effects in patients after acute myocardial infarction (AMI). However, their exact mechanisms of action are not well recognized yet. Our aim was to evaluate effects of early introduced n-3 PUFA supplementation on endothelial function and serum adipokine concentrations in patients with AMI. Material and methods Thirty-eight patients with AMI and successful coronary stent implantation were randomized to the study group (PUFA group: n = 19; standard therapy + PUFA 1 g daily) and the control group (control group: n = 19; standard therapy). The study group patients were given n-3 PUFA (Omacor 1 g daily) starting from the 3rd day of AMI. Ultrasound vascular indexes (flow-mediated dilatation [FMD], nitroglycerine-mediated dilation [NMD]) and serum concentrations of adiponectin and resistin (ELISA) were evaluated before and after 30 days of pharmacotherapy. Results Comparison of the mean delta values (baseline/after 30 days of therapy) between groups revealed significant differences for delta FMD (PUFA 7.6 ±12.4% vs. control –1.7 ±10.5%, p = 0.019) and delta resistin concentrations (PUFA 1.0 ±3.8pg/ml vs. control –1.6 ±2.9pg/ml, p = 0.028). Multiple linear regression analysis for all subjects revealed the n-3 PUFA supplementation (r = 10.933, p = 0.004) and waist circumference (r = –0.467, p = 0.01) as independent factors associated with delta FMD values (R-adjusted 0.29; p = 0.002). Conclusions Early and short-term n-3 PUFA supplementation in AMI with successful primary PCI and optimal pharmacotherapy improves endothelial function. However, increased resistin serum levels observed after 1-month n-3 PUFA supplementation merits further investigations. PMID:22291823

  3. Association of Serum Adiponectin, Leptin, and Resistin Concentrations with the Severity of Liver Dysfunction and the Disease Complications in Alcoholic Liver Disease

    PubMed Central

    Surdacka, Agata; Smolen, Agata

    2013-01-01

    Background and aims. There is growing evidence that white adipose tissue is an important contributor in the pathogenesis of alcoholic liver disease (ALD). We investigated serum concentrations of total adiponectin (Acrp30), leptin, and resistin in patients with chronic alcohol abuse and different grades of liver dysfunction, as well as ALD complications. Materials and Methods. One hundred forty-seven consecutive inpatients with ALD were prospectively recruited. The evaluation of plasma adipokine levels was performed using immunoenzymatic ELISA tests. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. Results. Acrp30 and resistin levels were significantly higher in patients with ALD than in controls. Lower leptin levels in females with ALD compared to controls, but no significant differences in leptin concentrations in males, were found. High serum Acrp30 level revealed an independent association with advanced liver dysfunction, as well as the development of ALD complications, that is, ascites and hepatic encephalopathy. Conclusion. Gender-related differences in serum leptin concentrations may influence the ALD course, different in females compared with males. Serum Acrp30 level may serve as a potential prognostic indicator for patients with ALD. PMID:24259947

  4. 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

  5. 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.

  6. Increased Resistin Serum Concentrations in Patients with Type 1 Diabetes Mellitus

    PubMed Central

    Geyikli, İclal; Keskin, Mehmet; Kör, Yılmaz; Akan, Müslüm

    2013-01-01

    Objective: Adiponectin, leptin, and resistin are adipokines which play a significant role in the regulation of lipid and carbohydrate metabolism in patients with type 2 diabetes, while little is known about their role in type 1 diabetes mellitus (T1DM). The aim of this study was to measure serum adiponectin, leptin, and resistin levels and to investigate their relationships with some parameters in patients with T1DM and healthy controls. Methods: Fifty children and adolescents with T1DM (21 boys and 29 girls) and 33 healthy control subjects (18 boys and 15 girls) participated in the study. All subjects were patients followed in the Pediatric Endocrinology and Metabolism Unit of Gaziantep University Faculty of Medicine. None of the subjects had hypertension, obesity, hyperlipidemia, anemia, or infection. Adiponectin, leptin, and resistin levels were analyzed with ELISA. Results: There were no statistically significant differences related with age, sex, pubertal status, or body mass index distribution between the diabetic and control groups. Resistin levels were significantly higher in the diabetic group compared to controls (5.26±3.15 ng/mL vs. 3.50±1.26 ng/mL; p<0.01). Conclusion: Of the three investigated adipokines, only resistin was associated with T1DM. Resistin may play a role in the process of inflammation and also in the pathophysiology of T1DM. Conflict of interest:None declared. PMID:24072088

  7. Resistin/ADSF/FIZZ3 in obesity and diabetes.

    PubMed

    Sul, Hei Sook

    2004-08-01

    The role of adipocyte-secreted resistin/adipocyte-specific secretory factor (ADSF)/FIZZ3 in obesity and diabetes has been controversial at best. Recently generated resn knockout mice showed normal glucose and insulin sensitivity with lower fasting glucose levels. Upon feeding with a high-fat diet, the knockout mice exhibited increased glucose tolerance with decreased hepatic glucose output, possibly due to phosphorylation and activation of AMP-activated protein kinase and suppression of gluconeogenic genes. In comparison, transgenic mice overexpressing a dominant negative form of resistin/ADSF/FIZZ3 showed increased adiposity with elevated leptin and adiponectin levels, accompanying enhanced glucose tolerance and insulin sensitivity both on chow and high-fat diets. Although its underlying mechanisms need further elucidation, the in vivo studies demonstrate a role of resistin/ADSF/FIZZ3 in obesity and insulin resistance.

  8. Adiponectin is partially associated with exosomes in mouse serum.

    PubMed

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

    2014-06-06

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

  9. Increased serum resistin levels in patients with type 2 diabetes are not linked with markers of insulin resistance and adiposity.

    PubMed

    Hasegawa, G; Ohta, M; Ichida, Y; Obayashi, H; Shigeta, M; Yamasaki, M; Fukui, M; Yoshikawa, T; Nakamura, N

    2005-06-01

    The role of resistin in human biology remains uncertain. We measured serum resistin levels in Japanese patients with (n=111) and without (n=98) type 2 diabetes mellitus and investigated the significance of this hormone in the pathophysiology of diabetes. The levels of serum adiponectin and leptin were also measured. Resistin levels were increased significantly in patients with type 2 diabetes compared with non-diabetic subjects (24.7+/-2.6 vs. 15.0+/-1.2 ng/ml, p=0.0013). However, there was no correlation in either patient group between serum resistin levels and markers of insulin resistance, obesity or hyperlipidaemia. These results were in direct contrast to the data of leptin or adiponectin, both of which were closely related to these clinical markers of diabetes. Multivariate regression analysis on the combined data of the two groups demonstrated that the presence of diabetes and HDL cholesterol levels were significant predictors of serum resistin levels (diabetes: beta=0.159, p=0.035; HDL: beta=-0.172, p=0.039). No correlation was observed between C-reactive protein and resistin adjusted for BMI. Taken together, these findings demonstrate that serum resistin levels are increased in patients with type 2 diabetes, but this increase is not linked to markers of insulin resistance or adiposity. Further studies are necessary to elucidate the significance of serum resistin concentration in human pathophysiology.

  10. Resistin as an Intrahepatic Cytokine

    PubMed Central

    Bertolani, Cristiana; Sancho-Bru, Pau; Failli, Paola; Bataller, Ramon; Aleffi, Sara; DeFranco, Raffaella; Mazzinghi, Benedetta; Romagnani, Paola; Milani, Stefano; Ginés, Pere; Colmenero, Jordi; Parola, Maurizio; Gelmini, Stefania; Tarquini, Roberto; Laffi, Giacomo; Pinzani, Massimo; Marra, Fabio

    2006-01-01

    Obesity and insulin resistance accelerate the progression of fibrosis during chronic liver disease. Resistin antagonizes insulin action in rodents, but its role in humans is still controversial. The aims of this study were to investigate resistin expression in human liver and to evaluate whether resistin may affect the biology of activated human hepatic stellate cells (HSCs), key modulators of hepatic fibrogenesis. Resistin gene expression was low in normal human liver but was increased in conditions of severe fibrosis. Up-regulation of resistin during chronic liver damage was confirmed by immunohistochemistry. In a group of patients with alcoholic hepatitis, resistin expression correlated with inflammation and fibrosis, suggesting a possible action on HSCs. Exposure of cultured HSCs to recombinant resistin resulted in increased expression of the proinflammatory chemokines monocyte chemoattractant protein-1 and interleukin-8, through activation of nuclear factor (NF)-κB. Resistin induced a rapid increase in intracellular calcium concentration, mainly through calcium release from intracellular inositol triphosphate-sensitive pools. The intracellular calcium chelator BAPTA-AM blocked resistin-induced NF-κB activation and monocyte chemoattractant protein-1 expression. In conclusion, this study shows a role for resistin as an intrahepatic cytokine exerting proinflammatory actions in HSCs, via a Ca2+/NF-κB-dependent pathway and suggests involvement of this adipokine in the pathophysiology of liver fibrosis. PMID:17148667

  11. Characteristics of resistin in rheumatoid arthritis angiogenesis.

    PubMed

    Su, Chen-Ming; Huang, Chun-Yin; Tang, Chih-Hsin

    2016-06-01

    Adipokines have been reported to be involved in the regulation of various physiological processes, including the immune response. Rheumatoid arthritis (RA) is an example of a systemic immune disease that causes chronic inflammation of the synovium and bone destruction in the joint. Recent therapeutic strategies based on the understanding of the role of cytokines and cellular mechanisms in RA have improved our understanding of angiogenesis. On the other hand, endogenous endothelial progenitor cells, which are a population isolated from peripheral blood monocytes have recently been identified as a homing target for pro-angiogeneic factor and vessel formation. In this review, we summarize the effects of common adipokines, such as adiponectin, leptin and resistin in RA pathogenesis and discuss other potential mechanisms of relevance for the therapeutic treatment of RA.

  12. Visfatin and cardio-cerebro-vascular disease.

    PubMed

    Wang, Pei; Vanhoutte, Paul M; Miao, Chao-Yu

    2012-01-01

    Nicotinamide phosphoribosyltransferase is the rate-limiting enzyme that catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide from nicotinamide. This protein was originally cloned as a putative pre-B cell colony-enhancing factor and also found to be a visceral fat-derived adipokine (visfatin). As a multifunctional protein, visfatin plays an important role in immunity, metabolism, aging, inflammation, and responses to stress. Visfatin also participates in several pathophysiological processes contributing to cardio-cerebro-vascular diseases, including hypertension, atherosclerosis, ischemic heart disease, and ischemic stroke. However, whether visfatin is a friend or a foe in these diseases remains uncertain. This brief review focuses on the current understanding of the complex role of visfatin in the cardio-cerebro-vascular system under normal and pathophysiological conditions.

  13. Effect of rosiglitazone on visfatin and retinol-binding protein-4 plasma concentrations in HIV-positive patients.

    PubMed

    Haider, D G; Schindler, K; Mittermayer, F; Müller, M; Nowotny, P; Rieger, A; Luger, A; Ludvik, B; Wolzt, M

    2007-04-01

    Thiazolidinediones (TZD) may improve insulin resistance in patients with diabetes and HIV. The novel adipocytokines visfatin and retinol-binding protein-4 (RBP-4) have been proposed to influence the development of impaired glucose tolerance. The impact of TZD on these cytokines is yet unknown. In this randomized, double-blind, placebo-controlled parallel group study, 37 lean HIV-positive subjects aged 19-50 years were treated with 8 mg/day rosiglitazone (n=20) or placebo (n=17) for 6 months. Insulin sensitivity was estimated from the homeostasis model assessment (HOMA) index. Fasting visfatin, RBP-4, leptin, and adiponectin plasma concentrations were analyzed by immunoassays. Rosiglitazone had no effect on impaired insulin sensitivity, but increased median plasma visfatin from 6.2 ng/ml (95% CI: 5.9; 6.5) to 13.7 ng/ml (12.6; 19.1) (P<0.001) and adiponectin from 3.2 ng/ml (2.2; 4.0) to 4.0 ng/ml (3.3; 8.5; P<0.001). RBP-4 was lowered from 21.0 ng/ml (19.6; 23.1) to 16.3 ng/ml (15.2; 17.0; P<0.001), and leptin concentrations were unchanged. Adipocytokine concentrations were stable in subjects receiving placebo, where a deterioration in insulin sensitivity was detectable (P<0.05). Changes in visfatin and RBP-4 were correlated in subjects receiving rosiglitazone (r=-0.64, P<0.01) but not placebo (r=0.12, P=0.15). TZD treatment affects circulating adipocytokine concentrations in subjects with HIV. Reductions in RBP-4 and increases in visfatin may contribute to the pharmacodynamic action of TZD on glucose homeostasis. Quantification of adipocytokines might be useful to assess TZD treatment effectiveness in insulin-resistant subjects with HIV.

  14. Adipokine resistin predicts anti-inflammatory effect of glucocorticoids in asthma

    PubMed Central

    2011-01-01

    Background Adipokines are protein mediators secreted by adipose tissue. Recently, adipokines have also been involved in the regulation of inflammation and allergic responses, and suggested to affect the risk of asthma especially in obese female patients. We assessed if adipokines predict responsiveness to glucocorticoids and if plasma adipokine levels are associated with lung function or inflammatory activity also in non-obese (body mass index (BMI) ≤ 30 kg/m2) women with newly-diagnosed steroid-naïve asthma. Methods Lung function, exhaled NO, plasma levels of adipokines leptin, resistin, adiponectin and adipsin, and inflammatory markers were measured in 35 steroid-naïve female asthmatics and in healthy controls. The measurements were repeated in a subgroup of asthmatics after 8 weeks of treatment with inhaled fluticasone. Adipokine concentrations in plasma were adjusted for BMI. Results High baseline resistin concentrations were associated with a more pronounced decrease in serum levels of eosinophil cationic protein (ECP) (r = -0.745, p = 0.013), eosinophil protein X (EPX) (r = -0.733, p = 0.016) and myeloperoxidase (MPO) (r = -0.721, p = 0.019) during fluticasone treatment. In asthmatics, leptin correlated positively with asthma symptom score and negatively with lung function. However, no significant differences in plasma adipokine levels between non-obese asthmatics and healthy controls were found. The effects of resistin were also investigated in human macrophages in cell culture. Interestingly, resistin increased the production of proinflammatory factors IL-6 and TNF-α and that was inhibited by fluticasone. Conclusions High resistin levels predicted favourable anti-inflammatory effect of inhaled glucocorticoids suggesting that resistin may be a marker of steroid-sensitive phenotype in asthma. High leptin levels were associated with a more severe disease suggesting that the link between leptin and asthma is not restricted to obesity. PMID:21615949

  15. Linking resistin, inflammation, and cardiometabolic diseases

    PubMed Central

    Park, Hyeong Kyu; Kwak, Mi Kyung; Kim, Hye Jeong; Ahima, Rexford S.

    2017-01-01

    Adipose tissue secretes a variety of bioactive substances that are associated with chronic inflammation, insulin resistance, and an increased risk of type 2 diabetes mellitus. While resistin was first known as an adipocyte-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents, it is predominantly expressed and secreted by macrophages in humans. Epidemiological and genetic studies indicate that increased resistin levels are associated with the development of insulin resistance, diabetes, and cardiovascular disease. Resistin also appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and the formation of foam cells. Thus, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with cardiovascular disease and heart failure. Furthermore, recent evidence suggests that resistin is associated with atherogenic dyslipidemia and hypertension. The present review will focus on the role of human resistin in the pathogeneses of inflammation and obesity-related diseases. PMID:28192887

  16. Endoplasmic Reticulum Stress Regulates Adipocyte Resistin Expression

    PubMed Central

    Lefterova, Martina I.; Mullican, Shannon E.; Tomaru, Takuya; Qatanani, Mohammed; Schupp, Michael; Lazar, Mitchell A.

    2009-01-01

    OBJECTIVE Resistin is a secreted polypeptide that impairs glucose metabolism and, in rodents, is derived exclusively from adipocytes. In murine obesity, resistin circulates at elevated levels but its gene expression in adipose tissue is paradoxically reduced. The mechanism behind the downregulation of resistin mRNA is poorly understood. We investigated whether endoplasmic reticulum (ER) stress, which is characteristic of obese adipose tissue, regulates resistin expression in cultured mouse adipocytes. RESEARCH DESIGN AND METHODS The effects of endoplasmic stress inducers on resistin mRNA and secreted protein levels were examined in differentiated 3T3-L1 adipocytes, focusing on the expression and genomic binding of transcriptional regulators of resistin. The association between downregulated resistin mRNA and induction of ER stress was also investigated in the adipose tissue of mice fed a high-fat diet. RESULTS ER stress reduced resistin mRNA in 3T3-L1 adipocytes in a time- and dose-dependent manner. The effects of ER stress were transcriptional because of downregulation of CAAT/enhancer binding protein-α and peroxisome proliferator–activated receptor-γ transcriptional activators and upregulation of the transcriptional repressor CAAT/enhancer binding protein homologous protein-10 (CHOP10). Resistin protein was also substantially downregulated, showing a close correspondence with mRNA levels in 3T3-L1 adipocytes as well as in the fat pads of obese mice. CONCLUSIONS ER stress is a potent regulator of resistin, suggesting that ER stress may underlie the local downregulation of resistin mRNA and protein in fat in murine obesity. The paradoxical increase in plasma may be because of various systemic abnormalities associated with obesity and insulin resistance. PMID:19491212

  17. Increased visfatin concentrations in women with gestational diabetes mellitus.

    PubMed

    Krzyzanowska, Katarzyna; Krugluger, Walter; Mittermayer, Friedrich; Rahman, Rupa; Haider, Dominik; Shnawa, Nadja; Schernthaner, Guntram

    2006-05-01

    The recently discovered adipocytokine visfatin has insulin-like properties. It lowers blood glucose and improves insulin sensitivity; however, clinical data on visfatin are limited. To evaluate the role of visfatin in GDM (gestational diabetes mellitus), we determined visfatin levels in women with GDM and in healthy pregnant controls. Furthermore, visfatin concentrations were investigated longitudinally during pregnancy and after delivery in a subgroup of women with GDM. Blood for measurement of visfatin and metabolic parameters was obtained from 64 women with GDM [median week of gestation, 34 (interquartile range, 27-36) weeks] and 30 healthy pregnant controls [median week of gestation, 34 (interquartile range, 28-36) weeks]. In a subgroup of 24 women with GDM, visfatin, leptin and metabolic parameters were investigated twice during pregnancy (28-30 and 38-40 weeks of gestation) and 2 weeks after delivery. In the cross-sectional analysis, median visfatin levels were significantly elevated in women with GDM [64.0 (interquartile range, 50.9-74.8) ng/ml] compared with controls [46.0 (interquartile range, 36.9-54.6) ng/ml; P<0.0001]. In women with GDM, visfatin correlated with week of gestation at the time of blood draw (R=0.35, P=0.005). No association with fasting glucose, insulin, homoeostasis model assessment-insulin resistance or body mass index was observed. According to the longitudinal analysis, visfatin increased during pregnancy (P=0.002) and rose further after delivery (P=0.014), whereas leptin and insulin levels decreased after parturition (both P<0.001). In conclusion, visfatin is elevated in women with GDM and increases during the course of pregnancy as well as after delivery. Furthermore, visfatin shows no association with insulin and leptin in women with GDM.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  20. Adiponectin concentrations increase during acute FFA elevation in humans treated with rosiglitazone.

    PubMed

    Krzyzanowska, K; Mittermayer, F; Krugluger, W; Roden, M; Schernthaner, G; Wolzt, M

    2007-10-01

    The adipocytokine adiponectin is released by adipocytes upon activation of the peroxisome proliferator-activated receptor gamma (PPAR gamma). PPAR gamma has binding sites for thiazolidinediones and free fatty acids (FFAs). To evaluate if adiponectin serum concentrations are synergistically regulated by FFAs and thiazolidinediones IN VIVO plasma FFAs were acutely elevated in healthy subjects pre-treated with rosiglitazone or placebo. Sixteen healthy male subjects (23-37 years) were included in this double-blind, randomized, placebo-controlled parallel-group study. Rosiglitazone 8 mg or placebo was administered daily for 21 days. On the last day plasma FFA concentrations were increased by an intravenous triglyceride/heparin infusion. Blood for determination of adiponectin, C-reactive protein (CRP), leptin, resistin, FFAs, glucose, and insulin was drawn at baseline and on day 21 before and after 5 hours of triglyceride/heparin infusion. Adiponectin concentrations increased and FFA levels decreased in subjects receiving rosiglitazone (all p<0.05 VS. baseline). Lipid infusion significantly increased FFA plasma concentrations, with an attenuated elevation in rosiglitazone-treated subjects. However, adiponectin concentrations were only increased in subjects on rosiglitazone (p=0.018 VS. before lipid infusion), but not in controls. Leptin increased during lipid infusion in subjects receiving placebo but not in those on rosiglitazone. CRP and resistin were not affected by rosiglitazone or FFAs. The acute increase in circulating adiponectin concentrations during acutely elevated FFA depends on PPAR gamma activation in healthy subjects.

  1. Free fatty acids normalize a rosiglitazone-induced visfatin release.

    PubMed

    Haider, Dominik G; Mittermayer, Friedrich; Schaller, Georg; Artwohl, Michaela; Baumgartner-Parzer, Sabina M; Prager, Gerhard; Roden, Michael; Wolzt, Michael

    2006-11-01

    The detrimental effect of elevated free fatty acids (FFAs) on insulin sensitivity can be improved by thiazolidinediones (TZDs) in patients with type 2 diabetes mellitus. It is unknown whether this salutary action of TZD is associated with altered release of the insulin-mimetic adipocytokine visfatin. In this study, we investigated whether visfatin concentrations are altered by FFA and TZD treatment. In a randomized, double-blind, placebo-controlled, parallel-group study 16 healthy volunteers received an infusion of triglycerides/heparin to increase plasma FFA after 3 wk of treatment with rosiglitazone (8 mg/day, n = 8) or placebo (n = 8), and circulating plasma visfatin was measured. As a corollary, human adipocytes were incubated with synthetic fatty acids and rosiglitazone to assess visfatin release in vitro. The results were that rosiglitazone treatment increased systemic plasma visfatin concentrations from 0.6 +/- 0.1 to 1.7 +/- 0.2 ng/ml (P < 0.01). Lipid infusion caused a marked elevation of plasma FFA but had no effect on circulating visfatin in controls. In contrast, elevated visfatin concentrations in subjects receiving rosiglitazone were normalized by lipid infusion. In isolated adipocytes, visfatin was released into supernatant medium by acute addition and long-term treatment of rosiglitazone. This secretion was blocked by synthetic fatty acids and by inhibition of phosphatidylinositol 3-kinase or Akt. In conclusion, release of the insulin-mimetic visfatin may represent a major mechanism of metabolic TZD action. The presence of FFA antagonizes this action, which may have implications for visfatin bioactivity.

  2. Associations of Resistin Levels with Resistin Gene Polymorphism and Metabolic Syndrome in Thais

    PubMed Central

    Suriyaprom, Kanjana; Tungtrongchitr, Rungsunn; Namjuntra, Pisit

    2015-01-01

    Summary Background Metabolic syndrome (MS) is a clinical constellation comprising risk factors associated with developing cardiovascular disease and type 2 diabetes. Resistin has been suggested as a linkage between obesity, inflammation and type 2 diabetes. This study aimed to investigate resistin concentrations and hematological-biochemical parameters in MS subjects and controls, and to determine whether two resistin gene (RETN) polymorphisms (−420C>G & +299G>A) are linked to resistin levels and MS among Thais. Methods This case-control study was performed with 322 Thai volunteers: 160 MS subjects and 162 controls. Anthropometric parameters and hematological-biochemical variables were determined. The RETN −420C>G (rs1862513) and +299G>A (rs3745367) polymorphisms were genotyped by PCR-RFLP technique. Results The resistin levels of the MS group were significantly higher than those of the control group. Resistin levels were positively correlated with anthropometric parameters and WBC count in the MS group. According to RETN −420C>G polymorphism, MS subjects with the G allele (CG/GG) (3.9 μg/L) had significantly higher resistin concentrations than in subjects with the CC genotype (2.4 μg/L); with regard to RETN +299G>A polymorphism, carriers with the A allele (GA/AA) (3.8 μg/L) had significantly higher resistin levels than subjects with the GG genotype (2.7 μg/L), after adjusting for potential covariates. However, the RETN −420C>G and +299G>A polymorphisms were not found to be associated with MS, hematological-biochemical parameters and anthropometric variables. Conclusions These findings suggest resistin levels are linked with MS and the RETN −420C>G and +299G>A polymorphisms have impacted the circulating resistin concentrations. However, these two RETN polymorphisms probably do not influence susceptibility to MS among Thais. PMID:28356829

  3. Adiponectin and colorectal cancer.

    PubMed

    Otani, Kensuke; Ishihara, Soichiro; Yamaguchi, Hironori; Murono, Koji; Yasuda, Koji; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Watanabe, Toshiaki

    2017-02-01

    Colorectal cancer is an obesity-related malignancy. Adiponectin is an adipokine produced exclusively by adipose tissue, and its concentration in the serum is reduced in obesity. A low serum level of adiponectin is associated with an increased risk of various types of malignancies including colorectal cancer. These facts suggest that the epidemiological link between obesity and cancer may have a significant association with adiponectin. Although numerous studies of colorectal cancer have been reported, the results are conflicting about the anti-cancer effect of adiponectin, and how adiponectin affects carcinogenesis or cancer development remains controversial. Because adiponectin has multiple systemic effects and exists as a high serum concentration protein, the main role of adiponectin should be regulation of homeostasis, and it would not likely act as an anti-cancerous hormone. However, as epidemiological evidence shows, a low adiponectin level may be a basic risk factor for colorectal cancer. We speculate that when the colonic epithelium is stimulated or damaged by another carcinogen under the condition of a low adiponectin level, carcinogenesis is promoted and cancer development is facilitated. In this report, we summarize recent findings of the correlation between adiponectin and colorectal cancer and investigate the effect of adiponectin on colorectal cancer.

  4. Pituitary resistin gene expression: effects of age, gender and obesity.

    PubMed

    Morash, Barbara A; Ur, Ehud; Wiesner, Glen; Roy, Jeremy; Wilkinson, Michael

    2004-03-01

    Resistin is a new adipocytokine which is expressed in rat, mouse and possibly human adipose tissue. Its putative role as a mediator of insulin resistance is controversial. We hypothesized that resistin, like leptin, would have multiple roles in non-adipose tissues and we reported that resistin is expressed in mouse brain and pituitary. Moreover, resistin expression in female mouse pituitary is developmentally regulated and maximal expression occurs peripubertally. Although the role of endogenous resistin in mouse brain and pituitary has not been determined, our data suggest that resistin could be important in the postnatal maturation of the hypothalamic-pituitary system. In the present study we compared the ontogeny of resistin gene expression in the pituitary of male and female mice using semi-quantitative RT-PCR analysis. We show that resistin expression is developmentally regulated in the pituitary of male and female CD1 mice. However, significant gender differences were evident (male > female at postnatal day 28 and 42) and this was not modified by neonatal treatment of female pups with testosterone. Since resistin expression in adipose tissue is also influenced by obesity, we evaluated resistin expression in fat, brain and pituitary of the obese ob/ob mouse. Resistin mRNA was significantly increased in both visceral and subcutaneous adipose depots in postnatal day 28 ob/ob mice compared to controls, but pituitary resistin expression was significantly reduced. In contrast to the prepubertal levels, and in agreement with other reports, adipose resistin expression was reduced in adult ob/ob mice. In a third set of experiments we examined the influence of food deprivation on pituitary and fat resistin mRNA. Resistin gene expression was severely down-regulated by a 24-hour fast in adipose and pituitary tissue but not in hypothalamus. In conclusion, pituitary resistin expression is age- and gender-dependent. In ob/ob mice, and in fasted mice, resistin is regulated

  5. Effect of weight loss on high-molecular weight adiponectin in obese children.

    PubMed

    Martos-Moreno, Gabriel Á; Barrios, Vicente; Martínez, Guillermo; Hawkins, Federico; Argente, Jesús

    2010-12-01

    Our aim was to determine the influence of weight reduction on total (T-) and high-molecular weight (HMW-) adiponectin in obese (OB) prepubertal children. Seventy OB prepubertal white patients were followed for 18 months and studied after reducing their BMI by 1 (n = 51) and 2 standard deviation scores (SDS) (n = 21) under conservative treatment, and 6 months after achieving weight loss (n = 44). Body composition dual-energy X-ray absorptiometry (DXA) and serum levels of T- and HMW-adiponectin, resistin, leptin, leptin soluble receptor (sOB-R), tumoral necrosis factor-α and interleukin-6 were determined. The control group consisted of 61 healthy prepubertal children. At diagnosis T-adiponectin was higher (P < 0.01; confidence interval (+0.04) - (+0.15)) and HMW-adiponectin lower (P < 0.001; confidence interval (-0.45) - (-0.21)) in OB children than in controls. A reduction in body fat increased T- and HMW-adiponectin and sOB-R (all P < 0.001) and decreased leptin (P < 0.001) and interleukin-6 levels (P < 0.05). After 6 months of sustained weight reduction a decrease in tumoral necrosis factor-α (P < 0.01) occurred, whereas weight recovery increased leptin (P < 0.001) and decreased T-adiponectin (P < 0.05). HMW-adiponectin levels negatively correlated with homeostasis model assessment (HOMA) index and BMI in the whole cohort (both P < 0.001), as did T-adiponectin levels and HOMA index in OB patients (P < 0.01), but neither T- nor HMW-adiponectin correlated with body fat content (BFC) in OB children. We conclude that the impairment of T- and HMW-adiponectin levels in childhood obesity is different to that in elder OB patients, showing closer relationship with carbohydrate metabolism parameters than with BFC, but increasing their levels after weight loss and in association with metabolic improvement.

  6. The effect of Ramadan fasting on sirtuin and visfatin levels

    PubMed Central

    Engin-Ustun, Yaprak; Caglayan, Emel Kiyak; Kara, Mustafa; Gocmen, Ayse Yesim; Polat, M. Fevzi; Aktulay, Ayla

    2016-01-01

    Objective Our aim was to determine how Ramadan fasting effects serum Human NAD-dependent deacetylase sirtuin 1 (SIRT1/SIR2L1) and visfatin levels during pregnancy. Materials and methods Thirty-six patients were included in this case-control study. The patient group consisted of 18 pregnant women who were Ramadan fasting. Another healthy 18 pregnant women with matching pregnancy weeks and ages formed the control group. Blood samples were obtained from the patients for biochemical analyses and serum adipokine level measurements. Results The mean sirtuin and visfatin levels in fasting pregnant women were 2.87 ± 0.95 and 60.18 ± 19.49 ng/mL, respectively, while the mean serum sirtuin and visfatin levels in the control group was determined to be 4.28 ± 1.45 and 23.26 ± 6.18 ng/mL, respectively. A statistically significant difference was determined between the groups (p = 0.002, p = 0.0001). A correlation analysis provided a negative correlation between number of fasting days and sirtuin levels (r = 0.45, p = 0.005) and a positive correlation with visfatin levels (r = 0.73, p = 0.0001). Conclusion As a result, while the serum sirtuin 1 level of pregnant women decreased due to fasting in Ramadan, we determined that their visfatin levels increased and this increase was in correlation with the days of fasting. PMID:28250976

  7. ADIPONECTIN IN SEVERE PREECLAMPSIA

    PubMed Central

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

    2008-01-01

    Aims Adiponectin is an adipokine with insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic properties. The aims of this study were to determine whether maternal plasma adiponectin concentrations differ between patients with severe preeclampsia and those with normal pregnancies, and to explore the relationship between plasma adiponectin and the results of Doppler velocimetry of the uterine arteries. Methods This case-control study included two groups: (1) patients with severe preeclampsia (n=50) and (2) patients with normal pregnancies (n=150). Pulsed-wave and color Doppler ultrasound examination of the uterine arteries were performed. Plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results (1) Patients with severe preeclampsia had a higher median plasma concentration of adiponectin than that of normal pregnant women. (2) The median plasma adiponectin concentration did not differ between women with severe preeclampsia who had a high impedance to blood flow in the uterine arteries and those with normal impedance to blood flow. (3) Among patients with normal pregnancies, plasma adiponectin concentrations were negatively correlated with BMI in the first trimester and at sampling. Conclusions Women with severe preeclampsia have a higher median plasma concentration of adiponectin than that of normal pregnant women. This may reflect a compensatory feedback mechanism to the metabolically-altered, anti-angiogenic and pro-atherogenic state of severe preeclampsia. PMID:17919115

  8. Liver X Receptor (LXR) activation negatively regulates visfatin expression in macrophages

    SciTech Connect

    Mayi, Therese Hervee; Rigamonti, Elena; Pattou, Francois; Staels, Bart; Chinetti-Gbaguidi, Giulia

    2011-01-07

    Research highlights: {yields} Synthetic LXR ligands decreased visfatin expression in human macrophages. {yields} LXR activation leads to a modest and transient decrease of NAD{sup +} concentration. {yields} LXR activation decreased PPAR{gamma}-induced visfatin in human macrophages. -- Abstract: Adipose tissue macrophages (ATM) are the major source of visfatin, a visceral fat adipokine upregulated during obesity. Also known to play a role in B cell differentiation (pre-B cell colony-enhancing factor (PBEF)) and NAD biosynthesis (nicotinamide phosphoribosyl transferase (NAMPT)), visfatin has been suggested to play a role in inflammation. Liver X Receptor (LXR) and Peroxisome Proliferator-Activated Receptor (PPAR){gamma} are nuclear receptors expressed in macrophages controlling the inflammatory response. Recently, we reported visfatin as a PPAR{gamma} target gene in human macrophages. In this study, we examined whether LXR regulates macrophage visfatin expression. Synthetic LXR ligands decreased visfatin gene expression in a LXR-dependent manner in human and murine macrophages. The decrease of visfatin mRNA was paralleled by a decrease of protein secretion. Consequently, a modest and transient decrease of NAD{sup +} concentration was observed. Interestingly, LXR activation decreased the PPAR{gamma}-induced visfatin gene and protein secretion in human macrophages. Our results identify visfatin as a gene oppositely regulated by the LXR and PPAR{gamma} pathways in human macrophages.

  9. Circulating visfatin level is associated with hepatocellular carcinoma in chronic hepatitis B or C virus infection.

    PubMed

    Tsai, I-Ting; Wang, Chao-Ping; Yu, Teng-Hung; Lu, Yung-Chuan; Lin, Chih-Wen; Lu, Li-Fen; Wu, Cheng-Ching; Chung, Fu-Mei; Lee, Yau-Jiunn; Hung, Wei-Chin; Hsu, Chia-Chang

    2017-02-01

    Adipocytokines play an important role in adipose tissue homeostasis, especially in obesity-associated disorders such as non-alcoholic fatty liver and their complications including hepatocellular carcinoma (HCC). Although visfatin is an adipocytokine highly expressed in visceral fat that has been demonstrated to play a critical role in the progression of human malignancies, little is known about the role of visfatin in HCC associated with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. In this study, we investigated whether plasma visfatin levels were altered in patients with HCC and the association between plasma visfatin levels and pretreatment hematologic profiles. Plasma visfatin levels were measured by enzyme-linked immunosorbent assays in 193 patients with different stages of HBV or HCV infection, and 92 healthy control subjects. The patients with HCC and chronic HCV or HBV infection had higher levels of visfatin than patients with HBV, HCV, and cirrhosis. In multivariate logistic regression analysis, levels of alpha-fetoprotein (AFP) (OR: 1.13, p=0.003), and plasma visfatin (OR: 1.17, p=0.046) were independently associated with HCC. Multiple stepwise regression analysis showed that plasma visfatin level was positively associated with age, aspartate aminotransferase to platelet ratio index (APRI), and AFP. Trend analyses confirmed that plasma visfatin concentration was associated with AFP>8ng/mL, cirrhosis, HCC, tumor size>5cm, and Barcelona Clinic Liver Cancer-C stage. These results suggested that the plasma visfatin level is associated with the presence of HCC, and that a higher plasma visfatin level may be important in the pathogenesis of HCC. Visfatin may act as both a protective and pro-inflammatory factor. Plasma visfatin concentration may serve as an additional tool to identify patients with more advanced necroinflammation.

  10. Visfatin as a Novel Mediator Released by Inflamed Human Endothelial Cells

    PubMed Central

    Romacho, Tania; Villalobos, Laura A.; Cercas, Elena; Carraro, Raffaele; Sánchez-Ferrer, Carlos F.; Peiró, Concepción

    2013-01-01

    Background Visfatin is a multifaceted adipokine whose circulating levels are enhanced in different metabolic diseases. Extracellular visfatin can exert various deleterious effects on vascular cells, including inflammation and proliferation. Limited evidence exists, however, on the capacity of human vascular cells to synthesize and release visfatin by themselves, under basal or pro-inflammatory conditions. Methods and Results Intracellular visfatin was detected by Western blot in non-stimulated human umbilical vein endothelial cells (HUVEC). However, exposing HUVEC for 18 h to a series of pro-inflammatory stimulus, such as interleukin (IL)-1β (1 to 10 ng/mL), tumor necrosis factor-α (1 to 10 ng/mL) or angiotensin II (10 pmol/L to 1 μmol/L) markedly enhanced intracellular visfatin content. Using IL-1β (10 ng/mL; 18 h), it was determined that the increase in intracellular visfatin, which was paralleled by enhanced visfatin mRNA levels, relied on a signalling mechanism involving both nuclear factor-κB and poly (ADP ribose) polymerase-1 activation. Moreover, IL-1β modified the sub-cellular localization of visfatin; while in non-stimulated HUVEC immunoreactive visfatin predominantly showed an intra-nuclear granular pattern, in IL-1β-inflamed cells an extra-nuclear filamentous staining, co-localising with F-actin fibers and suggesting a secretory pattern, was mainly found. Indeed, IL-1β promoted visfatin secretion, as determined by both ELISA and immunocytochemistry. Conclusions Human endothelial cells synthesize and release visfatin, particularly in response to inflammation. We suggest that the inflamed endothelium can be a source of visfatin, which arises as a local inflammatory mediator and a potential therapeutic target to interfere with vascular inflammation. PMID:24130902

  11. Decreased immunoreactivity of visfatin in the pancreas and liver of rats with renovascular hypertension.

    PubMed

    Piotrowska, Ż; Janiuk, I; Lewandowska, A; Kasacka, I

    2016-01-01

    Hypertension is one of the major endocrine and metabolic disorders, in which visfatin plays a significant role. The objective of this study was to evaluate the immunoreactivity of visfatin in pancreas and liver of “two kidney, one clip” (2K1C) renovascular hypertension model in rats. The studies were carried out on the pancreas and liver of rats. After a 6-week period of the renal artery clipping procedure, 2K1C rats developed a stable hypertension. Paraffin sections were stained with hematoxylin and eosin (for general histological examination) and processed for immunolocalization of visfatin. The intensity of immunohistochemical reaction was measured using Nikon NIS-Elements Advanced Research software. The hypertension significantly weakened the immunohistochemical reaction exhibiting visfatin in the pancreas and liver of hypertensive rats, compared to control animals. The changes induced by hypertension in the visfatin-containing cells in the pancreas and liver of the rats are discussed and needs further study.

  12. Circulating resistin protein and mRNA concentrations and clinical severity of coronary artery disease

    PubMed Central

    Sopic, Miron; Spasojevic-Kalimanovska, Vesna; Kalimanovska-Ostric, Dimitra; Andjelkovic, Kristina; Jelic-Ivanovic, Zorana

    2015-01-01

    Introduction Previous studies have implicated a strong link between circulating plasma resistin and coronary artery disease (CAD). The aim of this study was to evaluate the differences in peripheral blood mononuclear cells (PBMC) resistin mRNA and its plasma protein concentrations between the patients with CAD of different clinical severity. Material and methods This study included 33 healthy subjects as the control group (CG) and 77 patients requiring coronary angiography. Of the latter 30 was CAD negative whereas 47 were CAD positive [18 with stable angina pectoris (SAP) and 29 with acute coronary syndrome (ACS)]. Circulating resistin was measured by ELISA; PBMC resistin mRNA was determined by real-time PCR. Results Resistin protein was significantly higher in the ACS group compared to the CG (P = 0.001) and the CAD negative group (P = 0.018). Resistin mRNA expression did not vary across the study groups, despite the positive correlation seen with plasma resistin (ρ = 0.305, P = 0.008). In patients, plasma resistin and PBMC resistin mRNA negatively correlated with HDL-C (ρ = -0.404, P < 0.001 and ρ = -0.257, P = 0.032, respectively). Furthermore, the highest plasma resistin tertile showed the lowest HDL-C (P = 0.006). Plasma resistin was positively associated with serum creatinine (ρ = 0.353, P = 0.002). Conclusion Significant increase of plasma resistin in patients with ACS compared to CG and CAD negative patients was observed. Despite no change in PBMC resistin mRNA in different disease conditions a positive association between resistin mRNA and resistin plasma protein was evident. Both plasma resistin and PBMC resistin mRNA were negatively associated with plasma HDL-C, and plasma resistin positively with serum creatinine. PMID:26110037

  13. Adiponectin, the past two decades

    PubMed Central

    Wang, Zhao V.; Scherer, Philipp E.

    2016-01-01

    Adiponectin is an adipocyte-specific factor, first described in 1995. Over the past two decades, numerous studies have elucidated the physiological functions of adiponectin in obesity, diabetes, inflammation, atherosclerosis, and cardiovascular disease. Adiponectin, elicited through cognate receptors, suppresses glucose production in the liver and enhances fatty acid oxidation in skeletal muscle, which together contribute to a beneficial metabolic action in whole body energy homeostasis. Beyond its role in metabolism, adiponectin also protects cells from apoptosis and reduces inflammation in various cell types via receptor-dependent mechanisms. Adiponectin, as a fat-derived hormone, therefore fulfills a critical role as an important messenger to communicate between adipose tissue and other organs. A better understanding of adiponectin actions, including the pros and cons, will advance our insights into basic mechanisms of metabolism and inflammation, and potentially pave the way toward novel means of pharmacological intervention to address pathophysiological changes associated with diabetes, atherosclerosis, and cardiometabolic disease. PMID:26993047

  14. Visfatin correlates with hot flashes in postmenopausal women with metabolic syndrome: effects of genistein.

    PubMed

    Bitto, Alessandra; Arcoraci, Vincenzo; Alibrandi, Angela; D'Anna, Rosario; Corrado, Francesco; Atteritano, Marco; Minutoli, Letteria; Altavilla, Domenica; Squadrito, Francesco

    2017-03-01

    During menopause, an increased prevalence of metabolic syndrome (MetS) and central obesity seems to increase hot flashes (HFs). Visfatin is an inflammatory adipokine secreted by visceral fat. We investigated visfatin levels and its relationship with hot flash number and BMI, in postmenopausal women with MetS. We also evaluated the effect of genistein, an isoflavone effective in reducing HFs, on visfatin levels and HFs after 1 year of treatment. This was a randomized, double-blind, placebo-controlled trial. Postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein (n = 60), daily for 1 year. As main outcome measures, hot flashes number and circulating visfatin levels were evaluated. Visfatin significantly correlated with BMI and HFs number in women with MetS at basal. After 6 and 12 months, our results indicate a strong correlation and a significant effect of genistein in reducing both HFs and visfatin in women with MetS. The present study suggests that visfatin plays a role in the vasomotor symptoms, at least in postmenopausal women with metabolic syndrome. Genistein may reduce HFs decreasing the circulating levels of this inflammatory adipokine.

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

    PubMed

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

    2013-12-01

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

  16. High-Intensity Exercise and Carbohydrate Supplementation do not Alter Plasma Visfatin

    PubMed Central

    Mellick, Paul F.; Feger, Bryan J.; Oberlin, Douglas J.; Davis, Paul G.; Wideman, Laurie

    2017-01-01

    The purpose of the study was to examine the effect of high-intensity exercise and carbohydrate supplementation (CHO) on plasma visfatin. On 2 separate days, 10 sprint-trained males (age = 26.4 ± 5.3 yr; Ht = 1.77 ± 0.03 m; Wt = 78.78 ± 9.10 kg; BF% = 13.96 ± 7.28%) completed 4, 3-min bouts of cycling at 50% mean anaerobic power, with 6 min of rest between bouts. On CHO day, subjects ingested 50g of CHO 30 min before exercise. On control day, subjects ingested a sugar-free drink (CON) 30 min before exercise. Blood was drawn before supplementation, 15 min before exercise, before and after each exercise bout, and 15 and 30 min post exercise. Visfatin, glucose, and insulin were determined. Truncal fat was assessed by dual energy x-ray. Visfatin was not significantly different between treatments (CHO vs CON) at any time point (p = 0.163), and was not significantly altered by exercise (p = 0.692). Insulin [25.65 vs 8.35 mU/l, CHO vs CON, respectively] and glucose [138.57 vs 98.10 mg/dl, CHO vs CON, respectively] were significantly elevated after CHO ingestion and remained elevated throughout the first half of exercise. Baseline visfatin was significantly correlated with truncal fat (r2 = 0.7782, p < 0.05). Visfatin was correlated to truncal fat in sprint-trained males, but was not altered by exercise or CHO supplementation. Key points Plasma visfatin was not affected by exercise or carbohydrate supplementation. Plasma visfatin was significantly correlated to abdominal fat. Plasma visfatin did not follow a similar pattern to blood glucose or plasma insulin as has been shown in previous studies. PMID:28344453

  17. Adipokine Serum visfatin level in pregnancy induced hypertension and uncomplicated pregnancy

    PubMed Central

    Shaheen, Asmat; Nazli, Rubina; Fatima, Sadia; Ali, Roshan; Khan, Ihsanullah; Khattak, Salim

    2016-01-01

    Background and Objectives: Hypertensive disorder in pregnancy is the significant disease that badly affects the maternal and fetal prognosis and lead to higher mortality and morbidity in the prenatal period. Visfatin, potentially a new adipokine has emerged having high contribution in pathogenesis of pre-eclampsia. The objective of the study was to find the level of Visfatin in pregnancy induced hypertension and normal pregnant women. Methods: This study was carried out in tertiary care hospitals, Peshawar from March-October 2014. A total of 234 pregnant women (gestational age >20 weeks) were included in the study with distribution as Preeclampsia (PE=86), Eclampsia (E=74) and control (N=74). Blood was taken for measuring Visfatin level by Enzyme Linked Immunosorbent Assay (ELISA) technique. SPSS version 19 was used for statistical analysis. Student’s t test was performed to evaluate the mean differences in patients and control. Results: Serum level of visfatin was significantly higher in pregnancy induced hypertension when compared with control (P value<0.001).: Comparisons of mean value of visfatin with age group of 21-40 years, body mass index (BMI), primary parous and parity 2-4, gestational age of >36 weeks and both systolic and diastolic blood pressure were highly significant in pregnancy induced hypertension when compared with control (p value<0.001). Conclusion: Pregnancy induced hypertensive women showed increased level of serum Visfatin than normal pregnant women. PMID:28083037

  18. Remarkably increased resistin levels in anti-AChR antibody-positive myasthenia gravis.

    PubMed

    Zhang, Da-Qi; Wang, Rong; Li, Ting; Li, Xin; Qi, Yuan; Wang, Jing; Yang, Li

    2015-06-15

    Resistin is a pro-inflammatory cytokine involved in the pathogenesis of autoimmune diseases. To investigate serum resistin levels in patients with myasthenia gravis (MG) and determine if there are associations between resistin levels and disease severity, we measured serum resistin levels in 102 patients with anti-acetylcholine receptor antibody-positive MG (AChR-MG). We further analyzed associations between serum resistin levels and clinical variables in patients with MG. Our findings demonstrate that serum resistin levels are elevated in patients with AChR-generalized MG and AChR-MG with thymoma and are correlated with disease severity. Resistin has potential as a useful serum biomarker for inflammation in AChR-MG.

  19. Fenofibrate administration to arthritic rats increases adiponectin and leptin and prevents oxidative muscle wasting

    PubMed Central

    Castillero, Estíbaliz; Martín, Ana Isabel; Nieto-Bona, Maria Paz; Fernández-Galaz, Carmen; López-Menduiña, María; Villanúa, María Ángeles; López-Calderón, Asunción

    2012-01-01

    Chronic inflammation induces skeletal muscle wasting and cachexia. In arthritic rats, fenofibrate, a peroxisome proliferator-activated receptor α (PPARα (PPARA)) agonist, reduces wasting of gastrocnemius, a predominantly glycolytic muscle, by decreasing atrogenes and myostatin. Considering that fenofibrate increases fatty acid oxidation, the aim of this study was to elucidate whether fenofibrate is able to prevent the effect of arthritis on serum adipokines and on soleus, a type I muscle in which oxidative metabolism is the dominant source of energy. Arthritis was induced by injection of Freund's adjuvant. Four days after the injection, control and arthritic rats were gavaged daily with fenofibrate (300 mg/kg bw) or vehicle over 12 days. Arthritis decreased serum leptin, adiponectin, and insulin (P<0.01) but not resistin levels. In arthritic rats, fenofibrate administration increased serum concentrations of leptin and adiponectin. Arthritis decreased soleus weight, cross-sectional area, fiber size, and its Ppar α mRNA expression. In arthritic rats, fenofibrate increased soleus weight, fiber size, and Ppar α expression and prevented the increase in Murf1 mRNA. Fenofibrate decreased myostatin, whereas it increased MyoD (Myod1) and myogenin expressions in the soleus of control and arthritic rats. These data suggest that in oxidative muscle, fenofibrate treatment is able to prevent arthritis-induced muscle wasting by decreasing Murf1 and myostatin expression and also by increasing the myogenic regulatory factors, MyoD and myogenin. Taking into account the beneficial action of adiponectin on muscle wasting and the correlation between adiponectin and soleus mass, part of the anticachectic action of fenofibrate may be mediated through stimulation of adiponectin secretion. PMID:23781298

  20. Visfatin Impairs Endothelium-Dependent Relaxation in Rat and Human Mesenteric Microvessels through Nicotinamide Phosphoribosyltransferase Activity

    PubMed Central

    Angulo, Javier; Villalobos, Laura A.; Cercas, Elena; Leivas, Alejandra; Bermejo, Elena; Carraro, Raffaele; Sánchez-Ferrer, Carlos F.; Peiró, Concepción

    2011-01-01

    Visfatin, also known as extracellular pre–B-cell colony–enhancing factor (PBEF) and nicotinamide phosphoribosyltransferase (Nampt), is an adipocytokine whose circulating levels are enhanced in metabolic disorders, such as type 2 diabetes mellitus and obesity. Circulating visfatin levels have been positively associated with vascular damage and endothelial dysfunction. Here, we investigated the ability of visfatin to directly impair vascular reactivity in mesenteric microvessels from both male Sprague-Dawley rats and patients undergoing non-urgent, non-septic abdominal surgery. The pre-incubation of rat microvessels with visfatin (50 and 100 ng/mL) did not modify the contractile response to noradrenaline (1 pmol/L to 30 µmol/L), as determined using a small vessel myograph. However, visfatin (10 to 100 ng/mL) concentration-dependently impaired the relaxation to acetylcholine (ACh; 100 pmol/L to 3 µmol/L), without interfering with the endothelium-independent relaxation to sodium nitroprusside (1 nmol/L to 3 µmol/L). In both cultured human umbilical vein endothelial cells and rat microvascular preparations, visfatin (50 ng/mL) stimulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, as determined by lucigenin-derived chemiluminiscence. The relaxation to ACh impaired by visfatin was restored by the NADPH oxidase inhibitor apocynin (10 µmol/L). Additionally, the Nampt inhibitor APO866 (10 mmol/L to 10 µmol/L), but not an insulin receptor-blocking antibody, also prevented the stimulation of NADPH oxidase and the relaxation impairment elicited by visfatin. Accordingly, the product of Nampt activity nicotinamide mononucleotide (100 nmol/L to 1 mmol/L) stimulated endothelial NADPH oxidase activity and concentration-dependently impaired ACh-induced vasorelaxation. In human mesenteric microvessels pre-contracted with 35 mmol/L potassium chloride, the endothelium-dependent vasodilation to bradykinin (1 nmol/L to 3 µmol/L) was equally impaired by

  1. RESISTIN: A HORMONE WHICH INDUCES INSULIN RESISTANCE IS INCREASED IN NORMAL PREGNANCY

    PubMed Central

    Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Pineles, Beth L.; Friel, Lara A.; Espinoza, Jimmy; Goncalves, Luis; Santolaya, Joaquin; Gomez, Ricardo; Hong, Joon-Seok; Edwin, Samuel; Soto, Eleazar; Richani, Karina; Mazor, Moshe; Hassan, Sonia S.

    2008-01-01

    Aims Resistin, a newly discovered adipokine, is thought to play a key role in the regulation of insulin resistance. The objectives of this study were to develop a nomogram of maternal plasma concentrations of resistin from 11 weeks of gestation to term and to determine whether resistin concentrations differ between normal and overweight pregnant women. Methods In this cross-sectional study, plasma concentrations of resistin were determined in normal pregnant women of normal body mass index (BMI 18.5–24.9; n=261), overweight pregnant women (BMI ≥25; n=140), and non-pregnant women of normal weight (n=40). Blood samples were collected once from each woman between the first trimester and term. Percentiles for resistin concentration were determined for five pre-specified windows of gestational age. Plasma resistin concentration was determined by immunoassay. Non-parametric statistics were used for analysis. Results The median maternal plasma concentration of resistin between 11 to 14 weeks of gestation in women of normal weight was significantly higher than non-pregnant women; The plasma concentration of resistin increased with gestational age. Conclusions Normal pregnant women have a higher median plasma concentration of resistin than non-pregnant women and the concentration of this adipokine increases with advancing gestation. Alterations in the maternal plasma concentration of resistin during pregnancy may contribute to metabolic changes of pregnancy. PMID:17919114

  2. Plasma visfatin levels and mRNA expression of visfatin in peripheral blood mononuclear cells and peripheral blood monocyte-derived macrophages from normal weight females with polycystic ovary syndrome

    PubMed Central

    ZHANG, JING; ZHOU, LINGLING; TANG, LIULIN; XU, LIANGZHI

    2014-01-01

    Polycystic ovary syndrome (PCOS) is a common reproductive endocrinology disease, however, an explicit etiology is not known. Insulin resistance (IR) appears to be central to the pathogenesis of PCOS and inflammation may be significant in the pathogenesis of IR in PCOS. The aims of the present study were to investigate the plasma visfatin level and the gene expression of visfatin in peripheral blood mononuclear cells (PBMCs) and peripheral blood monocyte-derived macrophages (PBMMs) from PCOS patients, in addition to investigating the association between PCOS and IR. A total of 21 PCOS patients and 21 control subjects were enrolled in the study; the homeostasis model assessment of insulin resistance (HOMA-IR) was considered to be a stratified method for establishing the subgroups. Fasting blood samples were collected and the levels of sex hormones, insulin, glucose, blood lipids and visfatin were measured. In addition, visfatin gene expression levels in PBMCs and PBMMs were assessed using quantitative polymerase chain reaction. The plasma visfatin and gene expression levels of visfatin in PBMCs and PBMMs were not observed to increase in the normal weight PCOS and normal weight IR patients. Furthermore, plasma visfatin levels did not correlate with the normal weight PCOS patients or the normal weight IR patients per se. Further investigation into the role of visfatin in the pathogenesis of PCOS or IR should examine macrophages in the tissues, rather than macrophages in the peripheral blood. PMID:24940414

  3. 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

  4. Chemotherapy and plasma adipokines level in patients with colorectal cancer.

    PubMed

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

    2017-04-12

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

  5. 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

    2012-12-05

    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.

  6. Aerobic exercise training-induced decrease in plasma visfatin and insulin resistance in obese female adolescents.

    PubMed

    Lee, Kyu-Jin; Shin, Yun-A; Lee, Kyoung-Young; Jun, Tae-Won; Song, Wook

    2010-08-01

    The purpose of this study was to assess differences in the levels of plasma visfatin among female adolescents and changes in plasma visfatin and insulin resistance in obese female adolescents after 12 wk of aerobic exercise training. Twenty normal-weight female students (body-mass index [BMI] < 22.9 kg/m² and body fat ≤ 29.9) and 18 obese female students (BMI ≥ 25 kg/ m² and body fat ≥ 30%) participated in this study. Eleven obese students were assigned to an exercise group and completed a 12-wk aerobic exercise-training program that included four 40- to 50-min sessions per wk with an energy expenditure of 300-400 kcal/d. Seven obese students were assigned to a control group that received no exercise sessions or dietary restriction. The plasma visfatin levels of obese female adolescents were significantly higher (p < .05) than those of the normal-weight female adolescents. The plasma visfatin levels (294.00 ± 124.74 ng/ml to 185.55 ± 67.30 ng/ml, p < .01) and insulin resistance (p < .05) were significantly reduced after 12 wk of aerobic exercise. The results suggest that aerobic exercise resulting in an energy expenditure of 1,200-1,600 kcal/wk for 12 wk decreases plasma visfatin and insulin resistance in obese female adolescents.

  7. Down-regulated resistin level in consequence of decreased neutrophil counts in untreated Grave's disease

    PubMed Central

    Huang, Fengjiao; Chen, Xinxin; Zhou, Yulin; Ye, Lei; Wang, Weiqing; Ning, Guang; Wang, Shu

    2016-01-01

    Resistin, belongs to cysteine-rich secretory protein, is mainly produced by circulating leukocytes, such as neutrophils monocytes and macrophages in humans. To date, few but controversial studies have reported about resistin concentrations in hyperthyroid patients, especially in Graves' disease (GD). We undertaked a controlled, prospective study to explore the serum resistin concentration in GD patients before and after -MMI treatment. In addition, we also investigated the main influencing factor on serum resistin level and discuessed the potential role of serum resistin plays in GD patients. 39 untreated GD (uGD) patients, including 8 males and 31 females, were enrolled in our investigation. All of these patients were prescribed with MMI treatment, in addition to 25 healthy controls. Anthropometric parameters and hormone assessment were measured. Enzyme-linked immunosorbent assay was used to detect serum resistin concentration in different stages of GD patients. Furthermore, neutrophil cell line NB4 with or without T3 treatment to detect the effect of thyroid hormones on resistin expression. The serum resistin level and neutrophil counts in untreated GD patients were significantly declined. And all of these parameters were recovered to normal after MMI treatment in ethyroid GD (eGD) and TRAb-negative conversion (nGD) patients. Resistin concentration exhibited a negative correlation with FT3 and FT4, but a positive correlation with absolute number of neutrophiles in uGD patients, whereas did not correlate with thyroid autoimmune antibodies and BMI. Neutrophile cell line, NB4, produced decreased expression of resistin when stimulated with T3. Our study showed a decrease of serum resistin level in GD patients and we suggested that the serum resistin might primarily secreted from circulating neutrophils and down-regulated by excessive thyroid hormones in GD patients. PMID:27637079

  8. [Association of resistin gene 3'UTR+62G>A polymorphism with insulin resistance, adiposity and the adiponectin-resistin index in Mexican population].

    PubMed

    Chavarria-Ávila, Efraín; Ruíz Quezada, Sandra Luz; Guzmán-Ornelas, Milton-Omar; Castro-Albarrán, Jorge; Aguilar Aldrete, Maria Elena; Vásquez-Del Mercado, Mónica; Navarro-Hernández, Rosa-Elena

    2013-11-01

    Introducción: La resistencia a la insulina (RI) se caracteriza por susceptibilidad genética, incremento en la adiposidad y distribución irregular de grasa corporal, con alteración en la producción de adipocinas. Objetivo: Investigar la asociación del polimorfismo 3’UTR+62G>A en resistina con RI, índice adiponectina-resistina (ARindex), adiposidad y marcadores inmuno-metabólicos. Métodos: En un estudio transversal a 260 mestizos-mexicanos, clasificados con peso normal, exceso de peso, sin y con RI, se les evaluó: composición corporal, distribución de masa grasa y marcadores inmuno-metabólicos. Los alelos del polimorfismo 3’UTR+62G>A en resistina se identificaron por PCR-RFLP. La concentración sérica de insulina, adiponectina total y resistina se midieron por la técnica de ELISA. Resultados: Las frecuencias del alelo +62G para los individuos con peso normal y exceso de peso, fueron (95.4% y 98.4%, respectivamente) P=0.0343. Los portadores del genotipo GA con peso normal mostraron valores menores del ARindex, adiposidad y marcadores inmuno-metabólicos comparados con los portadores del genotipo GG. Se observó diferencia entre los individuos sin y con RI en el ARindex (P=0.002), concentración sérica de adiponectina (P=0.002) y resistina (P=0.033): 1.102±0.03, 5.167±0.36ug/mL y 8.827±0.42ng/mL versus 1.336±0.07, 3.577±0.34ug/mL y 10.480±0.65ng/mL, respectivamente. Los marcadores inmuno-metabólicos, reserva y distribución de grasa corporal correlacionan con ARindex (r=0.262 a 0.414), PA en los individuos mestizos-mexicanos con exceso de peso. El alelo +62A se asoció con incremento de adiponectina total, valores menores del ARindex, concentración de resistina, marcadores metabólicos y reserva de grasa corporal. El ARindex puede ser un indicador temprano de RI.

  9. Evaluation of serum Resistin in children with chronic renal failure undergoing hemodialysis

    PubMed Central

    Al-Hamshary, Abd El-Hamid Salah; El-Shaaer, Osama Saad; Soliman, Doaa Refaay; El-Mashad, Ghada Mohamed; Hussien, Ahmed Ibraheem

    2016-01-01

    Introduction High serum resistin levels are associated with the incidence of chronic kidney disease (CKD). The objectives of this study were to determine the serum concentrations of resistin in children that present with chronic renal failure (CRF) and end stage renal disease (ESRD), in order to examine the impact of hemodialysis (HD) on serum resistin levels, and to determine if a correlation exists between resistin and growth retardation in patients with CRF. Methods This case control study was undertaken in the pediatric hemodialysis unit of the Benha and Menoufia University hospitals from April 2014 to March 2015. The case group consisted of 50 patients with CRF aged from 6–18 years (25 of them under HD and 25 of them under conservative treatment) and 30 healthy children who constituted the control group. Urea, creatinine, and serum resistin were measured before and after the HD session for patients with CRF who are already under HD. Results A highly significant difference was found between the resistin levels in the two groups with mean level of 20.2 ± 7.58 ng/ml in the patient case group as compared to 4.9 ± 1.72 ng/ml in the control group. This highly significant difference found in the resistin level differed according to the Chronic Kidney Disease (CKD) stage of progression as patients on regular HD had resistin levels with a mean of 24.6 ± 7.28 ng/ml while the CKD patients under conservative treatment have resistin level mean of 15.6 ± 4.72 ng/ml. there was a highly significant difference in resistin levels before HD (mean = 24.6 ± 7.28) and after hemodialysis (mean = 14.7 ± 5.2). Conclusion Patients with CRF experienced higher than normal resistin levels as compared to the case control group and it was found that patients on HD had more elevated levels of resistin than did those patients who were on conservative treatment. HD treatments were found to be capable of lowering a patient’s resistin levels. A highly significant negative correlation

  10. Fulvic Acid Attenuates Resistin-Induced Adhesion of HCT-116 Colorectal Cancer Cells to Endothelial Cells

    PubMed Central

    Huang, Wen-Shih; Yang, Jen-Tsung; Lu, Chien-Chang; Chang, Shun-Fu; Chen, Cheng-Nan; Su, Yu-Ping; Lee, Ko-Chao

    2015-01-01

    A high level of serum resistin has recently been found in patients with a number of cancers, including colorectal cancer (CRC). Hence, resistin may play a role in CRC development. Fulvic acid (FA), a class of humic substances, possesses pharmacological properties. However, the effect of FA on cancer pathophysiology remains unclear. The aim of this study was to investigate the effect of resistin on the endothelial adhesion of CRC and to determine whether FA elicits an antagonistic mechanism to neutralize this resistin effect. Human HCT-116 (p53-negative) and SW-48 (p53-positive) CRC cells and human umbilical vein endothelial cells (HUVECs) were used in the experiments. Treatment of both HCT-116 and SW-48 cells with resistin increases the adhesion of both cells to HUVECs. This result indicated that p53 may not regulate this resistin effect. A mechanistic study in HCT-116 cells further showed that this resistin effect occurs via the activation of NF-κB and the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Co-treating cells with both FA and resistin revealed that FA significantly attenuated the resistin-increased NF-κB activation and ICAM-1/VCAM-1 expression and the consequent adhesion of HCT-116 cells to HUVECs. These results demonstrate the role of resistin in promoting HCT-116 cell adhesion to HUVECs and indicate that FA might be a potential candidate for the inhibition of the endothelial adhesion of CRC in response to resistin. PMID:26690142

  11. Effects of NAMPT polymorphisms and haplotypes on circulating visfatin/NAMPT levels in hypertensive disorders of pregnancy.

    PubMed

    Luizon, Marcelo R; Belo, Vanessa A; Palei, Ana Ct; Amaral, Lorena M; Lacchini, Riccardo; Sandrim, Valeria C; Duarte, Geraldo; Cavalli, Ricardo C; Tanus-Santos, Jose E

    2015-05-01

    Dysregulation of adipocytokines may be associated with endothelial dysfunction in women with preeclampsia (PE), who are at increased risk of future cardiovascular disease. Visfatin, an adipocytokine with a potential cardiovascular role, is also known as nicotinamide phosphorybosil transferase (NAMPT). NAMPT gene polymorphisms affect circulating visfatin/NAMPT levels in obesity. Most findings provide evidence for increased visfatin/NAMPT circulating levels in PE. However, no previous study has tested the hypothesis that NAMPT polymorphisms affect visfatin/NAMPT levels in hypertensive disorders of pregnancy. We studied the effects of the NAMPT polymorphisms T>C (rs1319501) and A>G (rs3801266), and the haplotypes formed by them on visfatin/NAMPT levels and whether these genetic markers are associated with gestational hypertension (GH) and PE. We studied 212 healthy pregnant (HP), 181 patients with GH and 208 with PE. Genotypes were determined by Taqman allele discrimination assays. Plasma visfatin/NAMPT levels were measured by ELISA. No significant differences in visfatin/NAMPT levels were found among the groups. However, higher visfatin/NAMPT levels (P<0.05) were found in GH patients carrying the AG or the GG genotypes for the rs3801266 polymorphism or the 'T, G' haplotype. The TC and CC genotypes and the C allele for the rs1319501 polymorphism were more frequent in the HP than in the PE group (P<0.05). Moreover, the 'C, A' haplotype was also more frequent in the HP than in the PE group (P<0.01). Our findings suggest that although the rs3801266 polymorphism and the 'T, G' haplotype affect visfatin/NAMPT levels in GH, the rs1319501 polymorphism and the 'C, A' haplotype affect the susceptibility to PE.

  12. Serum adipokine profiles in Kawasaki disease.

    PubMed

    Kemmotsu, Yasushi; Saji, Tsutomu; Kusunoki, Natsuko; Tanaka, Nahoko; Nishimura, Chiaki; Ishiguro, Akira; Kawai, Shinichi

    2012-02-01

    Adipokines are cytokines derived from adipose tissue. Recently it has been established that adipokines are closely linked to the pathophysiology of not only metabolic diseases, such as diabetes mellitus, obesity, and atherosclerosis, but also to inflammation and immune diseases. In this study we measured serum levels of adipokines in patients with acute Kawasaki disease to investigate the role of adipokines in the pathophysiology of Kawasaki disease. Serum resistin, high-molecular-weight (HMW) adiponectin, leptin, and visfatin levels were measured by enzyme-linked immunosorbent assay in a total of 117 subjects: 56 patients with acute Kawasaki disease, 30 healthy children, and 31 patients with acute infectious diseases. Serum resistin levels in patients with Kawasaki disease were significantly higher than those of healthy children and patients with acute infectious diseases. In contrast, mean serum HMW adiponectin, leptin, and visfatin levels in patients with Kawasaki disease exhibited no statistically significant differences compared with those in healthy children and patients with infectious diseases. Serum resistin levels decreased significantly after administration of intravenous immune globulin. Serum resistin levels on admission were significantly higher in nonresponders compared with responders to intravenous immune globulin therapy. A multivariate model revealed that C-reactive protein was a factor that was significantly related to elevated serum resistin level in patients with Kawasaki disease. In patients with Kawasaki disease, serum resistin levels were elevated, but decreased to nearly normal after intravenous administration of immune globulin. In contrast, serum HMW adiponectin, leptin, and visfatin levels showed no statistically significant changes. These findings suggest that resistin plays an important role, while other adipokines do not play a major role, in the pathogenesis of Kawasaki disease.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. Resistin confers resistance to doxorubicin-induced apoptosis in human breast cancer cells through autophagy induction

    PubMed Central

    Liu, Zhenyu; Shi, Aiping; Song, Dong; Han, Bing; Zhang, Zhiru; Ma, Le; Liu, Dongxu; Fan, Zhimin

    2017-01-01

    Clear evidence has linked obesity to a high risk of incidence as well as poor clinical outcome of breast cancer. It has been proven that changes in the levels of adipokines caused by obesity are associated with the initiation and progression of breast cancer. Resistin is a novel adipokine that is upregulated in breast cancer patients and promotes breast cancer cell growth, invasion, and migration. The aim of the study was to investigate whether resistin affected the efficacy of doxorubicin (Dox), one of the most effective anthracycline chemotherapeutic agents in the treatment of breast cancer. Treatment with resistin significantly attenuated Dox-induced apoptosis in a dose- and time-dependent manner, resulting in an increase in breast cancer cells survival. Moreover, resistin significantly induced autophagy flux and inhibition of autophagy abrogated the pro-survival effect of resistin in doxorubicin-treated cells. Furthermore, the AMPK/mTOR/ULK1 and JNK signaling pathways were activated by resistin treatment. Inhibition of these two pathways markedly reduced the ratio of LC3B-II/LC3B-I and increased cell apoptosis induced by Dox. For the first time, our findings indicate that resistin confers resistance to doxorubicin-induced apoptosis through autophagy induction and that this process involves the activation of AMPK/mTOR/ULK1 and JNK signaling pathways. Our findings suggest that resistin antagonism may be a novel strategy to overcome resistance to doxorubicin-based chemotherapy in breast cancer patients.

  15. Low Resistin Level is Associated with Poor Hospitalization-Free Survival in Hemodialysis Patients

    PubMed Central

    Chung, Wookyung; Jung, Eul Sik; Shin, Dongsu; Choi, Shung Han; Jung, Ji Yong; Chang, Jae Hyun; Lee, Hyun Hee; Kim, Dong Ki

    2012-01-01

    Malnutrition and inflammation are related to high rates of morbidity and mortality in hemodialysis patients. Resistin is associated with nutrition and inflammation. We attempted to determine whether resistin levels may predict clinical outcomes in hemodialysis patients. We conducted a prospective evaluation of 100 outpatients on hemodialysis in a single dialysis center (male, 46%; mean age, 53.7 ± 16.4 yr). We stratified the patients into 4 groups according to quartiles of serum resistin levels. During the 18-month observational period, patients with the lowest quartile of serum resistin levels had poor hospitalization-free survival (log rank test, P = 0.016). After adjustment of all co-variables, patients with the lowest quartile of serum resistin levels had poor hospitalization-free survival, compared with reference resistin levels. Higher levels of interleukin-6 were an independent predictor of poor hospitalization-free survival. In contrast, serum resistin levels were not correlated with interleukin-6 levels. The current data showed that low resistin levels may independently predict poor hospitalization free survival in hemodialysis patients. PMID:22468100

  16. Serum Resistin Levels May Contribute to an Increased Risk of Acute Cerebral Infarction.

    PubMed

    Dong, Xiao-Liu; Xu, Shi-Jun; Zhang, Li; Zhang, Xiu-Qing; Liu, Ting; Gao, Qiu-Yan; Qian, Qing-Qiang; Sun, Bao-Liang; Yang, Ming-Feng

    2017-04-01

    The objective of this study was to investigate the association between serum resistin levels and acute cerebral infarction (ACI). PubMed, SpringerLink, Wiley, EBSCO, Ovid, Web of Science, Wanfang, China National Knowledge Infrastructure, and VIP databases (last updated search in October 2014) were exhaustively searched, and data from the eligible studies were extracted and analyzed to assess the association between serum resistin levels and ACI. STATA software (version 12.0, Stata Corporation, College Station, TX, USA) was utilized for data analysis. Ten studies including 1829 ACI patients and 1557 healthy controls were eligible for inclusion in the meta-analysis. Our major result revealed that ACI patients exhibited higher serum resistin levels compared with healthy controls. Asubgroup analysis based on ethnicity showed a significant association between serum resistin levels and ACI in Asians, but surprisingly not in Caucasians. The results of our meta-analysis suggest that serum resistin levels are associated with an increased risk of ACI.

  17. Resistin competes with lipopolysaccharide for binding to toll-like receptor 4.

    PubMed

    Tarkowski, Andrej; Bjersing, Jan; Shestakov, Andrey; Bokarewa, Maria I

    2010-06-01

    Toll-like receptors (TLRs) are a family of cellular structures activated by recognition of pathogen associated molecular sequences. The activation of TLRs triggers a variety of intracellular mechanisms aiming to protect the host from the invading microorganisms. Lipopolysaccharide (LPS) is the main ligand for TLR4. Here we show that resistin, a cystein-rich protein believed to regulate carbohydrate metabolism, competes with LPS for binding to TLR4. Binding of recombinant resistin to human myeloid and epithelial cells was assessed by flow cytometry and its co-precipitation with TLR4 was demonstrated. Antibodies against TLR4 abolished resistin binding to human leucocytes and cytokine production by peripheral blood mononuclear cells in response to resistin stimulation. In contrast, isotype-matched murine IgG or TLR2 antibodies were unable to prevent binding of resistin to the cells. Similarly, TLR4-dependent pattern of resistin binding was observed in epithelial cell line HEK293 (human epithelial kidney cell), where TLR4 transfected, but not myeloid differentiation factor 2/CD14-transfected, TLR2 transfected or HEKnull cells, responded functionally to resistin stimulation. Intracellular signalling of resistin was assessed using inhibitors of transcription factors mitogen activated protein kinases, nuclear factor-kappaB, phosphoinositide 3-kinase and siRNA targeting TLR4 and human myeloid differentiation factor 88. Results demonstrate that TLR4 serves as a receptor for the pro-inflammatory effects of resistin in human cells. This may partly explain the multifunctional role of resistin in chronic inflammation, atherosclerosis and insulin resistance.

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

    PubMed Central

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

    2015-01-01

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

  19. Adiponectin as an anti-inflammatory factor

    PubMed Central

    Ouchi, Noriyuki; Walsh, Kenneth

    2009-01-01

    Obesity is characterized by low-grade systemic inflammation. Adiponectin is an adipose tissue-derived hormone, which is downregulated in obesity. Adiponectin displays protective actions on the development of various obesity-linked diseases. Several clinical studies demonstrate the inverse relationship between plasma adiponectin levels and several inflammatory markers including C-reactive protein. Adiponectin attenuates inflammatory responses to multiple stimuli by modulating signaling pathways in a variety of cell types. The anti-inflammatory properties of adiponectin may be a major component of its beneficial effects on cardiovascular and metabolic disorders including atherosclerosis and insulin resistance. In this reviews, we focus on the role of adiponectin in regulation of inflammatory response and discuss its potential as an antiinflammatory marker. PMID:17343838

  20. Sp1 mediates repression of the resistin gene by PPAR{gamma} agonists in 3T3-L1 adipocytes

    SciTech Connect

    Chung, S.S.; Choi, H.H.; Cho, Y.M.; Lee, H.K.; Park, K.S. . E-mail: kspark@snu.ac.kr

    2006-09-15

    Resistin is an adipokine related to obesity and insulin resistance. Expression of the resistin gene is repressed by the treatment of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists, thiazolidinediones (TZDs). In this study, we investigated the mechanism by which TZDs inhibit the resistin gene expression. Resistin gene expression was decreased by TZD in fully differentiated 3T3-L1 adipocytes, which was abolished after treatment of cycloheximide (a protein synthesis inhibitor). TZD could not repress the expression of the resistin gene in the presence of mithramycin A (an Sp1 binding inhibitor). Sp1 binding site of the resistin promoter (-122/-114 bp) was necessary for the repression. Further investigation of the effect of TZDs on the modification of Sp1 showed that the level of O-glycosylation of Sp1 was decreased in this process. These results suggest that PPAR{gamma} activation represses the expression of the resistin gene by modulating Sp1 activity.

  1. Plasma Levels of Cyclooxygenase-2 (COX-2) and Visfatin During Different Stages and Different Subtypes of Migraine Headaches

    PubMed Central

    Li, Chao; Zhu, Qiushi; He, Qiu; Wang, Junwei; Wang, Fengzhi; Zhang, Hemin

    2017-01-01

    Background The aim of this study was to determine the plasma levels of cyclooxygenase-2 (COX-2) and visfatin in different stages and different subtypes of migraine headaches compared to a control group to elucidate the pathological mechanisms involved. Material/Methods We recruited a case-control cohort of 182 adult migraine patients and 80 age-matched and gender-matched healthy controls. The migraine patients were divided into two groups: the headache-attack-period group (Group A, n=77) and the headache-free-period group (Group B, n=105). The two groups were further divided into subgroups according to whether they had aura symptoms. Solid phase double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma levels of COX-2 and visfatin. Statistical analysis was performed using SPSS 17.0. Results The plasma levels of COX-2 and visfatin in the headache-attack-period group were significantly higher than in the headache-free-period group and the control group; there were no significant differences between the headache-free group and the control group. There were no significant differences in plasma levels of COX-2 and visfatin between the subgroups: headache-attack-period with aura subgroup and the headache-attack-period without aura sub group. Conclusions COX-2 and visfatin participated in the pathogenesis of migraine headaches. The presence of aura had no effect on the serum levels of COX-2 and visfatin. PMID:28044053

  2. Plasma Levels of Cyclooxygenase-2 (COX-2) and Visfatin During Different Stages and Different Subtypes of Migraine Headaches.

    PubMed

    Li, Chao; Zhu, Qiushi; He, Qiu; Wang, Junwei; Wang, Fengzhi; Zhang, Hemin

    2017-01-03

    BACKGROUND The aim of this study was to determine the plasma levels of cyclooxygenase-2 (COX-2) and visfatin in different stages and different subtypes of migraine headaches compared to a control group to elucidate the pathological mechanisms involved. MATERIAL AND METHODS We recruited a case-control cohort of 182 adult migraine patients and 80 age-matched and gender-matched healthy controls. The migraine patients were divided into two groups: the headache-attack-period group (Group A, n=77) and the headache-free-period group (Group B, n=105). The two groups were further divided into subgroups according to whether they had aura symptoms. Solid phase double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma levels of COX-2 and visfatin. Statistical analysis was performed using SPSS 17.0. RESULTS The plasma levels of COX-2 and visfatin in the headache-attack-period group were significantly higher than in the headache-free-period group and the control group; there were no significant differences between the headache-free group and the control group. There were no significant differences in plasma levels of COX-2 and visfatin between the subgroups: headache-attack-period with aura subgroup and the headache-attack-period without aura sub group. CONCLUSIONS COX-2 and visfatin participated in the pathogenesis of migraine headaches. The presence of aura had no effect on the serum levels of COX-2 and visfatin.

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

    SciTech Connect

    Osawa, Haruhiko . E-mail: harosawa@m.ehime-u.ac.jp; Ochi, Masaaki; Kato, Kenichi; Yamauchi, Junko; Nishida, Wataru; Takata, Yasunori; Kawamura, Ryoichi; Onuma, Hiroshi; Takasuka, Tomomi; Shimizu, Ikki; Fujii, Yasuhisa; Ohashi, Jun; Makino, Hideichi

    2007-04-06

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

  4. Adiponectin Enhances Mouse Fetal Fat Deposition

    PubMed Central

    Qiao, Liping; Yoo, Hyung sun; Madon, Alysha; Kinney, Brice; Hay, William W.; Shao, Jianhua

    2012-01-01

    Maternal obesity increases offspring birth weight and susceptibility to obesity. Adiponectin is an adipocyte-secreted hormone with a prominent function in maintaining energy homeostasis. In contrast to adults, neonatal blood adiponectin levels are positively correlated with anthropometric parameters of adiposity. This study was designed to investigate the role of adiponectin in maternal obesityenhanced fetal fat deposition. By using high-fat diet–induced obese mouse models, our study showed that maternal obesity increased fetal fat tissue mass, with a significant elevation in fetal blood adiponectin. However, adiponectin gene knockout (Adipoq−/−) attenuated maternal obesity-induced high fetal fat tissue mass. We further studied the effects of fetal adiponectin on fetal fat deposition by using a cross breeding approach to create Adipoq−/+ and Adipoq−/− offspring, whereas maternal adiponectin was null. Adipoq−/+ offspring had more fat tissue mass at both birth and adulthood. Significantly high levels of lipogenic genes, such as sterol regulatory element–binding protein 1c and fatty acid synthase, were detected in the livers of Adipoq−/+ fetuses. In addition, expression of genes for placental fatty acid transport was significantly increased in Adipoq−/+ fetuses. Together, our study indicates that adiponectin enhances fetal fat deposition and plays an important role in maternal obesity-induced high birth weight. PMID:22872236

  5. Adiponectin as a routine clinical biomarker.

    PubMed

    Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

    2014-01-01

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

  6. Structure of Nampt/PBEF/visfatin, a mammalian NAD[superscript +]biosynthetic enzyme

    SciTech Connect

    Wang, Tao; Zhang, Xiangbin; Bheda, Poonam; Revollo, Javier R.; Imai, Shin-ichiro; Wolberger, Cynthia

    2010-07-22

    Nicotinamide phosphoribosyltransferase (Nampt) synthesizes nicotinamide mononucleotide (NMN) from nicotinamide in a mammalian NAD{sup +} biosynthetic pathway and is required for SirT1 activity in vivo. Nampt has also been presumed to be a cytokine (PBEF) or a hormone (visfatin). The crystal structure of Nampt in the presence and absence of NMN shows that Nampt is a dimeric type II phosphoribosyltransferase and provides insights into the enzymatic mechanism.

  7. A visfatin promoter polymorphism is associated with low-grade inflammation and type 2 diabetes.

    PubMed

    Zhang, Yuan-Yuan; Gottardo, Lucia; Thompson, Ryan; Powers, Christine; Nolan, David; Duffy, Jill; Marescotti, Maria Cristina; Avogaro, Angelo; Doria, Alessandro

    2006-12-01

    Visfatin (also known as pre-B cell colony-enhancing factor, or PBEF) is a pro-inflammatory adipokine expressed predominantly in visceral fat. We investigated whether polymorphisms at the visfatin/PBEF locus influence the risk of type 2 diabetes (T2D). Linkage disequilibrium analysis of 52 single nucleotide polymorphisms spanning the entire gene (34.7 kb) plus 20.5 kb of the upstream region and 25.5 kb of the downstream region revealed a single haplotype block that could be tagged by seven single nucleotide polymorphisms. These seven tags were typed in a group of T2D patients (n = 814) and a group of non-diabetic controls (n = 320) of white origin. A significant association was observed at -948C>A, with minor allele frequencies of 0.157 in T2D cases and 0.119 in non-diabetic controls (p = 0.021). In a non-diabetic population (n = 630), the same -948 allele that conferred increased risk of T2D was significantly associated with higher plasma levels of fibrinogen and C-reactive protein (p = 0.0022 and 0.0038, respectively). However, no significant associations were observed with BMI, waist circumference, serum glucose levels, or fasting insulin levels. Our findings suggest that the visfatin/PBEF gene may play a role in determining T2D susceptibility, possibly by modulating chronic, low-grade inflammatory responses.

  8. Clinical potential of resistin as a novel prognostic biomarker for cellulitis

    PubMed Central

    ERTURK, AYSE; CURE, MEDINE CUMHUR; CURE, ERKAN; KURT, AYSEL; CICEK, AYSEGUL COPUR; YUCE, SULEYMAN

    2015-01-01

    Cellulitis is an acute, subacute or chronic inflammation of the dermis and subdermal tissues, which is typically caused by bacteria, although other causes are possible. The present study aimed to evaluate the association between resistin levels and the recovery time of patients with cellulitis. In addition, the effect of resistin and insulin resistance on the prognosis of cellulitis was investigated. In total, 52 patients with cellulitis (male, 21; female, 31) and an age-matched group of 42 healthy individuals (male, 18; female, 24) were included in the study. The levels of serum resistin, fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR), C-reactive protein (CRP) and other biochemical parameters were compared between the groups. The mean resistin levels in the cellulitis and control groups were 9.4±5.3 and 5.8±3.1 ng/ml, respectively. The levels of resistin, FPG, HOMA-IR and CRP were significantly higher in the cellulitis group compared with the control group (P<0.001). Furthermore, the mean recovery time of the patients with cellulitis was 21.2±5.6 days. Thus, increased levels of resistin (P=0.002) and HOMA-IR (P=0.005) could be used as predictive factors for the recovery time. The enhanced levels of resistin and HOMA-IR were shown to correlate with the high CRP levels in the cellulitis group. Therefore, the results indicated that increased levels of resistin may function as a prognostic marker for cellulitis. PMID:26136908

  9. Serum Resistin and Kidney Function: A Family-Based Study in Non-Diabetic, Untreated Individuals

    PubMed Central

    Menzaghi, Claudia; Salvemini, Lucia; Fini, Grazia; Thompson, Ryan; Mangiacotti, Davide; Di Paola, Rosa; Morini, Eleonora; Giorelli, Maddalena; De Bonis, Concetta; De Cosmo, Salvatore; Doria, Alessandro; Trischitta, Vincenzo

    2012-01-01

    Background High serum resistin levels have been associated with kidney dysfunction. Most of these studies have been carried out in individuals with severe kidney impairment, diabetes, cardiovascular disease and related treatments. Thus, the observed association might have been influenced by these confounders. Our aim was to study the relationship between serum resistin, urinary albumin/creatinine ratio (ACR) and glomerular filtration rate (GFR) in a family-based sample, the Gargano Family Study (GFS) of 635 non diabetic, untreated Whites. Methods A linear mixed effects model and bivariate analyses were used to evaluate the phenotypic and genetic relations between serum resistin and both ACR and eGFR. All analyses were adjusted for sex, age, age squared, BMI, systolic blood pressure, smoking habits and physical exercise. Results After adjustments, resistin levels were slightly positively associated with ACR (β±SE = 0.049±0.023, p = 0.035) and inversely related to eGFR (β±SE = −1.43±0.61, p = 0.018) levels. These associations remained significant when either eGFR or ACR were, reciprocally, added as covariates. A genetic correlation (ρg = −0.31±0.12; adjusted p = 0.013) was observed between resistin and eGFR (but not ACR) levels. Conclusion Serum resistin levels are independently associated with ACR and eGFR in untreated non-diabetic individuals. Serum resistin and eGFR share also some common genetic background. Our data strongly suggest that resistin plays a role in modulating kidney function. PMID:22701635

  10. Serum resistin levels in women taking combined oral contraceptives containing desogestrel or gestodene.

    PubMed

    Rechberger, Tomasz; Tomaszewski, Jacek; Pieprzowska-Białek, Anna; Kulik-Rechberger, Beata; Skorupski, Paweł

    2004-06-01

    Resistin is a hormone secreted by adipose tissue that could be involved in the development of insulin resistance. Previous studies confirmed that endogenous sex steroids may influence serum resistin concentration in women. The aim of our study was to investigate the influence of combined oral contraceptives containing desogestrel or gestodene on circulating levels of resistin. Fifty-three women were enrolled in the study. Thirteen patients received 20 microg ethinylestradiol/150 microg desogestrel, 15 women were treated with 20 microg ethinylestradiol/75 microg gestodene, 11 with 30 microg ethinylestradiol/150 microg desogestrel and 14 with 30 microg ethinylestradiol/75 microg gestodene. Blood samples for estimation of serum resistin and insulin levels were drawn before administration of oral contraceptive and after 6 cycles of therapy. We found that serum resistin level remained unchanged in women receiving ethinylestradiol/desogestrel and was reduced in women treated with formulations containing gestodene. We conclude that ethinylestradiol combined with desogestrel or gestodene is unlikely to induce insulin resistance through resistin pathway.

  11. Resistin Regulates Pituitary Lipid Metabolism and Inflammation In Vivo and In Vitro

    PubMed Central

    Rodriguez-Pacheco, F.; Novelle, M. G.; Vazquez, M. J.; Garcia-Escobar, E.; Soriguer, F.; Rojo-Martinez, G.; García-Fuentes, E.; Malagon, M. M.; Dieguez, C.

    2013-01-01

    The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function and also regulates growth hormone (GH) secretion in rat adenopituitary cells cultures with the adipokine. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues, including the pituitary. The aim of this study is to investigate the possible action of resistin on the lipid metabolism in the pituitary gland in vivo (rats in two different nutritional status, fed and fast, treated with resistin on acute and a chronic way) and in vitro (adenopituitary cell cultures treated with the adipokine). Here, by a combination of in vivo and in vitro experimental models, we demonstrated that central acute and chronic administration of resistin enhance mRNA levels of the lipid metabolic enzymes which participated on lipolysis and moreover inhibiting mRNA levels of the lipid metabolic enzymes involved in lipogenesis. Taken together, our results demonstrate for the first time that resistin has a regulatory role on lipid metabolism in the pituitary gland providing a novel insight in relation to the mechanism by which this adipokine can participate in the integrated control of lipid metabolism. PMID:23710116

  12. High insulin and leptin increase resistin and inflammatory cytokine production from human mononuclear cells.

    PubMed

    Tsiotra, Panayoula C; Boutati, Eleni; Dimitriadis, George; Raptis, Sotirios A

    2013-01-01

    Resistin and the proinflammatory cytokines, such as TNF- α , IL-6, and IL-1 β , produced by adipocytes, and macrophages, are considered to be important modulators of chronic inflammation contributing to the development of obesity and atherosclerosis. Human monocyte-enriched mononuclear cells, from ten healthy individuals, were exposed to high concentrations of insulin, leptin, and glucose (alone or in combination) for 24 hours in vitro. Resistin, TNF- α , IL-6, and IL-1 β production was examined and compared to that in untreated cells. High insulin and leptin concentrations significantly upregulated resistin and the cytokines. The subsequent addition of high glucose significantly upregulated resistin and TNF- α mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1 β production. By comparison, exposure to dexamethasone reduced TNF- α , IL-6, and IL-1 β production, while at this time point it increased resistin protein secretion. These data suggest that the expression of resistin, TNF- α , IL-6, and IL-1 β from human mononuclear cells, might be enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and atherosclerosis. Therefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic inflammation, insulin sensitivity, and endothelial function of these patients.

  13. Circulating Adiponectin and Risk of Endometrial Cancer

    PubMed Central

    Zheng, Qiaoli; Wu, Haijian; Cao, Jiang

    2015-01-01

    Background Adiponectin is an insulin-sensitizing hormone produced by adipocytes. It has been suggested to be involved in endometrial tumorigenesis. Published data have shown inconsistent results for the association between circulating adiponectin levels and endometrial cancer. In this study, we conducted a meta-analysis to evaluate the predictive value of circulating adiponectin levels on the development of endometrial cancer. Methods PubMed, Embase, ISI web of knowledge, and Cochrane databases were searched for all eligible studies, and the summary relative risk (SRR) was calculated. Additionally, we performed dose-response analysis with eight eligible studies. Results A total of 1,955 cases and 3,458 controls from 12 studies were included. The SRR for the ‘highest’ vs ‘lowest’ adiponectin levels indicated high adiponectin level reduced the risk of endometrial cancer [SRR = 0.40, 95% confidence interval (CI), 0.33–0.66]. Results from the subgroup analyses were consistent with the overall analysis. The SRR for each 1 µg/ml increase of adiponectin indicated a 3% reduction in endometrial cancer risk (95% CI: 2%–4%), and a 14% reduction for each increase of 5 µg/ml (95% CI: 9%–19%). No evidence of publication bias was found. Conclusions This meta-analysis demonstrates that low level of circulating adiponectin is a risk factor for endometrial cancer. PMID:26030130

  14. Adiposity distribution influences circulating adiponectin levels.

    PubMed

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

    2014-10-01

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

  15. Activation of the hexosamine signaling pathway in adipose tissue results in decreased serum adiponectin and skeletal muscle insulin resistance.

    PubMed

    Hazel, Mark; Cooksey, Robert C; Jones, Deborah; Parker, Glendon; Neidigh, John L; Witherbee, Bryan; Gulve, Eric A; McClain, Donald A

    2004-05-01

    Overexpression of the rate-limiting enzyme for hexosamine synthesis (glutamine:fructose-6-phosphate amidotransferase) in muscle and adipose tissue of transgenic mice was previously shown to result in insulin resistance and hyperleptinemia. Explanted muscle from transgenic mice was not insulin resistant in vitro, suggesting that muscle insulin resistance could be mediated by soluble factors from fat tissue. To dissect the relative contributions of muscle and fat to hexosamine-induced insulin resistance, we overexpressed glutamine:fructose-6-phosphate amidotransferase 2.5-fold, specifically in fat under control of the aP2 promoter. Fasting glucose, insulin, and triglycerides were unchanged in the transgenic mice; leptin and beta-hydroxybutyrate levels were 91% and 29% higher, respectively. Fasted transgenic mice have mild glucose intolerance and skeletal muscle insulin resistance in vivo. In fasting transgenic mice, glucose disposal rates with hyperinsulinemia were decreased 27% in females and 10% in males. Uptake of 2-deoxy-D-glucose into muscle was diminished by 45% in female and 21% in male transgenics. Serum adiponectin was also lower in the fasted transgenics, by 37% in females and 22% in males. TNF alpha and resistin mRNA levels in adipose tissue were not altered in the fasted transgenics; levels of mRNA for leptin were increased and peroxisome proliferator-activated receptor gamma decreased. To further explore the relationship between adiponectin and insulin sensitivity, we examined mice that have been refed for 6 h after a 24-h fast. Refeeding wild-type mice resulted in decreased serum adiponectin and increased leptin. In transgenic mice, however, the regulation of these hormones by refeeding was lost for adiponectin and diminished for leptin. Refed transgenic female and male mice no longer exhibited decreased serum adiponectin in the refed state, and they were no longer insulin resistant as by lower or unchanged insulin and glucose levels. We conclude that

  16. Adenylyl cyclase-associated protein 1 is a receptor for human resistin and mediates inflammatory actions of human monocytes.

    PubMed

    Lee, Sahmin; Lee, Hyun-Chae; Kwon, Yoo-Wook; Lee, Sang Eun; Cho, Youngjin; Kim, Joonoh; Lee, Soobeom; Kim, Ju-Young; Lee, Jaewon; Yang, Han-Mo; Mook-Jung, Inhee; Nam, Ky-Youb; Chung, Junho; Lazar, Mitchell A; Kim, Hyo-Soo

    2014-03-04

    Human resistin is a cytokine that induces low-grade inflammation by stimulating monocytes. Resistin-mediated chronic inflammation can lead to obesity, atherosclerosis, and other cardiometabolic diseases. Nevertheless, the receptor for human resistin has not been clarified. Here, we identified adenylyl cyclase-associated protein 1 (CAP1) as a functional receptor for human resistin and clarified its intracellular signaling pathway to modulate inflammatory action of monocytes. We found that human resistin directly binds to CAP1 in monocytes and upregulates cyclic AMP (cAMP) concentration, protein kinase A (PKA) activity, and NF-κB-related transcription of inflammatory cytokines. Overexpression of CAP1 in monocytes enhanced the resistin-induced increased activity of the cAMP-dependent signaling. Moreover, CAP1-overexpressed monocytes aggravated adipose tissue inflammation in transgenic mice that express human resistin from their monocytes. In contrast, suppression of CAP1 expression abrogated the resistin-mediated inflammatory activity both in vitro and in vivo. Therefore, CAP1 is the bona fide receptor for resistin leading to inflammation in humans.

  17. Visfatin is present in bovine mammary epithelial cells, lactating mammary gland and milk, and its expression is regulated by cAMP pathway.

    PubMed

    Yonezawa, Tomo; Haga, Satoshi; Kobayashi, Yosuke; Takahashi, Tatsuyuki; Obara, Yoshiaki

    2006-12-11

    Visfatin was originally identified as a growth factor for immature B cells, and recently demonstrated to bind insulin receptor. Visfatin mRNA and protein were detected by RT-PCR and Western blot analysis in cloned bovine mammary epithelial cells, lactating bovine mammary gland and human breast cancer cell line, MCF-7. Immunocytochemical staining localized the visfatin protein in the cytosol and nucleus of both cells. Quantitative-RT-PCR analysis revealed that the expression of the visfatin mRNA was significantly elevated when treated with forskolin (500 microM), isopreterenol (1-10 microM) and dibutyric cyclic AMP (1 mM) for 24 h, and significantly reduced when treated with insulin (5-50 ng/ml) and dexsamethasone (0.5-250 nM) for 24 h. These results indicate that mammary epithelial cells express the visfatin protein and secrete them into the milk.

  18. Association between Risk Factors for Vascular Dementia and Adiponectin

    PubMed Central

    Lee, Won Taek; Park, Kyung Ah

    2014-01-01

    Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia. PMID:24860814

  19. Adiponectin Signaling Regulates Lipid Production in Human Sebocytes

    PubMed Central

    Jung, Yu Ra; Lee, Jin-Hyup; Sohn, Kyung-Cheol; Lee, Young; Seo, Young-Joon; Kim, Chang-Deok; Lee, Jeung-Hoon; Hong, Seung-Phil; Seo, Seong-Jun; Kim, Seong-Jin; Im, Myung

    2017-01-01

    Adiponectin plays important roles in metabolic function, inflammation and multiple biological activities in various tissues. However, evidence for adiponectin signaling in sebaceous glands is lacking, and its role remains to be clarified. This study investigated the role of adiponectin in lipid production in sebaceous glands in an experimental study of human sebocytes. We demonstrated that human sebaceous glands in vivo and sebocytes in vitro express adiponectin receptor and that adiponectin increased cell proliferation. Moreover, based on a lipogenesis study using Oil Red O, Nile red staining and thin layer chromatography, adiponectin strongly upregulated lipid production in sebocytes. In three-dimensional culture of sebocytes, lipid synthesis was markedly enhanced in sebocytes treated with adiponectin. This study suggested that adiponectin plays a significant role in human sebaceous gland biology. Adiponectin signaling is a promising target in the clinical management of barrier disorders in which sebum production is decreased, such as in atopic dermatitis and aged skin. PMID:28081218

  20. The Determinants of Leptin Levels in Diabetic and Nondiabetic Saudi Males

    PubMed Central

    2017-01-01

    Objective. This study aimed to identify the main determinants of serum leptin levels. Methods. A sample of 113 Saudi adult males (55 diabetic and 58 nondiabetic) was selected according to the inclusion and exclusion criteria identified below. Blood samples were taken from participants after fasting for 12 hours. For diabetic patients, the insulin dose was given 12 hours before. In general, the study instrument consisted of blood biochemical tests. Metabolic parameters, glycosylated hemoglobin (HbA1c), low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, and triglyceride (TG), and adipokines, leptin, adiponectin, visfatin, and resistin, were measured. Multivariate model was utilized to identify the relationship between leptin levels and the independent variables. Results. When adjusted for resistin in the diabetic group, the results demonstrated a significant relationship between visfatin, LDL and TG, and leptin levels (p < 0.05). However, when controlled for resistin, the effect of LDL and TG disappeared while that of visfatin stayed in the model. For the nondiabetic group, the results indicated a significant relationship between insulin, BMI, and leptin levels when adjusted for resistin (p < 0.05). However, the effect of insulin disappeared when the model was controlled for resistin. The study results found no relationship between leptin and adiponectin levels in either the diabetic or nondiabetic group and whether adjusted or controlled for resistin. Conclusion. This study provided better understanding of the metabolism of leptin and unveiled the major determinants of leptin levels in diabetic and nondiabetic males. In conclusion, these results show that the association between leptin and metabolic parameters decreases with the progress of disease. PMID:28348585

  1. The Relationship between Adiponectin and Breast Cancer

    PubMed Central

    Erbay, Burcu; Yılmaz, Tonguç Utku; Eraldemir, Ceyla; Üren, Nihal; Tiryaki, Çağrı; Ergül, Emel; Utkan, Zafer

    2016-01-01

    Objective Breast cancer is the most common type of cancer in women worldwide. It is indicated that increased body mass index elevates the risk of developing breast cancer, worsens prognosis, and decreases survival. Several polymorphisms of adiponectin have been shown to affect serum levels of adiponectin and their association with breast cancer. The aim of this study was to investigate the relationship between the adiponectin 45T/G and 276 G/T gene polymorphism and breast cancer in the East Marmara region. Materials and Methods A case-control study was performed in 97 patients with breast cancer and 101 controls in East Marmara in order to evaluate the prevalence of adiponectin gene polymorphism at positions 45 and 276. Patients with familial breast cancer and those who had received chemotherapy or radiotherapy were excluded from the study. Adiponectin gene polymorphisms were investigated using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Results Adiponectin 45T/G gene genotype frequencies of TT, TG, and GG were 61.9%, 37.1%, and 1% in patients with breast cancer, and 67.3%, 30.7%, and 2% in the control group, respectively. Adiponectin 276G/T gene genotype frequencies of GG, GT, and TT were 45.4%, 45.4%, and 9.3% in patients with breast cancer and 55.4%, 39.6%, and 5.0% in the control group, respectively. Conclusion Our study showed that adiponectin 45T/G and 276 G/T gene polymorphism is not associated with breast cancer risk in patients from the East Marmara region.

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

    PubMed Central

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

    2009-01-01

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

  3. Human resistin stimulates the pro-inflammatory cytokines TNF-{alpha} and IL-12 in macrophages by NF-{kappa}B-dependent pathway

    SciTech Connect

    Silswal, Nirupama; Singh, Anil K.; Aruna, Battu; Mukhopadhyay, Sangita; Ghosh, Sudip; Ehtesham, Nasreen Z. . E-mail: nas_ehtesham@yahoo.com

    2005-09-09

    Resistin, a recently discovered 92 amino acid protein involved in the development of insulin resistance, has been associated with obesity and type 2 diabetes. The elevated serum resistin in human diabetes is often associated with a pro-inflammatory milieu. However, the role of resistin in the development of inflammation is not well understood. Addition of recombinant human resistin protein (hResistin) to macrophages (both murine and human) resulted in enhanced secretion of pro-inflammatory cytokines, TNF-{alpha} and IL-12, similar to that obtained using 5 {mu}g/ml lipopolysaccharide. Both oligomeric and dimeric forms of hResistin were able to activate these cytokines suggesting that the inflammatory action of resistin is independent of its conformation. Heat denatured hResistin abrogated cytokine induction while treatment of recombinant resistin with polymyxin B agarose beads had no effect thereby ruling out the role of endotoxin in the recombinant hResistin mediated cytokine induction. The pro-inflammatory nature of hResistin was further evident from the ability of this protein to induce the nuclear translocation of NF-{kappa}B transcription factor as seen from electrophoretic mobility shift assays. Induction of TNF-{alpha} in U937 cells by hResistin was markedly reduced in the presence of either dominant negative I{kappa}B{alpha} plasmid or PDTC, a pharmacological inhibitor of NF-{kappa}B. A protein involved in conferring insulin resistance is also a pro-inflammatory molecule that has important implications.

  4. Resistin levels in morbid obese patients following the biliopancreatic diversion surgery.

    PubMed

    de Luis, D A; Terroba, M C; Cuellar, L; Conde, R; Primo, D; Aller, R; Sagrado, M G; Izaola, O

    2011-03-01

    Previous studies addressing the changes of resistin concentrations in morbidly obese patients after bariatric surgery have yielded conflicting results. The purpose of the present study was to investigate the changes in serum resistin levels 1 year after biliopancreatic diversion in morbidly obese patients without diabetes mellitus. A cohort of 39 morbidly obese patients without diabetes mellitus was operated. Biochemical and anthropometric evaluation were realized at basal visit and at each visit. The frequency of patients with hypertension and hyperlipidemia was recorded at each visit. Overall the mean patient age was 44.8 ± 14.1, and the mean preoperative BMI was 47.3 ± 6.5 kg/m². After one year of surgery, a significant decrease was observed in BMI, weight, waist circumference, fat mass, blood pressure, total cholesterol, LDL cholesterol, and triglyceride levels. Resistin levels did not change after surgery (5.61 ± 1.93 ng/ml vs. 6.41 ± 3.58 ng/ml; ns). Correlation analysis showed a positive association between basal resistin and weight (r = 0.68, p < 0.01) and fat mass (r = 0.65, p < 0.05). Resistin concentrations did not change after massive weight loss with biliopancreatic diversion in morbid obese patients without diabetes mellitus.

  5. Resistin, an Adipokine with Non-Generalized Actions on Sympathetic Nerve Activity

    PubMed Central

    Badoer, Emilio; Kosari, Samin; Stebbing, Martin J.

    2015-01-01

    The World Health Organization has called obesity a global epidemic. There is a strong association between body weight gain and blood pressure. A major determinant of blood pressure is the level of activity in sympathetic nerves innervating cardiovascular organs. A characteristic of obesity, in both humans and in animal models, is an increase in sympathetic nerve activity to the skeletal muscle vasculature and to the kidneys. Obesity is now recognized as a chronic, low level inflammatory condition, and pro-inflammatory cytokines are elevated including those produced by adipose tissue. The most well-known adipokine released from fat tissue is leptin. The adipokine, resistin, is also released from adipose tissue. Resistin can act in the central nervous system to influence the sympathetic nerve activity. Here, we review the effects of resistin on sympathetic nerve activity and compare them with leptin. We build an argument that resistin and leptin may have complex interactions. Firstly, they may augment each other as both are excitatory on sympathetic nerves innervating cardiovascular organs; In contrast, they could antagonize each other's actions on brown adipose tissue, a key metabolic organ. These interactions may be important in conditions in which leptin and resistin are elevated, such as in obesity. PMID:26617526

  6. Obesity in psoriasis: Leptin and resistin as mediators of cutaneous inflammation

    PubMed Central

    Johnston, A.; Arnadottir, S.; Gudjonsson, J. E.; Aphale, A.; Sigmarsdottir, A. A.; Gunnarsson, S. I.; Steinsson, J. T.; Elder, J. T.; Valdimarsson, H.

    2009-01-01

    Summary Background Obesity is a significant risk factor for psoriasis and body mass index (BMI) correlates with disease severity. Objectives To investigate the relationship between obesity and psoriasis, focusing on the role of adipokines such as leptin and resistin. Patients/Methods Psoriasis patients (n=30) were recruited and their BMI, waist circumference and disease severity (PASI) were recorded. Fasting serum samples were obtained on enrollment and after a course of UVB treatment. Age, sex and BMI-matched healthy controls were also recruited. Results On enrollment, serum leptin and soluble leptin receptor levels were not raised compared with the controls. However, resistin, IL-1β, IL-6, CCL2, CXCL8 and CXCL9 were all significantly elevated in the patient group and serum resistin correlated with disease severity (r=0.372, p=0.043). Improvement after UVB treatment was accompanied by decreased serum CXCL8. In vitro, both leptin and resistin could induce CXCL8 and TNF-α production by blood monocytes, and leptin could additionally induce IL-1β and IL-1ra production. Leptin also dose dependently increased secretion of the growth factor amphiregulin by ex vivo-cultured lesional psoriasis skin. Conclusions These data support the view that leptin and resistin may be involved in the pathogenesis of psoriasis in overweight individuals, possibly by augmenting the cytokine expression by the inflammatory infiltrate. PMID:18547319

  7. Resistin impairs glucose permeability in EA.hy926 cells by down-regulating GLUT1 expression.

    PubMed

    Li, Qiang; Cai, Yuxi; Huang, Jing; Yu, Xiaolan; Sun, Jun; Yang, Zaiqing; Zhou, Lei

    2016-10-15

    Type 2 diabetes mellitus (T2DM) is a chronic disease which is now affecting the health of more and more people in the world. Resistin, discovered in 2001, is considered to be closely related to metabolic dysfunction and obesity. Previous study showed that hyperglycemia is always accompanied by a high serum resistin concentration. We therefore investigated whether resistin can mediate glucose transfer across the blood-tissue barrier. Here, we employed a transwell system to analyze glucose permeability in EA.hy926 human endothelial cells treated without or with human resistin. In EA.hy926 cells treated with resistin, the permeability to glucose was heavily impaired. This was due to the down-regulation of GLUT1 expression as a result of the treatment, rather than regulation of tight junctions. In addition, overexpression of GLUT1 in EA.hy926 cells was able to recover the blocking effect of resistin on glucose permeability. We further found that resistin could inhibit the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and consequently impede the transcription of GLUT1. The results of the present study suggested that resistin could cause glucose retention in serum and thus result in hyperglycemia. This provides a novel explanation for hyperglycemia and a potential new way of treating type 2 diabetes mellitus.

  8. 13C metabolic flux analysis shows that resistin impairs the metabolic response to insulin in L6E9 myotubes

    PubMed Central

    2014-01-01

    Background It has been suggested that the adipokine resistin links obesity and insulin resistance, although how resistin acts on muscle metabolism is controversial. We aimed to quantitatively analyse the effects of resistin on the glucose metabolic flux profile and on insulin response in L6E9 myotubes at the metabolic level using a tracer-based metabolomic approach and our in-house developed software, Isodyn. Results Resistin significantly increased glucose uptake and glycolysis, altering pyruvate utilisation by the cell. In the presence of resistin, insulin only slightly increased glucose uptake and glycolysis, and did not alter the flux profile around pyruvate induced by resistin. Resistin prevented the increase in gene expression in pyruvate dehydrogenase-E1 and the sharp decrease in gene expression in cytosolic phosphoenolpyruvate carboxykinase-1 induced by insulin. Conclusions These data suggest that resistin impairs the metabolic activation of insulin. This impairment cannot be explained by the activity of a single enzyme, but instead due to reorganisation of the whole metabolic flux distribution. PMID:25217974

  9. Novel expression of resistin in rat testis: functional role and regulation by nutritional status and hormonal factors.

    PubMed

    Nogueiras, Ruben; Barreiro, M Luz; Caminos, Jorge E; Gaytán, Francisco; Suominen, Janne S; Navarro, Victor M; Casanueva, Felipe F; Aguilar, Enrique; Toppari, Jorma; Diéguez, Carlos; Tena-Sempere, Manuel

    2004-07-01

    Resistin, a recently cloned adipose-secreted factor, is primarily involved in the modulation of insulin sensitivity and adipocyte differentiation. However, additional metabolic or endocrine functions of this molecule remain largely unexplored. In this study, a series of experiments were undertaken to explore the potential expression, regulation and functional role of this novel adipocytokine in rat testis. Resistin gene expression was demonstrated in rat testis throughout postnatal development, with maximum mRNA levels in adult specimens. At this age, resistin peptide was immunodetected in interstitial Leydig cells and Sertoli cells within seminiferous tubules. Testicular expression of resistin was under hormonal regulation of pituitary gonadotropins and showed stage-specificity, with peak expression values at stages II-VI of the seminiferous epithelial cycle. In addition, testicular resistin mRNA was down-regulated by the selective agonist of PPARgamma, rosiglitazone, in vivo and in vitro. Similarly, fasting and central administration of the adipocyte-derived factor, leptin, evoked a significant reduction in testicular resistin mRNA levels, whereas they remained unaltered in a model of diet-induced obesity. From a functional standpoint, resistin, in a dose-dependent manner, significantly increased both basal and choriogonadotropin-stimulated testosterone secretion in vitro. Overall, our present results provide the first evidence for the expression, regulation and functional role of resistin in rat testis. These data underscore a reproductive facet of this recently cloned molecule, which may operate as a novel endocrine integrator linking energy homeostasis and reproduction.

  10. Resistin Enhances Inflammatory Cytokine Production in Coronary Artery Tissues by Activating the NF-κB Signaling

    PubMed Central

    Gao, Fang; Si, Feifei; Feng, Siqi; Liu, Ruixi

    2016-01-01

    Purpose. Kawasaki disease (KD) is a systemic vasculitis and is a leading cause of coronary artery lesions (CALs) in childhood. Our previous study has shown higher levels of serum Resistin in KD patients with coronary aneurysm. This study aimed at examining the association of Resistin with inflammatory cytokine expression in mouse model of coronary arteritis and determining the potential mechanisms. Methods. C57BL/6 mice were injected with Lactobacillus cell wall extract (LCWE) to induce coronary arteritis. The relative levels of Resistin, TNF-α, IL-1β, and MMP-9 expression and inflammatory infiltrates in the coronary arteries were determined longitudinally by quantitative RT-PCR, ELISA, and histology. The effect of TLR4 and NF-κB activation on Resistin-induced TNF-α and IL-1β expression in human coronary artery endothelium cells (HCAECs) was examined by quantitative RT-PCR. Results. Higher levels of Resistin, TNF-α, IL-1β, and MMP-9 expression were associated with the degrees of inflammatory infiltrates in the coronary artery walls of the LCWE-injected mice. Resistin enhanced TNF-α and IL-1β expression in HCAECs at 18 or 24 hours after stimulation. Pretreatment with anti-TLR4 attenuated Resistin-enhanced IL-1β, but not TNF-α, expression and pretreatment with parthenolide or QNZ demolished Resistin-enhanced TNF-α expression in HACECs. Pretreatment with parthenolide, but not QNZ, blocked Resistin-enhanced IL-1β expression in HCAECs. Conclusion. Resistin may enhance inflammation by cross-talking with TLR4/NF-κB signaling during the development of coronary arteritis in mice. PMID:27800490

  11. Serum Resistin Levels Are Associated with Adiposity and Insulin Sensitivity in Obese Hispanic Subjects

    PubMed Central

    Nieva-Vazquez, Adriana; Torres-Rasgado, Enrique; López-López, José G.; Romero, Jose R.

    2014-01-01

    Abstract Background and Aims: Resistin is involved in the development of obesity and insulin resistance (IR) in mice and may play a similar role in humans through mechanisms that remain unresolved. The objective of this study was to characterize the relationship between resistin levels in obese subjects with and without IR among Hispanic subjects. Material and Methods: A cross-sectional study was performed on 117 nondiabetic Hispanic subjects of both genders that were allocated into three study groups: A control group (n=47) of otherwise healthy individuals in metabolic balance, a group with obesity (OB) (n=36), and a group with obesity and IR (OB-IR) (n=34). Anthropometric and clinical characterization was carried out, and resistin levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: We found that resistin levels were higher in OB and OB-IR groups when compared to the control group (1331.79±142.15 pg/mL, 1266.28±165.97 pg/mL vs. 959.21±171.43 pg/mL; P<0.05), an effect that was not confounded by age (control, 34.04±10.00 years; OB, 37.30±10.78 years; and OB-IR, 35.67±10.15 years). In addition, we observed a significant correlation (P<0.001) between resistin levels and higher adiposity and insulin sensitivity (IS) in our cohort. Conclusions: Our results suggest that higher resistin levels are associated with higher adiposity and lower IS among obese Hispanic subjects. PMID:24266722

  12. Nampt/PBEF/Visfatin Upregulation in Colorectal Tumors, Mirrored in Normal Tissue and Whole Blood of Colorectal Cancer Patients, Is Associated with Metastasis, Hypoxia, IL1β, and Anemia

    PubMed Central

    Bednarz Misa, Iwona; Kapturkiewicz, Bartosz; Gamian, Andrzej; Krzystek-Korpacka, Malgorzata

    2015-01-01

    Targeting Nampt/PBEF/visfatin is considered a promising anticancer strategy, yet little is known about its association with colorectal cancer (CRC). We quantified Nampt/PBEF/visfatin expression in bowel and blood (mRNA and protein), referring it to CRC advancement and inflammatory, angiogenic, hypoxia, and proliferation indices. Tumor Nampt/PBEF/visfatin upregulation was associated with metastasis, anemia, tumor location, HIF1α, and inflammatory and angiogenic indices, of which HIF1α, IL1β, and anemia explained 70% in Nampt/PBEF/visfatin variability. Nampt/PBEF/visfatin expression in nontumor tissue, both mRNA and protein, increased in patients with metastatic disease and mild anemia, and, on transcriptional level, correlated with HIF1α, IL1β, IL8, CCL2, and CCL4 expression. Whole blood Nampt/PBEF/visfatin tended to be elevated in patients with metastatic cancer or anemia and correlated with inflammatory indices, of which IL1β, IL8, and hematocrit explained 60% of its variability. Circulating visfatin was associated with lymph node metastasis and inflammatory and angiogenic indices. In vitro experiments on SW620 cells demonstrated Nampt/PBEF/visfatin downregulation in response to serum withdrawal but its upregulation in response to serum induction and hypoxia. Stimulation with recombinant visfatin did not provide growth advantage. Summarizing, our results link Nampt/PBEF/visfatin with tumor metastatic potential and point at inflammation and hypoxia as key inducers of its upregulation in CRC. PMID:26075243

  13. Nampt/PBEF/visfatin upregulation in colorectal tumors, mirrored in normal tissue and whole blood of colorectal cancer patients, is associated with metastasis, hypoxia, IL1β, and anemia.

    PubMed

    Neubauer, Katarzyna; Misa, Iwona Bednarz; Diakowska, Dorota; Kapturkiewicz, Bartosz; Gamian, Andrzej; Krzystek-Korpacka, Malgorzata

    2015-01-01

    Targeting Nampt/PBEF/visfatin is considered a promising anticancer strategy, yet little is known about its association with colorectal cancer (CRC). We quantified Nampt/PBEF/visfatin expression in bowel and blood (mRNA and protein), referring it to CRC advancement and inflammatory, angiogenic, hypoxia, and proliferation indices. Tumor Nampt/PBEF/visfatin upregulation was associated with metastasis, anemia, tumor location, HIF1α, and inflammatory and angiogenic indices, of which HIF1α, IL1β, and anemia explained 70% in Nampt/PBEF/visfatin variability. Nampt/PBEF/visfatin expression in nontumor tissue, both mRNA and protein, increased in patients with metastatic disease and mild anemia, and, on transcriptional level, correlated with HIF1α, IL1β, IL8, CCL2, and CCL4 expression. Whole blood Nampt/PBEF/visfatin tended to be elevated in patients with metastatic cancer or anemia and correlated with inflammatory indices, of which IL1β, IL8, and hematocrit explained 60% of its variability. Circulating visfatin was associated with lymph node metastasis and inflammatory and angiogenic indices. In vitro experiments on SW620 cells demonstrated Nampt/PBEF/visfatin downregulation in response to serum withdrawal but its upregulation in response to serum induction and hypoxia. Stimulation with recombinant visfatin did not provide growth advantage. Summarizing, our results link Nampt/PBEF/visfatin with tumor metastatic potential and point at inflammation and hypoxia as key inducers of its upregulation in CRC.

  14. Genetic associations of the visfatin G-948T polymorphism with obesity-related metabolic traits in an Iranian population

    PubMed Central

    Javanmard, Shaghayegh Haghjooy; Dehghananzadeh, Raheleh; Rafiee, Laleh; Naji, Hajar; Rezayat, Azadeh; Sarrafzadegan, Nizal

    2016-01-01

    Background: Obesity is a global public health problem. Visfatin, as an adipocytokine, is coded by a gene known as nicotinamide phosphoribosyltransferase. So far, results were conflicted regarding correlations of visfatin with obesity and metabolic variables. The present study aimed to explore the association between G-948T polymorphism of visfatin gene with obesity and lipid profile in a nationally representative sample of Iranian population. Materials and Methods: In this case–control study, we assessed 129 randomly selected patients with obesity and 182 healthy normal weight controls from participants of Isfahan Healthy Heart Program. Genomic DNA was isolated from peripheral blood cells, and high-resolution melt polymerase chain reaction was performed to explore the presence of G-948T polymorphism. Results: T carriers “GT + TT” were statistically more frequent in the obese patients than the controls (P = 0.013; odds ratio = 1.9, 95% confidence interval = 1.1–3.1). The serum levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly different between T carriers and GG homozygote genotype (P = 0.03 and 0.02, respectively). Conclusion: We concluded that visfatin G-948T polymorphism was correlated with obesity, total cholesterol, and LDL-C levels in our population.

  15. Serum Visfatin and Fetuin-A Levels and Glycemic Control in Patients with Obese Type 2 Diabetes Mellitus

    PubMed Central

    Gunduz, Fethiye Oztop; Temizel, Mustafa; Faki, Yilmaz; Cakmak, Mustafa; Durmuscan, Mustafa; Sezgin, Funda

    2011-01-01

    Background Visfatin is an adipokine produced by visceral adipose tissue and has insulin-mimicking effects. Fetuin-A is a hepatic secretory protein that binds the insulin receptor and inhibits insulin action both in vivo and in vitro. The authors of the present study aimed to investigate the levels of serum visfatin and fetuin-A and their correlation with hemoglobin A1c (HbA1c) and urine albumin levels in patients with type 2 diabetes mellitus (T2DM). Methods A total of 40 obese patients with T2DM (11 males and 29 females; age, 54.47±10.83 years and 23 obese nondiabetic controls (8 males and 15 females; age, 53.04±11.33 years) were included in the study. Age, sex, and body mass index were similar in the 2 groups. Serum visfatin and fetuin-A levels were measured by enzyme-linked immunosorbent assay. HbA1c and urine albumin levels were measured by high performance liquid chromatography and nephelometric method, respectively. Results Serum levels of visfatin in patients with T2DM (4.03±2.44 ng/mL) were similar to the control group (3.65±3.02 ng/mL). Serum fetuin-A levels were significantly lower in patients with T2DM than the controls (298.75±78.86 and 430.73±94.46 µg/mL, respectively). HbA1c levels were significantly higher in the T2DM group compared with controls (7.33±1.32 and 5.44±0.84%, respectively). Correlations between visfatin, fetuin-A and HbA1c levels were not observed. Conclusion The present study suggests fetuin-A may play a role in the pathogenesis of T2DM. PMID:22111044

  16. Resistin is not an appropriate biochemical marker to predict severity of acute pancreatitis: A case-controlled study

    PubMed Central

    Al-Maramhy, Hamdi; Abdelrahman, Abdelrahman I; Sawalhi, Samer

    2014-01-01

    AIM: To assess levels of serum resistin upon hospital admission as a predictor of acute pancreatitis (AP) severity. METHODS: AP is both a common and serious disease, with severe cases resulting in a high mortality rate. Several predictive inflammatory markers have been used clinically to assess severity. This prospective study collected data from 102 patients who were diagnosed with an initial acute biliary pancreatitis between March 2010 and February 2013. Measurements of body mass index (BMI) and waist circumference (WC) were obtained and serum resistin levels were analyzed at the time of hospital admission using enzyme-linked immunosorbent assay. Additionally, resistin levels were measured from a control group after matching gender, BMI and age. RESULTS: A total of 102 patients (60 females and 42 males) were diagnosed with acute gallstone-induced pancreatitis. The mean age was 45 years, and mean BMI value was 30.5 kg/m2 (Obese, class I). Twenty-two patients (21.6%) had severe AP, while eighty-eight patients had mild pancreatitis (78.4%). Our results showed that BMI significantly correlated with pancreatitis severity (P = 0.007). Serum resistin did not correlate with BMI, weight or WC. Furthermore, serum resistin was significantly higher in patients with AP compared to control subjects (P < 0.0001). The mean resistin values upon admission were 17.5 ng/mL in the severe acute biliary pancreatitis group and 16.82 ng/mL in the mild AP group (P = 0.188), indicating that resistin is not an appropriate predictive marker of clinical severity. CONCLUSION: We demonstrate that obesity is a risk factor for developing severe AP. Further, although there is a correlation between serum resistin levels and AP at the time of hospital admission, resistin does not adequately serve as a predictive marker of clinical severity. PMID:25386084

  17. Obesity, Serum Resistin and Leptin Levels Linked to Coronary Artery Disease

    PubMed Central

    Montazerifar, Farzaneh; Bolouri, Ahmad; Paghalea, Raheleh Sharifian; Mahani, Mahbubeh Khodadadpour; Karajibani, Mansour

    2016-01-01

    Background Clinical studies have demonstrated that adipocytokines play an important role in developing atherosclerotic cardiovascular diseases. Objective The aim of study was to evaluate the relationship between serum resistin and leptin levels with obesity and coronary artery disease (CAD). Methods In a cross-sectional study, we assessed the levels of serum resistin and leptin, C-reactive protein (CRP), lipid profile and cardiac enzyme tests (AST, CPK, LDH, CK-MB) in 40 CAD patients compared to 40 healthy controls. Anthropometric measurements including weight and height for calculating of body mass index (BMI), and waist circumference (WC) were performed for evaluation of obesity. Results CAD patients had increased levels of leptin and CRP, (p < 0.001), cholesterol (p < 0.05), triglyceride (p < 0.01), and WC (p < 0.05) compared to healthy controls. There was no statistical difference between CAD and control subjects for resistin (p = 0.058). In a multiple regression analysis, only an association between serum leptin with BMI (β = 0.480, p < 0.05) and WC (β = 1.386, p < 0.05) was found. Conclusions The findings suggest that leptin is a better marker of fat mass value than resistin and may be considered an independent risk factor for cardiac disorders that is largely dependent on obesity. However, further prospective studies are needed to confirm these results. PMID:27627223

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

    PubMed

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

    2013-07-01

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

  19. Interlinking Periodontitis and Type 2 Diabetes Mellitus by Assessment of Crevicular Visfatin Levels in Health and in Disease Before and After Initial Periodontal Therapy

    PubMed Central

    Shettar, Leena; Bajaj, Mahesh; Math, Abhishek Savir; Thakur, Srinath L.

    2016-01-01

    Introduction Visfatin is a new adipocytokine associated with both chronic periodontitis and type 2 diabetes mellitus independently. Aim We aimed to estimate and compare the changes in the levels of visfatin in the Gingival Crevicular Fluid (GCF) of healthy subjects and in subjects with periodontitis with or without controlled Type 2 Diabetes Mellitus (T2DM) after administration of non-surgical periodontal therapy. Materials and Methods Forty two subjects were equally divided into Group 1 (healthy), Group 2 (systemically healthy with chronic periodontitis), Group 3 (subjects with chronic periodontitis having controlled T2DM). Defined clinical parameters were recorded at baseline and at one month follow-up period. Visfatin was assessed using enzyme linked immunosorbent assay. One way ANOVA and Tukey’s multiple post hoc procedures were used. Pearson’s correlation coefficient was used for correlation. Results Significant increase in the visfatin levels was seen with the highest values observed in diabetes with periodontal disease. Visfatin responded to non-surgical periodontal therapy as observed by significant decrease in levels after one month but even at this period diabetics showed the highest levels. Conclusion Visfatin levels are highest in individuals with both periodontal disease and diabetes even after periodontal therapy. Individuals with T2DM may be at higher risk of developing periodontal disease. PMID:27656567

  20. [Adiponectin: an anti-carcinogenic adipokine?].

    PubMed

    Fève, Bruno

    2013-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. Leptin and adiponectin in the female life course.

    PubMed

    Lecke, S B; Morsch, D M; Spritzer, P M

    2011-05-01

    Adipose tissue secretes a variety of adipokines, including leptin and adiponectin, which are involved in endocrine processes regulating glucose and fatty metabolism, energy expenditure, inflammatory response, immunity, cardiovascular function, and reproduction. The present article describes the fluctuations in circulating leptin and adiponectin as well as their patterns of secretion in women from birth to menopause. During pregnancy, leptin and adiponectin seem to act in an autocrine/paracrine fashion in the placenta and adipose tissue, playing a role in the maternal-fetal interface and contributing to glucose metabolism and fetal development. In newborns, adiponectin levels are two to three times higher than in adults. Full-term newborns have significantly higher leptin and adiponectin levels than preterms, whereas small-for-gestational-age infants have lower levels of these adipokines than adequate-for-gestational-age newborns. However, with weight gain, leptin concentrations increase significantly. Children between 5 and 8 years of age experience an increase in leptin and a decrease in adiponectin regardless of body mass index, with a reversal of the newborn pattern for adiponectin: plasma adiponectin levels at age five are inversely correlated with percentage of body fat. In puberty, leptin plays a role in the regulation of menstrual cycles. In adults, it has been suggested that obese individuals exhibit both leptin resistance and decreased serum adiponectin levels. In conclusion, a progressive increase in adiposity throughout life seems to influence the relationship between leptin and adiponectin in women.

  4. Effects of eicosapentaenoic acid ethyl ester on visfatin and apelin in lean and overweight (cafeteria diet-fed) rats.

    PubMed

    Pérez-Echarri, Nerea; Pérez-Matute, Patricia; Marcos-Gómez, Beatriz; Martínez, J Alfredo; Moreno-Aliaga, María J

    2009-04-01

    Previous studies have demonstrated that the n-3 fatty acid EPA improves insulin resistance induced by high-fat diets. The aim of the present study was to investigate the potential role of visfatin and apelin in the insulin-sensitising effects of EPA ethyl ester. The effects of EPA on muscle and adipose GLUT mRNA, as well as on liver glucokinase (GK) and glucose-6-phosphatase (G6Pase) activity, were investigated. Male Wistar rats fed on a standard diet or a high-fat cafeteria diet were daily treated by oral administration with EPA ethyl ester (1 g/kg) for 5 weeks. A significant decrease (P < 0.01) in white adipose tissue (WAT) visfatin mRNA levels was found in the cafeteria-fed rats, which was reversed by EPA administration (P < 0.05). Moreover, a negative relationship was observed between homeostatic model assessment (HOMA) and the visfatin:total WAT ratio. In contrast, cafeteria-diet feeding caused a significant increase (P < 0.01) in apelin mRNA in visceral WAT. EPA increased (P < 0.01) apelin gene expression, and a negative relationship between HOMA index with visceral apelin mRNA and serum apelin:total WAT ratio was also observed. EPA treatment did not induce changes in skeletal muscle GLUT1, GLUT4 or insulin receptor mRNA levels. Neither liver GK and G6Pase activity nor the GK:G6Pase ratio was modified by EPA. These data suggest that somehow the insulin-sensitising effects of EPA could be related to its stimulatory action on both visfatin and apelin gene expression in visceral fat, while changes in skeletal muscle GLUT, as well as in hepatic glucose production, are not likely to be the main contributing factors in the improvement in insulin resistance induced by EPA.

  5. Genetic variant in visfatin gene promoter contributes to reduced risk of hepatocellular carcinoma in a Chinese population

    PubMed Central

    Huang, Yiyong; Zhu, Shengbo; Feng, Yi; Ye, Huifen; Liu, Chunming; Tang, Shifu

    2016-01-01

    Knowledge on the role of gene variants in the visfatin promoter region in the hepatitis B virus (HBV)-related liver diseases is limited. In this study, we genotyped two potentially functional single nucleotide polymorphisms (SNPs) in the visfatin promoter region, -1535C>T (rs61330082) and -3187G>A (rs11977021), in 120 HBV-related chronic hepatitis B (CHB) patients, 140 HBV-related liver cirrhosis (HBV-LC) patients, 243 HBV-related hepatocellular carcinoma (HBV-HCC) patients, and 224 asymptomatic HBV carriers. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. The results showed subjects with a TT genotype of -1535C>T had a significantly decreased risk of HBV-HCC related to the CC and CC + CT genotypes (adjusted OR = 0.493, 95% CI = 0.313-0.778; OR = 0.535, 95% CI = 0.362-0.791, respectively). A lowered risk also appeared in the comparison between allele T and allele C (OR = 0.734, 95%, CI = 0.581-0.950). However, these associations existed only in people with Zhuang ethnicity, but not in people with Han ethnicity. There were no significant associations between -3187G>A polymorphisms and the risk of HBV-related liver diseases. Our results suggested that visfatin -1535C>T polymorphisms might be associated with decreased risk of HBV-HCC among the ethnic Zhuang population in Guangxi, China. PMID:27792999

  6. Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice

    SciTech Connect

    Ezaki, Hisao; Yoshida, Yuichi; Saji, Yukiko; Takemura, Takayo; Fukushima, Juichi; Matsumoto, Hitoshi; Kamada, Yoshihiro; Wada, Akira; Igura, Takumi; Kihara, Shinji; Funahashi, Tohru; Shimomura, Iichiro; Tamura, Shinji; Kiso, Shinichi Hayashi, Norio

    2009-01-02

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

  7. Adiponectin and end-stage renal disease.

    PubMed

    Markaki, Anastasia; Psylinakis, Emmanuel; Spyridaki, Aspasia

    2016-07-01

    Adiponectin (ADPN) is an adipokine with significant anti-inflammatory, insulin-sensitizing and anti-atherogenic properties, which is generally associated with a beneficial cardiometabolic profile. Paradoxically, end-stage renal disease (ESRD) is characterized by markedly increased plasma ADPN levels and increased cardiovascular risk. In spite of the cardioprotective properties attributed to adiponectin, cardiovascular complications remain the main cause of mortality in the ESRD population. Furthermore, these patients have enhanced chronic inflammation, increased insulin resistance and persistent protein-energy wasting. Studies of the impact of ADPN on clinical outcomes among ESRD patients have so far yielded contradictory results. This review article summarizes the current knowledge on ADPN functions and explores the role of ADPN in ESRD patients, with specific focus on inflammation, insulin resistance, cardiovascular disease and wasting.

  8. Adiponectin inhibits Lrp6 phosphorylation and β-catenin signaling

    PubMed Central

    Reinke, Lauren; Lam, Anna P.; Flozak, Annette S.; Varga, John; Gottardi, Cara J.

    2016-01-01

    Adiponectin is a pleiotropic adipokine implicated in obesity, metabolic syndrome and cardiovascular disease. Recent studies have identified adiponectin as a negative regulator of tissue fibrosis. Wnt/β-catenin signaling has also been implicated in metabolic syndrome and can promote tissue fibrosis, but the extent to which adiponectin cross-regulates Wnt/β-catenin signaling is unknown. Using primary human dermal fibroblasts and recombinant purified proteins, we show that adiponectin can limit β-catenin accumulation and downstream gene activation by inhibiting Lrp6 phosphorylation, a key activation step in canonical Wnt signaling. Inhibition of Wnt3a-mediated Lrp6 phospho-activation is relatively rapid (e.g., by 30 minutes), and is not dependent on established adiponectin G-protein coupled receptors, AdipoR1 and R2, suggesting a more direct relationship to Lrp6 signaling. In contrast, the ability of adiponectin to limit Wnt-induced and baseline collagen production in fibroblasts requires AdipoR1/R2. These results suggest the possibility that the pleiotropic effects of adiponectin may be mediated through distinct cell surface receptor complexes. Accordingly, we propose that the anti-fibrotic activity of adiponectin may be mediated through AdipoR1/R2 receptors, while the ability of adiponectin to inhibit Lrp6 phospho-activation may be relevant to other recently established roles for Lrp6 signaling in glucose metabolism and metabolic syndrome. PMID:26797284

  9. Characterization of the weak calcium binding of trimeric globular adiponectin.

    PubMed

    Yu, Dongmei; Zhang, Chao; Wang, Han; Qin, Peiwu

    2013-06-01

    Adiponectin is secreted from adipose tissue and functions as a protein hormone in regulating glucose metabolism and fatty acid catabolism. Adiponectin plays an important role as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. Crystal structures of globular adiponectin have been resolved with three calcium-binding sites on the top of its central tunnel. However, the calcium-binding property of adiponectin remains elusive. Mouse globular adiponectin was cloned into pET11a and expressed in Escherichia coli. The folding of adiponectin was indicated by the spread of resonances in HSQC spectrum. Luminescence resonance energy transfer was used to obtain the binding constant (K(d)) of Tb(3+) and the inhibitor constant (K(i)) of Ca(2+) for globular adiponectin. The obtained calcium-binding affinity to adiponectin is relatively low (~2 mM), which indicates that the high concentration of adiponectin in circulating system may function as calcium storage bank and buffer the free calcium concentration.

  10. Enhanced Metabolic Flexibility Associated with Elevated Adiponectin Levels

    PubMed Central

    Asterholm, Ingrid Wernstedt; Scherer, Philipp E.

    2010-01-01

    Metabolically healthy individuals effectively adapt to changes in nutritional state. Here, we focus on the effects of the adipocyte-derived secretory molecule adiponectin on adipose tissue in mouse models with genetically altered adiponectin levels. We found that higher adiponectin levels increased sensitivity to the lipolytic effects of adrenergic receptor agonists. In parallel, adiponectin-overexpressing mice also display enhanced clearance of circulating fatty acids and increased expansion of subcutaneous adipose tissue with chronic high fat diet (HFD) feeding. These adaptive changes to the HFD were associated with increased mitochondrial density in adipocytes, smaller adipocyte size, and a general transcriptional up-regulation of factors involved in lipid storage through efficient esterification of free fatty acids. The physiological response to adiponectin overexpression resembles in many ways the effects of chronic exposure to β3-adrenergic agonist treatment, which also results in improvements in insulin sensitivity. In addition, using a novel computed tomography-based method for measurements of hepatic lipids, we resolved the temporal events taking place in the liver in response to acute HFD exposure in both wild-type and adiponectin-overexpressing mice. Increased levels of adiponectin potently protect against HFD-induced hepatic lipid accumulation and preserve insulin sensitivity. Given these profound effects of adiponectin, we propose that adiponectin is a factor that increases the metabolic flexibility of adipose tissue, enhancing its ability to maintain proper function under metabolically challenging conditions. PMID:20093494

  11. Effect of diet on adiponectin levels in blood.

    PubMed

    Silva, Flávia M; de Almeida, Jussara C; Feoli, Ana M

    2011-10-01

    Dietary management has been considered an alternative means of modulating adiponectin levels. The purpose of this review is to examine the scientific evidence regarding the effect of diet on adiponectin levels in blood. Clinical trials were selected from Medline until April 2010 using the following MeSH terms: adipokines OR adiponectin AND diet OR lifestyle. A total of 220 articles were identified in the initial search, and 52 studies utilizing three different methods of dietary management were included in the present review: low-calorie diets (n = 9 studies), modification of diet composition (n = 33), and diet plus exercise (n = 10). Daily intake of fish or omega-3 supplementation increased adiponectin levels by 14-60%. Weight loss achieved with a low-calorie diet plus exercise increased adiponectin levels in the range of 18-48%. A 60-115% increase in adiponectin levels was obtained with fiber supplementation. In conclusion, dietary management can be an effective therapeutic means of increasing adiponectin levels. Studies investigating different forms of adiponectin and changes in the types of adipose tissue are necessary in order to elucidate the mechanisms involved in the modulation of adiponectin levels.

  12. Crystal structures of the human adiponectin receptors

    PubMed Central

    Tanabe, Hiroaki; Fujii, Yoshifumi; 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

    2015-01-01

    Adiponectin stimulation of its receptors, AdipoR1 and AdipoR2, increases AMPK and PPAR activities, 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 receptor (GPCR)s. 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 GPCRs, enclose a large cavity where three conserved histidine residues coordinate a zinc ion. The zinc-binding structure may play a role in the adiponectin-stimulated AMPK phosphorylation and UCP2 upregulation. Adiponectin may broadly interact with the extracellular face, rather than the C-terminal flexible 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

  13. 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.

  14. The Serum Levels of Resistin and Its Relationship with Other Proinflammatory Cytokines in Patients with Alzheimer’s Disease

    PubMed Central

    Demirci, Seden; Aynalı, Ayşe; Demirci, Kadir; Demirci, Serpil; Arıdoğan, Buket Cicioğlu

    2017-01-01

    Objective The present study aims to analyze the levels of resistin, tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-18, and C-reactive protein (CRP) in patients with Alzheimer’s disease (AD) and also investigate a potential relationship between resistin levels and TNF-α, IL-1β, IL-6, IL-18, and CRP levels in patients with AD. Methods The study included fifty patients with AD and 30 healthy controls with normal cognitive functions. The serum resistin, TNF-α, IL-1β, IL-6, IL-18, and CRP levels were assessed. We performed a Mini-Mental State Examination (MMSE) to evaluate the general cognitive performance. Results The mean serum resistin, IL-1β, IL-18, and TNF-α levels were significantly higher in patients with AD compared with the controls (p=0.026, p=0.002, p=0.003, and p=0.038, respectively). The IL-6 and CRP levels did not differ between the groups (p=0.874 and p=0.941). The resistin levels were positively correlated with the levels of CRP and IL-18 (r=0.526, p<0.001; r=0.402, p=0.004, respectively). MMSE scores and inflammatory markers were not correlated (p>0.05 for all). Conclusion Serum resistin levels were significantly increased and correlated with some inflammatory markers in AD patients, suggesting that resistin might play a role in the inflammatory process of AD. PMID:28138112

  15. Serum resistin and high sensitive CRP levels in patients with subclinical hypothyroidism before and after L-thyroxine therapy

    PubMed Central

    Aksoy, Duygu Yazgan; Cinar, Nese; Harmanci, Ayla; Karakaya, Jale; Yildiz, Bulent Okan; Usman, Aydan; Bayraktar, Miyase

    2013-01-01

    Background Subclinical hypothyroidism (SH) is defined by increased thyrotropin (TSH) and normal free thyroxine (fT4) and free triiodothyronine (fT3) levels. Resistin is secreted from adipose tissue and is reported to be associated with insulin resistance and/or inflammation. High sensitive CRP (hs-CRP) is a reliable marker of inflammation. Data related to levels of resistin and hs-CRP in SH and the effect of L-thyroxine treatment on those is limited. We aimed to determine the levels of resistin and hs-CRP in women with SH, and potential effects of L-thyroxine therapy on those levels. Material/Methods Thirty-six patients with SH and 27 age- and BMI-matched healthy control women were included. Waist circumference (Wc), waist-to-hip ratio (WHR), resting energy expenditure (REE), fat mass (FM) and lean mass (LM), TSH, free T4 (fT4), free T3 (fT3), total cholesterol (TC), triglycerides (TG), and HDL- and LDL-cholesterol were determined in all participants. Patients received L-thyroxine treatment for 6 months, after which all measurements were repeated. Resistin and hs-CRP levels were studied from frozen samples after the completion of the study. Results The 2 groups had similar values for Wc, WHR, FM, LM, TC, TG, HDL-C, LDL-C, resistin, and hs-CRP at the beginning. fT4 were higher, whereas TSH was lower in the control group. Resistin and hs-CRP levels did not change after treatment. hs-CRP correlated with BMI and FM before and after treatment. Conclusions Our results suggest that achievement of euthyroid status by replacement therapy did not change resistin or hs-CRP levels in women with SH. hs-CRP correlated with parameters of obesity, which emphasizes the role of body weight in inflammation. PMID:23518675

  16. Association of Variants in RETN With Plasma Resistin Levels and Diabetes-Related Traits in the Framingham Offspring Study

    PubMed Central

    Hivert, Marie-France; Manning, Alisa K.; McAteer, Jarred B.; Dupuis, Josée; Fox, Caroline S.; Cupples, L. Adrienne; Meigs, James B.; Florez, Jose C.

    2009-01-01

    OBJECTIVE— The RETN gene encodes the adipokine resistin. Associations of RETN with plasma resistin levels, type 2 diabetes, and related metabolic traits have been inconsistent. Using comprehensive linkage disequilibrium mapping, we genotyped tag single nucleotide polymorphisms (SNPs) in RETN and tested associations with plasma resistin levels, risk of diabetes, and glycemic traits. RESEARCH DESIGN AND METHODS— We examined 2,531 Framingham Offspring Study participants for resistin levels, glycemic phenotypes, and incident diabetes over 28 years of follow-up. We genotyped 21 tag SNPs that capture common (minor allele frequency >0.05) or previously reported SNPs at r2 > 0.8 across RETN and its flanking regions. We used sex- and age-adjusted linear mixed-effects models (with/without BMI adjustment) to test additive associations of SNPs with traits, adjusted Cox proportional hazards models accounting for relatedness for incident diabetes, and generated empirical P values (Pe) to control for type 1 error. RESULTS— Four tag SNPs (rs1477341, rs4804765, rs1423096, and rs10401670) on the 3′ side of RETN were strongly associated with resistin levels (all minor alleles associated with higher levels, Pe<0.05 after multiple testing correction). rs10401670 was also associated with fasting plasma glucose (Pe = 0.02, BMI adjusted) and mean glucose over follow-up (Pe = 0.01; BMI adjusted). No significant association was observed for adiposity traits. On meta-analysis, the previously reported association of SNP −420C/G (rs1862513) with resistin levels remained significant (P = 0.0009) but with high heterogeneity across studies (P < 0.0001). CONCLUSIONS— SNPs in the 3′ region of RETN are associated with resistin levels, and one of them is also associated with glucose levels, although replication is needed. PMID:19074981

  17. Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels

    PubMed Central

    Qi, Qibin; Menzaghi, Claudia; Smith, Shelly; Liang, Liming; de Rekeneire, Nathalie; Garcia, Melissa E.; Lohman, Kurt K.; Miljkovic, Iva; Strotmeyer, Elsa S.; Cummings, Steve R.; Kanaya, Alka M.; Tylavsky, Frances A.; Satterfield, Suzanne; Ding, Jingzhong; Rimm, Eric B.; Trischitta, Vincenzo; Hu, Frank B.; Liu, Yongmei; Qi, Lu

    2012-01-01

    Resistin is a polypeptide hormone that was reported to be associated with insulin resistance, inflammation and risk of type 2 diabetes and cardiovascular disease. We conducted a genome-wide association (GWA) study on circulating resistin levels in individuals of European ancestry drawn from the two independent studies: the Nurses' Health Study (n = 1590) and the Health, Aging and Body Composition Study (n = 1658). Single-nucleotide polymorphisms (SNPs) identified in the GWA analysis were replicated in an independent cohort of Europeans: the Gargano Family Study (n = 659). We confirmed the association with a previously known locus, the RETN gene (19p13.2), and identified two novel loci near the TYW3/CRYZ gene (1p31) and the NDST4 gene (4q25), associated with resistin levels at a genome-wide significant level, best represented by SNP rs3931020 (P = 6.37 × 10–12) and SNP rs13144478 (P = 6.19 × 10−18), respectively. Gene expression quantitative trait loci analyses showed a significant cis association between the SNP rs3931020 and CRYZ gene expression levels (P = 3.68 × 10−7). We also found that both of these two SNPs were significantly associated with resistin gene (RETN) mRNA levels in white blood cells from 68 subjects with type 2 diabetes (both P = 0.02). In addition, the resistin-rising allele of the TYW3/CRYZ SNP rs3931020, but not the NDST4 SNP rs13144478, showed a consistent association with increased coronary heart disease risk [odds ratio = 1.18 (95% CI, 1.03–1.34); P = 0.01]. Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels. More studies are needed to verify the associations of the SNP rs13144478 with NDST4 gene expression and resistin-related disease. PMID:22843503

  18. Novel Locus FER Is Associated With Serum HMW Adiponectin Levels

    PubMed Central

    Qi, Lu; Menzaghi, Claudia; Salvemini, Lucia; De Bonis, Concetta; Trischitta, Vincenzo; Hu, Frank B.

    2011-01-01

    OBJECTIVE High molecular weight (HMW) adiponectin is a predominant isoform of circulating adiponectin and has been related to type 2 diabetes. Previous linkage studies suggest that different genetic components might be involved in determining HMW and total adiponectin levels. RESEARCH DESIGN AND METHODS We performed a genome-wide association study (GWAS) of serum HMW adiponectin levels in individuals of European ancestry drawn from the Nurses’ Health Study (NHS) (N = 1,591). The single nucleotide polymorphisms (SNPs) identified in the GWAS analysis were replicated in an independent cohort of Europeans (N = 626). We examined the associations of the identified variations with diabetes risk and metabolic syndrome. RESULTS We identified a novel locus near the FER gene (5q21) at a genome-wide significance level, best represented by SNP rs10447248 (P = 4.69 × 10−8). We also confirmed that variations near the adiponectin-encoding ADIPOQ locus (3q27) were related to serum HMW adiponectin levels. In addition, we found that FER SNP rs10447248 was related to HDL cholesterol levels (P = 0.009); ADIPOQ variation was associated with fasting glucose (P = 0.04), HDL cholesterol (P = 0.04), and a metabolic syndrome score (P = 0.002). CONCLUSIONS Our results suggest that different loci may be involved in regulation of circulating HMW adiponectin levels and provide novel insight into the mechanisms that affect HMW adiponectin homeostasis. PMID:21700879

  19. 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

  20. Differential neutrophil responses to bacterial stimuli: Streptococcal strains are potent inducers of heparin-binding protein and resistin-release.

    PubMed

    Snäll, Johanna; Linnér, Anna; Uhlmann, Julia; Siemens, Nikolai; Ibold, Heike; Janos, Marton; Linder, Adam; Kreikemeyer, Bernd; Herwald, Heiko; Johansson, Linda; Norrby-Teglund, Anna

    2016-02-18

    Neutrophils are critical for the control of bacterial infections, but they may also contribute to disease pathology. Here we explore neutrophil responses, in particular the release of sepsis-associated factors heparin-binding protein (HBP) and resistin in relation to specific bacterial stimuli and sepsis of varying aetiology. Analyses of HBP and resistin in plasma of septic patients revealed elevated levels as compared to non-infected critically ill patients. HBP and resistin correlated significantly in septic patients, with the strongest association seen in group A streptococcal (GAS) cases. In vitro stimulation of human neutrophils revealed that fixed streptococcal strains induced significantly higher release of HBP and resistin, as compared to Staphylococcus aureus or Escherichia coli. Similarly, neutrophils stimulated with the streptococcal M1-protein showed a significant increase in co-localization of HBP and resistin positive granules as well as exocytosis of these factors, as compared to LPS. Using a GAS strain deficient in M1-protein expression had negligible effect on neutrophil activation, while a strain deficient in the stand-alone regulator MsmR was significantly less stimulatory as compared to its wild type strain. Taken together, the findings suggest that the streptococcal activation of neutrophils is multifactorial and involves, but is not limited to, proteins encoded by the FCT-locus.

  1. SGK1 Activity is Modulated by Resistin in Vascular Smooth Muscle Cells and in the Aorta in Response to Diet-Induced Obesity

    PubMed Central

    Scott, Takara A.; Babayeva, Oguljahan; Banerjee, Saswati; Zhong, Wei; Francis, Sharon C.

    2016-01-01

    Objective Enhanced serum and glucocorticoid-inducible kinase 1 (SGK1) activity contributes to the pathogenesis of vascular disease. We evaluated SGK1 modulation in vascular smooth muscle cells by the adipokine, resistin and in aortic tissue in a murine model of diet-induced obesity (DIO). Methods Modulation of SGK1 by resistin was assessed in human aortic smooth muscle cells (HAoSMC) in vitro by quantitative RT-PCR and western blot analyses. To induce the lean or obese phenotype, mice were fed a 10 kcal% low-fat or 60 kcal% high-fat diet, respectively for eight weeks. Upon study completion, plasma resistin was assessed and aortic tissue was harvested to examine the effect of DIO on regulation of SGK1 in vivo. Results Resistin increased SGK1 mRNA, total protein abundance and its activation as determined by phosphorylation of its serine 422 residue (pSGK1) in HAoSMC. Resistin-mediated SGK1 phosphorylation was dependent upon phosphatidylinositol-3-kinase and Toll-like receptor 4. Furthermore, inhibition of SGK1 attenuated resistin-induced proliferation in HAoSMC. DIO led to upregulation of total SGK1 protein levels and pSGK1 in association with increased plasma resistin. Conclusions These data suggest that high levels of resistin observed during obesity may activate SGK1 in the vasculature and contribute to the development of obesity-related vascular disease. PMID:26833885

  2. Exercise improves adiponectin concentrations irrespective of the adiponectin gene polymorphisms SNP45 and the SNP276 in obese Korean women.

    PubMed

    Lee, Kyoung-Young; Kang, Hyun-Sik; Shin, Yun-A

    2013-03-10

    The effects of exercise on adiponectin levels have been reported to be variable and may be attributable to an interaction between environmental and genetic factors. The single nucleotide polymorphisms (SNP) 45 (T>G) and SNP276 (G>T) of the adiponectin gene are associated with metabolic risk factors including adiponectin levels. We examined whether SNP45 and SNP276 would differentially influence the effect of exercise training in middle-aged women with uncomplicated obesity. We conducted a prospective study in the general community that included 90 Korean women (age 47.0±5.1 years) with uncomplicated obesity. The intervention was aerobic exercise training for 3 months. Body composition, adiponectin levels, and other metabolic risk factors were measured. Prior to exercise training, only body weight differed among the SNP276 genotypes. Exercise training improved body composition, systolic blood pressure, maximal oxygen consumption, high-density lipoprotein cholesterol, and leptin levels. In addition, exercise improved adiponectin levels irrespective of weight gain or loss. However, after adjustments for age, BMI, body fat (%), and waist circumference, no differences were found in obesity-related characteristics (e.g., adiponectin) following exercise training among the SNP45 and the 276 genotypes. Our findings suggest that aerobic exercise affects adiponectin levels regardless of weight loss and this effect would not be influenced by SNP45 and SNP276 in the adiponectin gene.

  3. Diabetes and hypertension markedly increased the risk of ischemic stroke associated with high serum resistin concentration in a general Japanese population: the Hisayama Study

    PubMed Central

    2009-01-01

    Background Resistin, secreted from adipocytes, causes insulin resistance in mice. The relationship between resistin and coronary artery disease is highly controversial, and the information regarding resistin and ischemic stroke is limited. In the present study, the association between serum resistin concentration and cardiovascular disease (CVD) was investigated in a general Japanese population. Methods A total of 3,201 community-dwelling individuals aged 40 years or older (1,382 men and 1,819 women) were divided into quintiles of serum resistin, and the association between resistin and CVD was examined cross-sectionally. The combined effect of either diabetes or hypertension and high serum resistin was also assessed. Serum resistin was measured using ELISA. Results Compared to those without CVD, age- and sex-adjusted mean serum resistin concentrations were greater in subjects with CVD (p = 0.002) or ischemic stroke (p < 0.001), especially in those with lacunar and atherothrombotic infarction, but not elevated in subjects with hemorrhagic stroke or coronary heart disease. When analyzed by quintile of serum resistin concentration, the age- and sex-adjusted odds ratio (OR) for having CVD and ischemic stroke increased with quintile of serum resistin (p for trends, 0.02 for CVD, < 0.001 for ischemic stroke), while such associations were not observed for hemorrhagic stroke or coronary heart disease. Compared to the first quintile, the age- and sex-adjusted OR of ischemic stroke was greater in the third (OR = 3.54; 95% confidence interval [CI], 1.17-10.67; p = 0.02), fourth (OR = 4.48; 95% CI, 1.53-13.09; p = 0.006), and fifth quintiles (OR = 4.70; 95% CI, 1.62-13.61; p = 0.004). These associations remained substantially unchanged even after adjustment for other confounding factors including high-sensitivity C-reactive protein. In the stratified analysis, the combination of high serum resistin and either diabetes or hypertension markedly increased the risk of ischemic

  4. Adipokines in human reproduction.

    PubMed

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

    2015-10-01

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

  5. Activation of AMPK by berberine promotes adiponectin multimerization in 3T3-L1 adipocytes.

    PubMed

    Li, Yun; Wang, Pengcheng; Zhuang, Yuan; Lin, Huan; Li, Yehua; Liu, Ling; Meng, Qinghang; Cui, Ting; Liu, Jing; Li, Zhen

    2011-06-23

    Adiponectin is assembled into trimer (LMW), hexamer (MMW) and high-molecular-weight (HMW) multimer in adipocytes. The HMW adiponectin is more metabolically active and closely associated with peripheral insulin sensitivity. In this study, we reported that berberine, an isoquinoline alkaloid with insulin-sensitizing effect, inhibits the expression of adiponectin, but promotes the assembly of HMW adiponectin and increases the ratio of HMW to total adiponectin. Berberine activates AMPK. Knockdown of AMPKα1 abolishes the effect of berberine. Activation of AMPK by AICAR also increases the level of HMW adiponectin. Our study suggested that activation of AMPK by berberine promotes adiponectin multimerization.

  6. Role of adiponectin in insulin-resistant hypertension and atherosclerosis.

    PubMed

    Murakami, Hideyuki; Ura, Nobuyuki; Furuhashi, Masato; Higashiura, Katsuhiro; Miura, Tetsuji; Shimamoto, Kazuaki

    2003-09-01

    Insulin resistance is one of the major risk factors associated with development of hypertension and atherosclerosis. Recent studies have shown that adiponectin, an adipocyte-derived hormone, may be involved in insulin resistance and development of atherosclerosis in diabetes patients. The aim of this study was to examine adiponectin levels in patients with essential hypertension to determine the relationships between adiponectin levels and insulin sensitivity and to examine the relationship of adiponectin with pulse wave velocity (PWV) in a general population based on the results of an epidemiological survey in Japan. In a clinical study, 20 normotensives (NT) and 30 non-treated essential hypertensives (EHT) were hospitalized, and euglycemic hyperinsulinemic glucose clamp (GC) was performed to evaluate insulin sensitivity defined as M value. EHT were divided into insulin-resistant EHT (EHT-R) and insulin-nonresistant EHT (EHT-N) according to the mean -1 SD of the M value of NT as a cut-off point. Fasting plasma glucose (FPG), immunoreactive insulin (IRI), and adiponectin concentrations were measured. There were no significant differences in body mass index (BMI) or FPG among the NT, EHT-N, and EHT-R groups. The M value and adiponectin concentration in EHT-R were significantly lower than those in the NT or EHT-N. The IRI level in the EHT-R was significantly higher than those in the other groups. A positive correlation between adiponectin concentration and M value was found in all subjects, and adiponectin concentration and M value were found to be significant determinants of each other in multiple regression analysis. In an epidemiological study, we studied 391 male inhabitants of rural communities in Hokkaido, Japan. Systolic blood pressure (SBP), BMI, FPG, IRI, and adiponectin were measured in all subjects early in the morning. Homeostasis model assessment (HOMA) values were calculated as an index of insulin sensitivity, and PWV was used as an index of

  7. Characteristics and potential functions of human milk adiponectin.

    PubMed

    Newburg, David S; Woo, Jessica G; Morrow, Ardythe L

    2010-02-01

    Adiponectin is a protein hormone produced by adipose tissue, whose circulating levels are inversely related to adiposity and inflammation. Adiponectin circulates as oligomers, from the low-molecular-weight trimer to the high-molecular-weight octodecamer (18 mer). Each oligomer has distinct biological activities, which include enhancement of insulin sensitivity and metabolic control and suppression of inflammation. Adiponectin occurs in human milk at higher concentrations than leptin. The adiponectin in human milk is almost entirely of the high-molecular-weight form, the form with the highest activity in controlling many types of metabolic processes. Human adiponectin fed to infant mice is transported across the intestinal mucosa into the serum. An inverse relationship between adiponectin levels in milk and adiposity (weight-for-height) of the breast-fed infant was observed and could be due to modulation of infant metabolism by milk adiponectin and may be related to the observed protection against obesity by breast-feeding. Human milk may be a medium whereby the hormonal milieu (in response to internal factors and the environment) of the mother can be used to communicate with the breast-fed infant to modify infant metabolic processes. Transmission of information from mother to infant through milk may allow adaptation to fluctuating environmental conditions.

  8. Evaluation of salivary adiponectin profile in obese patients.

    PubMed

    Nigro, E; Piombino, P; Scudiero, O; Monaco, M L; Schettino, P; Chambery, A; Daniele, A

    2015-01-01

    Obesity is a chronic inflammatory disease significantly risen worldwide, especially among children. Adipokines, secreted from adipose tissue, are hormones involved in various cellular processes such as energy metabolism and inflammation. Among the others, adiponectin is gaining increasing interest for its insulin-sentitizing, anti-atherogenic and anti-inflammatory properties. This adipokine undergoes different post-translational modifications, after which it circulates as oligomers of high, medium and low molecular weight (HMW, MMW, LMW); HMW are the most biologically active oligomers. Serum adiponectin levels as well as the amount of its oligomers are inversely correlated to BMI and closely associated with obesity and related diseases. In this study, we analyzed total adiponectin expression and its oligomeric profile in saliva samples from 27 obese compared to 27 age- and sex-matched controls. Moreover, we compared adiponectin oligomerization between serum and saliva samples. The analysis of the different adiponectin oligomers reveals a slightly higher expression of total, HMW and LMW salivary adiponectin in obese patients compared to controls. Finally, FPLC analysis evidenced that HMW oligomers in saliva have a higher molecular weight than in serum confirming the presence of more complex oligomers in saliva, previously identified as super HMW (S-HMW). Saliva is considered a potential source of novel biomarkers for the diagnosis of metabolic disorders. The assessment of total adiponectin and its oligomeric profiles in saliva samples may represent a promising biological marker for the analysis of metabolic diseases.

  9. 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

  10. Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue.

    PubMed

    Pravenec, Michal; Mlejnek, Petr; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Šilhavý, Jan; Strnad, Hynek; Eigner, Sebastian; Eigner Henke, Kateřina; Škop, Vojtěch; Malínská, Hana; Trnovská, Jaroslava; Kazdová, Ludmila; Drahota, Zdeněk; Mráček, Tomáš; Houštěk, Josef

    2016-06-01

    Resistin has been originally identified as an adipokine that links obesity to insulin resistance in mice. In our previous studies in spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin (Retn) transgene specifically in adipose tissue (SHR-Retn), we have observed an increased lipolysis and serum free fatty acids, ectopic fat accumulation in muscles, and insulin resistance. Recently, brown adipose tissue (BAT) has been suggested to play an important role in the pathogenesis of metabolic disturbances. In the current study, we have analyzed autocrine effects of transgenic resistin on BAT glucose and lipid metabolism and mitochondrial function in the SHR-Retn vs. nontransgenic SHR controls. We observed that interscapular BAT isolated from SHR-Retn transgenic rats compared with SHR controls showed a lower relative weight (0.71 ± 0.05 vs. 0.91 ± 0.08 g/100 g body wt, P < 0.05), significantly reduced both basal and insulin stimulated incorporation of palmitate into BAT lipids (658 ± 50 vs. 856 ± 45 and 864 ± 47 vs. 1,086 ± 35 nmol/g/2 h, P ≤ 0.01, respectively), and significantly decreased palmitate oxidation (37.6 ± 4.5 vs. 57 ± 4.1 nmol/g/2 h, P = 0.007) and glucose oxidation (277 ± 34 vs. 458 ± 38 nmol/g/2 h, P = 0.001). In addition, in vivo microPET imaging revealed significantly reduced (18)F-FDG uptake in BAT induced by exposure to cold in SHR-Retn vs. control SHR (232 ± 19 vs. 334 ± 22 kBq/ml, P < 0.05). Gene expression profiles in BAT identified differentially expressed genes involved in skeletal muscle and connective tissue development, inflammation and MAPK and insulin signaling. These results provide evidence that autocrine effects of resistin attenuate differentiation and activity of BAT and thus may play a role in the pathogenesis of insulin resistance in the rat.

  11. Changes of adiponectin oligomer composition by moderate weight reduction.

    PubMed

    Bobbert, Thomas; Rochlitz, Helmut; Wegewitz, Uta; Akpulat, Suzan; Mai, Knut; Weickert, Martin O; Möhlig, Matthias; Pfeiffer, Andreas F H; Spranger, Joachim

    2005-09-01

    Adiponectin affects lipid metabolism and insulin sensitivity. However, adiponectin circulates in three different oligomers that may also have distinct biological functions. We aimed to analyze the role of these oligomers in obesity and lipid metabolism after weight reduction. A total of 17 obese volunteers (15 women and 2 men) participated in a weight reduction program. Individuals were characterized before and after 6 months of a balanced diet. Adiponectin was determined by enzyme-linked immunosorbent assay, and oligomers were detected by nondenaturating Western blot. BMI decreased (35.1 +/- 1.2 to 32.8 +/- 1.1 kg/m(2), P < 0.001), which was associated with an improved metabolite profile. Total adiponectin increased from 5.3 +/- 0.5 to 6.1 +/- 0.6 microg/ml (P = 0.076). High (HMW) and medium molecular weight (MMW) adiponectin oligomers significantly increased during weight reduction (HMW: 0.37 +/- 0.07 to 0.4 +/- 0.08 microg/ml, P = 0.042; MMW: 2.3 +/- 0.2 to 2.9 +/- 0.3 microg/ml, P = 0.007), while low molecular weight (LMW) did not significantly change. Body weight inversely correlated with HMW (r = -0.695, P = 0.002) and positively with LMW (r = 0.579, P = 0.015). Interestingly, HDL cholesterol and HMW were strongly correlated (r = 0.665, P = 0.007). Indeed, HMW and free fatty acids before weight reduction predicted approximately 60% of HDL changes during intervention. In conclusion, weight reduction results in a relative increase of HMW/MMW adiponectin and a reduction of LMW adiponectin. Total adiponectin and especially HMW adiponectin are related to circulating HDL cholesterol.

  12. Visfatin/Pre-B Cell Colony-Enhancing Factor in Amniotic Fluid in Normal Pregnancy, Spontaneous Labor at Term, Preterm Labor and Prelabor Rupture of Membranes: an Association with Subclinical Intrauterine Infection in Preterm Parturition

    PubMed Central

    Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Mittal, Pooja; Than, Nandor Gabor; Nhan-Chang, Chia-lang; Hamill, Neil; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Edwin, Samuel S.; Nien, Jyh Kae; Gomez, Ricardo; Espinoza, Jimmy; Kendal-Wright, Claire; Hassan, Sonia S.; Bryant-Greenwood, Gillian

    2008-01-01

    Objective Visfatin, a novel adipokine originally discovered as a pre-B-cell colony enhancing factor, is expressed by amniotic epithelium, cytotrophoblast, and decidua and is over-expressed when fetal membranes are exposed to mechanical stress and/or pro-inflammatory stimuli. Visfatin expression by fetal membranes is dramatically up-regulated after normal spontaneous labor. The aims of this study were to determine if visfatin is detectable in amniotic fluid (AF) and whether its concentration changes with gestational age, spontaneous labor, preterm prelabor rupture of membranes (preterm PROM) and in the presence of microbial invasion of the amniotic cavity (MIAC). Methods In this cross-sectional study, visfatin concentration in AF was determined in patients in the following groups: 1) mid-trimester (n=75); 2) term not in labor (n=27); 3) term in spontaneous labor (n=51); 4) patients with preterm labor with intact membranes (PTL) without MIAC who delivered at term (n=35); 5) patients with PTL without MIAC who delivered preterm (n=52); 6) patients with PTL with MIAC (n=25); 7) women with preterm PROM without MIAC (n=26); and 8) women with preterm PROM with MIAC (n=26). Non-parametric statistics were used for analysis. Results 1) The median AF concentration of visfatin was significantly higher in patients at term than in midtrimester; 2) Among women with PTL who delivered preterm, the median visfatin concentration was significantly higher in patients with MIAC than those without MIAC; 3) Similarly, patients with PTL and MIAC had a higher median AF visfatin concentration than those with PTL who delivered at term; 4) Among women with preterm PROM, the median AF visfatin concentration was significantly higher in patients with MIAC than those without MIAC. Conclusions 1) Visfatin is a physiologic constituent of AF; 2) The concentration of AF visfatin increases with advancing gestational age; 3) AF visfatin concentration is elevated in patients with MIAC, regardless of the

  13. Circulating leptin and adiponectin concentrations in healthy exceptional longevity.

    PubMed

    Pareja-Galeano, Helios; Santos-Lozano, Alejandro; Sanchis-Gomar, Fabian; Fiuza-Luces, Carmen; Garatachea, Nuria; Gálvez, Beatriz G; Lucia, Alejandro; Emanuele, Enzo

    2017-03-01

    People reaching exceptional longevity free of major age-related diseases represent the paradigm of successful aging. Adipose tissue function declines as we age, potentially resulting in changes of circulating adipokines (e.g., leptin and adiponectin). Here, we measured circulating levels of leptin and adiponectin in healthy centenarians (n=81; 100-104 years) and younger elderly controls (n=46; 70-80 years). Centenarians had significant higher serum levels of leptin compared with controls (p<0.001), whereas no significant differences were observed for adiponectin. Further research including also other blood variables will be needed to elucidate whether high leptin levels could serve as a hallmark of healthy exceptional longevity.

  14. Caloric restriction increases adiponectin expression by adipose tissue and prevents the inhibitory effect of insulin on circulating adiponectin in rats.

    PubMed

    Ding, Qi; Ash, Catherine; Mracek, Tomas; Merry, Brian; Bing, Chen

    2012-08-01

    Aging is associated with redistribution of body fat and the development of insulin resistance. White adipose tissue emerges as an important organ in controlling life span. Caloric restriction (CR) delays the rate of aging possibly modulated partly by altering the amount and function of adipose tissue. Adiponectin is a major adipose-derived adipokine that has anti-inflammatory and insulin-sensitizing properties. This study examined the effects of CR on adiposity and gene expression of adiponectin, its receptors (AdipoR1 and AdipoR2) in adipose tissue and in isolated adipocytes of Brown Norway rats that had undergone CR for 4 months or fed ad libitum. The study also determined plasma concentrations of adiponectin and insulin in these animals and whether insulin infusion for 7 days affects adiponectin expression and its circulating concentrations under CR conditions. CR markedly reduced body weight as anticipated, epididymal fat mass and adipocyte size. CR led to an increase in plasma free fatty acid and glycerol (both twofold), and adipose triglyceride lipase messenger RNA (mRNA) in adipose tissue and isolated adipocytes (both >2-fold). Adiponectin mRNA levels were elevated in adipose tissue and adipocytes (both >2-fold) as was plasma adiponectin concentration (2.8-fold) in CR rats. However, CR did not alter tissue or cellular AdipoR1 and AdipoR2 expression. Seven days of insulin infusion decreased adiponectin mRNA in adipose tissue but did not reverse the CR-induced up-regulation of circulating adiponectin levels. Our results suggest that the benefits of CR could be, at least in part, dependent on enhanced expression and secretion of adiponectin by adipocytes.

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

    PubMed

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

    2015-05-10

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

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

    PubMed Central

    Bhardwaj, Arun; Singh, Ajay P.; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L.; Zotto, Valeria Dal; Carter, James E.; Singh, Seema

    2015-01-01

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978

  17. Resistin-Like Molecule-β in Scleroderma-Associated Pulmonary Hypertension

    PubMed Central

    Angelini, Daniel J.; Su, Qingning; Yamaji-Kegan, Kazuyo; Fan, Chunling; Teng, Xingwu; Hassoun, Paul M.; Yang, Stephen C.; Champion, Hunter C.; Tuder, Rubin M.; Johns, Roger A.

    2009-01-01

    Scleroderma is a systemic, mixed connective tissue disease that can impact the lungs through pulmonary fibrosis, vascular remodeling, and the development of pulmonary hypertension and right heart failure. Currently, little is known about the molecular mechanisms that drive this condition, but we have recently identified a novel gene product that is up-regulated in a murine model of hypoxia-induced pulmonary hypertension. This molecule, known as hypoxia-induced mitogenic factor (HIMF), is a member of the newly described resistin gene family. We have demonstrated that HIMF has mitogenic, angiogenic, vasoconstrictive, inflammatory, and chemokine-like properties, all of which are associated with vascular remodeling in the lung. Here, we demonstrate that the human homolog of HIMF, resistin-like molecule (RELM)-β, is expressed in the lung tissue of patients with scleroderma-associated pulmonary hypertension and is up-regulated compared with normal control subjects. Immunofluorescence colocalization revealed that RELM-β is expressed in the endothelium and vascular smooth muscle of remodeled vessels, as well as in plexiform lesions, macrophages, T cells, and myofibroblast-like cells. We also show that addition of recombinant RELM-β induces proliferation and activation of ERK1/2 in primary cultured human pulmonary endothelial and smooth muscle cells. These results suggest that RELM-β may be involved in the development of scleroderma-associated pulmonary hypertension. PMID:19251945

  18. Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colorectal Cancer Risk

    PubMed Central

    Kaklamani, Virginia G.; Wisinski, Kari B.; Sadim, Maureen; Gulden, Cassandra; Do, Albert; Offit, Kenneth; Baron, John A.; Ahsan, Habibul; Mantzoros, Christos; Pasche, Boris

    2008-01-01

    Context Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and colorectal cancer risk. Adiponectin is a hormone secreted by the adipose tissue, and serum levels are inversely correlated with obesity and hyperinsulinemia. While there is evidence of an association between circulating adiponectin levels and colorectal cancer risk, no association between genes of the adiponectin pathway and colorectal cancer have been reported to date. Objective To determine the association of 10 haplotype-tagging single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancer risk. Design, Setting, and Patients Two case-control studies including patients with a diagnosis of colorectal cancer and controls were recruited between 2000 and 2007. Case-control study 1 included a total of 441 patients with a diagnosis of colorectal cancer and 658 controls; both groups were of Ashkenazi Jewish ancestry and from New York, New York. Case-control study 2 included 199 patients with a diagnosis of colorectal cancer and 199 controls from Chicago, Illinois, matched 1:1 for sex, age, and ethnicity. Main Outcome Measures ADIPOQ and ADIPOR1 SNP frequency among cases and controls. Results In study 1, after adjustment for age, sex, and SNPs from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP were associated with colorectal cancer risk: rs266729 (adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.55–0.95) and rs822396 (AOR, 0.37; 95% CI, 0.14–1.00) were associated with decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09–2.84) and rs1342387 (AOR, 1.79; 95% CI, 1.18–2.72) were associated with increased risk. In study 2, after adjustment for age, sex, race, and SNPs from the same gene, the ADIPOQ SNP rs266729 was associated with a decreased colorectal cancer risk of similar magnitude as in study 1 (AOR, 0.52; 95% CI, 0.34–0.78). Combined analysis of both studies shows an

  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. Associations of adiponectin and fertility estimates in Holstein bulls.

    PubMed

    Kasimanickam, Vanmathy R; Kasimanickam, Ramanathan K; Kastelic, John P; Stevenson, Jeffrey S

    2013-03-15

    Adiponectin is a pleiotropic regulator of numerous biological functions, including gonadal steroidogenesis and might play a role in sperm structures and functions. The objectives were to: (1) determine associations among serum concentrations of adiponectin, testosterone, and prolactin, and the sperm DNA fragmentation index; (2) associate sperm adiponectin mRNA abundance with estimates of fertility (sire conception rate); and (3) determine sperm protein expression of adiponectin and its receptor in pre- and postcapacitated sperm from Holstein bulls. In experiment 1, biweekly serum concentrations of adiponectin, prolactin, and testosterone were greater (P < 0.05) for high fertility bulls compared with average and low fertility bulls. Furthermore, sperm DNA fragmentation index was greater (P < 0.05) for low fertility compared with both average and high fertility bulls. In experiment 2, samples of sperm from a single collection from commercial Holstein bulls (N = 34) were used to evaluate relative sperm mRNA expression of adiponectin and its receptors, AdipoR1 and AdipoR2, and protein levels of adiponectin and its receptors, AdipoR1 and AdipoR2, in pre- and postcapacitation sperm. The mRNA abundance of adiponectin and its receptors, AdipoR1 and AdipoR2, were greater for high fertility bulls (>2 to ≤4 sire conception rate) compared with average (≥2 to ≤2) and low (>-2 to ≤-4) fertility bulls. Based on the sperm capacitation assay, average fertility bulls had a greater percentage of acrosome-reacted sperm at 5 hours than high and low fertility bulls, whereas high fertility bulls had a greater percentage of acrosome-reacted sperm than low fertility bulls. After capacitation, levels of adiponectin protein were lower in average fertility bulls, AdipoR1 was lower in all fertility groups, and AdipoR2 was lower in average and high fertility bulls. In conclusion, adiponectin and its receptors had vital roles in sperm structural and functional traits and consequently

  1. Association of adiponectin multimers with Barrett’s oesophagus

    PubMed Central

    Rubenstein, J H; Kao, J Y; Madanick, R D; Zhang, M; Wang, M; Spacek, M B; Donovan, J L; Bright, S D; Shaheen, N J

    2012-01-01

    Objective Barrett’s oesophagus is associated with abdominal obesity. Adiponectin is a peptide that is secreted from adipocytes and circulates in three multimeric forms: low molecular weight (LMW), middle molecular weight (MMW), and high molecular weight (HMW). The anti-inflammatory effects of adiponectin are specific to individual multimers, with LMW being most anti-inflammatory. We postulated that circulating levels of adiponectin and its multimers would be associated with the risk of Barrett’s oesophagus. Design Cross-sectional study. Setting Outpatient clinic in North Carolina, USA. Patients Cases of Barrett’s oesophagus and controls undergoing upper endoscopy for gastro-oesophageal reflux disease (GORD). Main outcome measures Adjusted odds ratios of plasma adiponectin levels and its multimers for Barrett’s oesophagus. Results There were 112 cases of Barrett’s oesophagus and 199 GORD controls. Total adiponectin was not associated with Barrett’s oesophagus (3rd tertile vs 1st tertile adjusted odds ratio (aOR) = 0.88; 95% confidence interval (CI) = 0.44 to 1.78). High levels of LMW adiponectin were associated with a decreased risk of Barrett’s oesophagus (3rd tertile vs 1st tertile aOR = 0.33; 95% CI, 0.16 to 0.69), and a high LMW/total ratio appeared particularly inversely associated with Barrett’s oesophagus (3rd tertile vs 1st tertile aOR = 0.27; 95% CI, 0.13 to 0.58). Conclusions High levels of LMW adiponectin are associated with a decreased risk of Barrett’s oesophagus among patients with GORD. Further human studies are required to confirm these findings, and in vitro studies are needed to understand if there is a mechanism whereby adiponectin may affect Barrett’s metaplasia. PMID:19570765

  2. Potential Neuroprotective Effects of Adiponectin in Alzheimer’s Disease

    PubMed Central

    Ng, Roy Chun-Laam; Chan, Koon-Ho

    2017-01-01

    The adipocyte-secreted protein adiponectin (APN) has several protective functions in the peripheral tissues including insulin sensitizing, anti-inflammatory and anti-oxidative effects that may benefit neurodegenerative diseases such as Alzheimer’s disease (AD). In addition, dysregulation of cerebral insulin sensitivities and signaling activities have been implicated in AD. Emerging insights into the mechanistic roles of adiponectin and AD highlight the potential therapeutic effects for AD through insulin signaling. PMID:28282917

  3. Allelic variation in porcine resistin (RETN) gene is associated with fatness traits in a Wild Boar x Meishan reference family

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cloning and comparative sequencing of the porcine resistin (RETN) gene and 5’ flanking region, located at 64 cM on SSC2, revealed 9 SNPs and 2 indels. A European Wild Boar x Meishan family encompassing 335 F2 animals measured for 46 traits including growth, fat deposition and muscle accretion was sc...

  4. [Possible connection between ghrelin, resistin and TNF-alpha levels and the metabolic syndrome caused by atypical antipsychotics].

    PubMed

    Birkás Kováts, Dezso; Palik, Eva; Faludi, Gábor; Cseh, Károly

    2005-09-01

    Second generation antipsychotics (SGA) are obesitogenic and diabetogenic. Role of ghrelin (RIA), resistin and TNF-alpha (ELISA) in weight gain and insulin resistance (fasting plasma insulin, HOMA, ELISA) was studied in Hungarian psychiatryic patients (n=60) treated with SGA (clozapine, olanzapine, risperidone, quetiapine, 15 each). After 1 year, 80% of patients became overweight/obese (BMI > 27/30) and 35% (n= 21/60) presented impaired glucose tolerance (13/60) or diabetes (8/60). Ghrelin (1.3 +/- 0.6 ng/ml), resistin (9.8 +/- 3.7 ng/ml), TNF-alpha (5.8 +/- 1.7 pg/ml), insulin (10.4 +/- 7.6 U/ml, HOMA A: 2.5 +/- 1.8, HOMA B: 133 +/- 62.5) were significantly higher in patients than in healthy matched controls. Resistin and TNF-alpha positively correlated with each other, insulin, HOMA, and negatively with ghrelin. Ghrelin contributes to weight gain, resistin and TNF-alpha to insulin resistance. A negative feedback regulation may exist between adipocytokines and ghrelin production. SGA drugs enhance ghrelin production despite the suppressive effect of adipocytokines. All four SGA drugs are equally obesitogenic and diabetogenic.

  5. Expression of lipogenic factors galectin-12, resistin, SREBP-1, and SCD in human sebaceous glands and cultured sebocytes.

    PubMed

    Harrison, Wesley J; Bull, Jonathan J; Seltmann, Holger; Zouboulis, Christos C; Philpott, Michael P

    2007-06-01

    The transcription factors CCAAT enhancer-binding protein alpha, beta, and delta, and peroxisome proliferator-activated receptor gamma are known to be crucial to the differentiation of adipocytes and are expressed in sebaceous gland cells. As lipogenesis is key to both adipocyte and sebocyte differentiation we hypothesize that sebocytes follow a similar program of differentiation to adipocytes. We have investigated the expression of known adipogenic factors resistin, galectin-12, sterol response-element-binding protein-1 (SREBP-1) and stearoyl-CoA desaturase in the immortalized sebaceous gland cell line SZ95 and whole skin. Reverse transcriptase-PCR analysis showed the expression of galectin-12, resistin, SREBP-1, and stearoyl-CoA desaturase mRNAs in SZ95 sebocytes. Immunoreactivity was observed for galectin-12 and SREBP-1 in the nuclei and resistin in the cytoplasm of basal sebocytes, and stearoyl CoA desaturase in the cytoplasm of basal and luminal sebocytes of human scalp skin. Expression of galectin-12, resistin, and SREBP-1 in SZ95 sebocytes was confirmed by Western blot analysis. These data provide further evidence that pathways of differentiation in adipocytes and sebocytes could be similar and therefore further understanding of sebaceous gland differentiation and lipogenesis and potential therapies for sebaceous gland disorders may be obtained from our knowledge of adipocyte differentiation.

  6. Signaling mechanisms underlying the insulin-sensitizing effects of adiponectin.

    PubMed

    Cheng, Kenneth K Y; Lam, Karen S L; Wang, Baile; Xu, Aimin

    2014-01-01

    Adiponectin is an insulin-sensitizing adipokine with protective effects against a cluster of obesity-related metabolic and cardiovascular disorders. The adipokine exerts its insulin-sensitizing effects by alleviation of obesity-induced ectopic lipid accumulation, lipotoxicity and chronic inflammation, as well as by direct cross-talk with insulin signaling cascades. Adiponectin and insulin signaling pathways converge at the adaptor protein APPL1. On the one hand, APPL1 interacts with adiponectin receptors and mediates both metabolic and vascular actions of adiponectin through activation of AMP-activated protein kinase and p38 MAP kinase. On the other hand, APPL1 potentiates both the actions and secretion of insulin by fine-tuning the Akt activity in multiple insulin target tissues. In obese animals, reduced APPL1 expression contributes to both insulin resistance and defective insulin secretion. This review summarizes recent advances on the molecular mechanisms by which adiponectin sensitizes insulin actions, and discusses the roles of APPL1 in regulating both adiponectin and insulin signaling cascades.

  7. 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.

  8. 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

  9. 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.

  10. Association of resistin with impaired membrane fluidity of red blood cells in hypertensive and normotensive men: an electron paramagnetic resonance study.

    PubMed

    Tsuda, Kazushi

    2016-10-01

    Abnormalities in physical properties of the cell membranes may strongly be linked to hypertension. Recent evidence indicates that resistin may actively participate in the pathophysiology of insulin resistance, diabetes mellitus, hypertension and other circulatory disorders. The present study was undertaken to investigate the possible relationships among plasma resistin, oxidative stress and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertension. We measured the membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive men using an electron paramagnetic resonance (EPR) and spin-labeling method. The order parameter (S) for the spin-label agents (5-nitroxide stearate) in EPR spectra of red blood cell (RBC) membranes was significantly higher in hypertensive men than in normotensive men, indicating that membrane fluidity was decreased in hypertension. Plasma resistin levels were correlated with systolic blood pressure and 8-iso-prostaglandin F2α levels (an index of oxidative stress). Furthermore, the order parameter (S) of RBCs significantly correlated with plasma resistin and plasma 8-isoPG F2α, suggesting that reduced membrane fluidity of RBCs might be associated with hyperresistinemia and increased oxidative stress. Multivariate regression analysis showed that, after adjustment for confounding factors, plasma resistin might be an independent determinant of membrane fluidity of RBCs. The EPR study suggests that resistin might have a close correlation with impaired rheologic behavior of RBCs and microcirculatory dysfunction in hypertension, at least in part, via an oxidative stress-dependent mechanism.

  11. Annexin A6 regulates adipocyte lipid storage and adiponectin release.

    PubMed

    Krautbauer, Sabrina; Haberl, Elisabeth M; Eisinger, Kristina; Pohl, Rebekka; Rein-Fischboeck, Lisa; Rentero, Carles; Alvarez-Guaita, Anna; Enrich, Carlos; Grewal, Thomas; Buechler, Christa; Neumeier, Markus

    2017-01-05

    Lipid storage and adipokine secretion are critical features of adipocytes. Annexin A6 (AnxA6) is a lipid-binding protein regulating secretory pathways and its role in adiponectin release was examined. The siRNA-mediated AnxA6 knock-down in 3T3-L1 preadipocytes impaired proliferation, and differentiation of AnxA6-depleted cells to mature adipocytes was associated with higher soluble adiponectin and increased triglyceride storage. The latter was partly attributed to reduced lipolysis. Accordingly, AnxA6 overexpression in 3T3-L1 adipocytes lowered cellular triglycerides and adiponectin secretion. Indeed, serum adiponectin was increased in AnxA6 deficient mice. Expression analysis identified AnxA6 protein to be more abundant in intra-abdominal compared to subcutaneous adipose tissues of mice and men. AnxA6 protein levels increased in white adipose tissues of obese mice and here, levels were highest in subcutaneous fat. AnxA6 protein in adipocytes was upregulated by oxidative stress which might trigger AnxA6 induction in adipose tissues and contribute to impaired fat storage and adiponectin release.

  12. Prediagnostic Plasma Adiponectin and Survival among Patients with Colorectal Cancer.

    PubMed

    Chong, Dawn Q; Mehta, Raaj S; Song, Mingyang; Kedrin, Dmitriy; Meyerhardt, Jeffrey A; Ng, Kimmie; Wu, Kana; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Chan, Andrew T

    2015-12-01

    Circulating adiponectin is inversely related to the risk of colorectal cancer. However, its influence on colorectal cancer survival is unclear. We conducted a prospective study to evaluate the association between prediagnostic plasma levels of adiponectin and mortality in patients with colorectal cancer. We identified 621 incident colorectal cancer cases who provided blood specimens prior to diagnosis within the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). After a median follow-up of 9 years, there were 269 (43%) total deaths, of which 181 (67%) were due to colorectal cancer. Compared with participants in the lowest quartile of adiponectin, those in the highest quartile had multivariate HRs of 1.89 (95% CI, 1.21-2.97; P(trend) = 0.01) for colorectal cancer-specific mortality and 1.66 (95% CI, 1.15-2.39; P(trend) = 0.009) for overall mortality. The apparent increased risk in colorectal cancer-specific mortality was more pronounced in patients with metastatic disease (HR, 3.02: 95% CI, 1.50-6.08). Among patients with colorectal cancer, prediagnostic plasma adiponectin is associated with an increased risk of colorectal cancer-specific and overall mortality and is more apparent in patients with metastatic disease. Adiponectin may be a marker for cancers which develop through specific pathways that may be associated with worsened prognosis. Further studies are needed to validate these findings.

  13. Prediagnostic Plasma Adiponectin and Survival among Patients with Colorectal Cancer

    PubMed Central

    Chong, Dawn Q.; Mehta, Raaj S.; Song, Mingyang; Kedrin, Dmitriy; Meyerhardt, Jeffrey A.; Ng, Kimmie; Wu, Kana; Fuchs, Charles S.; Giovannucci, Edward L.; Ogino, Shuji; Chan, Andrew T.

    2015-01-01

    Circulating adiponectin is inversely related to the risk of colorectal cancer (CRC). However, its influence on CRC survival is unclear. We conducted a prospective study to evaluate the association between prediagnostic plasma levels of adiponectin and mortality in patients with CRC. We identified 621 incident CRC cases who provided blood specimens prior to diagnosis within the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After a median follow-up of 9 years, there were 269 (43%) total deaths, of which 181 (67%) were due to CRC. Compared with participants in the lowest quartile of adiponectin, those in the highest quartile had multivariate HRs of 1.89 (95% CI, 1.21–2.97; Ptrend = 0.01) for CRC-specific mortality and 1.66 (95% CI, 1.15–2.39; Ptrend = 0.009) for overall mortality. The apparent increased risk in CRC-specific mortality was more pronounced in patients with metastatic disease (HR 3.02, 95% CI, 1.50–6.08). Among patients with CRC, prediagnostic plasma adiponectin is associated with an increased risk of CRC-specific and overall mortality, and is more apparent in patients with metastatic disease. Adiponectin may be a marker for cancers which develop through specific pathways that may be associated with worsened prognosis. Further studies are needed to validate these findings. PMID:26382604

  14. Role of leptin and adiponectin in insulin resistance.

    PubMed

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

    2013-02-18

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

  15. Effect of Drinking on Adiponectin in Healthy Men and Women

    PubMed Central

    Imhof, Armin; Plamper, Ines; Maier, Steffen; Trischler, Gerlinde; Koenig, Wolfgang

    2009-01-01

    OBJECTIVE Moderate alcohol consumption is associated with reduced incidence of type 2 diabetes and cardiovascular mortality and increases adiponectin concentrations, but effects might differ according to sex and beverage consumed. RESEARCH DESIGN AND METHODS A total of 72 healthy individuals (22–56 years) were enrolled in this randomized controlled crossover trial. After washout, two interventions for 3 weeks followed: ethanol (concentration 12.5%), beer (5.6%), or red wine (12.5%) equivalent to 30 g ethanol/day for men and 20 g/day for women or the same de-alcoholized beverages or water. Adiponectin was measured by sandwich enzyme-linked immunosorbent assay. RESULTS Among women, adiponectin significantly increased after consuming red wine (29.8%, P < 0.05) and increased among men after ethanol solution (17.4%, P < 0.05) and consuming beer (16.1%, P < 0.05). De-alcoholized beverages had no substantial effect on adiponectin concentrations. CONCLUSIONS Moderate amounts of ethanol-containing beverages increased adiponectin concentrations, but sex-specific effects might depend on type of beverage consumed. PMID:19244090

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

    PubMed

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

    2010-07-01

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

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

    PubMed

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

    2013-12-01

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

  18. 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 ...

  19. [Adiponectin receptor-targeted therapy for lifestyle-related diseases].

    PubMed

    Iwabu, Masato; Yamauchi, Toshimasa; Okada-Iwabu, Miki; Kadowaki, Takashi

    2016-03-01

    Given that appropriate control of responses of the body to nutritional status is assumed to modulate the pace of aging, thus prolonging lifespan and maintaining youth in humans, expectations are mounting worldwide for modalities targeting the pathways in metabolic regulation for healthy longevity. Of these, this review focuses attention on adiponectin-targeted therapy and discusses milestones in this approach, which include the discovery of the ability of adiponectin to protect against lifestyle-related diseases, identification of its receptors (AdipoRs), elucidation of AdipoR-mediated signaling pathways that promote healthy longevity and acquisition of small-molecule AdipoR agonist, and explores future prospects on adiponectin-targeted therapy.

  20. Obesity and Cardiovascular Risk: Variations in Visfatin Gene Can Modify the Obesity Associated Cardiovascular Risk. Results from the Segovia Population Based-Study. Spain

    PubMed Central

    Martínez Larrad, María Teresa; Corbatón Anchuelo, Arturo; Fernández Pérez, Cristina; Pérez Barba, Milagros; Lazcano Redondo, Yera; Serrano Ríos, Manuel

    2016-01-01

    Objectives Our aim was to investigate if genetic variations in the visfatin gene (SNPs rs7789066/ rs11977021/rs4730153) could modify the cardiovascular-risk (CV-risk) despite the metabolic phenotype (obesity and glucose tolerance). In addition, we investigated the relationship between insulin sensitivity and variations in visfatin gene. Material and Methods A population-based study in rural and urban areas of the Province of Segovia, Spain, was carried out in the period of 2001–2003 years. A total of 587 individuals were included, 25.4% subjects were defined as obese (BMI ≥30 Kg/m2). Results Plasma visfatin levels were significantly higher in obese subjects with DM2 than in other categories of glucose tolerance. The genotype AA of the rs4730153 SNP was significantly associated with fasting glucose, fasting insulin and HOMA-IR (Homeostasis model assessment-insulin resistance) after adjustment for gender, age, BMI and waist circumference. The obese individuals carrying the CC genotype of the rs11977021 SNP showed higher circulating levels of fasting proinsulin after adjustment for the same variables. The genotype AA of the rs4730153 SNP seems to be protective from CV-risk either estimated by Framingham or SCORE charts in general population; and in obese and non-obese individuals. No associations with CV-risk were observed for other studied SNPs (rs11977021/rs7789066). Conclusions In summary, this is the first study which concludes that the genotype AA of the rs4730153 SNP appear to protect against CV-risk in obese and non–obese individuals, estimated by Framingham and SCORE charts. Our results confirm that the different polymorphisms in the visfatin gene might be influencing the glucose homeostasis in obese individuals. PMID:27166797

  1. 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

  2. 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.

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

    PubMed

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

    2016-12-26

    Background/ObjectiveAdipokines are involved in the etiology of diabetes, insulin resistance, and the development of atherosclerosis and other latent-onset complications. The objective of this meta-analysis was to determine the effectiveness of exercise interventions on adipokines in pediatric obesity.Subjects/MethodA computerized search was made using three databases. The analysis was restricted to studies that examined the effect of exercise interventions on adipokines (adiponectin, leptin, resistin, and visfatin) in pediatric obesity (6-18 years old). Fourteen randomized controlled trials (347 youths) were included. Weighted mean difference (WMD) and 95% confidence intervals were calculated.ResultsExercise was associated with a significant increase in adiponectin (WMD=0.882 μg/ml, 95% CI, 0.271 to 1.493) but did not alter leptin and resistin level. Likewise, exercise intensity and change in body fat; as well as total exercise program duration, duration of the sessions, and change in body fat all significantly influenced the effect of exercise on adiponectin and leptin, respectively.ConclusionsExercise seems to increase adiponectin levels in childhood obesity. Our results also suggested that exercise on its own, without the concomitant presence of changes in body composition levels, does not affect leptin levels.International Journal of Obesity accepted article preview online, 26 December 2016. doi:10.1038/ijo.2016.230.

  4. Adiponectin regulate growth hormone secretion via adiponectin receptor mediated Ca(2+) signalling in rat somatotrophs in vitro.

    PubMed

    Steyn, F J; Boehme, F; Vargas, E; Wang, K; Parkington, H C; Rao, J R; Chen, C

    2009-08-01

    Obesity is associated with reduced levels of growth hormone (GH) and the disruption of pulsatile GH secretion. This results in relative GH deficiency. It is likely that a regulatory relationship between GH secretion and adipose tissue exists as the secretion of GH recovers to normal levels after a reduction in body weight. This report characterise the expression and interaction of adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) and adiponectin, respectively, in regulating the activity of GH secreting cells. Polymerase chain reaction analysis of the GH3 cell line, rat anterior pituitary gland and isolated somatotroph cells from transgenic GFP expressing mice confirmed the expression of both AdipoR1 and AdipoR2 in GH secretory cells. Because GH cells expressed both receptors, it is likely that the measured increase in GH secretion, observed in primary cultured rat pituitary cells after 30 min of incubation with full-length murine adiponectin, was mediated by a direct receptor regulated process. Adiponectin induced an increase in intracellular Ca(2+) through both the influx of extracellular Ca(2+) and the release of intracellular Ca(2+) stores resulting in the secretion of GH. Furthermore, results confirm that this increase in GH secretion depended mainly on an increase in Ca(2+) influx through L-type Ca(2+) channels. It is concluded that adiponectin directly regulates GH secretion from somatotrophs by binding to either adiponectin receptor, and that this is mediated via a similar process observed after the stimulation of GH secretion by GH-releasing hormone.

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

    PubMed Central

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

    2008-01-01

    Aims Adiponectin is an adipokine that has anti-diabetic, anti-atherogenic, anti-inflammatory and angiogenic properties. This hormone has been implicated in both the physiological adaptation to normal pregnancy and obstetrical complications. The aims of this study were to determine normal maternal plasma concentrations of adiponectin throughout gestation and to explore the relationships between plasma adiponectin concentration, pregnancy, and maternal overweight. Study design A cross-sectional study was designed to include normal pregnant women (normal weight and overweight; 11–42 weeks of gestation), and non-pregnant women. Plasma adiponectin concentration was determined by immunoassay. Non-parametric statistics were used for analysis. Results (1) Adiponectin was detectable in the plasma of all patients; (2) there was no significant difference in the median adiponectin concentrations between pregnant and non-pregnant women; (3) plasma adiponectin concentrations were negatively correlated with gestational age only among normal weight pregnant women; and (4) overweight patients had significantly lower adiponectin concentrations than normal weight women. Conclusion Consistent with the increased insulin resistance and weight gain that occur in pregnancy, adiponectin concentrations were negatively correlated with gestational age. The results of this study and the nomogram herein presented can serve as the basis to explore the relationship between adiponectin and pregnancy complications and facilitate the clinical use of this important adipokine. Condensation Plasma adiponectin concentrations decrease with advancing gestational age only in nonobese women. PMID:17919116

  6. Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form.

    PubMed

    Fuerst, Melissa; Taylor, Carla G; Wright, Brenda; Tworek, Leslee; Zahradka, Peter

    2012-10-01

    Accelerated atherosclerosis is the primary cardiovascular manifestation of diabetes and correlates inversely with levels of circulating adiponectin, an anti-atherosclerotic adipokine that declines in diabetes. We therefore initiated a study to examine the mechanisms by which adiponectin, a hormone released from adipose tissue, influences the proliferation of vascular smooth muscle cells (SMCs). Addition of adiponectin to quiescent porcine coronary artery SMCs increased both protein and DNA synthesis and concurrently activated ERK1/2 and Akt. By contrast, globular adiponectin, a truncated form of this protein, exhibited anti-mitogenic properties as indicated by the inhibition of protein and DNA synthesis in SMCs stimulated with platelet-derived growth factor (PDGF). Whereas globular adiponectin did not stimulate growth-related signal transduction pathways, it was able to block the PDGF-dependent phosphorylation of eukaryotic elongation factor 2 kinase, a regulator of protein synthesis. Proteolysis of adiponectin with trypsin, which produces globular adiponectin, reversed the growth-stimulating actions of the undigested protein. As the existence of globular adiponectin remains controversial, western blotting was used to establish its presence in rat serum. We found that globular adiponectin was detectable in rat serum, but this result was not obtained with all antibodies. The contrasting properties of adiponectin and its globular form with respect to SMC proliferation suggest that protection against atherosclerosis may therefore be mediated, in part, by the level of globular adiponectin.

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

    PubMed

    Lin, Huan; Li, Zhen

    2012-01-01

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

  8. 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

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

    PubMed Central

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

    2013-01-01

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

  10. 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.

  11. 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

  12. 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

  13. Reverse regulation of soluble receptor for advanced glycation end products and proinflammatory factor resistin and S100A12 in Kawasaki disease

    PubMed Central

    2012-01-01

    Introduction Kawasaki disease (KD), an acute febrile disease, characterized by systemic vasculitis, predominantly affects infants and children under 5 years of age. Coronary artery lesions (CALs) are its most critical complication, and the etiology remains unknown yet. In order to explore the value of resistin, S100A12 and soluble receptor for advanced glycation end products (sRAGE) in the pathophysiology of KD, we studied the serum levels of resistin, S100A12 and sRAGE in different stages of KD. Methods Serum levels of resistin, S100A12 and sRAGE were measured by enzyme-linked immunosorbent assay (ELISA) method in 15 healthy children and 40 KD patients at acute, afebrile and subacute stage. Results The resistin and S100A12 levels, including the ratio of resistin to sRAGE and S100A12 to sRAGE increased significantly in the acute stage, and decreased progressively in the afebrile and subacute stage. However, the sRAGE levels decreased significantly in the acute stage, and increased progressively in the afebrile and subacute stage. In the acute, afebrile and subacute stage, the resistin levels were higher in intravenous immunoglobulin (IVIG) non-responders (0.64 ± 0.30, 0.48 ± 0.35, 0.28 ± 0.19, × 102 ng/ml) than in IVIG responders (0.35 ± 0.24, 0.21 ± 0.19, 0.12 ± 0.05, × 102 ng/ml). In the acute and subacute stage, the S100A12 levels were higher in IVIG non-responders (7.92 ± 2.61, 4.98 ± 4.75, × 102 ng/ml) than in IVIG responders (5.05 ± 3.22, 2.35 ± 2.26, × 102 ng/ml). In the afebrile and subacute stage, the sRAGE levels were lower in IVIG non-responders (3.51 ± 2.64, 3.65 ± 3.27, × 102 pg/ml) than in IVIG responders (6.00 ± 2.78, 7.19 ± 2.88, × 102 pg/ml). The resistin levels were positively correlated with S100A12 levels. The sRAGE levels were negatively related with S100A12 and resistin levels. Conclusions Resistin, S100A12 and sRAGE are involved in the pathophysiology of KD. PMID:23171632

  14. Docosahexaenoic acid increases cellular adiponectin mRNA and secreted adiponectin protein, as well as PPARγ mRNA, in 3T3-L1 adipocytes.

    PubMed

    Oster, Richard T; Tishinsky, Justine M; Yuan, Zongfei; Robinson, Lindsay E

    2010-12-01

    Adiponectin, a protein secreted from adipose tissue, has been shown to have anti-diabetic and anti-inflammatory effects, but its regulation is not completely understood. Long-chain n-3 fatty acids eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA) may be involved in adiponectin regulation as they are potential ligands for peroxisome proliferator-activated receptor-γ (PPARγ), a key transcription factor for the adiponectin gene. To examine this, 3T3-L1 adipocytes were incubated with 125 µmol·L-1 EPA, DHA, palmitic, or oleic acids complexed to albumin, or with albumin alone (control) for 24 h. Adipocytes were also incubated for 24 h with EPA and DHA plus bisphenol-A-diglycidyl ether (BADGE), a PPARγ antagonist. Both EPA and DHA increased (p < 0.05) secreted adiponectin concentration compared with the control (44% and 102%, respectively), but did not affect cellular adiponectin protein content. Incubation with BADGE and DHA inhibited increases in secreted adiponectin protein, suggesting that DHA may act through a PPARγ-dependent mechanism. However, BADGE had no effect on EPA-induced increases in secreted adiponectin protein. Only DHA enhanced (p < 0.05) PPARγ and adiponectin mRNA expression compared wtih the control. Our results demonstrate that DHA increases cellular adiponectin mRNA and secreted adiponectin protein in 3T3-L1 adipocytes, possibly by a mechanism involving PPARγ. Moreover, DHA increased adiponectin concentration to a greater extent (40% more, p < 0.05) compared with EPA, emphasizing the need to consider the independent actions of EPA and DHA in adipocytes.

  15. The ratio of high-molecular weight adiponectin and total adiponectin differs in preterm and term infants.

    PubMed

    Yoshida, Tomohide; Nagasaki, Hiraku; Asato, Yoshihide; Ohta, Takao

    2009-05-01

    Adiponectin consists of three subspecies (high-, middle- and low-molecular weight adiponectin). Among these, high-molecular weight adiponectin (H-adn) is suggested to be an active form of this protein. To assess the relationship between H-adn and postnatal growth in preterm infants (PIs), serum H-adn and total adiponectin (T-adn) were measured in 46 PIs at birth and at corrected term, and 26 term infants (TI) at birth. T-adn and H-adn concentrations, and the ratio of H-adn to T-adn (H/T-adn) were significantly greater in TI and PI at corrected term than in PI at birth (p < 0.001). T-adn and H-adn concentrations in PI at corrected term were similar to those in TI, but H/T-adn in PI at corrected term was less than that in TI (p < 0.02). Stepwise multiple regression analysis revealed that the factors contributing to H/T-adn and serum concentrations of T- and H-adn in PI at corrected term were different from those in TI. These data suggest that quality of early postnatal growth in PIs is different from that in normally developed TI. Postnatal growth accompanying adipose tissue similar to TI may be important for PI to prevent future development of cardiovascular disease.

  16. Central resistin regulates hypothalamic and peripheral lipid metabolism in a nutritional-dependent fashion.

    PubMed

    Vázquez, María J; González, C Ruth; Varela, Luis; Lage, Ricardo; Tovar, Sulay; Sangiao-Alvarellos, Susana; Williams, Lynda M; Vidal-Puig, Antonio; Nogueiras, Rubén; López, Miguel; Diéguez, Carlos

    2008-09-01

    Evidence suggests that the adipocyte-derived hormone resistin (RSTN) directly regulates both feeding and peripheral metabolism through, so far, undefined hypothalamic-mediated mechanisms. Here, we demonstrate that the anorectic effect of RSTN is associated with inappropriately decreased mRNA expression of orexigenic (agouti-related protein and neuropeptide Y) and increased mRNA expression of anorexigenic (cocaine and amphetamine-regulated transcript) neuropeptides in the arcuate nucleus of the hypothalamus. Of interest, RSTN also exerts a profound nutrition-dependent inhibitory effect on hypothalamic fatty acid metabolism, as indicated by increased phosphorylation levels of both AMP-activated protein kinase and its downstream target acetyl-coenzyme A carboxylase, associated with decreased expression of fatty acid synthase in the ventromedial nucleus of the hypothalamus. In addition, we also demonstrate that chronic central RSTN infusion results in decreased body weight and major changes in peripheral expression of lipogenic enzymes, in a tissue-specific and nutrition-dependent manner. Thus, in the fed state central RSTN is associated with induced expression of fatty acid synthesis enzymes and proinflammatory cytokines in liver, whereas its administration in the fasted state does so in white adipose tissue. Overall, our results indicate that RSTN controls feeding and peripheral lipid metabolism and suggest that hepatic RSTN-induced insulin resistance may be mediated by central activation of de novo lipogenesis in liver.

  17. 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.

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

    PubMed

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

    2012-12-01

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

  19. Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD.

    PubMed

    Busso, Nathalie; Karababa, Mahir; Nobile, Massimo; Rolaz, Aline; Van Gool, Frédéric; Galli, Mara; Leo, Oberdan; So, Alexander; De Smedt, Thibaut

    2008-05-21

    Nicotinamide phosphoribosyltransferase (NAMPT), also known as visfatin, is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide. Since its expression is upregulated during inflammation, NAMPT represents a novel clinical biomarker in acute lung injury, rheumatoid arthritis, and Crohn's disease. However, its role in disease progression remains unknown. We report here that NAMPT is a key player in inflammatory arthritis. Increased expression of NAMPT was confirmed in mice with collagen-induced arthritis, both in serum and in the arthritic paw. Importantly, a specific competitive inhibitor of NAMPT effectively reduced arthritis severity with comparable activity to etanercept, and decreased pro-inflammatory cytokine secretion in affected joints. Moreover, NAMPT inhibition reduced intracellular NAD concentration in inflammatory cells and circulating TNFalpha levels during endotoxemia in mice. In vitro pharmacological inhibition of NAMPT reduced the intracellular concentration of NAD and pro-inflammatory cytokine secretion by inflammatory cells. Thus, NAMPT links NAD metabolism to inflammatory cytokine secretion by leukocytes, and its inhibition might therefore have therapeutic efficacy in immune-mediated inflammatory disorders.

  20. The effect of Stevia rebaudiana on serum omentin and visfatin level in STZ-induced diabetic rats.

    PubMed

    Akbarzadeh, Samad; Eskandari, Fatemeh; Tangestani, Hadis; Bagherinejad, Somaieh Tangerami; Bargahi, Afshar; Bazzi, Parviz; Daneshi, Adel; Sahrapoor, Azam; O'Connor, William J; Rahbar, Ali Reza

    2015-03-01

    Recently the role of adipocytokines in relationship to incidence of diabetes has been demonstrated. One of the medicinal plants that are used in the treatment of diabetes is stevia. This study investigates the effect of stevia on serum omentin and visfatin levels as novel adipocytokines in diabetic induced rats to find potential mechanisms for the anti hyperglycemic effect of stevia. Forty male wistar rats weighing 180-250 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ). The animals were divided into 5 groups of 8. Rats in group 1 (non-diabetic control) and group 2 (diabetic control) were treated with distilled water, and the rats in the treated groups, group 3 (T250), group 4 (T500), and group 5 (T750) were treated with stevia, gavaged every day at 9 a.m. in doses of 250, 500, and 750 mg/kg, respectively. At the end of the study significant reductions in fasting blood sugar (FBS), the homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), alkaline phosphatase (ALP), and Omentin level were found in groups 3 and 4 in comparison with group 2. Pancreatic histopathology slides demonstrated that stevia extract did not induce any increase in the number of β-cells. The conclusion is that prescription of stevia in the doses of 250 and 500 mg/kg/d decreases the omentin level indirectly via activating insulin sensitivity and lowering blood glucose in STZ-induced diabetic rats.

  1. Adiponectin does not bind to gelatin: a new and easy way to purify high-molecular-weight adiponectin from human plasma.

    PubMed

    Nakano, Yasuko; Shoji, Ayako; Arakawa, Atsushi; Iizuka, Yumiko; Kikuchi, Yuriko; Kobayashi, Maya; Tobe, Takashi

    2010-01-01

    Human plasma contains three forms of adiponectin, a trimer, a hexamer, and a high-molecular-weight (HMW) multimer. We previously reported HMW adiponectin was a gelatin-binding protein of 28 kDa (GBP28), it having been purified due to its affinity to gelatin-Cellulofine (Nakano, Y., et al. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J. Biochem. 1996. 120: 803-12). Although HMW adiponectin binds to gelatin-Cellulofine, it cannot bind to gelatin-Sepharose. Gelatin-Cellulofine was made of formyl-Cellulofine and gelatin, and we found that HMW adiponectin binds to reduced formyl-Cellulofine with similar affinity as to gelatin-Cellulofine. Through only two steps using reduced formyl-Cellulofine and DEAE-Sepharose, HMW adiponectin can be effectively purified from human plasma.

  2. Uncovering Adiponectin Replenishing Property of Sujiaonori Algal Biomaterial in Humans.

    PubMed

    Ngatu, Nlandu Roger; Ikeda, Mitsunori; Watanabe, Hiroyuki; Tanaka, Mamoru; Inoue, Masataka; Kanbara, Sakiko; Nojima, Sayumi

    2017-02-08

    The replenishment of adiponectin-an adipocyte-derived hormone with salutary health effects-has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p < 0.01); whereas no significant change was observed in controls (3.58 and 3.51 ng/mL, respectively) (p > 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans.

  3. Suggestive evidence of a multi-cytokine resistin pathway in humans and its role on cardiovascular events in high-risk individuals

    PubMed Central

    Menzaghi, Claudia; Marucci, Antonella; Antonucci, Alessandra; De Bonis, Concetta; Ortega Moreno, Lorena; Salvemini, Lucia; Copetti, Massimiliano; Trischitta, Vincenzo; Di Paola, Rosa

    2017-01-01

    In cells and tissues resistin affects IL-1β, IL-6, IL-8, IL-12 and TNF-α expression, thus suggesting the existence of a multi-cytokine “resistin pathway”. We investigated whether such pathway does exist in humans and, if so, if it is associated with cardiovascular risk factors and with major adverse cardiovascular events (MACE). Serum cytokines were measured in 280 healthy subjects from the Gargano Study 2 (GS2) whose BMI, waist circumference, HOMAIR, triglycerides, HDL-cholesterol, systolic and diastolic blood pressure data were available and in 353 patients with type 2 diabetes and coronary artery disease from the Gargano Heart Study (GHS)-prospective design (follow-up 5.4 ± 2.5 years; 71 MACE). In GS2, cytokines mRNA levels in white blood cells were also measured. In GS2, resistin mRNA was correlated with all cytokines expression (all p < 0.001), but IL-12B. Consistently, serum resistin was correlated with all serum cytokines (all p < 0.001), but IL-12. Expression (eRPS) and serum (sRPS) resistin pathway scores (excluding IL-12) were each other correlated (p < 0.001) and both associated with cardiovascular risk factors (all p < 0.01). In GHS, sRPS was independently associated with MACE (HR = 1.44, 95% CI = 1.10–1.90). Our data indicate the existence of a resistin pathway, which is associated with cardiovascular risk factors and which strongly and independently predicts MACE. PMID:28290549

  4. 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.

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

    PubMed Central

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

    2009-01-01

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

  6. 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.

  7. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-09-01

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

  10. Cooperation between HMGA1 and HIF-1 Contributes to Hypoxia-Induced VEGF and Visfatin Gene Expression in 3T3-L1 Adipocytes

    PubMed Central

    Messineo, Sebastiano; Laria, Anna Elisa; Arcidiacono, Biagio; Chiefari, Eusebio; Luque Huertas, Raúl M.; Foti, Daniela P.; Brunetti, Antonio

    2016-01-01

    The architectural transcription factor high-mobility group AT-hook 1 (HMGA1) is a chromatin regulator with implications in several biological processes, including tumorigenesis, inflammation, and metabolism. Previous studies have indicated a role for this factor in promoting the early stages of adipogenesis, while inhibiting adipocyte terminal differentiation, and decreasing fat mass. It has been demonstrated that hypoxia – through the hypoxia-inducible factor 1 (HIF-1) – plays a major role in triggering changes in the adipose tissue of the obese, leading to inhibition of adipocyte differentiation, adipose cell dysfunction, inflammation, insulin resistance, and type 2 diabetes. To examine the possible cooperation between HMGA1 and HIF-1, herein, we investigated the role of HMGA1 in the regulation of Visfatin and VEGF, two genes normally expressed in adipose cells, which are both responsive to hypoxia. We demonstrated that HMGA1 enhanced Visfatin and VEGF gene expression in human embryonic kidney (HEK) 293 cells in hypoxic conditions, whereas HMGA1 knockdown in differentiated 3T3-L1 adipocytes reduced these effects. Reporter gene analysis showed that Visfatin and VEGF transcriptional activity was increased by the addition of either HMGA1 or HIF-1 and even further by the combination of both factors. As demonstrated by chromatin immunoprecipitation in intact cells, HMGA1 directly interacted with the VEGF gene, and this interaction was enhanced in hypoxic conditions. Furthermore, as indicated by co-immunoprecipitation studies, HMGA1 and HIF-1 physically interacted with each other, supporting the notion that this association may corroborate a functional link between these factors. Therefore, our findings provide evidence for molecular cross-talk between HMGA1 and HIF-1, and this may be important for elucidating protein and gene networks relevant to obesity. PMID:27445976

  11. Fetuin-A downregulates adiponectin through Wnt-PPARγ pathway in lipid induced inflamed adipocyte.

    PubMed

    Agarwal, Soumik; Chattopadhyay, Mrittika; Mukherjee, Sandip; Dasgupta, Suman; Mukhopadhyay, Satinath; Bhattacharya, Samir

    2017-01-01

    Adiponectin secreted from adipocytes is an anti-diabetic and anti-atherogenic adipokine. Adiponectin level is known to fall significantly in obesity induced type 2 diabetes which worsen insulin sensitivity because of aberrant lipid management. However, underlying mechanism of adiponectin decrease in obese diabetic condition is yet unclear. We report here that lowering of plasma adiponectin coincided with the higher Fetuin A (FetA) level in high fat diet (HFD) induced obese diabetic mice. Knock down of FetA gene (FetA(KD)) elevated adiponectin level markedly in HFD mice, while reinforcement of FetA into FetA(KD)HFD mice reduced its level again. These results indicate FetA's involvement in the lowering of adiponectin level in obesity induced diabetic mice. Our findings to understand how FetA could affect adiponectin decrease demonstrated that FetA could enhance Wnt3a expression in the adipocyte of HFD mice. FetA addition to 3T3L1 adipocyte incubation elevated Wnt3a expression in a dose dependent manner. Overexpression of Wnt3a by FetA inhibited PPARγ and adiponectin. FetA failed to reduce PPARγ and adiponectin in Wnt3a gene knocked down 3T3L1` adipocytes. All these suggest that FetA mediate its inhibitory effect on adiponectin through Wnt3a-PPARγ pathway. Inhibition of adiponectin expression through FetA and Wnt3a significantly compromised with the activation of AMPK and its downstream signalling molecules which adversely affected lipid management causing loss of insulin sensitivity. Downregulation of adiponectin in inflamed adipocyte by FetA through the mediation of Wnt3a and PPARγ is a new report.

  12. 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.

  13. Unique profile of chicken adiponectin, a predominantly heavy molecular weight multimer, and relationship to visceral adiposity.

    PubMed

    Hendricks, Gilbert L; Hadley, Jill A; Krzysik-Walker, Susan M; Prabhu, K Sandeep; Vasilatos-Younken, Regina; Ramachandran, Ramesh

    2009-07-01

    Adiponectin, a 30-kDa adipokine hormone, circulates as heavy, medium, and light molecular weight isoforms in mammals. Plasma heavy molecular weight (HMW) adiponectin isoform levels are inversely correlated with the incidence of type 2 diabetes in humans. The objectives of the present study were to characterize adiponectin protein and quantify plasma adiponectin levels in chickens, which are naturally hyperglycemic relative to mammals. Using gel filtration column chromatography and Western blot analysis under nonreducing and non-heat-denaturing native conditions, adiponectin in chicken plasma, and adipose tissue is predominantly a multimeric HMW isoform that is larger than 669 kDa mass. Under reducing conditions and heating to 70-100 C, however, a majority of the multimeric adiponectin in chicken plasma and adipose tissue was reduced to oligomeric and/or monomeric forms. Immunoprecipitation and elution under neutral pH preserved the HMW adiponectin multimer, whereas brief exposure to acidic pH led to dissociation of HMW multimer into multiple oligomers. Mass spectrometric analysis of chicken adiponectin revealed the presence of hydroxyproline and differential glycosylation of hydroxylysine residues in the collagenous domain. An enzyme immunoassay was developed and validated for quantifying plasma adiponectin in chickens. Plasma adiponectin levels were found to be significantly lower in 8- compared with 4-wk-old male chickens and inversely related to abdominal fat pad mass. Collectively, our results provide novel evidence that adiponectin in chicken plasma and tissues is predominantly a HMW multimer, suggesting the presence of unique multimerization and stabilization mechanisms in the chicken that favors preponderance of HMW adiponectin over other oligomers.

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

    PubMed Central

    Swarbrick, Michael M.

    2008-01-01

    Abstract Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans. PMID:18510434

  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. Adiponectin modulates excitability of rat paraventricular nucleus neurons by differential modulation of potassium currents.

    PubMed

    Hoyda, Ted D; Ferguson, Alastair V

    2010-07-01

    The adipocyte-derived hormone adiponectin acts at two seven-transmembrane domain receptors, adiponectin receptor 1 and adiponectin receptor 2, present in the paraventricular nucleus of the hypothalamus to regulate neuronal excitability and endocrine function. Adiponectin depolarizes rat parvocellular preautonomic neurons that secrete either thyrotropin releasing hormone or oxytocin and parvocellular neuroendocrine corticotropin releasing hormone neurons, leading to an increase in plasma adrenocorticotropin hormone concentrations while also hyperpolarizing a subgroup of neurons. In the present study, we investigate the ionic mechanisms responsible for these changes in excitability in parvocellular paraventricular nucleus neurons. Patch clamp recordings of currents elicited from slow voltage ramps and voltage steps indicate that adiponectin inhibits noninactivating delayed rectifier potassium current (I(K)) in a majority of neurons. This inhibition produced a broadening of the action potential in cells that depolarized in the presence of adiponectin. The depolarizing effects of adiponectin were abolished in cells pretreated with tetraethyl ammonium (0/15 cells depolarize). Slow voltage ramps performed during adiponectin-induced hyperpolarization indicate the activation of voltage-independent potassium current. These hyperpolarizing responses were abolished in the presence of glibenclamide [an ATP-sensitive potassium (K(ATP)) channel blocker] (0/12 cells hyperpolarize). The results presented in this study suggest that adiponectin controls neuronal excitability through the modulation of different potassium conductances, effects which contribute to changes in excitability and action potential profiles responsible for peptidergic release into the circulation.

  17. 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.

  18. Genetic Background, Adipocytokines, and Metabolic Disorders in Postmenopausal Overweight and Obese Women.

    PubMed

    Grygiel-Górniak, Bogna; Kaczmarek, Elżbieta; Mosor, Maria; Przysławski, Juliusz; Bogacz, Anna

    2016-10-01

    The relationship between the genetic background, adipocytokines, and metabolic state in postmenopausal women has not yet been fully described. The aim of this study was to determine the relationship between PPAR gamma-2 (Pro12Ala, C1431T) and ADRB3 (Trp64Arg) polymorphisms and serum adipocytokines (adiponectin, visfatin, and resistin) and metabolic disorders in 176 postmenopausal women with increased body mass (BMI ≥ 25 kg m(-2)). The distributions of selected alleles and genotype frequencies were determined with the PCR-RFLP method. The bioimpedance method was used to determine nutritional status, and enzyme-linked immunosorbent assays were applied to determine serum concentrations of adipocytokines. Viscerally obese postmenopausal women had higher body mass, body fat content, serum glucose, insulin, total cholesterol, LDL, triglycerides, uric acid, and HOMA-IR and a higher prevalence of the Ala12 allele. In models based on cytokine concentration, higher body mass and glucose concentration (visfatin model, p = 0.008) and higher insulin and triglyceride levels (resistin model, p = 0.002) were observed in visceral fat deposition and this was potentiated by the presence of the T1431 allele. In resistin models, co-existence of Ala12/X polymorphisms with the T1431 allele was associated with higher resistin and triglyceride concentrations (p = 0.045). In postmenopausal women, metabolic parameters are mainly determined by the distribution of body fat, but Ala12/X polymorphism may increase the metabolic disorders and this effect can be enhanced by the T1431 allele.

  19. Uncovering Adiponectin Replenishing Property of Sujiaonori Algal Biomaterial in Humans

    PubMed Central

    Ngatu, Nlandu Roger; Ikeda, Mitsunori; Watanabe, Hiroyuki; Tanaka, Mamoru; Inoue, Masataka; Kanbara, Sakiko; Nojima, Sayumi

    2017-01-01

    The replenishment of adiponectin—an adipocyte-derived hormone with salutary health effects—has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p < 0.01); whereas no significant change was observed in controls (3.58 and 3.51 ng/mL, respectively) (p > 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans

  20. Adiponectin increases glucose-induced insulin secretion through the activation of lipid oxidation.

    PubMed

    Patané, G; Caporarello, N; Marchetti, P; Parrino, C; Sudano, D; Marselli, L; Vigneri, R; Frittitta, L

    2013-12-01

    The expression of adiponectin receptors has been demonstrated in human and rat pancreatic beta cells, where globular (g) adiponectin rescues rat beta cells from cytokine and fatty acid-induced apoptosis. The aim of our study was to evaluate whether adiponectin has a direct effect on insulin secretion and the metabolic pathways involved. Purified human pancreatic islets and rat beta cells (INS-1E) were exposed (1 h) to g-adiponectin, and glucose-induced insulin secretion was measured. A significant increase in glucose-induced insulin secretion was observed in the presence of g-adiponectin (1 nmol/l) with respect to control cells in both human pancreatic islets (n = 5, p < 0.05) and INS-1E cells (n = 5, p < 0.001). The effect of globular adiponectin on insulin secretion was independent of AMP-dependent protein kinase (AMPK) activation or glucose oxidation. In contrast, g-adiponectin significantly increased oleate oxidation (n = 5, p < 0.05), and the effect of g-adiponectin (p < 0.001) on insulin secretion by INS-1E was significantly reduced in the presence of etomoxir (1 μmol/l), an inhibitor of fatty acid beta oxidation. g-Adiponectin potentiates glucose-induced insulin secretion in both human pancreatic islets and rat beta cells via an AMPK independent pathway. Increased fatty acid oxidation rather than augmented glucose oxidation is the mechanism responsible. Overall, our data indicate that, in addition to its anti-apoptotic action, g-adiponectin has another direct effect on beta cells by potentiating insulin secretion. Adiponectin, therefore, in addition to its well-known effect on insulin sensitivity, has important effects at the pancreatic level.

  1. 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

  2. Distinct response of fat and gastrointestinal tissue to glucose in gestational diabetes mellitus and polycystic ovary syndrome.

    PubMed

    Vejrazkova, D; Lischkova, O; Vankova, M; Stanicka, S; Vrbikova, J; Lukasova, P; Vcelak, J; Vacinova, G; Bendlova, B

    2016-12-16

    Gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS) are distinct pathologies with impaired insulin sensitivity as a common feature. The aim of this study was to evaluate the response of fat tissue adipokines and gastrointestinal incretins to glucose load in patients diagnosed with one of the two disorders and to compare it with healthy controls. Oral glucose tolerance test (oGTT) was performed in 77 lean young women: 22 had positive history of GDM, 19 were PCOS patients, and 36 were healthy controls. Hormones were evaluated in fasting and in 60 min intervals during the 3 hour oGTT using Bio-Plex ProHuman Diabetes 10-Plex Assay for C-peptide, ghrelin, GIP, GLP1, glucagon, insulin, leptin, total PAI1, resistin, visfatin and Bio-Plex ProHuman Diabetes Adipsin and Adiponectin Assays (Bio-Rad). Despite lean body composition, both PCOS and GDM women were more insulin resistant than controls. Significant postchallenge differences between the GDM and PCOS groups were observed in secretion of adipsin, leptin, glucagon, visfatin, ghrelin, GIP, and also GLP1 with higher levels in GDM. Conversely, PCOS was associated with the highest resistin, C-peptide, and PAI1 levels. Our data suggest that decreased insulin sensitivity observed in lean women with GDM and PCOS is associated with distinct hormonal response of fat and gastrointestinal tissue to glucose load.

  3. Adiponectin oligomers and ectopic fat in liver and skeletal muscle in humans.

    PubMed

    Kantartzis, Konstantinos; Staiger, Harald; Machann, Jürgen; Schick, Fritz; Claussen, Claus D; Machicao, Fausto; Fritsche, Andreas; Häring, Hans-Ulrich; Stefan, Norbert

    2009-02-01

    We aimed at determining which circulating forms of the adipokine adiponectin that increases lipid oxidation in liver and skeletal muscle are related to ectopic fat in these depots in humans. Plasma total-, high-molecular weight (HMW)-, middle-molecular weight (MMW)-, and low-molecular weight (LMW) adiponectin were quantified by an enzyme-linked immunosorbent assay. Their relationships with liver- and intramyocellular fat, measured using (1)H magnetic resonance spectroscopy, were investigated in 54 whites without type 2 diabetes. Liver fat, adjusted for gender, age, and total body fat, was associated only with HMW adiponectin (r = -0.35, P = 0.012), but not with total-, MMW-, or LMW adiponectin. In addition, subjects with fatty liver (liver fat > or =5.56%, n = 15) had significantly lower HMW- (P = 0.04), but not total-, MMW-, or LMW adiponectin levels, compared to controls (n = 39). Similarly, intramyocellular fat correlated only with HMW (r = -0.32, P = 0.039), but not with the other circulating forms of adiponectin. These data indicate that, among circulating forms of adiponectin, HMW is strongly related to ectopic fat, thus possibly representing the form of adiponectin regulating lipid oxidation in liver and skeletal muscle.

  4. Adiponectin Induces Oncostatin M Expression in Osteoblasts through the PI3K/Akt Signaling Pathway

    PubMed Central

    Su, Chen-Ming; Lee, Wei-Lin; Hsu, Chin-Jung; Lu, Ting-Ting; Wang, Li-Hong; Xu, Guo-Hong; Tang, Chih-Hsin

    2015-01-01

    Rheumatoid arthritis (RA), a common autoimmune disorder, is associated with a chronic inflammatory response and unbalanced bone metabolism within the articular microenvironment. Adiponectin, an adipokine secreted by adipocytes, is involved in multiple functions, including lipid metabolism and pro-inflammatory activity. However, the mechanism of adiponectin performance within arthritic inflammation remains unclear. In this study, we observed the effect of adiponectin on the expression of oncostatin M (OSM), a pro-inflammatory cytokine, in human osteoblastic cells. Pretreatment of cells with inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt, and nuclear factor (NF)-κB reduced the adiponectin-induced OSM expression in osteoblasts. Stimulation of the cells with adiponectin increased phosphorylation of PI3K, Akt, and p65. Adiponectin treatment of osteoblasts increased OSM-luciferase activity and p65 binding to NF-κB on the OSM promoter. Our results indicate that adiponectin increased OSM expression via the PI3K, Akt, and NF-κB signaling pathways in osteoblastic cells, suggesting that adiponectin is a novel target for arthritis treatment. PMID:26712749

  5. Regulation and Quality Control of Adiponectin Assembly by Endoplasmic Reticulum Chaperone ERp44*

    PubMed Central

    Hampe, Lutz; Radjainia, Mazdak; Xu, Cheng; Harris, Paul W. R.; Bashiri, Ghader; Goldstone, David C.; Brimble, Margaret A.; Wang, Yu; Mitra, Alok K.

    2015-01-01

    Adiponectin, a collagenous hormone secreted abundantly from adipocytes, possesses potent antidiabetic and anti-inflammatory properties. Mediated by the conserved Cys39 located in the variable region of the N terminus, the trimeric (low molecular weight (LMW)) adiponectin subunit assembles into different higher order complexes, e.g. hexamers (middle molecular weight (MMW)) and 12–18-mers (high molecular weight (HMW)), the latter being mostly responsible for the insulin-sensitizing activity of adiponectin. The endoplasmic reticulum (ER) chaperone ERp44 retains adiponectin in the early secretory compartment and tightly controls the oxidative state of Cys39 and the oligomerization of adiponectin. Using cellular and in vitro assays, we show that ERp44 specifically recognizes the LMW and MMW forms but not the HMW form. Our binding assays with short peptide mimetics of adiponectin suggest that ERp44 intercepts and converts the pool of fully oxidized LMW and MMW adiponectin, but not the HMW form, into reduced trimeric precursors. These ERp44-bound precursors in the cis-Golgi may be transported back to the ER and released to enhance the population of adiponectin intermediates with appropriate oxidative state for HMW assembly, thereby underpinning the process of ERp44 quality control. PMID:26060250

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

    PubMed

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

    2014-03-01

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

  7. Adiponectin and its receptors: partners contributing to the "vicious circle" leading to the metabolic syndrome?

    PubMed

    Vasseur, Francis

    2006-06-01

    Although already described five years ago, it is only from year 2000, following intensive research in the field of genetics that the adiponectin protein was related with insulin sensitivity, type 2 diabetes and the metabolic syndrome. The story began with a paradox as this protein exclusively secreted by fat tissue was dramatically decreased in patients presenting an excess of fat mass. Later this decrease was reported with insulin resistance and metabolic syndrome associated phenotypes. The search for genetic variants in the adiponectin encoding ACDC gene and epidemio genetic investigations allowed to associate genetic variations of the gene and phenotypic traits of the metabolic syndrome. One of the major points was the correlation of the levels of circulating adiponectin with insulin sensitivity, leading to a better knowledge of the role of adiponectin. Indeed it is now clearly admitted that adiponectin is an insulin sensitizing cytokine. Recently two adiponectin receptors were described and genetic variations in their genes were associated with features of the metabolic syndrome. Interactions of adiponectin with various partners are discussed in view of a better understanding of adiponectin resistance and insulin resistance.

  8. 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.

  9. Adiponectin expression is decreased in the involved skin and sera of diffuse cutaneous scleroderma patients.

    PubMed

    Arakawa, Hiroki; Jinnin, Masatoshi; Muchemwa, Faith C; Makino, Takamitsu; Kajihara, Ikko; Makino, Katsunari; Honda, Noritoshi; Sakai, Keisuke; Fukushima, Satoshi; Ihn, Hironobu

    2011-09-01

    In this study, we determined the adiponectin expression in the serum and lesional skin of patients with scleroderma (SSc). Serum adiponectin concentrations were measured in 32 patients with SSc, 10 patients with SLE, 12 patients with dermatomyositis patients and 13 healthy subjects with specific enzyme-linked immunosorbent assays. Adiponectin mRNA was determined in skin tissues of five patients with diffuse cutaneous SSc (dcSSc), seven patients with limited cutaneous SSc (lcSSc) and seven healthy subjects with real-time polymerase chain reaction. There was a significant reduction in serum adiponectin levels in patients with dcSSc. SSc patients with decreased serum adiponectin levels had higher total skin thickness score and higher incidence of pulmonary fibrosis. Adiponectin mRNA levels in skin tissues from patients with dcSSc were also reduced. Serum adiponectin levels may be a useful biomarker for fibrotic condition in patients with SSc. Clarifying the role of adiponectin in collagen diseases may lead to further understanding of the pathogenesis and new therapeutic approach.

  10. 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:...

  11. Adiponectin receptors: a review of their structure, function and how they work.

    PubMed

    Yamauchi, Toshimasa; Iwabu, Masato; Okada-Iwabu, Miki; Kadowaki, Takashi

    2014-01-01

    The discovery of adiponectin and subsequently the receptors it acts upon have lead to a great surge forward in the understanding of the development of insulin resistance and obesity-linked diseases. Adiponectin is a hormone that is derived from adipose tissue and is reduced in obesity-linked diseases including insulin resistance/type 2 diabetes and atherosclerosis. Adiponectin exerts its effects by binding to adiponectin receptors, two of which, AdipoR1 and AdipoR2, have been cloned. This has enabled researchers to carry out detailed studies elucidating the role played by these receptors and the metabolic pathways that are involved following their activation. Such studies have clearly shown that the stimulation of these receptors is associated with glucose homeostasis and ongoing research into their role will clarify the underlying molecular mechanisms of adiponectin. Such knowledge can then be used to provide therapeutic targets aimed at managing obesity-linked diseases including type 2 diabetes and metabolic syndrome.

  12. 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.

  13. Adiponectin deficiency contributes to the development and progression of benign prostatic hyperplasia in obesity.

    PubMed

    Fu, Shi; Xu, Huan; Gu, Meng; Liu, Chong; Wang, Qiong; Wan, Xiang; Chen, Yanbo; Chen, Qi; Peng, Yubing; Cai, Zhikang; Zhou, Juan; Wang, Zhong

    2017-03-03

    The incidence of benign prostatic hyperplasia (BPH) is increasing among obese individuals, but few studies have fully explained the underlying mechanisms. We aimed to elucidate the relationship between obesity and BPH. Herein, we show that in prostatic epithelial and stromal cells, adiponectin exerts multifunctional effects including anti-proliferation, blocking of G1/S-phase progression and the promotion of apoptosis via inhibiting the MEK-ERK-p90RSK axis. Furthermore, we found that a high-fat diet (HFD) led to adiponectin deficiency and microscopic BPH in a mouse model of obesity. And an adiponectin supplement protected the obese mice from microscopic BPH. The present study provides evidence that adiponectin is a protective regulator in the development and progression of BPH and that adiponectin deficiency causally links BPH with obesity.

  14. Adult Neurogenic and Antidepressant Effects of Adiponectin: A Potential Replacement for Exercise?

    PubMed

    Li, Ang; Yau, Suk-Yu; Machado, Sergio; Yuan, Ti-Fei; So, Kwok-Fai

    2015-01-01

    Physical exercise has long been recognized to benefit locomotor and cardiovascular systems. Although an increasing body of evidence also suggests it to be an effective non-medicinal remedy for mental disorders such as depression, the underlying mechanisms remain elusive. A recent study has demonstrated that increases of the adipocyte-secreted hormone adiponectin in the central nervous system following exercise may be responsible for these neuropsychological changes, including enhanced generation of neurons in the adult hippocampus, as well as mitigation of depressive severity. The present review introduces the previously-reported functions of adult hippocampal neurogenesis and adiponectin, and discusses the potential relevance of adiponectin signaling in exercise-induced neural changes. Revealing these novel biological effects of adiponectin in the brain may help hunt reliable biomarkers to better guide the anti-depressive therapy with exercise intervention; meanwhile, pharmaceutical agents that raise endogenous levels of adiponectin or mimic its biological effects might serve as a replacement for physical exercise.

  15. Adiponectin deficiency contributes to the development and progression of benign prostatic hyperplasia in obesity

    PubMed Central

    Fu, Shi; Xu, Huan; Gu, Meng; Liu, Chong; Wang, Qiong; Wan, Xiang; Chen, Yanbo; Chen, Qi; Peng, Yubing; Cai, Zhikang; Zhou, Juan; Wang, Zhong

    2017-01-01

    The incidence of benign prostatic hyperplasia (BPH) is increasing among obese individuals, but few studies have fully explained the underlying mechanisms. We aimed to elucidate the relationship between obesity and BPH. Herein, we show that in prostatic epithelial and stromal cells, adiponectin exerts multifunctional effects including anti-proliferation, blocking of G1/S-phase progression and the promotion of apoptosis via inhibiting the MEK-ERK-p90RSK axis. Furthermore, we found that a high-fat diet (HFD) led to adiponectin deficiency and microscopic BPH in a mouse model of obesity. And an adiponectin supplement protected the obese mice from microscopic BPH. The present study provides evidence that adiponectin is a protective regulator in the development and progression of BPH and that adiponectin deficiency causally links BPH with obesity. PMID:28256562

  16. 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

  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

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

    2016-07-14

    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.

  18. Adiponectin-Mediated Analgesia and Anti-Inflammatory Effects in Rat

    PubMed Central

    Iannitti, Tommaso; Graham, Annette; Dolan, Sharron

    2015-01-01

    The adipose tissue-derived protein, adiponectin, has significant anti-inflammatory properties in a variety of disease conditions. Recent evidence that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in central nervous system, suggests that it may also have a central modulatory role in pain and inflammation. This study set out to investigate the effects of exogenously applied recombinant adiponectin (via intrathecal and intraplantar routes; 10–5000 ng) on the development of peripheral inflammation (paw oedema) and pain hypersensitivity in the rat carrageenan model of inflammation. Expression of adiponectin, AdipoR1 and AdipoR2 mRNA and protein was characterised in dorsal spinal cord using real-time polymerase chain reaction (PCR) and Western blotting. AdipoR1 and AdipoR2 mRNA and protein were found to be constitutively expressed in dorsal spinal cord, but no change in mRNA expression levels was detected in response to carrageenan-induced inflammation. Adiponectin mRNA, but not protein, was detected in dorsal spinal cord, although levels were very low. Intrathecal administration of adiponectin, both pre- and 3 hours post-carrageenan, significantly attenuated thermal hyperalgesia and mechanical hypersensitivity. Intrathecal administration of adiponectin post-carrageenan also reduced peripheral inflammation. Intraplantar administration of adiponectin pre-carrageenan dose-dependently reduced thermal hyperalgesia but had no effect on mechanical hypersensitivity and peripheral inflammation. These results show that adiponectin functions both peripherally and centrally at the spinal cord level, likely through activation of AdipoRs to modulate pain and peripheral inflammation. These data suggest that adiponectin receptors may be a novel therapeutic target for pain modulation. PMID:26352808

  19. Serum Adiponectin and Cardiometabolic Risk in Patients with Acute Coronary Syndromes

    PubMed Central

    Oliveira, Gustavo Bernardes de Figueiredo; França, João Ítalo Dias; Piegas, Leopoldo Soares

    2013-01-01

    Background The adipose tissue is considered not only a storable energy source, but mainly an endocrine organ that secretes several cytokines. Adiponectin, a novel protein similar to collagen, has been found to be an adipocyte-specific cytokine and a promising cardiovascular risk marker. Objectives To evaluate the association between serum adiponectin levels and the risk for cardiovascular events in patients with acute coronary syndromes (ACS), as well as the correlations between adiponectin and metabolic, inflammatory, and myocardial biomarkers. Methods We recruited 114 patients with ACS and a mean 1.13-year follow-up to measure clinical outcomes. Clinical characteristics and biomarkers were compared according to adiponectin quartiles. Cox proportional hazard regression models with Firth's penalization were applied to assess the independent association between adiponectin and the subsequent risk for both primary (composite of cardiovascular death/non-fatal acute myocardial infarction (AMI)/non-fatal stroke) and co-primary outcomes (composite of cardiovascular death/non-fatal AMI/non-fatal stroke/ rehospitalization requiring revascularization). Results There were significant direct correlations between adiponectin and age, HDL-cholesterol, and B-type natriuretic peptide (BNP), and significant inverse correlations between adiponectin and waist circumference, body weight, body mass index, Homeostasis Model Assessment (HOMA) index, triglycerides, and insulin. Adiponectin was associated with higher risk for primary and co-primary outcomes (adjusted HR 1.08 and 1.07/increment of 1000; p = 0.01 and p = 0.02, respectively). Conclusion In ACS patients, serum adiponectin was an independent predictor of cardiovascular events. In addition to the anthropometric and metabolic correlations, there was a significant direct correlation between adiponectin and BNP. PMID:24029961

  20. 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

  1. 4-Hydroxynonenal differentially regulates adiponectin gene expression and secretion via activating PPARγ and accelerating ubiquitin–proteasome degradation

    PubMed Central

    Wanga, Zhigang; Dou, Xiaobing; Gu, Dongfang; Shen, Chen; Yao, Tong; Nguyen, Van; Braunschweig, Carol; Song, Zhenyuan

    2011-01-01

    Although well-established, the underlying mechanisms involved in obesity-related plasma adiponectin decline remain elusive. Oxidative stress is associated with obesity and insulin resistance and considered to contribute to the progression toward obesity-related metabolic disorders. In this study, we investigated the effects of 4-hydroxynonenal (4-HNE), the most abundant lipid peroxidation end product, on adiponectin production and its potential implication in obesity-related adiponectin decrease. Long-term high-fat diet feeding led to obesity in mouse, accompanied by decreased plasma adiponectin and increased adipose tissue 4-HNE content. Exposure of adipocytes to exogenous 4-HNE resulted in decreased adiponectin secretion in a dose-dependent manner, which was consistent with significantly decreased intracellular adiponectin protein abundance. In contrast, adiponectin gene expression was significantly elevated by 4-HNE treatment, which was concomitant with increased peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression and transactivity. The effect was abolished by T0070907, a PPAR-γ antagonist, suggesting that PPAR-γ activation plays a critical role in this process. To gain insight into mechanisms involved in adiponectin protein decrease, we examined the effects of 4-HNE on adiponectin protein degradation. Cycloheximide (CHX)-chase assay revealed that 4-HNE exposure accelerated adiponectin protein degradation, which was prevented by MG132, a potent proteasome inhibitor. Immunoprecipitation assay showed that 4-HNE exposure increased ubiquitinated adiponectin protein levels. These data altogether indicated that 4-HNE enhanced adiponectin protein degradation via ubiquitin–proteasome system. Finally, we demonstrated that supplementation of HF diet with betaine, an antioxidant and methyl donor, alleviated high-fat-induced adipose tissue 4-HNE increase and attenuated plasma adiponectin decline. Taken together, our findings suggest that the lipid

  2. Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity.

    PubMed

    Kyriakou, Theodosios; Collins, Laura J; Spencer-Jones, Nicola J; Malcolm, Claire; Wang, Xiaoling; Snieder, Harold; Swaminathan, Ramasamyiyer; Burling, Keith A; Hart, Deborah J; Spector, Tim D; O'Dell, Sandra D

    2008-01-01

    Adiponectin is an insulin sensitiser in muscle and liver, and low serum levels characterise obesity and insulin resistance. Eight tagging single nucleotide polymorphisms (tSNPs) in the ADIPOQ gene and promoter were selected, and association with serum adiponectin was tested, in two independent samples of Caucasian women: the Chingford Study (n = 808, mean age 62.8 +/- 5.9 years) and Twins UK (n = 2,718, mean age 47.4 +/- 12.6 years). In the Chingford cohort, -11391 G/A, -10066 G/A (rs182052), -7734 C/A (rs16861209), +276 G/T (rs1501299) and +3228 C/T (rs1063537) were significantly associated with fasting serum adiponectin (Ps = 1.00 x 10(-4) to 1.40 x 10(-2)). Associations with all except +3228 C/T were replicated in the Twins UK cohort (Ps = 3.19 x 10(-9) to 6.00 x 10(-3)). In Chingford subjects, the 12 most common 8-SNP haplotypes (frequency 1.90%) explained 2.85% (p = 5.00 x 10(-2)) and in Twins UK subjects, the four most common 5-SNP haplotypes (frequency > 5.00%) explained 1.66% of the variance (p = 5.83 x 10(-7)). To investigate effects of -11391 G/A (rs17300539) and -11377 C/G (rs266729) on promoter activity, 1.2 kb of the ADIPOQ promoter region was cloned in a luciferase reporter plasmid, and the four haplotypes were transfected in differentiated 3T3-L1 adipocytes. No significant allelic effects on promoter activity were found.

  3. 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

  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. 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

  6. Molecular mechanisms of diabetes and atherosclerosis: role of adiponectin.

    PubMed

    Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

    2012-06-01

    Type 2 diabetes mellitus (T2DM) is a disease characterized by inadequate beta-cell response due to progressive insulin resistance that typically accompanies physical inactivity and weight gain. T2DM is associated with substantial morbidity and mortality related to the associated atherosclerotic cardiovascular risks and diabetic vasculopathies, including microangiopathies (e.g., blindness and renal failure) and macroangiopathies (atherosclerosis). The increasing global prevalence of T2DM is linked to the rising rates of obesity, especially abdominal obesity. Visceral fat accumulation is upstream of obesity-related disorders including atherosclerotic cardiovascular disease (ACVD), and is associated with impaired insulin sensitivity and atherosclerosis through dysregulated production of adipocytokines, especially hypoadiponectinemia. This review article discusses the pathophysiological mechanisms responsible for T2DM and atherosclerosis, focusing on adiponectin. Clinical and experimental studies have shown that hypoadiponectinemia contributes to a variety of life style-related diseases including T2DM and atherosclerosis. It is likely that life-style modification, visceral fat reduction and use of medications that increase serum adiponectin levels (e.g., rimonabant, thiazolidinediones, fibrates, angiotensin receptor blocker and mineralocorticoid receptor blockade) when provided in combination can improve hypoadiponectinemia and thus prevent the development of life style-related diseases including T2DM and ACVD.

  7. Ellagic acid improves hepatic steatosis and serum lipid composition through reduction of serum resistin levels and transcriptional activation of hepatic ppara in obese, diabetic KK-A(y) mice.

    PubMed

    Yoshimura, Yukihiro; Nishii, Saori; Zaima, Nobuhiro; Moriyama, Tatsuya; Kawamura, Yukio

    2013-05-10

    Ellagic acid (EA) is a polyphenol found in a wide variety of plant foods that not only exhibits free radical-scavenging activity, but also confers protective effects against liver injury. Previously, we reported that pomegranate fruit extract (PFE) had an inhibitory effect on resistin secretion from differentiated murine 3T3-L1 adipocytes and identified EA contained in PFE as a potent suppressor of resistin secretion. Resistin, an adipocytokine, is considered the link between obesity and type 2 diabetes. In this study, we explored whether EA supplementation reduces serum resistin and improves hepatic steatosis and serum lipid profile by using KK-A(y) mice fed high-fat diet as a model for obese type 2 diabetes. We found that EA supplementation improved serum lipid profile and hepatic steatosis, and reduced serum resistin levels without altering mRNA expression levels in adipose tissue. Moreover, EA supplementation upregulated mRNA expression of apoa1, ldlr, cpt1a, and ppara genes in the liver. In conclusion, our findings indicate that EA is a potent suppressor of resistin secretion in vivo and a transcriptional activator of ppara in the liver, suggesting a possibility for improving obesity-induced dyslipidemia and hepatic steatosis in KK-A(y) mice.

  8. Circulating Adiponectin Levels Following Treatment Can Predict Late Clinical Outcomes in Chronic Heart Failure

    PubMed Central

    Yu, Ho-Ping; Jen, Hsu-Lung; Yin, Wei-Hsian; Wei, Jeng

    2017-01-01

    Background Circulating adiponectin concentration increases in patients with chronic heart failure (HF). We sought to explore the prognostic value of temporal changes in adiponectin concentration following treatment for chronic HF. Methods Serum adiponectin levels were measured at baseline and after a 3-month anti-failure treatment in 124 patients with symptomatic chronic systolic HF. Major adverse cardiac events (MACE) including death, heart transplantation, or hospitalization with worsening HF during a median follow-up period of 752 days were determined. Results Univariate and multivariate analysis showed that high levels of adiponectin after a 3-month treatment were associated with a 3.8-fold increased risk of MACE (p = 0.03), independent of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Moreover, the combining of circulating levels of adiponectin with NT-proBNP provided independent and additional prognostic value in identifying high risk patients with MACE during follow-up. Conclusions Changes in adiponectin and NT-proBNP over time provide prognostic information. When adiponectin is used in conjunction with NT-proBNP in chronic HF, the prognostic value may be better than if each biomarker is used separately. PMID:28344417

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

    PubMed

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

    2012-11-01

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

  10. Exendin-4 Upregulates Adiponectin Level in Adipocytes via Sirt1/Foxo-1 Signaling Pathway

    PubMed Central

    Wang, Anping; Li, Ting; An, Ping; Yan, Wenhua; Zheng, Hua; Wang, Baoan; Mu, Yiming

    2017-01-01

    Glucagon-like peptide-1 (GLP-1) receptor plays an essential role in regulating glucose metabolism. GLP-1 receptor agonists have been widely used for treating diabetes and other insulin resistance-related diseases. However, mechanisms underlying the anti-diabetic effects of GLP-1 receptor agonists remain largely unknown. In this study, we investigated the effects of GLP-1 agonist exendin-4 on the expression of adiponectin, an insulin sensitizing hormone. We found that exendin-4 increased the expression and secretion of adiponectin both in vitro and in vivo. Our data showed that exendin-4 upregulated adiponectin expression at both mRNA and protein levels in adipocytes and adipose tissues. The effects of exendin-4 on adiponectin expression were dependent on the GLP-1 receptor. We further demonstrated important roles of Sirt1 and transcriptional factor Foxo-1 in mediating the function of exendin-4 in regulating adiponectin expression. Suppression of Sirt1 or Foxo-1 expression significantly impaired exendin-4-induced adiponectin expression. Consistently, exendin-4 up-regulated Sirt1 and Foxo-1 expression in vivo. Our work is the first study demonstrating the role of Sirt1/Foxo-1 in regulating the regulatory function of a GLP-1 receptor agonist in adiponectin expression both in vitro and in vivo. The results provide important information for the mechanism underlying the function of GLP-1R on improving insulin resistance and related diseases. PMID:28122026

  11. Associations of Two Obesity-Related Single-Nucleotide Polymorphisms with Adiponectin in Chinese Children

    PubMed Central

    Gao, Liwang; Zhao, Xiaoyuan; Zhang, Meixian; Wu, Jianxin

    2017-01-01

    Purpose. Genome-wide association studies have found two obesity-related single-nucleotide polymorphisms (SNPs), rs17782313 near the melanocortin-4 receptor (MC4R) gene and rs6265 near the brain-derived neurotrophic factor (BDNF) gene, but the associations of both SNPs with other obesity-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNPs and adiponectin that has a regulatory role in glucose and lipid metabolism. Methods. We examined the associations of the SNPs with adiponectin in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study. Results. The SNP rs6265 was significantly associated with adiponectin under an additive model (P = 0.02 and 0.024, resp.) after adjustment for age, gender, and BMI or obesity statuses. The SNP rs17782313 was significantly associated with low adiponectin under a recessive model. No statistical significance was found between the two SNPs and low adiponectin after correction for multiple testing. Conclusion. We demonstrate for the first time that the SNP rs17782313 near MC4R and the SNP rs6265 near BDNF are associated with adiponectin in Chinese children. These novel findings provide important evidence that adiponectin possibly mediates MC4R and BDNF involved in obesity.

  12. Beneficial effects of adiponectin on periodontal ligament cells under normal and regenerative conditions.

    PubMed

    Nokhbehsaim, Marjan; Keser, Sema; Nogueira, Andressa Vilas Boas; Cirelli, Joni Augusto; Jepsen, Søren; Jäger, Andreas; Eick, Sigrun; Deschner, James

    2014-01-01

    Type 2 diabetes and obesity are increasing worldwide and linked to periodontitis, a chronic disease which is characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium. The mechanisms underlying the association of diabetes mellitus and obesity with periodontal destruction and compromised periodontal healing are not well understood, but decreased plasma levels of adiponectin, as found in diabetic and obese individuals, might be a critical mechanistic link. The aim of this in vitro study was to examine the effects of adiponectin on periodontal ligament (PDL) cells under normal and regenerative conditions, and to study the regulation of adiponectin and its receptors in these cells. Adiponectin stimulated significantly the expression of growth factors and extracellular matrix, proliferation, and in vitro wound healing, reduced significantly the constitutive tumor necrosis factor-α expression, and caused a significant upregulation of its own expression. The beneficial actions of enamel matrix derivative on a number of PDL cell functions critical for periodontal regeneration were partially enhanced by adiponectin. The periodontopathogen Porphyromonas gingivalis inhibited the adiponectin expression and stimulated the expression of its receptors. In conclusion, reduced levels of adiponectin, as found in type 2 diabetes and obesity, may compromise periodontal health and healing.

  13. 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.

  14. Serum Adiponectin is Associated with Adverse Outcomes of Asthma in Men but Not in Women

    PubMed Central

    Sood, Akshay; Dominic, Elizabeth; Qualls, Clifford; Steffes, Michael W.; Thyagarajan, Bharat; Smith, Lewis J.; Lewis, Cora E.; Jacobs, David R.

    2011-01-01

    Background: Murine studies suggest a beneficial effect of systemic adiponectin on asthma. Our objective was to determine the association between serum adiponectin concentrations and asthma control/severity outcomes in men and women separately. Methods: Cross-sectional and longitudinal analyses of data from years 10, 15, and 20 examinations of the prospective coronary artery risk development in young adults study in the United States were performed. Asthma was defined by self-reported provider diagnosis at or prior to year 15 examination. Outcomes included presence of active disease, number of respiratory symptoms, and number of asthma medications; as well as longitudinal decline in absolute FEV1. Year 15 serum adiponectin concentration was the predictor variable. Results: In a multivariable analysis of 411 eligible subjects, after adjusting for body mass index and covariates, higher serum adiponectin concentrations were associated with more frequent active disease (including more frequent use of any asthma medication), and greater number of respiratory symptoms and asthma medications among men but not among women with asthma (p for interactions between sex and adiponectin for all analyses < 0.05). Conclusions: Higher serum adiponectin concentrations may be independently associated with adverse clinical outcomes of asthma in men but not in women. If biological effect is confirmed in future studies, modification of systemic adiponectin concentrations may open up newer ways to treat asthma in men. PMID:22007173

  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. Effects of aging on the plasma levels of nesfatin-1 and adiponectin

    PubMed Central

    LI, JIANG-BO; NISHIDA, MIYUKI; KAIMOTO, KAORI; ASAKAWA, AKIHIRO; CHAOLU, HUHE; CHENG, KAI-CHUN; LI, YING-XIAO; TERASHI, MUTSUMI; KOYAMA, KEN ICHIRO; AMITANI, HARUKA; SAKOGUCHI, TAKEO; USHIKAI, MIHARU; IKEDA, SATOSHI; AOYAMA, KOHJI; HORIUCHI, MASAHISA; LI, JIAN-ZHONG; INUI, AKIO

    2014-01-01

    Gastric and adipose tissue secrete a number of hormones that are involved in energy metabolism. The biological functions of these hormones, including their effects on aging, are currently under investigation. Adiponectin was shown to be directly involved in appetite and the control of body weight. However, the effects of aging of nesfatin-1, an appetite-suppressing peptide that was recently identified, have not yet been fully elucidated. The aim of this study was to determine the effects of aging on the plasma levels of nesfatin-1 and adiponectin. Our results demonstrated no significant differences in the nesfatin-1 plasma levels among three age groups (2, 6 and 24 months) of female BALB/c mice. The plasma nesfatin-1 levels/visceral fat (VF) ratio in the 24-month-old mice was significantly lower compared to that in the 2- and 6-month-old mice. In addition, there were no significant differences in the plasma adiponectin levels among the three age groups. The plasma adiponectin levels/VF ratio in the 24-month-old mice was significantly lower compared to that in the 2- and 6-month-old mice. In conclusion, there were no age-related changes in the plasma levels of nesfatin-1 and adiponectin, although the ratio of plasma levels of nesfatin-1 and adiponectin per VF was decreased with advancing age. Our results indicated that nesfatin-1 and adiponectin may be involved in controlling energy balance during aging. PMID:24649088

  17. The role of leptin/adiponectin ratio in metabolic syndrome and diabetes.

    PubMed

    López-Jaramillo, Patricio; Gómez-Arbeláez, Diego; López-López, Jose; López-López, Cristina; Martínez-Ortega, Javier; Gómez-Rodríguez, Andrea; Triana-Cubillos, Stefany

    2014-04-01

    The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with insulin resistance and 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. Attention has focused on the visceral adipose tissue production of cytokines (adipokines) in metabolic syndrome and type 2 diabetes mellitus, 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. In this review, we will give special attention to the role of the leptin/adiponectin ratio. We have previously demonstrated that in individuals with severe coronary artery disease, abdominal obesity 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-α and interleukin-6; these are associated with insulin resistance and type 2 diabetes mellitus. In contrast, adiponectin has anti-inflammatory properties and downregulates the expression and release of a number of proinflammatory immune mediators. Therefore, it appears that interactions between angiotensin II and leptin/adiponectin imbalance may be important mediators of the elevated risk of developing type 2 diabetes mellitus and cardiovascular diseases associated with abdominal obesity.

  18. Adiponectin Deficiency Leads to Female Subfertility and Ovarian Dysfunctions in Mice.

    PubMed

    Cheng, Lixian; Shi, Hui; Jin, Yan; Li, Xiaoxi; Pan, Jinshun; Lai, Yimei; Lin, Yan; Jin, Ya; Roy, Gaurab; Zhao, Allan; Li, Fanghong

    2016-12-01

    Adipose tissue plays an important role in regulating female fertility, owing to not only its energy stores but also the endocrine actions of secreted adipokines. As one of the adipokines, adiponectin is almost exclusively secreted from the fat, and its circulating concentration is paradoxically reduced in obesity. Although recent studies implied a purported positive role of adiponectin in ovarian functions, definitive in vivo evidence has been sorely lacking. We have consistently observed subfertility in female adiponectin null mice and therefore postulated a protective role of adiponectin in ovarian functions. Female adiponectin null mice displayed impaired fertility, reduced retrieval of oocytes, disrupted estrous cycle, elevated number of atretic follicles, and impaired late folliculogenesis. Analysis of their sera revealed a significant decrease in estradiol and FSH but an increase in LH and testosterone at proestrus. In addition, we found marked reduction of progesterone levels at diestrus, a significant decrease in LH receptor expression as well as in the number of GnRH immunoreactive neurons. Adiponectin deficiency also altered the peak concentrations of LH surge and led to lower expression of Cytochrome P450 family 11 subfamily A member 1 (P450scc), an enzyme critical for progesterone synthesis, as well as an increase in BCL2 associated X, apoptosis regulator and Insulin like growth factor binding protein 4 in atretic follicles. These physiological and molecular events were independent of insulin sensitivity. Thus, we have revealed a novel mechanism linking adiponectin and female fertility that entails regulation of reproductive hormone balance and ovarian follicle development.

  19. The Role of Alcohol Consumption in Regulating Circulating Levels of Adiponectin: A Prospective Cohort Study

    PubMed Central

    Britton, Annie

    2015-01-01

    Context: The role of alcohol intake in influencing longitudinal trajectories of adiponectin is unclear. Objective: The objective of the study was to examine the association between alcohol intake and changes in the circulating levels of adiponectin over repeat measures. Design, Setting, and Participants: A prospective cohort study of 2855 men and women (74% men with a mean age of 50 y at baseline) drawn from the Whitehall II study. Data from study phases 3 (1991–1993), 5 (1997–1999), and 7 (2002–2004) were used. Main Outcome Measure: Adiponectin serum concentrations (nanograms per milliliter) were measured, and alcohol intake was defined in terms of number of UK units (1 U = 8 g ethanol) consumed in the previous 7 days on three occasions. Cross-sectional associations between alcohol and adiponectin levels were calculated using linear regression. A bivariate dual-change score model was used to estimate the effect of alcohol intake on upcoming change in adiponectin. Models were adjusted for age, sex, ethnicity, and smoking status. Results: Alcohol consumption was cross-sectionally associated with (log transformed) adiponectin levels (β ranging from .001 to .004, depending on phase and level of adjustment) but was not associated with changes in adiponectin levels over time [γ = −0.002 (SE 0.002), P = 0.246]. Conclusion: Alcohol intake is not associated with changes in circulating adiponectin levels in this cohort. This finding provides evidence that adiponectin levels are unlikely to mediate the relationship between moderate alcohol consumption and reduced risk of type 2 diabetes. It is important to consider dynamic longitudinal relationships rather than cross-sectional associations. PMID:26000546

  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. 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.

  2. 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

  3. Higher Circulating Adiponectin Levels Are Associated with Increased Risk of Atrial Fibrillation in Older Adults

    PubMed Central

    Macheret, Fima; Bartz, Traci M.; Djousse, Luc; Ix, Joachim H.; Mukamal, Kenneth J.; Zieman, Susan J.; Siscovick, David S.; Tracy, Russell P.; Heckbert, Susan R.; Psaty, Bruce M.; Kizer, Jorge R.

    2016-01-01

    Background Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner. Methods We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74±5 years). Results During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1–76, the hazard ratio (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05–1.24), while that for HMW adiponectin was 1.17 (1.08–1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids, and inflammation, did not significantly affect these estimates. Conclusions The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age. PMID:25855796

  4. 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

  5. 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

  6. The rapid increase of circulating adiponectin in neonatal calves depends on colostrum intake.

    PubMed

    Kesser, J; Hill, M; Heinz, J F L; Koch, C; Rehage, J; Steinhoff-Wagner, J; Hammon, H M; Mielenz, B; Sauerwein, H; Sadri, H

    2015-10-01

    Adiponectin, an adipokine, regulates metabolism and insulin sensitivity. Considering that the transplacental transfer of maternal proteins of high molecular weight is hindered in ruminants, this study tested the hypothesis that the blood concentration of adiponectin in neonatal calves largely reflects their endogenous synthesis whereby the intake of colostrum might modify the circulating concentrations. We thus characterized the adiponectin concentrations in neonatal and young calves that were fed either colostrum or formula. Three trials were performed: in trial 1, 20 calves were all fed colostrum for 3 d, and then formula until weaning. Blood samples were collected on d 0 (before colostrum feeding), and on d 1, 3, 11, 22, 34, 43, 52, 70, 90, and 108 postnatum. In trial 2, 14 calves were studied for the first 4 d of life. They were fed colostrum (n=7) or formula (n=7), and blood samples were taken right after birth and before each morning feeding on d 2, 3, and 4. In trial 3, calves born preterm (n=7) or at term received colostrum only at 24 h postnatum. Blood was sampled at birth, and before and 2 h after feeding. Additionally, allantoic fluid and blood from 4 Holstein cows undergoing cesarean section were sampled. Adiponectin was quantified by ELISA. In trial 1, the serum adiponectin concentrations recorded on d 3 were 4.7-fold higher than before colostrum intake. The distribution of the molecular weight forms of adiponectin differed before and after colostrum consumption. In trial 2, the colostrum group had consistently greater plasma adiponectin concentrations than the formula group after the first meal. In trial 3, the preterm calves tended to have lower concentrations of plasma adiponectin than the term calves at birth and before and 2 h after feeding. Furthermore, the adiponectin concentrations were substantially lower in allantoic fluid than in the sera from neonatal calves and from cows at parturition. Our results show that calves are born with very low

  7. Adiponectin resistance in skeletal muscle: pathophysiological implications in chronic heart failure

    PubMed Central

    Van Berendoncks, An M; Hoymans, Vicky Y; Vrints, Christiaan J

    2015-01-01

    Abstract Skeletal muscle wasting is a common complication of chronic heart failure (CHF) and linked to poor patient prognosis. In recent years, adiponectin was postulated to be centrally involved in CHF‐associated metabolic failure and muscle wasting. This review discusses current knowledge on the role of adiponectin in CHF. Particular emphasis will be given to the complex interaction mechanisms and the intracellular pathways underlying adiponectin resistance in skeletal muscle of CHF patients. In this review, we propose that the resistance process is multifactorial, integrating abnormalities emanating from insulin signalling, mitochondrial biogenesis, and ceramide metabolism. PMID:27239409

  8. 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

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

    PubMed

    Han, Yun; Zheng, Yan-li; Fan, Yu-ping; Liu, Man-hua; Lu, Xiao-yan; Tao, Qian

    2015-02-01

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

  10. The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain.

    PubMed

    Hampton, Eric N; Knuth, Mark W; Li, Jun; Harris, Jennifer L; Lesley, Scott A; Spraggon, Glen

    2007-09-11

    Mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) are strongly associated with levels of low-density lipoprotein cholesterol in the blood plasma and, thereby, occurrence or resistance to atherosclerosis and coronary heart disease. Despite this importance, relatively little is known about the biology of PCSK9. Here, the crystal structure of a full-length construct of PCSK9 solved to 1.9-A resolution is presented. The structure contains a fully folded C-terminal cysteine-rich domain (CRD), showing a distinct structural similarity to the resistin homotrimer, a small cytokine associated with obesity and diabetes. This structural relationship between the CRD of PCSK9 and the resistin family is not observed in primary sequence comparisons and strongly suggests a distant evolutionary link between the two molecules. This three-dimensional homology provides insight into the function of PCSK9 at the molecular level and will help to dissect the link between PCSK9 and CHD.

  11. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26703682

  13. Integral role of PTP1B in adiponectin-mediated inhibition of oncogenic actions of leptin in breast carcinogenesis.

    PubMed

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

    2013-01-01

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

  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. Role of Adiponectin and Its Receptors in Cancer

    PubMed Central

    Obeid, Stephanie; Hebbard, Lionel

    2012-01-01

    Adiponectin (APN), a novel hormone/cytokine derived from adipocyte tissue, is involved in various physiological functions. Genetics, nutrition, and adiposity are factors contributing to circulating plasma concentrations of APN. Clinical correlation studies have shown that lower levels of serum APN are associated with increased malignancy of various cancers, such as breast and colon cancers, suggesting that APN has a role in tumorigenesis. APN affects insulin resistance, thus further influencing cancer development. Tumor cells may express receptors for APN. Cellular signaling is the mechanism by which APN exerts its host-protective responses. These factors suggest that serum APN levels and downstream signaling targets of APN may serve as potential diagnostic markers for malignancies. Further research is necessary to clarify the exact role of APN in cancer diagnosis and therapy. PMID:23691481

  16. Adipokines in connective tissue diseases.

    PubMed

    Sawicka, Karolina; Krasowska, Dorota

    2016-01-01

    Adipokines, pleiotropic molecules produced by white adipose tissue (WAT) have attracted the attention of scientists since 1994. The role of adipokines in metabolic syndrome is known and fixed. Adipokines exerting a variety of metabolic activities have contributed to the ethiopathogenesis and the consequences of metabolic syndrome. Furthermore, adipokines are involved in the regulation of inflammatory processes and autoimmunity in the light of pathogenesis of connective tissue diseases. Given some evidence for the influence of adipokines in metabolic syndrome, there may be a link between CVDs and rheumatic diseases. This review provides an overview of the literature focusing on the role of adipokines in rheumatic diseases by putting special emphasis on the potential role of leptin, resistin, adiponectin, chemerin, visfatin and novel adipokines in connective tissue diseases.

  17. From Placenta to Polycystic Ovarian Syndrome: The Role of Adipokines.

    PubMed

    Sartori, Chiara; Lazzeroni, Pietro; Merli, Silvia; Patianna, Viviana Dora; Viaroli, Francesca; Cirillo, Francesca; Amarri, Sergio; Street, Maria Elisabeth

    2016-01-01

    Adipokines are cytokines produced mainly by adipose tissue, besides many other tissues such as placenta, ovaries, peripheral-blood mononuclear cells, liver, muscle, kidney, heart, and bone marrow. Adipokines play a significant role in the metabolic syndrome and in cardiovascular diseases, have implications in regulating insulin sensitivity and inflammation, and have significant effects on growth and reproductive function. The objective of this review was to analyze the functions known today of adiponectin, leptin, resistin, and visfatin from placenta throughout childhood and adolescence. It is well known now that their serum concentrations during pregnancy and lactation have long-term effects beyond the fetus and newborn. With regard to puberty, adipokines are involved in the regulation of the relationship between nutritional status and normal physiology or disorders of puberty and altered gonadal function, as, for example, premature pubarche and polycystic ovarian syndrome (PCOS). Cytokines are involved in the maturation of oocytes and in the regular progression of puberty and pregnancy.

  18. From Placenta to Polycystic Ovarian Syndrome: The Role of Adipokines

    PubMed Central

    Sartori, Chiara; Lazzeroni, Pietro; Merli, Silvia; Patianna, Viviana Dora; Viaroli, Francesca; Cirillo, Francesca; Amarri, Sergio

    2016-01-01

    Adipokines are cytokines produced mainly by adipose tissue, besides many other tissues such as placenta, ovaries, peripheral-blood mononuclear cells, liver, muscle, kidney, heart, and bone marrow. Adipokines play a significant role in the metabolic syndrome and in cardiovascular diseases, have implications in regulating insulin sensitivity and inflammation, and have significant effects on growth and reproductive function. The objective of this review was to analyze the functions known today of adiponectin, leptin, resistin, and visfatin from placenta throughout childhood and adolescence. It is well known now that their serum concentrations during pregnancy and lactation have long-term effects beyond the fetus and newborn. With regard to puberty, adipokines are involved in the regulation of the relationship between nutritional status and normal physiology or disorders of puberty and altered gonadal function, as, for example, premature pubarche and polycystic ovarian syndrome (PCOS). Cytokines are involved in the maturation of oocytes and in the regular progression of puberty and pregnancy. PMID:27746590

  19. Biochemistry of adipose tissue: an endocrine organ.

    PubMed

    Coelho, Marisa; Oliveira, Teresa; Fernandes, Ruben

    2013-04-20

    Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example). This paper reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance.

  20. Biochemistry of adipose tissue: an endocrine organ

    PubMed Central

    Coelho, Marisa; Oliveira, Teresa

    2013-01-01

    Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example). This paper reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance. PMID:23671428

  1. Adiponectin: an attractive marker for metabolic disorders in Chronic Obstructive Pulmonary Disease (COPD).

    PubMed

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

    2013-10-14

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

  2. Adiponectin serum levels correlate with insulin resistance in type 2 diabetic patients

    PubMed Central

    Aleidi, Shereen; Issa, Ala; Bustanji, Haidar; Khalil, Mohammad; Bustanji, Yasser

    2014-01-01

    The adipose tissue is not only an inert storage depot for lipids, but also it secretes a variety of bioactive molecules, known as adipokines, which affect whole-body homeostasis. Adiponectin is the most abundant of these adipocytokines and is known to have a regulatory effect on the metabolism of glucose and lipid. The main objectives of this study were to evaluate the serum levels of adiponectin and to establish a correlation between adiponectin serum levels and the degree of insulin resistance in type 2 diabetic patients. Eighty participants were enrolled in this study; 61 type 2 diabetic patients and 19 apparently healthy subjects. Serum level of adiponectin was measured by enzyme-linked immunosorbent assay (ELISA) for each participant. Data collection sheet was filled with all required information for each participant. Adiponectin level in the diabetic patients (5.05 ± 2.61 μg/ml) was lower than in non-diabetic healthy controls (5.71 ± 2.35 μg/ml). When the results were compared according to gender, diabetic females showed significantly higher adiponectin levels (5.76 ± 2.64 μg/ml) than diabetic males (4.366 ± 2.43 μg/ml, P = 0.035). In addition, female diabetic patients with abdominal obesity (waist circumference (WC) ⩾ 88 cm) had lower adiponectin levels (5.58 ± 2.58 μg/ml) than diabetic females without abdominal obesity (6.96 ± 3.12 μg/ml). The correlation analysis indicated that adiponectin had a significant positive correlation with age (r = −0.450, P < 0.001). In conclusion, female diabetic patients had a statistically significant higher adiponectin level than male diabetic patients which could indicate a gender effect. Adiponectin levels were inversely related to insulin resistance; as patients with abdominal obesity had lower serum levels of adiponectin. PMID:26106273

  3. 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.

  4. 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.

  5. 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.

  6. Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension.

    PubMed

    Furuhashi, Masato; Ura, Nobuyuki; Higashiura, Katsuhiro; Murakami, Hideyuki; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Daisuke; Shimamoto, Kazuaki

    2003-07-01

    Adiponectin, an adipocyte-derived protein, has been suggested to play an important role in insulin sensitivity. We examined the association between insulin sensitivity (M value) evaluated by the euglycemic-hyperinsulinemic glucose clamp and adiponectin concentrations in 30 essential hypertensives (EHT) and 20 normotensives (NT) and investigated the effect of blockade of the renin-angiotensin system (RAS) on adiponectin concentrations. EHT were divided into 12 insulin-resistant EHT (EHT-R) and 18 non-insulin-resistant EHT (EHT-N) using mean-1 SD of the M value in NT. There were no intergroup differences in age, gender, and body mass index (BMI). EHT-R had significantly higher levels of insulin and triglyceride and lower levels of adiponectin than did NT and EHT-N. EHT-R had higher levels of free fatty acid and lower levels of high-density lipoprotein (HDL) cholesterol than did EHT-N. Adiponectin concentrations were positively correlated with M value and HDL cholesterol and negatively correlated with BMI, insulin, free fatty acid, and triglyceride but not with blood pressure. M value, BMI, and HDL cholesterol were independent determinants of adiponectin concentrations in multiple and stepwise regression analyses. Sixteen EHT were treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; n=9) or an angiotensin II receptor blocker (candesartan, 8 mg/d; n=7) for 2 weeks. Treatment with temocapril or candesartan significantly decreased blood pressure and increased M value and adiponectin concentrations but did not affect BMI and HDL cholesterol. These results suggest that hypoadiponectinemia is related to insulin resistance in essential hypertension and that RAS blockade increases adiponectin concentrations with improvement in insulin sensitivity.

  7. 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.

  8. Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk.

    PubMed

    Blanco-Colio, Luis M; Martín-Ventura, Jose L; Gómez-Guerrero, Carmen; Masramon, Xavier; de Teresa, Eduardo; Farsang, Csaba; Gaw, Allan; Gensini, GianFranco; Leiter, Lawrence A; Langer, Anatoly; Egido, Jesús

    2008-05-31

    Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes, reducing their phagocytic activity, and suppressing the accumulation of modified lipoproteins in the vascular wall. Contradictory data have been reported about the effect of statins on adiponectin plasma levels. In this work, adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study, a 12-week, prospective, multi-centre, open-label trial which enrolled subjects with coronary heart disease, coronary heart disease-equivalent or a 10-year coronary heart disease risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on low-density lipoprotein (LDL)-cholesterol concentration at screening. For comparison, age and gender-matched blood donors (N=40) were used as controls. Control subjects did not present hypertension, hypercholesterolemia, diabetes, metabolic syndrome and history of cardiovascular diseases. Adiponectin levels were diminished in patients at high cardiovascular risk compared with control subjects [4166 (3661-4740) vs 5806 (4764-7075) ng/ml respectively; geometric mean (95% CI); P<0.0001]. In the whole population, atorvastatin treatment increased adiponectin levels [9.7 (3.2-16.7);% Change (95% CI); P=0.003]. This increment was in a dose-dependent manner; maximal effect observed with atorvastatin 80 mg/d [24.7 (5.7-47.1); P=0.01]. Adiponectin concentrations were positively correlated with high-density lipoprotein-cholesterol both before and after atorvastatin treatment. No association was observed between adiponectin and LDL-cholesterol before and after atorvastatin treatment. In conclusion, atorvastatin increased adiponectin plasma levels in subjects at high cardiovascular risk, revealing a novel anti-inflammatory effect of this drug.

  9. CTX Correlation to Disease Duration and Adiponectin in Egyptian Children with T1DM

    PubMed Central

    Hashim, Amel A.; Emara, Ibrahim A.; El-Hefnawy, Mohamed H.

    2016-01-01

    Summary Background In this study, we investigated the relationship of adiponectin with bone marker changes in Egyptian children and adolescents with T1DM and the effect of disease duration on these markers, as well as the possible correlations between adiponectin and bone markers in these patients. Methods Sixty Egyptian children and adolescent patients with T1DM were studied. Serum adiponectin and collagen breakdown products (cross-linked C-terminal telopeptide of collagen type l »CTX«) were measured and compared to the results of 20 age-matched healthy controls. Results After adjustment for age, BMI, Tanner stage and gender; (total) adiponectin was significantly higher in all T1DM patients. Serum level of CTX and 25(OH)D showed a marked decrease in diabetics with disease duration > 5 years. Serum level of (total) calcium and inorganic phosphorus (Pi) did not show significant difference from control. CTX was inversely correlated to FBG and T1DM duration. Pi was inversely, while 25(OH)D was directly correlated to FBG. Total calcium showed an inverse correlation with HbA1c. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. Conclusions Adiponectin showed no correlation with either CTX or bone homeostatic indices. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. We recommend further investigation of adiponectin isoforms in a population-based study, to establish a good age- and sex-related reference.

  10. Relationship of Plasma Adiponectin and Waist-hip Ratio with Coronary Artery Disease

    PubMed Central

    Rashiti, Premtim; Elezi, Shpend; Behluli, Ibrahim; Mucaj, Sefedin

    2016-01-01

    Background: This study aimed to investigate correlation between adiponectin and waist-hip-ratio with severity of coronary artery disease (CAD). There is uncertainty about the association between circulating concentrations of adiponectin and CAD. Methods: We enrolled eighty-two consecutive patients undergoing non-urgent coronary angiography for CAD survey. According to the angiography results, the patients were divided into two groups in 1:1 ratio patients admitted with a diagnosis of CAD and non-CAD. We conducted hospital based research, involving study group with documented angiographically CAD, and control group without evidence of CAD. Angiograms were also quantified for the extent and severity of CAD by the Gensini scoring system. We measured baseline adiponectin levels in stored serum samples of all patients, anthropometric and biochemical risk factors were assessed in both groups. Results: The presence of CAD was associated with current smoking, male gender, waist–hip ratio (WHR) and left ventricular ejection fraction (LVEF). Baseline adiponectin concentrations correlated significantly in terms of the lipid parameters, positively with HDL cholesterol concentrations (r=0.327, P=0.028, P<0.05) and serum triglyceride concentrations were correlated negatively (r=-0.513, P<0.001). No significant difference between median adiponectin levels at baseline was observed between cases and controls. Conclusion: There is a significant positive correlation between waist–hip ratio and presence and severity of coronary artery disease. In conclusion, there is a significant positive correlation between adiponectin and Gensini score among Kosovar patients. PMID:28210011

  11. Changes in Serum Adiponectin in Mice Chronically Exposed to Inorganic Arsenic in Drinking Water.

    PubMed

    Song, Xuanbo; Li, Ying; Liu, Junqiu; Ji, Xiaohong; Zhao, Lijun; Wei, Yudan

    2017-02-11

    Cardiovascular disease and diabetes mellitus are prominent features of glucose and lipid metabolism disorders. Adiponectin is a key adipokine that is largely involved in glucose and lipid metabolism processes. A growing body of evidence suggests that chronic exposure to inorganic arsenic is associated with cardiovascular disease and diabetes mellitus. We hypothesized that arsenic exposure may increase the risk of cardiovascular disease and diabetes mellitus by affecting the level of adiponectin. In this study, we examined serum adiponectin levels, as well as serum levels of metabolic measures (including fasting blood glucose, insulin, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol) in C57BL/6 mice exposed to inorganic arsenic in drinking water (5 and 50 ppm NaAsO2) for 18 weeks. Body mass and adiposity were monitored throughout the study. We found no significant changes in serum insulin and glucose levels in mice treated with arsenic for 18 weeks. However, arsenic exposure decreased serum levels of adiponectin, triglyceride, and HDL-cholesterol. Further, an inverse relationship was observed between urinary concentrations of total arsenic and serum levels of adiponectin. This study suggests that arsenic exposure could disturb the metabolism of lipids and increase the risk of cardiovascular disease by reducing the level of adiponectin.

  12. [Adiponectin, insulin and glucose concentrations in overweight and obese subjects after a complex carbohydrates (fiber) diet].

    PubMed

    González Rodríguez, Dora Cristina; Solano R, Liseti; González Martínez, Julio César

    2009-09-01

    Adiponectin one of the cytokines secreted by the adipose tissue that regulates the energetic metabolism through glucose and insulin interactions, stimulates the oxidation of fatty acids, reduces the plasmatic triglycerides and improves glucose metabolism by increasing insulin sensibility. Serum concentrations of adiponectin, insulin and glucose were assessed in order to establish association to weight loss after a dietary regime based on consumption of complex carbohydrates (fiber) during six weeks. Overweight and obese subjects (n=56) were studied by anthropometry. Adiponectin and insulin were measured by ELISA and glucose by Colorimetry. Data was analyzed by non parametric tests to compare independent or related samples. 12 men and 44 women, aged 20 to 55 years, 17 overweight and 39 obese were assessed. Adiponectin concentration was significantly low at basal determination in all the subjects (4,47 +/- 1,64); being higher in women (4,62 +/- 1,57 vs 3,93 +/- 1,86 microU/mL in men), while glucose and insulin values were at normal range (82,46 +/-26,51 mg/dL and 14,12 +/- 10,15 microU/mL) respectively with no significant differences for sex. Overweight subjects had significantly higher adiponectin concentrations than obese participants, at all measurements. Dietary regime promoted significant increase in adiponectin concentration at second and sixth week, with a negative correlation to body mass index and gender as they lost body weight.

  13. The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity

    PubMed Central

    Castro, Natália P.; Euclydes, Verônica V.; Simões, Fernanda A.; Vaz-de-Lima, Lourdes R. A.; De Brito, Cyro A.; Luzia, Liania A.; Devakumar, Delan; Rondó, Patrícia H. C.

    2017-01-01

    Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM%) was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI), weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin (p = 0.001) and pre-pregnancy BMI (p < 0.001; adj. R2 = 0.19) were positively associated with FM% of newborn males, indicating that maternal adiponectin is involved in fetal fat deposition in a sex-specific manner. Large-scale epidemiological, longitudinal studies are necessary to confirm our results. PMID:28241462

  14. 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.

  15. The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study.

    PubMed

    Alvarez, Granada; Visitación Bartolomé, M; Miana, María; Jurado-López, Raquel; Martín, Ruben; Zuluaga, Pilar; Martinez-Martinez, Ernesto; Nieto, M Luisa; Alvarez-Sala, Luis A; Millán, Jesús; Lahera, Vicente; Cachofeiro, Victoria

    2012-01-01

    The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.

  16. 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

  17. 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

    2012-09-04

    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.

  18. 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.

  19. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-06-01

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

  2. CRP and adiponectin and its oligomers in the metabolic syndrome: evaluation of new laboratory-based biomarkers.

    PubMed

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

    2008-05-01

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

  3. Adiponectin reduces ER stress-induced apoptosis through PPARα transcriptional regulation of ATF2 in mouse adipose

    PubMed Central

    Liu, Zhenjiang; Gan, Lu; Wu, Tianjiao; Feng, Fei; Luo, Dan; Gu, Huihui; Liu, Shimin; Sun, Chao

    2016-01-01

    Adiponectin is a cytokine produced predominantly by adipose tissue and correlates with glucose and lipid homeostasis. However, the effects of adiponectin on endoplasmic reticulum (ER) stress and apoptosis of adipose tissue remain elusive. In this study, we found that tunicamycin-induced ER stress increased serum free fatty acid (FFA) and impaired glucose tolerance, elevated the mRNA levels of GRP78, Chop, ATF2 and caspase 3, but reduced adiponectin mRNA level in white adipose tissue. Moreover, ER stress-triggered adipocyte apoptosis by increasing cellular FFA level and Ca2+ level. Further analysis revealed that adiponectin alleviated ER stress-induced adipocyte apoptosis by elevating peroxisome proliferator-activated receptor alpha (PPARα) mRNA level. Our data also confirmed that adiponectin reduced early apoptotic cells and blocked the mitochondrial apoptosis pathway by activating the AdipoR1/AMP-activated protein kinase (AMPK) signal pathway. In addition, PPARα bound to ATF2 promoter region and inhibited transcription of ATF2. The inhibition of adipocyte apoptosis by adiponectin was correlated with transcriptional suppression of ATF2. Furthermore, adiponectin inhibited ER stress-induced apoptosis by activating the AMPK/PKC pathway. In summary, our data demonstrate adiponectin inhibited ER stress and apoptosis of adipocyte in vivo and in vitro by activating the AMPK/PPARα/ATF2 pathway. Our study establishes that adiponectin is an important adipocytokine for preventing and treating obesity. PMID:27882945

  4. Total and high molecular weight adiponectin levels in the rat model of post-myocardial infarction heart failure.

    PubMed

    Kalisz, M; Baranowska, B; Wolinska-Witort, E; Maczewski, M; Mackiewicz, U; Tulacz, D; Gora, M; Martynska, L; Bik, W

    2015-10-01

    Adiponectin is a protein secreted primarily by adipose tissue. It has been suggested that adiponectin plays a protective role in the early phase following myocardial infarction. Our primary aim was to investigate the effects of post-myocardial infarction heart failure well-characterized by left ventricular hemodynamic parameters on the total and high molecular weight adiponectin concentrations in plasma, fat and cardiac tissue. Eight weeks after myocardial infarction or sham operation, total and high molecular weight adiponectin concentrations in plasma, fat, and cardiac tissues were assayed in rats. In addition, hemodynamic parameters and expression of the genes encoding atrial natriuretic peptide and brain natriuretic peptide in left ventricle were evaluated. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in left ventricle tissue were higher in rats with myocardial infarction-induced heart failure compared with the controls. Similarly, total adiponectin concentration was increased in left ventricle (but not in right ventricle) in rats with post-myocardial infarction heart failure. In contrast, adiponectin levels in plasma and cardiac adipose tissue in rats with post-myocardial infarction heart failure were lower than in sham-operated animals. Furthermore, there were no significant differences in levels of high molecular weight adiponectin in plasma, cardiac tissue or adipose tissue between these two groups. We conclude that in the rat model of post-myocardial infarction heart failure, adiponectin level is increased in left ventricle tissue. This is accompanied by decreased adiponectin levels in plasma and cardiac adipose tissue.

  5. Polarizing the T helper 17 response in Citrobacter rodentium infection via expression of resistin-like molecule α.

    PubMed

    Chen, Gang; Chan, Alexander J; Chung, Josiah I; Jang, Jessica C; Osborne, Lisa C; Nair, Meera G

    2014-01-01

    Citrobacter rodentium infection is a murine model of pathogenic Escherichia coli infection that allows investigation of the cellular and molecular mechanisms involved in host-protective immunity and bacterial-induced intestinal inflammation. We recently demonstrated that following C. rodentium infection, the absence of Resistin-Like Molecule (RELM) α resulted in attenuated Th17 cell responses and reduced intestinal inflammation with minimal effects on bacterial clearance. In this addendum, we investigated the cytokine modulatory effects of RELMα and RELMα expression in the intestinal mucosa following C. rodentium infection. We show that in addition to promoting Th17 cytokine responses, RELMα inhibits Th2 cytokine expression and Th2-cytokine effector macrophage responses in the C. rodentium-infected colons. Second, utilizing reporter C. rodentium, we examined RELMα expression and macrophage recruitment at the host pathogen interface. We observed infection-induced macrophage infiltration and RELMα expression by intestinal epithelial cells. The influence of infection-induced RELMα on macrophage recruitment in the intestine is discussed.

  6. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice

    PubMed Central

    DiSilvestro, David J.; Melgar-Bermudez, Emiliano; Yasmeen, Rumana; Fadda, Paolo; Lee, L. James; Kalyanasundaram, Anuradha; Gilor, Chen L.; Ziouzenkova, Ouliana

    2016-01-01

    The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin. PMID:27055280

  7. 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

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

    PubMed Central

    2013-01-01

    Background Adiponectin circulates in different multimer complexes comprised of low molecular weight trimeric form (LMW), hexamer of middle molecular weight (MMW) and high molecular weight multimers (HMW). In Japanese-Brazilians, a population with high prevalence of glucose metabolism disturbances, we examined the associations of total adiponectin and its multimers with diabetes mellitus. Methods Two study groups were examined: 26 patients with diabetes mellitus (DM,14 women and 12 men, aged 55.3 ± 8.6 years) and 27 age-matched control subjects with normal glucose tolerance (NGT,12 women and 15 men, aged 54.0 ± 9.2 years). Results We found no significant differences in total [NGT: 6.90 ug/ml (4.38-13.43); DM: 5.38 ug/ml (3.76-8.56), p = 0.35], MMW [NGT:2.34 ug/ml (1.38-3.25); DM: 1.80 ug/ml (1.18-2.84), p = 0.48] or LMW adiponectin [NGT: 2.07 ug/ml (1.45-3.48), DM: 2.93 ug/ml (1.78-3.99), p = 0.32] between groups. In contrast, HMW adiponectin levels were significantly lower in patients with DM [TGN: 2.39 ug/ml (1.20-4.75); DM: 1.04 ug/ml (0.42-1.60), p = 0.001]. A logistic regression analysis was done to identify independent associations with diabetes mellitus. The results showed that HOMA-IR and HMW adiponectin in women were independently associated with diabetes mellitus. Conclusion The current investigation demonstrates that in Japanese-Brazilians HMW adiponectin is selectively reduced in individuals with type 2 diabetes, while no differences were found in MMW and LMW adiponectin isoforms. PMID:23570346

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

    PubMed Central

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

    2011-01-01

    Purpose Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients. This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity. Here, we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality. Patients and Methods We measured glucose, insulin, and adiponectin levels in fasting serum samples from 527 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between adiponectin and insulin and glucose levels (expressed as the Homeostatic Model Assessment [HOMA] score) represented as continuous measures and median split categories, along with breast cancer mortality and all-cause mortality, using Cox proportional hazards models. Results Increasing HOMA scores were associated with reduced breast cancer survival (hazard ratio [HR], 1.12; 95% CI, 1.05 to 1.20) and reduced all-cause survival (HR, 1.09; 95% CI, 1.02 to 1.15) after adjustment for possible confounders. Higher levels of adiponectin (above the median: 15.5 μg/mL) were associated with longer breast cancer survival (HR, 0.39; 95% CI, 0.15 to 0.95) after adjustment for covariates. A continuous measure of adiponectin was not associated with either breast cancer–specific or all-cause mortality. Conclusion Elevated HOMA scores and low levels of adiponectin, both associated with obesity, were associated with increased breast cancer mortality. To the best of our knowledge, this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors. PMID:21115858

  10. Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies

    PubMed Central

    Peng, Xin; Wu, Li-Ling; Yu, Guang-Yan

    2016-01-01

    Early detection of cancers is challenging for lack of specific biomarkers. Adiponectin is an adipokine predominantly derived from adipocytes and hypoadiponectinemia has been reported to associate with risk of many types of cancers. However, available evidence is controversial. Some studies show that increased adiponectin levels correlate with cancer risk. Therefore, we performed a meta-analysis of the association between circulating adiponectin levels and cancer development. A systematic search of PubMed, EMBASE, Wiley Online Library and Cochrane Library was conducted for eligible studies involving circulating adiponectin and malignancies from inception to August 8, 2015. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated by use of a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. 107 studies were included with 19,319 cases and 25,675 controls. The pooled analysis indicated that circulating adiponectin levels were lower in patients with various cancers than in controls, with a pooled SMD of −0.334 μg/ml (95% CI, −0.465 to −0.203, P = 0.000). No evidence of publication bias was observed. Circulating high molecular weight adiponectin levels were also lower in cancer patients than in controls, with a pooled SMD of −0.502 μg/ml (95% CI, −0.957 to −0.047, P = 0.000). This meta-analysis provides further evidence that decreased adiponectin levels is associated with risk of various cancers. Hypoadiponectinemia may represent a useful biomarker for early detection of cancers. PMID:27119501

  11. Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies.

    PubMed

    Wei, Tai; Ye, Peng; Peng, Xin; Wu, Li-Ling; Yu, Guang-Yan

    2016-07-26

    Early detection of cancers is challenging for lack of specific biomarkers. Adiponectin is an adipokine predominantly derived from adipocytes and hypoadiponectinemia has been reported to associate with risk of many types of cancers. However, available evidence is controversial. Some studies show that increased adiponectin levels correlate with cancer risk. Therefore, we performed a meta-analysis of the association between circulating adiponectin levels and cancer development. A systematic search of PubMed, EMBASE, Wiley Online Library and Cochrane Library was conducted for eligible studies involving circulating adiponectin and malignancies from inception to August 8, 2015. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated by use of a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. 107 studies were included with 19,319 cases and 25,675 controls. The pooled analysis indicated that circulating adiponectin levels were lower in patients with various cancers than in controls, with a pooled SMD of -0.334 μg/ml (95% CI, -0.465 to -0.203, P = 0.000). No evidence of publication bias was observed. Circulating high molecular weight adiponectin levels were also lower in cancer patients than in controls, with a pooled SMD of -0.502 μg/ml (95% CI, -0.957 to -0.047, P = 0.000). This meta-analysis provides further evidence that decreased adiponectin levels is associated with risk of various cancers. Hypoadiponectinemia may represent a useful biomarker for early detection of cancers.

  12. 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.

  13. Adiponectin, Leptin and Objectively Measured Physical Activity in Adults: A Narrative Review

    PubMed Central

    Nurnazahiah, Ali; Lua, Pei Lin; Shahril, Mohd Razif

    2016-01-01

    The objective of this study was to compile and analyse existing scientific evidences reporting the effects of objectively measured physical activity on the levels of adiponectin and leptin. Articles related to the effects of objectively measured physical activity on the levels of adiponectin and leptin were searched from the Medline and PubMed databases. The search was limited to ‘objectively measured’ physical activity, and studies that did not objectively measure the physical activity were excluded. Only English articles were included in the search and review. A total of 18 articles encompassing 2,026 respondents met the inclusion criteria. The eligible articles included all forms of evidence (e.g., cross-sectional and intervention). Seventeen and 11 studies showed the effects of objectively measured physical activity on adiponectin and leptin, respectively. Five and four cross-sectional studies showed the effects of objectively measured physical activity on adiponectin and leptin, respectively. Two out of five studies showed a weak to moderate positive association between adiponectin and objectively measured physical activity, while three out of four studies showed a weak to moderate inverse association between leptin and objectively measured physical activity. For intervention studies, six out of 12 studies involving adiponectin and five out of seven studies involving leptin showed a significant effect between the proteins and objectively measured physical activity. However, a definitive conclusion could not be drawn due to several methodological flaws in the existing articles and the acute lack of additional research in this area. In conclusion, the existing evidences are encouraging but yet not compelling. Hence, further well-designed large trials are needed before the effectiveness of objectively measured physical activity in elevating adiponectin levels and in decreasing leptin levels could be strongly confirmed. PMID:28090175

  14. Portal vein and systemic adiponectin concentrations are closely linked with hepatic glucose and lipoprotein kinetics in extremely obese subjects.

    PubMed

    Magkos, Faidon; Fabbrini, Elisa; Patterson, Bruce W; Eagon, J Christopher; Klein, Samuel

    2011-11-01

    Low systemic plasma adiponectin concentrations are associated with abnormalities in hepatic glucose and lipoprotein metabolism in obese people. However, the relationship between the delivery of adiponectin to the liver via the portal vein and hepatic glucose and lipoprotein metabolism is not known. We examined the relationship between hepatic substrate metabolism (glucose rate of appearance into plasma and hepatic very low-density lipoprotein [VLDL]-triglyceride [TG] and VLDL-apolipoprotein B-100 [apoB-100] secretion rates, determined by using stable isotope-labeled tracer techniques) and portal vein adiponectin concentration, in 8 insulin-resistant, extremely obese subjects (body mass index, 65 ± 7 kg/m(2)). Portal vein adiponectin concentration was inversely associated with basal glucose rate of appearance (r = -0.820, P = .013) and VLDL-TG (r = -0.823, P = .012) and VLDL-apoB-100 (r = -0.787, P = .020) secretion rates. Very similar correlations were obtained for radial artery adiponectin as a result of a mirroring relationship between portal and arterial adiponectin concentrations (r = 0.899, P = .002) and the absence of significant arteriovenous concentration differences (P = .570). Insulin resistance, assessed with the homeostasis model assessment score, was also strongly associated with hepatic glucose and lipid metabolic parameters, as well as with adiponectin concentrations in the portal vein and radial artery. These results suggest that adiponectin delivery to the liver, whether via the portal or the systemic circulation, may be an important regulator of basal hepatic glucose, VLDL-TG, and VLDL-apoB-100 production rates in obese people, possibly through direct effects on the liver or changes in hepatic insulin sensitivity. However, portal vein adiponectin does not appear to be superior to arterial adiponectin as a marker of hepatic metabolic dysregulation. Additional studies are needed to elucidate the mechanism(s) responsible for the strong association

  15. The role of adiponectin in human vascular physiology.

    PubMed

    Vaiopoulos, Aristeidis G; Marinou, Kyriakoula; Christodoulides, Constantinos; Koutsilieris, Michael

    2012-03-08

    Adiponectin (ApN) is an adipose tissue-derived hormone which is involved in a wide variety of physiological processes including energy metabolism, inflammation, and vascular physiology via actions on a broad spectrum of target organs including liver, skeletal muscle, and vascular endothelium. Besides possessing insulin sensitizing and anti-inflammatory properties ApN also exerts a pivotal role in vascular protection through activation of multiple intracellular signaling cascades. Enhancement of nitric oxide generation and attenuation of reactive oxygen species production in endothelial cells along with reduced vascular smooth muscle cell proliferation and migration constitute some of ApN's vasoprotective actions. Additionally, recent data indicate that ApN has direct myocardio-protective effects. Decreased plasma ApN levels are implicated in the pathogenesis of the metabolic syndrome and atherosclerosis and may serve as a diagnostic and prognostic biomarker as well as a rational pharmaco-therapeutic target to treat these disorders. This review article summarizes recent work on the cardiovascular actions of ApN.

  16. Cardioprotection of ischemic preconditioning in rats involves upregulating adiponectin.

    PubMed

    Wang, Hui; Wu, Wenjing; Duan, Jun; Ma, Ming; Kong, Wei; Ke, Yuannan; Li, Gang; Zheng, Jingang

    2017-02-20

    It has been reported that ischemic preconditioning (IPC) and adiponectin (APN) are cardioprotective in many cardiovascular disorders. However, whether APN mediates the effect of IPC on myocardial injury has not been elucidated. This study was conducted to investigate whether IPC affects myocardial ischemic injury by increasing APN expression. Male adult rats with cardiac knockdowns of APN and its receptors via intramyocardial small-interfering RNA injection were subjected to IPC and then myocardial infarction (MI) at 24 h post-IPC. Globular APN (gAd) was injected at 10 min before MI. APN mRNA and protein levels in myocardium as well as the plasma APN concentration were markedly high at 6 and 12 h after IPC. IPC ameliorated myocardial injury as evidenced by improved cardiac functions and a reduced infarct size. Compared with the control MI group, rats in the IPC + MI group had elevated levels of left ventricular ejection fraction and fractional shortening, and a smaller MI size (P<0.05). However, the aforementioned protective effects were ameliorated in the absence of APN and APN receptors, followed by inhibition of AMP-activated protein kinase (AMPK) phosphorylation, but reversed by gAd treatment in wild-type rats, and AMPK phosphorylation increased (P<0.05). Overall, our results suggest that the cardioprotective effects of IPC are partially due to upregulation of APN, and provide a further insight into IPC-mediated signaling effects.

  17. Plasma Adiponectin Concentration and Its Association with Metabolic Syndrome in Patients with Heart Failure

    PubMed Central

    Won, Hoyoun; Shin, Min-Jeong; Oh, Jaewon; Hong, Namki; Park, Sungha; Lee, Sang-Hak; Jang, Yangsoo; Chung, Namsik

    2012-01-01

    Purpose Plasma adiponectin concentrations are inversely related with metabolic syndrome (MetS), and MetS is associated with increased risk for heart failure (HF). However, the relationship between adiponectin and MetS in HF remains undetermined. Therefore, we tested whether MetS was associated with the degree of plasma adiponectin concentrations in HF patients. Materials and Methods One hundred twenty eight ambulatory HF patients with left ventricular ejection fraction of <50% (80 males, 61.8±11.9 years old) were enrolled for this cross-sectional study. Echocardiographic measurements were performed, and plasma concentrations of adiponectin, lipoproteins, apolipoproteins (apoB, apoA1) and high sensitive C-reactive protein (hsCRP) were measured. Results Adiponectin concentrations in HF patients with MetS (n=43) were significantly lower than those without MetS (n=85) (9.7±7.0 vs. 15.8±10.9 µg/mL, p=0.001). Higher concentrations of apoB (p=0.017), apoB/A1 ratio (p<0.001), blood urea nitrogen (p=0.034), creatinine (p=0.003), and fasting insulin (p=0.004) were observed in HF patients with MetS compared with those without MetS. In HF patients with MetS, adiponectin concentrations were negatively correlated with hsCRP (r=-0.388, p=0.015) and positively correlated with the ratio of early mitral inflow velocity to early diastolic mitral annular velocity, E/E' (r=0.399, p=0.015). There was a significant trend towards decreased adiponectin concentrations with an increasing number of components of MetS (p for trend=0.012). Conclusion Our study demonstrated that adiponectin concentrations decreased in HF patients with MetS, and that relationship between adiponectin, inflammation and abnormal diastolic function, possibly leading to the progression of HF. PMID:22187237

  18. Association between the level of circulating adiponectin and prediabetes: A meta-analysis

    PubMed Central

    Lai, Huasheng; Lin, Nie; Xing, Zhenzhen; Weng, Huanhuan; Zhang, Hua

    2015-01-01

    Aims/Introduction Adiponectin has been proposed to have an essential role in the regulation of insulin sensitivity and metabolism, but previous studies on levels of adiponectin in prediabetes remain inconsistent. The present study aimed to assess the differences of adiponectin levels between prediabetes patients and healthy controls by carrying out a meta-analysis. Materials and Methods We carried out a systematic literature search of PubMed, EMBASE, and other databases for case–control studies and cohort studies measuring adiponectin levels in serum or plasma from prediabetes patients and healthy controls. The pooled weighted mean difference (WMD) and 95% confidence interval (CI) were used to estimate the association between adiponectin levels and prediabetes. Results Three cohort studies and 15 case–control studies with a total of 41,841 participants were included in the meta-analysis. The results showed that circulating adiponectin levels in prediabetes patients were significantly lower than that of healthy controls (WMD –1.694 μg/mL; 95% CI –2.151, –1.237; P < 0.001). Subgroup analysis showed more significant differences between prediabetes patients and healthy controls when the ratio of the homeostatic model assessment of insulin resistance was >2.12 (WMD −2.95 μg/mL; 95% CI –4.103, –1.806; P < 0.001) and average age was >60 years (WMD −2.20 μg/mL; 95% CI –3.207, –1.201; P < 0.001). Additionally, WMD in adiponectin showed a trend of direct correlation in subgroups of homeostatic model assessment of insulin resistance ratio, body mass index and age. Conclusions The present meta-analysis supports adiponectin levels in prediabetes patients being lower than that of healthy controls,indicating that the level of circulating adiponectin decreases before the onset of diabetes. PMID:26221520

  19. Serum Adiponectin Levels, Neuroimaging, and Cognition in the Mayo Clinic Study of Aging

    PubMed Central

    Wennberg, Alexandra M. V.; Gustafson, Deborah; Hagen, Clinton E.; Roberts, Rosebud O.; Knopman, David; Jack, Clifford; Petersen, Ronald C.; Mielke, Michelle M.

    2016-01-01

    BACKGROUND Adiponectin, a protein involved in inflammatory pathways, may impact the development and progression of Alzheimer’s disease (AD). Adiponectin levels have been associated with mild cognitive impairment (MCI) and AD; however, its association with Alzheimer-associated neuroimaging and cognitive outcomes is unknown. OBJECTIVE Determine the cross-sectional association between plasma adiponectin and neuroimaging and cognitive outcomes in an older population-based sample. METHODS Multivariable adjusted regression models were used to investigate the association between plasma adiponectin and hippocampal volume (HVa), PiB-PET, FDG PET, cortical thickness, MCI diagnosis, and neuropsychological test performance. Analyses included 535 non-demented participants aged 70 and older enrolled in the Mayo Clinic Study of Aging. RESULTS Women had higher adiponectin than men (12,631 ng/mL vs. 8,908 ng/mL, P < .001). Among women, higher adiponectin was associated with smaller HVa (B=−0.595; 95% CI −1.19, −0.005), poorer performance in language (B−0.676; 95% CI −1.23, −0.121) and global cognition (B=−0.459; 95% CI −0.915, −0.002), and greater odds of a MCI diagnosis (OR=6.23; 95% CI 1.20, 32.43). In analyses stratified by sex and elevated amyloid (PiB-PET SUVR>1.4), among women with elevated amyloid, higher adiponectin was associated with smaller HVa (B=−0.723; 95% CI −1.43, −0.014), poorer performance in memory (B=−1.02; 95% CI −1.73, −0.312), language (B=−0.896; 95% CI −1.58, −0.212), and global (B=−0.650; 95% CI −1.18, −0.116) cognition, and greater odds of MCI (OR=19.34; 95% CI 2.72, 137.34). CONCLUSION Higher plasma adiponectin was associated with neuroimaging and cognitive outcomes among women. Longitudinal analyses are necessary to determine whether higher adiponectin predicts neurodegeneration and cognitive decline. PMID:27163809

  20. Three-month treatment with pioglitazone reduces circulating C1q-binding adiponectin complex to total-adiponectin ratio, without changes in body mass index, in people with type 2 diabetes.

    PubMed

    Nakatsuji, Hideaki; Kishida, Ken; Kobayashi, Hironori; Funahashi, Tohru; Shimomura, Iichiro

    2013-01-01

    We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after 3-month treatment with pioglitazone in people with type 2 diabetes. The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index.

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

    PubMed

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

    2013-01-01

    Purpose. To investigate the mechanism of action in peripheral tissues of novel complex drug containing release-active dilutions of antibodies to the beta subunit of the insulin receptor and antibodies to endothelial nitric oxide synthase (Subetta), which has shown efficacy in animal models of diabetes. Methods. Human mature adipocytes were incubated either with Subetta, with one of negative controls (placebo or vehicle), with one of nonspecific controls (release-active dilutions of antibodies to cannabinoid receptor type I or release-active dilutions of rabbit nonimmune serum), or with dimethyl sulfoxide (DMSO) at 37°C in a humidified incubator at 5% CO2 for three days. Rosiglitazone was used as reference drug. Secretion of adiponectin was measured by quantitative enzyme-linked immunosorbent assay (ELISA). Results. Only Subetta significantly stimulates adiponectin production by mature human adipocytes. Nonspecific controls did not significantly affect adiponectin secretion, resulting in adiponectin levels comparable to background values of the negative controls and DMSO. Conclusion. Increasing adiponectin production in absence of insulin by Subetta probably via modulating effect on the beta subunit of the insulin receptor might serve as one of the mechanisms of the antidiabetic effect of this drug. These in vitro results give first insight on possible mechanism of action of Subetta and serve as a background for further studies.

  2. Adiponectin induces A20 expression in adipose tissue to confer metabolic benefit.

    PubMed

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

    2015-01-01

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

  3. 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.

  4. Adiponectin plays an important role in efficient energy usage under energy shortage.

    PubMed

    Saito, Kiyomi; Arata, Satoru; Hosono, Tomohiko; Sano, Yoshihiro; Takahashi, Katsuhiko; Choi-Miura, Nam-Ho; Nakano, Yasuko; Tobe, Takashi; Tomita, Motowo

    2006-07-01

    Adiponectin is an adipose tissue-specific secretory protein known to be an insulin-sensitizing protein. In this study, we generated adiponectin sense and antisense transgenic (Tg) mice to investigate whether adiponectin plays a role in the regulation of energy homeostasis during the growth stage. Spontaneous motor activity of antisense Tg mice were markedly reduced during fasting, particularly in young female mice, compared with wild type (Wt) and sense Tg mice. Furthermore, both body weight and adipose tissue mass of the antisense female Tg mice drastically reduced during fasting. To examine the relationship between the collapse of abdominal white adipose tissue (WAT) and serum adiponectin level, we measured the expression of genes related to energy expenditure, such as uncoupling protein (UCP). Notably, the mRNA of UCP1 in the WAT of antisense Tg female mice was markedly less than that of Wt mice and the UCP1 mRNA was strongly increased during fasting. These findings suggest that the serum adiponectin is important to maintaining energy homeostasis under energy shortage conditions, such as over female pubertal development.

  5. Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes.

    PubMed

    Bodles, Angela M; Banga, Anannya; Rasouli, Neda; Ono, Fumiyo; Kern, Philip A; Owens, Randall J

    2006-11-01

    Adiponectin is an adipocyte-derived serum protein that plays important roles in energy homeostasis, obesity, and insulin sensitivity. Using sucrose gradients and Western blotting of nondenaturing gels, we examined the adiponectin isoforms secreted from human adipose tissue, human and mouse adipocytes, and cell lines in response to pioglitazone added in vitro. The predominant form secreted from adipose tissue in vitro was the high-molecular-weight (HMW) isoform, with small amounts of low-molecular-weight (LMW) forms present. The addition of pioglitazone (1-3 micromM) in vitro increased the secretion of the HMW isoform, with no significant effect on the other isoforms. Human adipose tissue was also examined for changes in adiponectin mRNA levels upon pioglitazone treatment. No difference was detected, suggesting that the effect of pioglitazone is not at the transcriptional level but, rather, at a posttranscriptional phase of the secretory pathway. Additional experiments were conducted to determine whether adiponectin expression was mechanistically similar in other adipose cells. Examination of primary human adipocytes revealed an increase in intracellular HMW isoform with a decline in LMW forms following pioglitazone treatment, with a corresponding increase in the secreted HMW form. Similar results were observed with primary mouse adipocytes, 3T3-F422A cells, and SGBS human adipocyte cells, although differences in the distribution of HMW and LMW isoforms were apparent between cell types. Although there are differences in isoforms between species, in all cases pioglitazone served to increase the secretion of the HMW form of adiponectin.

  6. 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.

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

    PubMed Central

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

    2016-01-01

    Objectives We tested the hypothesis that there is a positive association between maternal body mass index (BMI) and the concentration of appetite-regulating hormones leptin, insulin, ghrelin and resistin in breast milk. We also aimed to describe the change in breast milk hormone concentration within each feed, and over time. Setting Mothers were recruited from the postpartum ward at a university hospital in London. Breast milk samples were collected at the participants’ homes. Participants We recruited 120 healthy, primiparous, breastfeeding mothers, aged over 18 years. Mothers who smoked, had multiple births or had diabetes were excluded. Foremilk and hindmilk samples were collected from 105 women at 1 week postpartum and 92 women at 3 months postpartum. Primary and secondary outcome measures We recorded maternal and infant anthropometric measurements at each sample collection and measured hormone concentrations using a multiplex assay. Results The concentration of leptin in foremilk correlated with maternal BMI at the time of sample collection, at 7 days (r=0.31, p=0.02) and 3 months postpartum (r=0.30, p=<0.00). Foremilk insulin correlated with maternal BMI at 3 months postpartum (r=0.22, p=0.04). Breast milk ghrelin and resistin were not correlated with maternal BMI. Ghrelin concentrations at 3 months postpartum were increased in foremilk compared with hindmilk (p=0.01). Concentrations of ghrelin were increased in hindmilk collected at 1  week postpartum compared with samples collected at 3 months postpartum (p=0.03). A trend towards decreased insulin concentrations in hindmilk was noted. Concentrations of leptin and resistin were not seen to alter over a feed. Conclusions A positive correlation between maternal BMI and foremilk leptin concentration at both time points studied, and foremilk insulin at 3 months postpartum was observed. This may have implications for infant appetite regulation and obesity risk. PMID:27388351

  8. Carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults in the Framingham Offspring Cohort

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diet may influence circulating adiponectin levels by improving insulin sensitivity. We examined the associations between carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults aged 26–81 y (n= 979 men and 1227 women). Dietary intakes were assessed using a FFQ. Fasting...

  9. 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...

  10. Study of Adiponectin Level in Diabetic Adolescent Girls in Relation to Glycemic Control and Complication of Diabetes

    PubMed Central

    Dayem, Soha M. Abd El; Nazif, Hayam K.; EI-Kader, Mona Abd; El-Tawil, Maha

    2015-01-01

    AIM: To study the relation between adiponectin level with glycemic control and complication of diabetes. PATIENTS AND METHODS: The study included 40 female adolescent type 1 diabetic patients and 40 healthy volunteers of the same age and sex. Blood sample was taken for assessment of glycosylated hemoglobin, lipid profile and adiponectine. Urine sample was taken for assessment of albumin/creatinine ratio. RESULTS: Diabetic patients had a significantly higher diastolic blood pressure, triglyceride, total cholesterol, LDL and adiponectin than controls. Patients with diabetes complication had a significant lower BMI and HDL. On the other hand, they had higher disease duration, total cholesterol, HbA1, albumin/creatinine ratio and adiponectin. Patients with microalbuminuria had a lower BMI, higher disease duration, diastolic blood pressure and adiponectin. Patients with diabetic retinopathy had higher disease duration, insulin dose, HbA1, microalbuminuria and adiponectin. Adiponectin in diabetic patients had a significant negative correlation with BMI and positive correlation with systolic blood pressure and microlabuminuria. CONCLUSION: Serum adiponectin level is high in adolescent type 1 diabetic girls. It can be used as a predictor of diabetes complications rather than a sensitive biochemical marker for glycemic control. PMID:27275296

  11. Clinical insights from adiponectin analysis in breast cancer patients reveal its anti-inflammatory properties in non-obese women.

    PubMed

    Panis, C; Herrera, A C S A; Aranome, A M F; Victorino, V J; Michelleti, P L; Morimoto, H K; Cecchini, A L; Simão, A N C; Cecchini, R

    2014-01-25

    Adiponectin is a cytokine reported as a determinant of poor prognosis in women with breast cancer. However, because data regarding its role in breast cancer have been obtained primarily from studies employing overweight or obese women, the adiponectin profile in non-obese women is poorly understood. In this study, we determined adiponectin levels in plasma from non-obese women with breast cancer and investigated a possible correlation with systemic inflammatory status. We determined the plasma adiponectin levels as well as biochemical and oxidative stress parameters in 80 women. Our results revealed that plasma adiponectin levels were affected by chemotherapy, estrogen receptor status, and disease progression. Adiponectin was positively correlated with antioxidant levels, without affecting either the metastatic behavior of disease or patient outcome. These findings highlight adiponectin as a novel player in the endocrine signaling that modulates the oxidative inflammatory response in human breast cancer, and contribute to the understanding of the role of adiponectin in pathological conditions in non-obese women.

  12. Association between adipose tissue expression and serum levels of leptin and adiponectin in women with polycystic ovary syndrome.

    PubMed

    Lecke, S B; Morsch, D M; Spritzer, P M

    2013-02-28

    We reviewed emerging evidence linking serum levels and adipose tissue expression of leptin and adiponectin in women with polycystic ovary syndrome (PCOS). Previous data obtained by our group from a sample of overweight/obese PCOS women and a control sample of normal weight controls, both stratified by BMI, were reanalyzed. Circulating levels of leptin and adiponectin were determined by commercially available enzyme-linked immunosorbent assays. Adipose tissue total RNA was reserve-transcripted into complementary DNA samples, which were used as templates for quantitative real-time PCR amplification. Positive correlations were found between serum and mRNA levels for both leptin (r = 0.321; P = 0.005) and adiponectin (r = 0.266; P = 0.024). Determination of leptin and adiponectin serum levels could serve as an indirect method to assess adipocyte production, since leptin and adiponectin are predominantly produced by subcutaneous adipocytes in women.

  13. 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.

  14. Adiponectin, leptin and IL-1 β in elderly diabetic patients with mild cognitive impairment.

    PubMed

    Gorska-Ciebiada, Malgorzata; Saryusz-Wolska, Malgorzata; Borkowska, Anna; Ciebiada, Maciej; Loba, Jerzy

    2016-04-01

    The aim of the study was to determine the serum levels of adiponectin, leptin and IL-1 β in elderly diabetic patients with and without mild cognitive impairment (MCI) and to examine the associations of these markers with clinical and cognitive parameters. A biochemical evaluation was performed of 62 seniors with type 2 diabetes (T2DM) and MCI, and 132 seniors with T2DM but without MCI (controls). Serum leptin and IL-1 β levels were higher and adiponectin concentration was lower in MCI patients than controls. In MCI subjects, adiponectin level was negatively correlated with leptin, IL-1 β levels and BMI. Leptin concentration was correlated with IL-1 β level. Univariate logistic regression models revealed that the factors which increased the likelihood of diagnosis of MCI in elderly patients with T2DM were higher levels of HbA1c, leptin, IL-1 β and triglycerides, as well as lower levels of adiponectin and HDL cholesterol. Similarly, previous CVD, hypertension, hyperlipidemia, retinopathy, nephropathy, hypoglycemia, longer duration of diabetes, increased number of co-morbidities, older age, fewer years of formal education were found to be associated with MCI. The multivariable model indicated fewer years of formal education, previous CVD, hypertension, increased number of co-morbidities, higher HbA1c and IL-1 β levels and lower adiponectin level. Elderly diabetic patients with MCI have higher levels of leptin and IL-1 β and lower levels of adiponectin. Further prospective studies are needed to determine the role of these markers in the progression to dementia.

  15. Adiponectin Receptors Form Homomers and Heteromers Exhibiting Distinct Ligand Binding and Intracellular Signaling Properties*

    PubMed Central

    Almabouada, Farid; Diaz-Ruiz, Alberto; Rabanal-Ruiz, Yoana; Peinado, Juan R.; Vazquez-Martinez, Rafael; Malagon, Maria M.

    2013-01-01

    Adiponectin binds to two widely expressed receptors (AdipoR1 and AdipoR2) that contain seven transmembrane domains but, unlike G-protein coupled receptors, present an extracellular C terminus and a cytosolic N terminus. Recently, AdipoR1 was found to associate in high order complexes. However, it is still unknown whether AdipoR2 may also form homomers or heteromers with AdipoR1 or if such interactions may be functionally relevant. Herein, we have analyzed the oligomerization pattern of AdipoRs by FRET and immunoprecipitation and evaluated both the internalization of AdipoRs in response to various adiponectin isoforms and the effect of adiponectin binding to different AdipoR combinations on AMP-activated protein kinase phosphorylation and peroxisome proliferator-activated receptor α activation. Transfection of HEK293AD cells with AdipoR1 and AdipoR2 showed that both receptors colocalize at both the plasma membrane and the endoplasmic reticulum. Co-transfection with the different AdipoR pairs yielded high FRET efficiencies in non-stimulated cells, which indicates that AdipoR1 and AdipoR2 form homo- and heteromeric complexes under resting conditions. Live FRET imaging suggested that both homo- and heteromeric AdipoR complexes dissociate in response to adiponectin, but heteromers separate faster than homomers. Finally, phosphorylation of AMP-activated protein kinase in response to adiponectin was delayed in cells wherein heteromer formation was favored. In sum, our findings indicate that AdipoR1 and AdipoR2 form homo- and heteromers that present unique interaction behaviors and signaling properties. This raises the possibility that the pleiotropic, tissue-dependent functions of adiponectin depend on the expression levels of AdipoR1 and AdipoR2 and, therefore, on the steady-state proportion of homo- and heteromeric complexes. PMID:23255609

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

    PubMed Central

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

    2014-01-01

    Background: To investigate the relationship between adiponectin, metabolic and hor- monal parameters, and insulin resistance in patients with non-treated polycystic ovary syndrome. Materials and Methods: In this cross-sectional observational study, 81 patients admitted to out-patient clinic with complaints of menstrual irregularity, hirsutism and obesity were enrolled. Serum adiponectin, biochemical and hormonal parameters, and 75 gram oral glu- cose tolerance test (OGTT) were measured. Spearman’s correlation coefficient was used for statistical analysis. Results: We observed inverse correlations between serum adiponectin level and body mass index, homeostasis model assessment insulin-resistance score, insulin level, fast- ing glucose level, and prolactin level (p=0.001, p=0.02, p=0.04, p=0.02, and p=0.005, respectively). No significant correlations were found between serum adiponectin level and age, height, weight, Ferriman-Gallwey score, 2 hours OGTT test value and free tes- tosterone level (p=0.3, p=0.6, p=0.2, p=0.8, p=0.9, and p=0.01, respectively). Conclusion: The present study demonstrated that in polycystic ovary syndrome patients, when serum adiponectin level decreased, degree of insulin resistance increased. Our find- ings indicate that serum adiponectin level is likely to be an adequate marker for deter- mination of the degree of insulin resistance, and may be a predictor of diseases, such as type 2 diabetes mellitus (T2DM) and metabolic syndrome, which develop on the basis of insulin resistance. PMID:24520503

  17. Optimization of adiponectin-derived peptides for inhibition of cancer cell growth and signaling.

    PubMed

    Otvos, Laszlo; Kovalszky, Ilona; Olah, Julia; Coroniti, Roberta; Knappe, Daniel; Nollmann, Friederike I; Hoffmann, Ralf; Wade, John D; Lovas, Sandor; Surmacz, Eva

    2015-05-01

    Adiponectin, an adipose tissue-excreted adipokine plays protective roles in metabolic and cardiovascular diseases and exerts anti-cancer activities, partially by interfering with leptin-induced signaling. Previously we identified the active site in the adiponectin protein, and generated both a nanomolar monomeric agonist of the adiponectin receptor (10-mer ADP355) and an antagonist (8-mer ADP400) to modulate various adiponectin receptor-mediated cellular functions. As physiologically circulating adiponectin forms multimeric complexes, we also generated an agonist dimer with improved biodistribution and in vitro efficacy. In the current report, we attempted to optimize the monomeric agonist structure. Neither extension of the peptide up to 14-mer analogs nor reinstallation of native residues in permissible positions enhanced significantly the activity profile. The only substitutions that resulted in 5-10-fold improved agonistic activity were the replacement of turn-forming Gly4 and Tyr7 residues with Pro and Hyp, respectively, yielding the more active native β-sheet structure. All peptides retained good stability in human serum exhibiting half-lives >2 h. The cellular efficacy and stability rankings among the peptides followed expected structure-activity relationship trends. To investigate whether simultaneous activation of adiponectin pathways and inhibition of leptin-induced signals can result in cytostatic and anti-oncogenic signal transduction processes, we developed a chimera of the leptin receptor antagonist peptide Allo-aca (placed to the N-terminus) and ADP355 (at the C-terminus). The in vitro anti-tumor activity and intracellular signaling of the chimera were dominated by the more active Allo-aca component. The ADP355 part, however, reversed unfavorable in vivo metabolic effects of the leptin receptor antagonist.

  18. Adiponectin Potentially Contributes to the Antidepressive Effects of Baduanjin Qigong Exercise in Women With Chronic Fatigue Syndrome-Like Illness.

    PubMed

    Chan, Jessie S M; Li, Ang; Ng, Siu-Man; Ho, Rainbow T H; Xu, Aimin; Yao, Tzy-Jyun; Wang, Xiao-Min; So, Kwok-Fai; Chan, Cecilia L W

    2017-03-13

    Our recent study demonstrates that adiponectin signaling plays a significant role in mediating physical exercise-exerted effects on hippocampal neurogenesis and antidepression in mice. Whether the findings can be translated to humans remains unknown. This study aimed to investigate the effects of Baduanjin Qigong exercise on adiponectin and to evaluate whether adiponectin is involved in the antidepressive effects of Qigong exercise on chronic fatigue syndrome (CFS)-like illness. This is a randomized, waitlist-controlled trial. One hundred eight female participants were randomly assigned to either Qigong exercise or waitlist groups. Sixteen 1.5-h Qigong lessons were conducted. Outcome measures were taken at three time points. Baseline adiponectin levels were negatively associated with body weight, body mass index, waist circumference, hip circumference, and waist/hip ratio in women with CFS-like illness. Compared with the waitlist control, Qigong exercise significantly reduced anxiety and depression symptoms and significantly raised plasma adiponectin levels (median = 0.8 vs. -0.1, p < 0.05). More interestingly, increases in adiponectin levels following Qigong exercise were associated with decreases in depression scores for the Qigong group (r = -0.38, p = 0.04). Moreover, adjusted linear regression analysis further identified Qigong exercise and change in adiponectin levels as the significant factors accounting for reduction of depression symptoms. Baduanjin Qigong significantly increased adiponectin levels in females with CFS-like illness. Decreases in depression symptoms were associated with increases in adiponectin levels following Qigong exercise, indicating that the potential contribution of adiponectin to Qigong exercise elicited antidepressive effects in human subjects.

  19. Inhibitory role of adiponectin peptide I on rat choroidal neovascularization

    PubMed Central

    Lyzogubov, Valeriy V.; Tytarenko, Ruslana G.; Bora, Nalini S.; Bora, Puran S.

    2013-01-01

    Age-related macular degeneration (AMD) is a leading cause of central blindness in elderly population. Wet type of AMD is characterized by extensive growth of new vessels. One of the effective strategies to treat wet AMD is to limit the choroidal neovascularization (CNV). We studied effect of adiponectin peptide I (APNpI) on new vessel growth in laser-induced rat model of wet AMD and on rat choroidal endothelial cell (CEC) culture. CNV size and vessel density was investigated by microscopy. Immunohistochemical staining (IHC) for Von Willebrand Factor (vWF), APN, APN receptors 1 (AdipoR1), 2 (AdipoR2), VEGF, VEGF receptor 2 (VEGF-R2), proliferating cell nuclear antigen (PCNA) was performed in CNV area. The mRNA expression of VEGF and VEGF-R2 in RPE-choroid was investigated by RT-PCR and real-time PCR. APNpI inhibited area of CNV by 4 fold, number of vWF positive vessels by 99% and area of subretinal tissue by 40%. The expression of VEGF and VEGF-R2 at mRNA and protein levels were decreased after APNpI treatment in vivo. Proliferative index (PCNA) was 5 fold less in laser spots of APNpI treated rats compared to controls. In conclusion, APNpI inhibited formation of new vessels in rat model of CNV by decreasing VEGF, VEGF-R2 expression and cell proliferation. Thus, APNpI may have potential therapeutic use for AMD treatment since it significantly inhibited CNV. PMID:22633972

  20. 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

  1. 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.

  2. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses.

    PubMed

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-09-01

    Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle microvascular recruitment. We demonstrated that a high-fat diet induces vascular adiponectin and insulin resistance but globular adiponectin administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK- and nitric oxide-dependent mechanism. This suggests that globular adiponectin might have a therapeutic potential for improving insulin resistance and preventing cardiovascular complications in patients with diabetes via modulation of microvascular insulin responses. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague-Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by

  3. Adiponectin concentration is associated with muscle insulin sensitivity, AMPK phosphorylation, and ceramide content in skeletal muscles of men but not women.

    PubMed

    Høeg, Louise D; Sjøberg, Kim A; Lundsgaard, Anne-Marie; Jordy, Andreas B; Hiscock, Natalie; Wojtaszewski, Jørgen F P; Richter, Erik A; Kiens, Bente

    2013-03-01

    Adiponectin is an adipokine that regulates metabolism and increases insulin sensitivity. Mechanisms behind this insulin-sensitizing effect have been investigated in rodents, but little is known in humans, especially in skeletal muscle. Women have higher serum concentrations of adiponectin than men and are generally more insulin sensitive in skeletal muscle than men. We show here that large differences exist between men and women with regard to apparent adiponectin regulation of insulin-stimulated glucose uptake in skeletal muscle. Serum adiponectin was significantly associated with leg glucose uptake in healthy, young, lean men, but the association was absent in women. In addition, serum adiponectin was significantly associated with AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscles of men but not in women. Serum adiponectin was also significantly, negatively associated with skeletal muscle ceramide content in men only, and interestingly, ceramide content was negatively associated with adiponectin receptor 1 (AdipoR1) expression in skeletal muscles of men. Women had lower AdipoR1 expression in skeletal muscle and a lower percentage of glycolytic adiponectin-sensitive type 2 muscle fibers than men. These associations suggest that the insulin-sensitizing effect of adiponectin on human male skeletal muscles may be mediated via AdipoR1 to activation of AMPK, leading to lowering of ceramide content. The lower skeletal muscle AdipoR1 protein expression and lower expression of adiponectin-sensitive type 2 muscle fibers in women than in men may explain the apparent lesser sensitivity to adiponectin in women.

  4. 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

  5. Peroxisome proliferator-activated receptor γ enhances adiponectin secretion via up-regulating DsbA-L expression.

    PubMed

    Jin, Dan; Sun, Jun; Huang, Jing; Yu, Xiaoling; Yu, An; He, Yiduo; Li, Qiang; Yang, Zaiqing

    2015-08-15

    Disulfide-bond A oxidoreductase like-protein (DsbA-L) was identified as a molecular chaperone facilitating the assembly and secretion of adiponectin, an adipokine with multiple beneficial effects. In obesity the level of DsbA-L is reduced with a concomitant decrease of the circulating adiponectin level, especially of the high molecular weight form (HMW). Both rodent and human studies have shown that the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-γ agonists increase adiponectin levels in serum by activating PPARγ, which up-regulates critical endoplasmic reticulum (ER) chaperones thus facilitating protein folding. As shown in the present study, overexpression of PPARγ in human embryonic kidney (HEK) 293 cells elicited the cellular release of HMW adiponectin. PPARγ enhanced expression of DsbA-L by binding directly to peroxisome proliferator response element (PPRE) site within the DsbA-L promoter. Conversely, in differentiated 3T3-L1 cells, PPARγ knockdown resulted in decreased expression of Adiponectin, DsbA-L and ERp44. DsbA-L expression increased after PPARγ agonist treatment and decreased upon treatment with PPARγ antagonist in 3T3-L1 adipocytes. DsbA-L deficiency in differentiated 3T3-L1 cells impaired the secretion of adiponectin. We therefore propose that DsbA-L plays an important role in facilitating HMW adiponectin formation and release from cells under the regulation of PPARγ.

  6. Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy

    PubMed Central

    Georgoulidou, Anastasia; Roumeliotis, Athanasios; Roumeliotis, Stefanos; Giannakopoulou, Efstathia; Papanas, Nikolaos; Passadakis, Ploumis; Manolopoulos, Vangelis G.; Vargemezis, Vassilis

    2015-01-01

    Aims. We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). Methods. Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. Results. Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P = 0.002), on the contrary to ox-LDL which decreased with disease severity (P < 0.001). cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P = 0.022). Adiponectin was a significant negative predictor of ox-LDL levels (β = −5.45, P = 0.023), independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy. Conclusions. There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought. PMID:26064982

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Adiponectin: a biomarker of obesity-induced insulin resistance in adipose tissue and beyond.

    PubMed

    Lu, Jin-Ying; Huang, Kuo-Chin; Chang, Lin-Chau; Huang, Ying-Shing; Chi, Yu-Chiao; Su, Ta-Chan; Chen, Chi-Ling; Yang, Wei-Shiung

    2008-09-01

    Adiponectin is one of the most thoroughly studied adipocytokines. Low plasma levels of adiponectin are found to associate with obesity, metabolic syndrome, diabetes and many other human diseases. From animal experiments and human studies, adiponectin has been shown to be a key regulator of insulin sensitivity. In this article, we review the evidence and propose that hypo-adiponectinemia is not a major cause of obesity. Instead, it is the result of obesity-induced insulin resistance in the adipose tissue. Hypo-adiponectinemia then mediates the metabolic effects of obesity on the other peripheral tissues, such as liver and skeletal muscle and may also exert some direct effects on end-organ damage. We propose that deciphering the molecular details governing the adiponectin gene expression and protein secretion will lead us to more comprehensive understanding of the mechanisms of insulin resistance in the adipose tissue and provide us new avenues for the therapeutic intervention of obesity and insulin resistance-related human disorders.

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

    PubMed

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

    2006-08-01

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

  10. 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.

  11. 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

  12. The Balance between Leptin and Adiponectin in the Control of Carcinogenesis- Focus on Mammary Tumorigenesis

    PubMed Central

    Grossmann, Michael E.

    2013-01-01

    A number of studies indicate that a growing list of cancers may be influenced by obesity. In obese individuals these cancers can be more frequent and more aggressive resulting in reduced survival. One of the most prominent and well characterized cancers in this regard is breast cancer. Obesity plays a complex role in breast cancer and is associated with increased inflammation, angiogenesis and alterations in serum levels of potential growth factors such as adiponectin, leptin and estrogen in the serum. Reduced levels of serum adiponectin have been reported in breast cancer patients compared to healthy controls, particularly in postmenopausal women. The role of serum leptin levels in breast cancer appears to be more complex. Some studies have shown leptin to be increased in women with breast cancer but other studies have found leptin to be decreased or unchanged. This may be due to a number of confounding issues. We and others propose that it may be the levels of adiponectin and leptin as well as the balance of adiponectin and leptin that are the critical factors in breast and other obesity related cancer tumorigenesis. PMID:22728769

  13. 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

  14. Globular adiponectin improves high glucose-suppressed endothelial progenitor cell function through endothelial nitric oxide synthase dependent mechanisms.

    PubMed

    Huang, Po-Hsun; Chen, Jia-Shiong; Tsai, Hsiao-Ya; Chen, Yung-Hsiang; Lin, Feng-Yen; Leu, Hsin-Bang; Wu, Tao-Cheng; Lin, Shing-Jong; Chen, Jaw-Wen

    2011-07-01

    Plasma levels of adiponectin, an adipose-specific protein with putative anti-atherogenic properties, could be down-regulated in obese and diabetic subjects. Recent insights suggest that the injured endothelial monolayer is regenerated by circulating endothelial progenitor cells (EPCs), but high glucose reduces number and functions of EPCs. Here, we tested the hypothesis that globular adiponectin can improve high glucose-suppressed EPC functions by restoration of endothelial nitric oxide synthase (eNOS) activity. Late EPCs isolated from healthy subjects appeared with cobblestone shape at 2-4 weeks. EPCs were incubated with high glucose (25 mM) and treatment with globular adiponectin for functional study. Migration and tube formation assays were used to evaluate the vasculogenetic capacity of EPCs. The activities of eNOS, Akt and concentrations of nitric oxide (NO) were also determined. Administration of globular adiponectin at physiological concentrations promoted EPC migration and tube formation, and dose-dependently upregulated phosphorylation of eNOS, Akt and augmented NO production. Chronic incubation of EPCs in high-glucose medium significantly impaired EPC function and induced cellular senescence, but these suppression effects were reversed by treatment with globular adiponectin. Globular adiponectin reversed high glucose-impaired EPC functions through NO- and p38 MAPK-related mechanisms. In addition, nude mice that received EPCs treated with adiponectin in high glucose medium showed a significant improvement in blood flow than those received normal saline and EPCs incubated in high glucose conditions. The administration of globular adiponectin improved high glucose-impaired EPC functions in vasculogenesis by restoration of eNOS activity. These beneficial effects may provide some novel rational to the vascular protective properties of adiponectin.

  15. The Role of Adiponectin in Breast Cancer: A Meta-Analysis

    PubMed Central

    Liu, Li-Yuan; Wang, Meng; Ma, Zhong-Bing; Yu, Li-Xiang; Zhang, Qiang; Gao, De-Zong; Wang, Fei; Yu, Zhi-Gang

    2013-01-01

    Published results suggests that high adiponectin level may decrease the risk of breast cancer. However, available evidence on breast cancer is conflicting. Therefore a meta-analysis was performed to assess the association between blood adiponectin and breast cancer risk. PubMed database, Web of Science, Elsevier Science, Springer Link and bibliographies of retrieved articles were searched for epidemiological studies published up to March 2013. Meta-analysis was performed on the combined effect values (OR) as well as standardized mean difference (SMD) including 17 studies. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. The publication bias was assessed by the Egger’s regression asymmetry test and Begg’s rank correlation test with Begg’s funnel plot. Subgroup analyses and sensitivity analysis were also performed. A total of 13 studies involving 3578 breast cancer cases and 4363 controls contributed to the OR analysis. The high adiponectin level did not significantly affect breast cancer risk (OR=0.902, 95% CI=0.773–1.053). After excluding articles that were the key contributors to between-study heterogeneity, the OR of high adiponectin level was associated with decreased breast cancer risk (OR=0.838, 95% CI=0.744–0.943). There was a significantly association between high adiponectin level and postmenopausal breast cancer women (OR=0.752, 95%CI=0.604-0.936); and it was not associated with premenopausal breast cancer women (OR=0.895, 95%CI=0.638-1.256). The result of pooled measure on SMD was that the high adiponectin level was associated with decreased breast cancer risk (SMD= -0.348, 95% CI= -0.533--0.614) after excluding articles which were the key contributors to between-study heterogeneity. Our findings indicate that high adiponectin level might decrease the risk of postmenopausal breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with

  16. 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.

  17. 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

  18. Adiponectin is Protective against Oxidative Stress Induced Cytotoxicity in Amyloid-Beta Neurotoxicity

    PubMed Central

    Chan, Koon-Ho; Lam, Karen Siu-Ling; Cheng, On-Yin; Kwan, Jason Shing-Cheong; Ho, Philip Wing-Lok; Cheng, Kenneth King-Yip; Chung, Sookja Kim; Ho, Jessica Wing-Man; Guo, Vivian Yawei; Xu, Almin

    2012-01-01

    Beta-amyloid (Aβ ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T2DM) which is characterized by insulin resistance. Interestingly, T2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties) against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y) transfected with the Swedish amyloid precursor protein (Sw-APP) mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH) released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK) activation and enhanced nuclear factor-kappa B (NF-κB) activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1) AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif) and possibly 2) suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists. PMID:23300647

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

    PubMed

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

    2014-03-28

    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 (PI3K) 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.

  20. Effects of radioiodine administration on serum concentrations of matrix metalloproteinases, adiponectin and thrombospondin-1

    PubMed Central

    2013-01-01

    Background In order to assess safety of radioactive iodine administration in the treatment of thyrotoxicosis, we measured concentrations of matrix metalloproteinase-2 (MMP-2), its main inhibitor – TIMP-2 (tissue inhibitor of MMP-2), matrix metalloproteinase-9 (MMP-9), its main inhibitor – TIMP-1, adiponectin, as well as pro-inflammatory and procancerogenic thrombospondin-1 (TSP-1). Design and patients The study involved 23 patients treated with radioiodine for thyrotoxicosis. Serum concentrations of TSH, free T4, free T3, MMP-2, MMP-9, TIMP-1, TIMP-2, total adiponectin and TSP-1 were measured by immunoassays just before radioiodine administration (visit 1), and subsequently, after 7 days (visit 2), 3 months (visit 3), 6 to 8 months (visit 4) and 15–18 months after radioiodine administration (visit 5). Results There were no acute changes in serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, adiponectin and TSP-1 (visit 1 vs. 2). Subsequently, there was an increase in MMP-2 (from 393±106 ng/ml to 774±424 ng/ml), TIMP-1 (from 177±76 ng/ml to 296±118 ng/ml), and adiponectin (from 16442±9490 ng/ml to 23518±9840 ng/ml), visit 1 to 5, respectively (p < 0.01). Further analysis revealed no significant change in MMP-2/TIMP-2 ratio, but there was a significant decrease in MMP-9/TIMP-1 ratio (p < 0.05), suggestive of possible decrease in free MMP-9 concentrations. Conclusions Our data reveal a significant and sustained increase in serum adiponectin, as well as possible decrease of free MMP-9 concentration after radioiodine administration. In contrast, there was no significant change of TSP-1. This might indicate overall safety of radioiodine treatment of thyrotoxicosis in terms of the risks of subsequent cardiovascular and neoplastic disease. PMID:23919647

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

    PubMed

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

    2016-02-01

    The transition from pregnancy to lactation is characterized by major changes in glucose and adipose tissue metabolism. Anti- and prolipolytic pathways mediated via the hydroxycarboxylic acid receptors 1 (HCAR1) and 2 (HCAR2) and tumor necrosis factor-α receptor 1 (TNFR1), as well as the adipokines apelin and resistin, are likely involved in regulating these processes. This study aimed to determine the mRNA abundance of the aforementioned receptors in both subcutaneous and visceral adipose tissue, to characterize the adipokine concentrations in serum, and to test the effects of feeding diets with either high or low portions of concentrate and a concomitant niacin supplementation from late gestation to early lactation. Twenty pluriparous German Holstein cows were all kept on the same silage-based diet until d 42 antepartum, when they were allocated to 2 feeding groups: until d 1 antepartum, 10 animals each were assigned to either a high-concentrate (60:40 concentrate-to-roughage ratio) or a low-concentrate diet (30:70). Both groups were further subdivided into a control and a niacin group, the latter receiving 24 g/d of nicotinic acid from d -42 until 24. From d 1 to 24 postpartum, the concentrate portion was increased from 30 to 50% for all cows. Biopsies of subcutaneous (SCAT) and retroperitoneal adipose tissue (RPAT) were taken at d -42, 1, 21, and 100 relative to parturition. Blood samples were drawn along with the biopsies and on d -14, 3, 7, 14, and 42. The concentrations of the adipokines apelin and resistin in serum were measured via ELISA. The mRNA of the 3 receptors in AT was quantified as well as the protein abundance of HCAR2 by Western blot. The feeding regimen did not affect the variables examined. The concentrations of apelin remained fairly constant during the observation period, whereas the resistin concentrations increased toward parturition and decreased to precalving levels within 1 wk after calving. The mRNA abundance of HCAR1, HCAR2, and TNFR1

  2. Comparison of the effects of barnidipine+losartan compared with telmisartan+hydrochlorothiazide on several parameters of insulin sensitivity in patients with hypertension and type 2 diabetes mellitus.

    PubMed

    Derosa, Giuseppe; Querci, Fabrizio; Franzetti, Ivano; Dario Ragonesi, Pietro; D'Angelo, Angela; Maffioli, Pamela

    2015-10-01

    The aim of this study was to evaluate the effects of barnidipine+losartan compared with telmisartan+hydrochlorothiazide on several parameters of insulin sensitivity in patients with hypertension and type 2 diabetes mellitus. We enrolled 148 normocholesterolemic patients with mild-to-moderate hypertension and type 2 diabetes mellitus. Patients were treated with barnidipine, 20 mg day(-1), in combination with losartan, 100 mg day(-1), or with telmisartan+hydrochlorothiazide, 80/12.5 mg day(-1), for 6 months. We assessed blood pressure (BP) on a monthly basis; additionally, blood samples were collected to assess, at baseline and after 6 months, the following parameters: fasting plasma glucose; glycated hemoglobin; fasting plasma insulin; HOMA index; and some adipocytokines, such as adiponectin (ADN), resistin, leptin, visfatin and vaspin. Patients were also subjected to an euglycemic hyperinsulinemic clamp to assess the M value and glucose infusion rate to ascertain their insulin sensitivity. One hundred and forty-one patients completed the study. The BP was reduced in both groups, although the reduction was greater with barnidipine+losartan (P<0.001 vs. baseline and P<0.01 vs. telmisartan+hydrochlorothiazide). Barnidipine+losartan increased the M value and glucose infusion rate during the euglycemic hyperinsulinemic clamp (P<0.05 vs. baseline and vs. telmisartan+hydrochlorothiazide). With respect to the levels of adipocytokines, ADN was increased (P<0.05), and resistin and leptin were reduced from baseline with barnidipine+losartan (P<0.05 vs. baseline), but they were not reduced with telmisartan+hydrochlorothiazide. Visfatin and vaspin were reduced by barnidipine+losartan compared with baseline (P<0.05). The adipocytokine levels obtained with barnidipine+losartan were significantly better than those obtained with telmisartan+hydrochlorothiazide (P<0.05 for all parameters). In addition to providing a greater BP reduction, barnidipine+losartan improved the insulin

  3. 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...

  4. 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

  5. Dietary Japanese millet protein ameliorates plasma levels of adiponectin, glucose, and lipids in type 2 diabetic mice.

    PubMed

    Nishizawa, Naoyuki; Togawa, Tubasa; Park, Kyung-Ok; Sato, Daiki; Miyakoshi, Yo; Inagaki, Kazuya; Ohmori, Norimasa; Ito, Yoshiaki; Nagasawa, Takashi

    2009-02-01

    Millet is an important food crop in Asia and Africa, but the health benefits of dietary millet are little known. This study defined the effects of dietary Japanese millet on diabetic mice. Feeding of a high-fat diet containing Japanese millet protein concentrate (JMP, 20% protein) to type 2 diabetic mice for 3 weeks significantly increased plasma levels of adiponectin and high-density lipoprotein cholesterol (HDL cholesterol) and decreased the levels of glucose and triglyceride as compared to control. The starch fraction of Japanese millet had no effect on glucose or adiponectin levels, but the prolamin fraction beneficially modulated plasma glucose and insulin concentrations as well as adiponectin and tumor necrosis factor-alpha gene expression. Considering the physiological significance of adiponectin and HDL cholesterol levels in type 2 diabetes, insulin resistance, and cardiovascular disease, our findings imply that dietary JMP has the potential to ameliorate these diseases.

  6. 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

  7. 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

  8. High serum adiponectin predicts incident fractures in elderly men: Osteoporotic fractures in men (MrOS) Sweden.

    PubMed

    Johansson, Helena; Odén, Anders; Lerner, Ulf H; Jutberger, Hans; Lorentzon, Mattias; Barrett-Connor, Elizabeth; Karlsson, Magnus K; Ljunggren, Osten; Smith, Ulf; McCloskey, Eugene; Kanis, John A; Ohlsson, Claes; Mellström, Dan

    2012-06-01

    Adipocytes and osteoblasts share a common progenitor, and there is, therefore, potential for both autocrine and endocrine effects of adiponectin on skeletal metabolism. The aim of the present study was to determine whether high serum adiponectin was associated with an increased risk of fracture in elderly men. We studied the relationship between serum adiponectin and the risk of fracture in 999 elderly men drawn from the general population and recruited to the Osteoporotic Fractures in Men (MrOS) study in Gothenburg, Sweden. Baseline data included general health questionnaires, lifestyle questionnaires, body mass index (BMI), bone mineral density (BMD), serum adiponectin, osteocalcin, and leptin. Men were followed for up to 7.4 years (average, 5.2 years). Poisson regression was used to investigate the relationship between serum adiponectin, other risk variables and the time-to-event hazard function of fracture. Median levels of serum adiponectin at baseline were 10.4 µg/mL (interquartile range, 7.7-14.3). During follow-up, 150 men sustained one or more fractures. The risk of fracture increased in parallel with increasing serum adiponectin (hazard ratio [HR]/SD, 1.46; 95% confidence interval [CI], 1.23-1.72) and persisted after multivariate-adjusted analysis (HR/SD, 1.30; 95% CI, 1.09-1.55). Serum adiponectin shows graded stepwise association with a significant excess risk of fracture in elderly men that was independent of several other risk factors for fracture. Its measurement holds promise as a risk factor for fracture in men.

  9. Globular adiponectin inhibits ethanol-induced apoptosis in HepG2 cells through heme oxygenase-1 induction.

    PubMed

    Nepal, Saroj; Kim, Mi Jin; Subedi, Amit; Lee, Eung-Seok; Yong, Chul Soon; Kim, Jung-Ae; Kang, WonKu; Kwak, Mi-Kyung; Arya, Dharamvir Singh; Park, Pil-Hoon

    2012-10-01

    Hepatocellular apoptosis is an essential pathological feature of alcoholic liver disease. Adiponectin, an adipokine predominantly secreted from adipose tissue, has been shown to play beneficial roles in alcoholic liver disease against various inflammatory and pro-apoptotic molecules. However, the effects of adiponectin on ethanol-induced apoptosis in liver cells are largely unknown. Herein, we investigated the role of globular adiponectin (gAcrp) in the prevention of ethanol-induced apoptosis and further tried to decipher the potential mechanisms involved. In the present study, we demonstrated that gAcrp significantly inhibits both ethanol-induced increase in Fas ligand expression and activation of caspase-3 in human hepatoma cell lines (HepG2 cells), suggesting that gAcrp plays a protective role against ethanol-induced apoptosis in liver cells. This protective effect of gAcrp was mediated through adiponectin receptor R1 (adipoR1). Further, globular adiponectin treatment caused induction of heme oxygenase-1 (HO-1) through, at least in part, nuclear factor (erythroid-derived 2)-like 2, (Nrf2) signaling. Treatment with SnPP, a pharmacological inhibitor of HO-1, and knockdown of HO-1 with small interfering RNA (siRNA) restored caspase-3 activity suppressed by gAcrp, indicating a critical role of HO-1 in mediating the protective role of gAcrp in ethanol-induced apoptosis in liver cells. In addition, carbon monoxide, a byproduct obtained from the catabolism of free heme was found to contribute to the anti-apoptotic effect of adiponectin. In conclusion, these data demonstrated that globular adiponectin prevents ethanol-induced apoptosis in HepG2 cells via HO-1 induction and revealed a novel biological response of globular adiponectin in the protection of liver injury from alcohol consumption.

  10. Effects of Rosuvastatin Alone or in Combination with Omega-3 Fatty Acid on Adiponectin Levels and Cardiometabolic Profile

    PubMed Central

    Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.

    2016-01-01

    Background: Adiponectin is an important adipocyte-related protein that has been postulated to participate in prevention of the development of metabolic syndrome. The relationship between adiponectin serum levels and risk of coronary artery disease (CAD) has been widely investigated and remains controversial. The aim of the present study was to evaluate the effects of rosuvastatin and/or omega-3 fatty acid on adiponectin serum levels in patients with insulin resistance (IR) and CAD. Patients and Methods: This study involved 87 patients with CADs and IR of different etiology, the patients were divided into three groups; 24 patients on treatment with rosuvastatin, 22 patients on treatment with omega-3 fatty acid, 23 patients on treatment with omega-3 fatty acid and rosuvastatin, 18 patients were not previously or currently treated with either rosuvastatin or omega-3 fatty acid, those regarded as control patients. Anthropometric measures, adiponectin serum levels, and other biochemical parameters were assessed in each treated group. Results: Rosuvastatin therapy leads to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 6.76 ± 1.03 ng/mL compared to control P < 0.01. Omega-3 fatty acid therapy leads to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 6.11 ± 1.29 ng/mL compared to control P < 0.01. Rosuvastatin plus omega-3 fatty acid therapy lead to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 7.99 ± 1.76 ng/mL compared to control P < 0.01. Conclusions: Rosuvastatin and/or omega-3 fatty acid lead to significant cardiometabolic protection through an increment in adiponectin serum levels. PMID:28104968

  11. B-type natriuretic peptide and adiponectin releases in rat model of myocardial damage induced by isoproterenol administration

    PubMed Central

    Hasić, Sabaheta; Hadžović-Džuvo, Almira; Jadrić, Radivoj; Kiseljaković, Emina

    2013-01-01

    B-type natriuretic peptide (BNP) and adiponectin play important role in the cardiovascular homeostasis regulation. We investigated BNP and adiponectin serum levels followed by isoproterenol (ISO) administration to rats and explored the relationship between them. Cardiac troponin I (cTnI) blood level was used as biochemical evidence of myocardial damage development. Adult male Wistar rats (average body weight 273.33±21.63 g) were distributed into groups: control group received saline (n=6) and ISO groups (n=12) treated with ISO (subcutaneous single dose 100 mg/kg of rat body weight). ISO group was divided into two groups according to the time of BNP, adiponectin and cTnI determination: ISO I (n=6; 2 hours after ISO administration); ISO II (n=6; 4 hours after ISO administration). Blood for determination of parameters was taken from rat abdominal aorta. BNP, adiponectin and cTnI were determined by ELISA method. Data were statistically analysed by using SPSS version13 computer program. P value less 0.05 was considered statistically significant. Blood BNP and adiponectin were lower at 2 hours after ISO administration in comparison with control group (p=0.004 for BNP and p=0.174 for adiponectin). Four hours after ISO administration, we have noted significant elevation of both parameters compared to ISO I group (p=0.004 for BNP;p=0.02 for adiponectin). Test of correlation have showed significant relation between their blood levels during experimental period (rho=0.577; p=0.01). BNP and adiponectin are not simple indicators of myocardial damage development. They have possible associated and additive effects in cardiovascular homeostasis regulation. PMID:24289757

  12. Adiponectin and adiponectin receptor system in the rat adrenal gland: ontogenetic and physiologic regulation, and its involvement in regulating adrenocortical growth and steroidogenesis.

    PubMed

    Paschke, Lukasz; Zemleduch, Tomasz; Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Malendowicz, Ludwik K

    2010-09-01

    Adiponectin (ADN) is a regulatory peptide secreted mostly by adipose tissue and acting via two receptors: AdipoR1 and AdipoR2. Our aim was to investigate expression of adiponectin system genes in the rat adrenal gland as well as its ontogenetic and physiological control. Furthermore, we examined the effects of acute and prolonged activation of HPA axis on ADN system in adipose tissue. By means of QPCR, ADN and AdipoR1 expression was demonstrated in rat adrenal cortex both at mRNA and protein levels, while AdipoR2 could only be detected at mRNA levels. ADN expression level was significantly upregulated in a developing and regenerating adrenal cortex. Globular domain of adiponectin at 10(-9) M stimulated corticosterone output and BrdU incorporation by cultured rat adrenocortical cells. Moreover, both acute (ACTH and ether stress) and prolonged (ACTH) adrenal stimulation resulted in lowered ADN levels, while expression of AdipoR1 and AdipoR2 was upregulated by the acute treatment. Depending on its site of origin, visceral (VAT) or subcutaneous (SAT) adipose tissue responded differently to alterations in HPA axis. VAT expression of ADN and its receptors remained almost unchanged by experimental manipulations. In SAT, on the other hand, expression of ADN and AdipoR2 was markedly increased by ACTH treatment and stress, while dexamethasone suppressed ADN and AdipoR1 mRNA levels. The results of this study provide new evidence for direct and indirect interactions between adipokines and HPA axis.

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

    PubMed

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

    2014-07-24

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

  14. 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

  15. 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.

  16. Low plasma adiponectin level, white blood cell count and Helicobacter pylori titre independently predict abnormal pancreatic beta-cell function.

    PubMed

    So, Wing-Yee; Tong, Peter C; Ko, Gary T; Ma, Ronald C; Ozaki, Risa; Kong, Alice P; Yang, Xilin; Ho, Chung-Shun; Lam, Christopher C; Chan, Juliana C

    2009-11-01

    Adiponectin is an adipocytokine with insulin sensitizing effect while chronic inflammation damages pancreatic beta-cells leading to reduced insulin response. We aimed to prove the hypothesis that adiponectin levels and inflammatory markers (white blood cell counts [WCC], Helicobacter pylori [HP] titers, high sensitivity C-reactive protein [hs-CRP]) may interact to affect risk of diabetes. We studied 288 Chinese men (age-median: 41.0 years, IQR: 35.3-46.0 years) being recruited from the community in Hong Kong. The mean adiponectin level was 5.39+/-2.81 microg/ml and 40.9% (n=107) had low adiponectin level (<4 microg/ml). On multiple regression analysis, adiponectin was negatively associated with diabetes, HOMA insulin resistance top quartile, plasma glucose (PG) and 2h insulin; and positively associated with HOMA insulin sensitivity index. WCC was independently associated with PG and 15' insulin, and negatively associated with HOMA insulin sensitivity top quartile. HP titre was associated with 30' PG level and diabetes. hs-CRP did not enter the multivariable model. In conclusion, adiponectin, WCC and HP titer are independent predictors for hyperglycemia and reduced insulin sensitivity in Chinese men. These findings may explain the high risk for diabetes in Chinese population despite their relatively low adiposity.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2014-09-01

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

  19. 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.

  20. Impact of Treatment with Rosiglitazone or Metformin on Biomarkers for Insulin Resistance and Metabolic Syndrome in Patients with Polycystic Ovary Syndrome

    PubMed Central

    Steiner, Charles A.; Janez, Andrej; Jensterle, Mojca; Reisinger, Katrin; Forst, Thomas; Pfützner, Andreas

    2007-01-01

    Background There is increasing evidence that insulin resistance (IR) has an important implication in the pathogenesis of polycystic ovary syndrome (PCOS), a common endocrinopathy in women. This study was performed to investigate the impact of different treatments for IR on five currently discussed markers for insulin resistance: intact proinsulin, adiponectin, retinol-binding protein 4 (RBP4), resistin, and visfatin in patients with PCOS. Methods Thirty-five women with clinically confirmed PCOS diagnosis were included in the study [age (mean±SD): 24.7±4.8 years; body mass index: 27.4±6.0 kg/m2]. They were randomized to receive either metformin (850 mg twice a day) or rosiglitazone (4 mg once a day). Blood samples for measurement of the HOMAIR score, visfatin, RBP4, intact proinsulin, resisitin, and adiponectin were taken at baseline and after 6 months of treatment. Results Both drugs improved ovulation, and an increase in insulin sensitivity was observed, especially in the rosiglitazone arm. Adiponectin levels increased in both treatment arms (metformin: 8.6±3.3 to 16.7±7.2 mg/liter, p < 0.001; rosiglitazone: 8.2±3.5 to 26.2±9.5 mg/liter, p < 0.001), but the increase was more pronounced with rosiglitazone (p < 0.001). While no changes of visfatin concentrations were observed during rosiglitazone therapy (15.4±6.9 ng/ml vs 17.4±4.8 ng/ml, n.s.), there was an increase in the metformin treatment arm (11.9±4.0 to 21.8±8.3 ng/ml, p < 0.001). Significant increases demonstrated for RBP4 in both treatment arms were more pronounced in the metformin group (metformin: +66%, rosiglitazone: +33%). All patients were in stage I or II of ß-cell dysfunction and none of them showed increased intact proinsulin levels or changes in resisitin at baseline or end point. Conclusions Both drugs slightly improved ovulation in our PCOS patient population during 6 months of therapy, which was accompanied by improved insulin sensitivity and an increase in adiponectin levels

  1. Normal total and high molecular weight adiponectin levels in adults with cystic fibrosis.

    PubMed

    Ziai, S; Elisha, B; Hammana, I; Tardif, A; Berthiaume, Y; Coderre, L; Rabasa-Lhoret, R

    2011-12-01

    Cystic fibrosis related diabetes (CFRD) is an important complication of CF that increases mortality. Adiponectin, an adipokine secreted from adipose tissue, plays an important role in fatty acid and glucose metabolism. Lower total adiponectin (TA) levels have been linked to the risk of developing type 2 diabetes. However, studies show that the high molecular weight isoform (HMW), thought to be more active than TA, might be a better indicator of insulin sensitivity. Our aim was to determine the association between HMW and insulin sensitivity in CF subjects and determine if other factors might modulate its levels. Thirteen control subjects and 47 CF adults (16 with normal glucose tolerance, 16 prediabetic and 15 with CFRD) underwent an oral glucose tolerance test. Blood samples were taken at time 0, 30, 60, 90 and 120 min. Body mass index, fibrinogen, glucose and insulin, TA and HMW were measured in every subject. Regression analysis was used to determine the association between TA, HMW and glucose (fasting glucose, 2h glucose and glucose AUC) as well as insulin (fasting insulin, insulin AUC, and Stumvoll insulin sensitivity index) parameters. TA and HMW levels were similar between CF patients and controls and were not associated to insulin sensitivity. TA was negatively associated to insulin AUC (p=0.0108) and 2h glucose (p=0.0116) in controls while these relationships were either weakly negative (p=0.0208) or weakly positive (p=0.0105) in CF patients. Also, HMW was negatively associated to insulin (p=0.00301) and glucose AUC (p=0.0546) in controls whereas these associations were positive in CF patients (p=0.0388, p=0.0232 respectively). In conclusion, our exploratory study on HMW adiponectin demonstrated similar levels of TA and HMW between CF patients and controls and different relationships between forms of adiponectin to glucose metabolism and insulin in CF.

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

    PubMed

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

    2008-07-01

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

  3. 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

  4. Gender differences in the association of visceral and subcutaneous adiposity with adiponectin in African Americans: the Jackson Heart Study

    PubMed Central

    2013-01-01

    Background Adiponectin, paradoxically reduced in obesity and with lower levels in African Americans (AA), modulates several cardiometabolic risk factors. Because abdominal visceral adipose tissue (VAT), known to be reduced in AA, and subcutaneous adipose tissue (SAT) compartments may confer differential metabolic risk profiles, we investigated the associations of VAT and SAT with serum adiponectin, separately by gender, with the hypothesis that VAT is more strongly inversely associated with adiponectin than SAT. Methods Participants from the Jackson Heart Study, an ongoing cohort of AA (n = 2,799; 64% women; mean age, 55 ± 11 years) underwent computer tomography assessment of SAT and VAT volumes, and had stored serum specimens analyzed for adiponectin levels. These levels were examined by gender in relation to increments of VAT and SAT. Results Compared to women, men had significantly lower mean levels of adiponectin (3.9 ± 3.0 μg/mL vs. 6.0 ± 4.4 μg/mL; p < 0.01) and mean volume of SAT (1,721 ± 803 cm3 vs. 2,668 ± 968 cm3; p < 0.01) but significantly higher mean volume of VAT (884 ± 416 cm3 vs. 801 ± 363 cm3; p < 0.01). Among women, a one standard deviation increment in VAT was inversely associated with adiponectin (β = − 0.13; p < 0.0001) after controlling for age, systolic blood pressure, fasting plasma glucose, high-density lipoprotein cholesterol, triglycerides, education, pack-years of smoking and daily intake of alcohol. The statistically significant inverse association of VAT and adiponectin persisted after additionally adjusting for SAT, body mass index (BMI) and waist circumference (WC), suggesting that VAT provides significant information above and beyond BMI and WC. Among men, after the same multivariable adjustment, there was a direct association of SAT and adiponectin (β = 0.18; p = 0.002) that persisted when controlling for BMI and WC, supporting a beneficial effect of

  5. 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

  6. 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

  7. Regulation of adiponectin receptor 1 in human hepatocytes by agonists of nuclear receptors

    SciTech Connect

    Neumeier, Markus; Weigert, Johanna; Schaeffler, Andreas; Weiss, Thomas; Kirchner, Stefan; Laberer, Sabine; Schoelmerich, Juergen; Buechler, Christa . E-mail: christa.buechler@klinik.uni-regensburg.de

    2005-09-02

    The adiponectin receptors AdipoR1 and AdipoR2 have been identified to mediate the insulin-sensitizing effects of adiponectin. Although AdipoR2 was suggested to be the main receptor for this adipokine in hepatocytes, AdipoR1 protein is highly abundant in primary human hepatocytes and hepatocytic cell lines. Nuclear receptors are main regulators of lipid metabolism and activation of peroxisome proliferator-activated receptor {alpha} and {gamma}, retinoid X receptor (RXR), and liver X receptor (LXR) by specific ligands may influence AdipoR1 abundance. AdipoR1 protein is neither altered by RXR or LXR agonists nor by pioglitazone. In contrast, fenofibric acid reduces AdipoR1 whereas hepatotoxic troglitazone upregulates AdipoR1 protein in HepG2 cells. Taken together this work shows for the first time that AdipoR1 protein is expressed in human hepatocytes but that it is not a direct target gene of nuclear receptors. Elevated AdipoR1 induced by hepatotoxic troglitazone may indicate a role of this receptor in adiponectin-mediated beneficial effects in liver damage.

  8. Cardioprotective effect of intermittent fasting is associated with an elevation of adiponectin levels in rats.

    PubMed

    Wan, Ruiqian; Ahmet, Ismayil; Brown, Martin; Cheng, Aiwu; Kamimura, Naomi; Talan, Mark; Mattson, Mark P

    2010-05-01

    It has been reported that dietary energy restriction, including intermittent fasting (IF), can protect heart and brain cells against injury and improve functional outcome in animal models of myocardial infarction (MI) and stroke. Here we report that IF improves glycemic control and protects the myocardium against ischemia-induced cell damage and inflammation in rats. Echocardiographic analysis of heart structural and functional variables revealed that IF attenuates the growth-related increase in posterior ventricular wall thickness, end systolic and diastolic volumes, and reduces the ejection fraction. The size of the ischemic infarct 24 h following permanent ligation of a coronary artery was significantly smaller, and markers of inflammation (infiltration of leukocytes in the area at risk and plasma IL-6 levels) were less, in IF rats compared to rats on the control diet. IF resulted in increased levels of circulating adiponectin prior to and after MI. Because recent studies have shown that adiponectin can protect the heart against ischemic injury, our findings suggest a potential role for adiponectin as a mediator of the cardioprotective effect of IF.

  9. 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

    2014-11-04

    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.

  10. Activation of autophagy by globular adiponectin is required for muscle differentiation.

    PubMed

    Gamberi, Tania; Modesti, Alessandra; Magherini, Francesca; D'Souza, Donna M; Hawke, Thomas; Fiaschi, Tania

    2016-04-01

    Regulated autophagy is a critical component for a healthy skeletal muscle mass, such that dysregulation of the autophagic processes correlates with severe myopathies. Thus, defining the biological molecules involved in the autophagic processes within skeletal muscle is of great importance. Here we demonstrate that globular adiponectin (gAd) activates autophagy in skeletal muscle myoblasts via an AMPK-dependent mechanism. Activation of autophagy through gAd promotes myoblast survival and apoptosis inhibition during serum starvation and the gAd-activated autophagy orchestrates the myogenic properties of the hormone. Consistent with this conclusion, inhibition of gAd-activated autophagy by both a pharmacological (chloroquine) or siRNA approach greatly inhibited muscle differentiation, as demonstrated by reductions in myosin heavy chain expression and myotube formation. Further support for the role of adiponectin in autophagy comes from the skeletal muscles of adiponectin KO mice which display decreased LC3 II expression and a myopathic phenotype (heterogeneous fiber sizes, numerous central nuclei). Overall, these findings demonstrate that gAd activates autophagy in myoblasts and that gAd-activated autophagy drives the myogenic properties of this hormone.

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

    PubMed Central

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

    2014-01-01

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

  12. Polymorphism of adiponectin (45T/G) and adiponectin receptor-2 (795G/A) in an Iranian population: relation with insulin resistance and response to treatment with pioglitazone in patients with type 2 diabetes mellitus.

    PubMed

    Namvaran, Fatemeh; Rahimi-Moghaddam, Parvaneh; Azarpira, Negar; Dabbaghmanesh, Mohammad Hosein

    2012-05-01

    Adiponectin, an adipose-derived plasma protein, is reduced in patients with obesity and type 2 diabetes. Thiazolidinediones can increase adiponectin levels and improve insulin sensitivity. This study investigated the associations between type 2 diabetes and two single-nucleotide polymorphisms in the adiponectin (45T/G) and adiponectin receptor-2 gene (795G/A), and investigated whether these genetic variants affect the response to pioglitazone in Iranian patients with type 2 diabetes. We genotyped 128 non-diabetic participants and 101 patients with type 2 diabetes for 45T/G and 795G/A with polymerase chain reaction-restriction fragment length polymorphism assays. Patients were treated with pioglitazone for 12 weeks, after which we compared laboratory parameters in these two groups. Fasting blood sugar differed significantly in individuals with different 795G/A genotypes after pioglitazone treatment (P = 0.009). The mean decrease in insulin/glucose ratio after treatment also differed significantly in individuals with different 45T/G genotypes (P = 0.035). The T allele frequency for 45T/G was 87.11% in controls versus 81.68% in patients (P = 0.071). The TG and GG genotypes were more frequent in patients (P = 0.032). The G allele frequency for 795G/A was 76.17% in controls versus 80.20% in patients (P = 0.179). 795G/A variants were not significantly different between patient and control group. The adiponectin gene 45T/G mutation may be an important determinant of type 2 diabetes in the Iranian population. However, adiponectin 45T/G and adiponectin receptor-2 795G/A polymorphisms were not significantly associated with the response to pioglitazone in our sample.

  13. Ethnicity Modifies the Relationships of Insulin Resistance, Inflammation, and Adiponectin With Obesity in a Multiethnic Asian Population

    PubMed Central

    Khoo, Chin Meng; Sairazi, Sarina; Taslim, Siska; Gardner, Daphne; Wu, Yi; Lee, Jeannette; van Dam, Rob M.; Shyong Tai, E.

    2011-01-01

    OBJECTIVE The development of obesity-related metabolic disorders varies with ethnicity. We examined whether ethnicity modifies the relationship between BMI and three metabolic pathways (insulin resistance, inflammation, and adiponectin) that are involved in the pathogenesis of diabetes and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS We analyzed data from 4,804 Chinese, Malay, and Asian-Indian residents of Singapore with complete data on insulin resistance (IR), C-reactive protein (CRP), and total adiponectin levels. Linear regression models with an interaction term ethnicity*BMI were used to evaluate whether ethnicity modifies the association between BMI and IR, CRP, and adiponectin. RESULTS In both uni- and multivariate analyses, BMI was directly associated with IR and CRP and inversely with adiponectin across all ethnic groups. When compared with Chinese and Malays, Asian-Indians had higher IR and CRP and lower adiponectin levels. The associations between BMI and its metabolic pathways were significantly stronger in Chinese than in other ethnic groups. The increase in IR and CRP and the decrease in adiponectin for each unit increase in BMI were greater in Chinese than in other ethnic groups. The findings were similar when waist circumference was used in the analyses instead of BMI. CONCLUSIONS The impact of BMI on IR, CRP, and adiponectin appears greater in Chinese as compared with other major Asian ethnic groups. This may partly explain the rapid increase in the prevalence of diabetes and CVD in Chinese populations and highlights the importance of weight management in Asian ethnic groups despite the apparently low levels of obesity. PMID:21464462

  14. Visceral Fat Area and Serum Adiponectin Level Predict the Development of Metabolic Syndrome in a Community-Based Asymptomatic Population

    PubMed Central

    Cho, Jae-Young; Lee, Seung Hun; Park, Jae Hyoung; Hong, Soon Jun; Yu, Cheol Woong; Lim, Do-Sun

    2017-01-01

    Background Although it has been demonstrated that visceral adipose tissue content and serum levels of adiponectin are associated with metabolic syndrome, their predictive potential for the development of metabolic syndrome remains to be elucidated. Methods We studied 1,130 participants of the Seoul Metabolic Syndrome cohort. A total of 337 subjects without metabolic syndrome underwent the follow-up evaluation and finally analyzed. Visceral fat area (VFA) was measured using dual bioelectrical impedance analysis. We compared the 1-year incidence rate of metabolic syndrome among four different groups: Group 1 (high adiponectin level and low VFA), Group 2 (low adiponectin level and low VFA), Group 3 (high adiponectin level and high VFA) and Group 4 (low adiponectin level and high VFA). Results Median follow-up duration was 17 months. Cut-off points of adiponectin level and VFA for metabolic syndrome were 7.34 ng/ml and 84 cm2 for men, and 12.55 and 58 cm2 ng/ml for women, respectively. The incidence of metabolic syndrome was the highest in Group 4 (Group 1; 16.47%, Group 2; 22.08%, Group 3; 25%, and Group 4; 46.15%, p<0.001). Adjusted logistic regression analyses for metabolic syndrome prediction demonstrated that Group 4 exhibited the highest odds ratio compared with Group 1 (4.918 [2.05–11.795]), which was predominantly affected by waist circumference and serum triglyceride levels. Notably, triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio was significantly higher in Group 4 (p = 0.017). Conclusion Incidence rate of metabolic syndrome was the highest in subjects with low serum adiponectin levels and high visceral fat area. Higher TG/HDL ratio in these subjects suggested insulin resistance may contribute to the development of metabolic syndrome. PMID:28046037

  15. Hypoxia-inducible Factor 1α Regulates a SOCS3-STAT3-Adiponectin Signal Transduction Pathway in Adipocytes*

    PubMed Central

    Jiang, Changtao; Kim, Jung-Hwan; Li, Fei; Qu, Aijuan; Gavrilova, Oksana; Shah, Yatrik M.; Gonzalez, Frank J.

    2013-01-01

    Obesity has been identified as a major risk factor for type 2 diabetes, characterized by insulin resistance in insulin target tissues. Hypoxia-inducible factor 1α (HIF1α) regulates pathways in energy metabolism that become dysregulated in obesity. Earlier studies revealed that HIF1α in adipose tissue is markedly elevated in high-fat diet-fed mice that are obese and insulin-resistant. Genetic ablation of HIF1α in adipose tissue decreased insulin resistance and obesity, accompanied by increased serum adiponectin levels. However, the exact mechanism whereby HIF1α regulates adiponectin remains unclear. Here, acriflavine (ACF), an inhibitor of HIF1α, induced the expression of adiponectin and reduced the expression of SOCS3 in cultured 3T3-L1 adipocytes. Mechanistic studies revealed that HIF1α suppressed the expression of adiponectin through a SOCS3-STAT3 pathway. Socs3 was identified as a novel HIF1α target gene based on chromatin immunoprecipitation and luciferase assays. STAT3 directly regulated adiponectin in vitro in cultured 3T3-L1 adipocytes. ACF was found to prevent diet-induced obesity and insulin resistance. In vivo, ACF also regulated the SOCS3-STAT3-adiponectin pathway, and inhibition of HIF1α in adipose tissue was essential for ACF to improve the SOCS3-STAT3-adiponectin pathway to counteract insulin resistance. This study provides evidence for a novel target gene and signal transduction pathway in adipocytes and indicates that inhibitors of HIF1α have potential utility for the treatment of obesity and type 2 diabetes. PMID:23255598

  16. Chronic effects of centrally administered adiponectin on appetite, metabolism and blood pressure regulation in normotensive and hypertensive rats.

    PubMed

    Bassi, Mirian; do Carmo, Jussara M; Hall, John E; da Silva, Alexandre A

    2012-09-01

    Acute studies suggest that adiponectin may reduce sympathetic activity and blood pressure (BP) via actions on the central nervous system (CNS). However, the chronic effects of adiponectin on energy expenditure and cardiovascular function are still poorly understood. We tested if chronic intracerebroventricular (ICV) infusion of adiponectin (1 or 7μg/day) in Sprague-Dawley rats fed a high fat diet (HFD) for 8 weeks and at the high dose (7μg/day) in spontaneously hypertensive rats (SHRs), a hypertensive model associated with sympathetic overactivity, evoked chronic reductions in BP and heart rate (HR). We also determined if chronic ICV adiponectin infusion alters appetite, whole body oxygen consumption (VO(2)), and insulin and leptin levels. Neither dose of adiponectin infused for 7 days significantly altered BP or HR in the HFD group (115±2 to 112±2mmHg and 384±6 to 379±6bpm at 1μg/day; 109±3 to 111±3mmHg and 366±5 and 367±5bpm at 7μg/day). The higher dose slightly reduced food intake (14±1 to 11±1g/day), whereas VO(2), insulin and leptin levels were not affected by the treatment. In SHRs, ICV adiponectin infusion reduced appetite (22±2 to 12±2g/day) and insulin levels (∼55%), but did not alter BP (162±4 to 164±3mmHg) or HR (312±5 to 322±8bpm). These results suggest that adiponectin, acting via its direct actions on the CNS, has a small effect to reduce appetite and insulin levels, but it has no long-term action to reduce BP or HR, or to alter whole body metabolic rate.

  17. CHRONIC EFFECTS OF CENTRALLY ADMINISTERED ADIPONECTIN ON APPETITE, METABOLISM AND BLOOD PRESSURE REGULATION IN NORMOTENSIVE AND HYPERTENSIVE RATS

    PubMed Central

    Bassi, Mirian; do Carmo, Jussara M.; Hall, John E.; da Silva, Alexandre A.

    2012-01-01

    Acute studies suggest that adiponectin may reduce sympathetic activity and blood pressure (BP) via actions on the central nervous system (CNS). However, the chronic effects of adiponectin on energy expenditure and cardiovascular function are still poorly understood. We tested if chronic intracerebroventricular (ICV) infusion of adiponectin (1 or 7 µg/day) in Sprague-Dawley rats fed a high fat diet (HFD) for 8 weeks and at the high dose (7 µg/day) in spontaneously hypertensive rats (SHR), a hypertensive model associated with sympathetic overactivity, evoked chronic reductions in BP and heart rate (HR). We also determined if chronic ICV adiponectin infusion alters appetite, whole body oxygen consumption (VO2), and insulin and leptin levels. Neither dose of adiponectin infused for 7 days significantly altered BP or HR in the HFD group (115±2 to 112±2 mmHg and 384±6 to 379±6 bpm at 1 µg/day; 109±3 to 111±3 mmHg and 366±5 and 367±5 bpm at 7µg/day). The higher dose slightly reduced food intake (14±1 to 11±1 g/day), whereas VO2, insulin and leptin levels were not affected by the treatment. In SHRs, ICV adiponectin infusion reduced appetite (22±2 to 12±2 g/day) and insulin levels (~55%), but did not alter BP (162±4 to 164±3 mmHg) or HR (312±5 to 322±8 bpm). These results suggest that adiponectin, acting via its direct actions on the CNS, has a small effect to reduce appetite and insulin levels, but it has no long-term action to reduce BP or HR, or to alter whole body metabolic rate. PMID:22749987

  18. 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

  19. 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

  20. The Impact of Full-Length, Trimeric and Globular Adiponectin on Lipolysis in Subcutaneous and Visceral Adipocytes of Obese and Non-Obese Women.

    PubMed

    Wedellova, Zuzana; Kovacova, Zuzana; Tencerova, Michaela; Vedral, Tomas; Rossmeislova, Lenka; Siklova-Vitkova, Michaela; Stich, Vladimir; Polak, Jan

    2013-01-01

    Contribution of individual adiponectin isoforms to lipolysis regulation remains unknown. We investigated the impact of full-length, trimeric and globular adiponectin isoforms on spontaneous lipolysis in subcutaneous abdominal (SCAAT) and visceral adipose tissues (VAT) of obese and non-obese subjects. Furthermore, we explored the role of AMPK (5'-AMP-activated protein kinase) in adiponectin-dependent lipolysis regulation and expression of adiponectin receptors type 1 and 2 (AdipoR1 and AdipoR2) in SCAAT and VAT. Primary adipocytes isolated from SCAAT and VAT of obese and non-obese women were incubated with 20 µg/ml of: A) full-length adiponectin (physiological mixture of all adiponectin isoforms), B) trimeric adiponectin isoform or C) globular adiponectin isoform. Glycerol released into media was used as a marker of lipolysis. While full-length adiponectin inhibited lipolysis by 22% in non-obese SCAAT, globular isoform inhibited lipolysis by 27% in obese SCAAT. No effect of either isoform was detected in non-obese VAT, however trimeric isoform inhibited lipolysis by 21% in obese VAT (all p<0.05). Trimeric isoform induced Thr172 p-AMPK in differentiated preadipocytes from a non-obese donor, while globular isoform induced Ser79 p-ACC by 32% (p<0.05) and Ser565 p-HSL by 52% (p = 0.08) in differentiated preadipocytes from an obese donor. AdipoR2 expression was 17% and 37% higher than AdipoR1 in SCAAT of obese and non-obese groups and by 23% higher in VAT of obese subjects (all p<0.05). In conclusion, the anti-lipolytic effect of adiponectin isoforms is modified with obesity: while full-length adiponectin exerts anti-lipolytic action in non-obese SCAAT, globular and trimeric isoforms show anti-lipolytic activity in obese SCAAT and VAT, respectively.

  1. 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

  2. Serum adiponectin in HIV-1 and hepatitis C virus mono- and co-infected Kenyan injection drug users

    PubMed Central

    Ndombi, Eric M; Budambula, Valentine; Webale, Mark K; Musumba, Francis O; Wesongah, Jesca O; Mibei, Erick; Ahmed, Aabid A; Lihana, Raphael; Were, Tom

    2015-01-01

    Adiponectin is an important marker of anthropometric profiles of adipose tissue. However, association of adiponectin and adiposity in HIV mono- and co-infected and hepatitis (HCV) injection drug users (IDUs) has not been elucidated. Therefore, the relationship of total adiponectin levels with anthropometric indices of adiposity was examined in HIV mono-infected (anti-retroviral treatment, ART-naive, n=16 and -experienced, n=34); HCV mono-infected, n=36; HIV and HCV co-infected (ART-naive, n=5 and -experienced, n=13); uninfected, n=19 IDUs; and healthy controls, n=16 from coastal Kenya. Anthropometric indices of adiposity were recorded and total circulating adiponectin levels were measured in serum samples using enzyme-linked immunosorbent assay. Adiponectin levels differed significantly amongst the study groups (P<0.0001). Post-hoc analyses revealed decreased levels in HIV mono-infected ART-naive IDUs in comparison to uninfected IDUs (P<0.05) and healthy controls (P<0.05). However, adiponectin levels were elevated in HCV mono-infected IDUs relative to HIV mono-infected ART-naive (P<0.001) and -experienced (P<0.001) as well as HIV and HCV co-infected ART-naive (P<0.05) IDUs. Furthermore, adiponectin correlated with weight (ρ=0.687; P=0.003) and BMI (ρ=0.598; P=0.014) in HIV mono-infected ART-naive IDUs; waist circumference (ρ=−0.626; P<0.0001), hip (ρ=−0.561; P=0.001) circumference, and bust-to-waist ratio (ρ=0.561; P=0.001) in HIV mono-infected ART-experienced IDUs; waist girth (ρ=0.375; P=0.024) in HCV mono-infected IDUs; and waist-to-hip ratio (ρ=−0.872; P=0.048) in HIV and HCV co-infected ART-naive IDUs. Altogether, these results suggest suppression of adiponectin production in treatment-naive HIV mono-infected IDUs and that circulating adiponectin is a useful surrogate marker of altered adiposity in treatment-naive and -experienced HIV and HCV mono- and co-infected IDUs. PMID:26306727

  3. Cut-Off Value of Total Adiponectin for Managing Risk of Developing Metabolic Syndrome in Male Japanese Workers

    PubMed Central

    Hata, Akiko; Yonemoto, Koji; Shikama, Yosuke; Aki, Nanako; Kosugi, Chisato; Tamura, Ayako; Ichihara, Takako; Minagawa, Takako; Kuwamura, Yumi; Miyoshi, Masashi; Nakao, Takayuki; Funaki, Makoto

    2015-01-01

    Aim To determine the optimal cut-off value of serum total adiponectin for managing the risk of developing metabolic syndrome (MetS) in male Japanese workers. Methods A total of 365 subjects without MetS aged 20–60 years were followed up prospectively for a mean of 3.1 years. The accelerated failure-time model was used to estimate time ratio (TR) and cut-off value for developing MetS. Results During follow-up, 45 subjects developed MetS. Age-adjusted TR significantly declined with decreasing total adiponectin level (≤ 4.9, 5.0–6.6, 6.7–8.8 and ≥ 8.9 μg/ml, P for trend = 0.003). In multivariate analyses, TR of MetS was 0.12 (95% CI 0.02–0.78; P = 0.03) in subjects with total adiponectin level of 5.0–6.6 μg/ml, and 0.15 (95% CI 0.02–0.97; P = 0.047) in subjects with total adiponectin level ≤ 4.9 μg/ml compared with those with total adiponectin level ≥ 8.9 μg/ml. The accelerated failure-time model showed that the optimal cut-off value of total adiponectin for managing the risk of developing MetS was 6.2 μg/ml. In the multivariate-adjusted model, the mean time to the development of MetS was 78% shorter for total adiponectin level ≤ 6.2 μg/ml compared with > 6.2 μg/ml (TR 0.22, 95% CI: 0.08–0.64, P = 0.005). Conclusion Our findings suggest that the cut-off value for managing the risk of developing MetS is 6.2 μg/ml in male Japanese workers. Subjects with total adiponectin level ≤ 6.2 μg/ml developed MetS more rapidly than did those with total adiponectin level > 6.2 μg/ml. PMID:25705909

  4. Adipose tissue hormones and appetite and body weight regulators in insulin resistance.

    PubMed

    Koleva, Daniela Iv; Orbetzova, Maria M; Atanassova, Pepa K

    2013-01-01

    Impaired sensitivity to insulin (the so called insulin resistance, IR) occurs in a number of genetic and acquired conditions, including obesity, non-insulin dependent diabetes mellitus, polycystic ovary syndrome (PCOS) and metabolic syndrome (MS). In this review we discuss the correlation between IR, the adipose tissue hormones and appetite and body weight regulators. Leptin acts as a major adipostat: it suppresses food intake and activates catabolic pathways associated with increased energy production. It improves the peripheral insulin sensitivity and affects beta-cell function. Adiponectin is the only adipocytokine discovered so far that has anti-atherogenic properties. There is a reverse correlation between the serum adiponectin levels and the degree of obesity, IR, impaired glucose tolerance, dyslipidemia and atherosclerosis. Ghrelin stimulates food intake; of all circulating orexigenic hormones ghrelin is the most thoroughly studied. Ghrelin levels are decreased in MS and PCOS patients as this hormone is negatively correlated with body mass. Resistin is a hormone secreted by adipose tissues; a growing body of evidence suggests that it might be implicated in the link between obesity and diabetes. It has been found that the hormone's levels are significantly higher in obese people than those in normal body mass people. The recently discovered adipose tissue hormones, vaspin, visfatin, omentin-1 and their effect on IR development, have been increasingly researched.

  5. Adiponectin Regulates the Polarization and Function of Microglia via PPAR-γ Signaling Under Amyloid β Toxicity

    PubMed Central

    Song, Juhyun; Choi, Seong-Min; Kim, Byeong C.

    2017-01-01

    Alzheimer’s disease (AD), characterized by the abnormal accumulation of amyloid beta (Aβ), is gradually increasing globally. Given that AD is considered a neuroinflammatory disease, recent studies have focused on the cellular mechanisms in brain inflammatory conditions that underlie AD neuropathology. Microglia are macrophage cells in the central nervous system (CNS) that are activated in response to Aβ condition. The function of microglia contributes to the neuroinflammation in AD brain, suggesting that microglia regulate the production of inflammatory mediators and contribute to the regeneration of damaged tissues. Adiponectin, an adipokine derived from adipose tissue, has been known to regulate inflammation and control macrophages during oxidative stress conditions. In present study, we investigated whether adiponectin influences the polarization and function of microglia under Aβ toxicity by examining alterations of BV2 microglia function and polarization by Acrp30 (a globular form of adiponectin) treatment using reverse transcription PCR, western blotting and immunofluorescence staining. Acrp30 promoted the induction of the M2 phenotype, and regulated the inflammatory responses through peroxisome proliferator-activated receptor (PPAR)-γ signaling under Aβ toxicity. In addition, Acrp30 boosted the capacity of Aβ scavenging in microglia. Taken together, we suggest that adiponectin may control the function of microglia by promoting anti-inflammatory responses through PPAR- γ signaling. Hence, we conclude that adiponectin may act as a critical controller of microglia function in the AD brain. PMID:28326017

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

    PubMed Central

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

    2012-01-01

    Objectives To 1) determine whether perinatal factors (including maternal anthropometry and nutrition and early life growth measures) are associated with adiponectin and leptin levels in 9-year-old children, and 2) assess relationships between adiponectin, leptin and concurrent lipid profile in these children. Methods We measured plasma adiponectin and leptin for 146 mother - 9-year-old child pairs from the ongoing longitudinal birth cohort followed by the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). Data on perinatal factors, including sociodemographics, maternal anthropometry and nutrition, and early life child growth were collected during pregnancy, birth and 6-month visits. Results Greater rate of weight and length gain during the first 6 months of life were associated with lower adiponectin in 9-year-olds (β=−2.0, P=0.04; β=−8.2, P=0.02, respectively) adjusting for child BMI. We found no associations between child adipokine levels and either maternal calorie, protein, total fat, saturated fat, fiber, sugar-sweetened beverage consumption during pregnancy or children’s concurrent sugar-sweetened beverage and fast food intake. Lipid profile in 9-year-old children closely reflected adiponectin but not leptin levels after adjustment for child BMI. Additionally, we report that child adipokine levels were closely related to their mothers’ levels at the 9-year-visit. Conclusion Overall, our results support the hypothesis that early life factors may contribute to altered adipokine levels in children. PMID:23325579

  7. Retinol-binding protein 7 is an endothelium-specific PPARγ cofactor mediating an antioxidant response through adiponectin

    PubMed Central

    Hu, Chunyan; Keen, Henry L.; Lu, Ko-Ting; Liu, Xuebo; Davis, Deborah R.; Ibeawuchi, Stella-Rita C.; Vogel, Silke; Quelle, Frederick W.; Sigmund, Curt D.

    2017-01-01

    Impaired PPARγ activity in endothelial cells causes oxidative stress and endothelial dysfunction which causes a predisposition to hypertension, but the identity of key PPARγ target genes that protect the endothelium remain unclear. Retinol-binding protein 7 (RBP7) is a PPARγ target gene that is essentially endothelium specific. Whereas RBP7-deficient mice exhibit normal endothelial function at baseline, they exhibit severe endothelial dysfunction in response to cardiovascular stressors, including high-fat diet and subpressor angiotensin II. Endothelial dysfunction was not due to differences in weight gain, impaired glucose homeostasis, or hepatosteatosis, but occurred through an oxidative stress–dependent mechanism which can be rescued by scavengers of superoxide. RNA sequencing revealed that RBP7 was required to mediate induction of a subset of PPARγ target genes by rosiglitazone in the endothelium including adiponectin. Adiponectin was selectively induced in the endothelium of control mice by high-fat diet and rosiglitazone, whereas RBP7 deficiency abolished this induction. Adiponectin inhibition caused endothelial dysfunction in control vessels, whereas adiponectin treatment of RBP7-deficient vessels improved endothelium-dependent relaxation and reduced oxidative stress. We conclude that RBP7 is required to mediate the protective effects of PPARγ in the endothelium through adiponectin, and RBP7 is an endothelium-specific PPARγ target and regulator of PPARγ activity. PMID:28352663

  8. Adiponectin inhibits neutrophil apoptosis via activation of AMP kinase, PKB and ERK 1/2 MAP kinase.

    PubMed

    Rossi, Alessandra; Lord, Janet M

    2013-12-01

    Neutrophils are abundant, short-lived leukocytes that play a key role in the immune defense against microbial infections. These cells die by apoptosis following activation and uptake of microbes and will also enter apoptosis spontaneously at the end of their lifespan if they do not encounter a pathogen. Adiponectin exerts anti-inflammatory effects on neutrophil antimicrobial functions, but whether this abundant adipokine influences neutrophil apoptosis is unknown. Here we report that adiponectin in the physiological range (1-10 μg/ml) reduced apoptosis in resting neutrophils, decreasing caspase-3 cleavage and maintaining Mcl-1 expression by stabilizing this anti-apoptotic protein. We show that adiponectin induced phosphorylation of AMP-activated kinase (AMPK), protein kinase B (PKB), extracellular signal-regulated kinase (ERK 1/2) and p38 mitogen activated protein kinase (MAPK). Pharmacological inhibition of AMPK, PKB and ERK 1/2 ablated the pro-survival effects of adiponectin and treatment of neutrophils with an AMPK specific activator (AICAR) and AMPK inhibitor (compound C) respectively decreased and increased apoptosis. Finally, activation of AMPK by AICAR or adiponectin also decreased ceramide accumulation in the neutrophil cell membrane, a process involved in the early stages of spontaneous apoptosis, giving another possible mechanism downstream of AMPK activation for the inhibition of neutrophil apoptosis.

  9. 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.

  10. Pro-insulin, C peptide, glucagon, adiponectin, TNF alpha, AMPK: neglected players in type 2 diabetes mellitus.

    PubMed

    Lele, R D

    2010-01-01

    This article emphasizes (1) the utility of routine measurement of pro-insulin to insulin ratio as a specific marker of insulin resistance and predictor of future T2DM, HT and CAD, (2) routine C-Peptide estimation to determine which T2DM needs insulin and to monitor the effect of newer drugs which promote beta cell regeneration, (3) routine estimation of adiponectin and TNF alpha and monitor response to thiozolidine drugs which increases adiponectin and decreases TNF alpha production by adipocytes, (4) crucial role of AMPK--Cellular energy sensor in mediating the beneficial effects of exercise as well as drugs (adiponectin, metformin) in T2DM, (5) Availability of glucogon suppressors will eliminate the need for giving insulin to T2 DM with normal C Pepetide levels which inevitably causes undesirable weight gain & hypoglycemia.

  11. 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.

  12. In contrast to matrix metalloproteinases, serum adiponectin concentrations increase after radioiodine treatment of thyrotoxicosis

    PubMed Central

    2012-01-01

    Background Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), remodel extracellular matrix under physiological and pathological conditions and are implicated in pathogenesis of cardiovascular diseases, cancer and in chronic inflammation. We have endeavoured to assess whether concentrations of MMPs, TIMPs, and anti-inflammatory adiponectin are altered by pharmacological treatment of acute thyrotoxicosis or by radioiodine therapy (RIT). Material and methods We measured serum concentrations of MMP-2, MM