Higher Serum Visfatin Research Articles

The Association between Visfatin as A Marker of Isolated Coronary Ectasia and Its Severity: A Cross-Sectional study

Abstract Aim and objectives to assess the association between Visfatin level-as an independent marker -and the presence of coronary artery ectasia in patients undergoing diagnostic coronary angiography. Patients and Methods A total of 90 participants were recruited from candidates undergoing diagnostic coronary angiography in the Cath lab of Cardiology Department at Ain Shams University. They were then divided into three groups. The first group included individuals with normal coronaries, the second patients with coronary artery disease (CAD) without ectasia, and the third is patients with isolated coronary artery ectasia (CAE). After history taking, they all underwent biochemical tests for serum Visfatin, HBA1C%, serum creatinine and CRP. Univariate and correlation analysis was done. Results regarding demographic and clinical characteristics of our study population, we found that only higher age and being a smoker was significantly associated with the presence of ectasia. High level of serum Visfatin was strongly significantly associated with the presence of ectasia. Serum creatinine and CRP displayed a similar pattern. Moreover, we found that the mean level of serum Visfatin increases with the severity of ectasia according to Markis classification. Finally, Roc showed that a cut- off value of > 34 ng/ml demonstrated a sensitivity of 89% and a specificity of 87% of predicting CAE. Conclusion high serum Visfatin level is significantly associated with the presence of coronary artery ectasia. Also, it is positively correlated with its severity according to Markis classification. Hence, it can be a valuable predictor of CAE.

Comparison of Serum Visfatin Levels in Post-Menopausal Pakistani Women with and Without Breast Carcinoma

Objective: To compare serum Visfatin levels in Pakistani post-menopausal women having breast carcinoma with healthy women. Study Design: Comparative cross-sectional study. Place and Duration of Study: Physiology Department, Army Medical College, in collaboration with Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from Dec 2019 to Dec 2020. Methodology: Eighty post-menopausal Pakistani women were included, out of which forty women were post-menopausal newly diagnosed and histologically confirmed cases of breast carcinoma awaiting their treatment. Menopause was confirmed through interviews and relevant history. Serum Visfatin levels were determined using an enzyme-linked immunosorbent assay (ELISA). Result: Mean serum Visfatin levels were significantly higher in the Breast Carcinoma-Group (28.14±8.17 ng/ml) compared to the Healthy Control-Group (13.64±1.07 ng/ml). Moreover, serum Visfatin levels correlated positively with weight (r=0.735), body mass index (r=0.678), waist circumference(r=0.295) and waist-to-hip ratio (r=0.220). Conclusion: Serum Visfatin levels were markedly elevated in post-menopausal women with breast carcinoma as compared toHealthy Controls. Higher serum Visfatin may be regarded as a potential risk factor in the development of breast carcinoma.

Pre-procedural high serum visfatin and tumor necrosis factor-α might predict recurrent atrial fibrillation after catheter ablation

BackgroundMany patients would require repeated ablation procedures owing to recurrent atrial fibrillation with its associated symptoms. Identifying those who are at risk of recurrent AF could assist us to develop preventive strategies and to properly select those who will benefit more from catheter ablation. Our aim is to study the role of preprocedural serum level of certain biomarkers in the prediction of AF recurrence after catheter ablation.ResultsThe present study included 117 patients: 26 patients with persistent and 91 patients with paroxysmal AF. Blood samples for estimation of serum levels of studied cytokines were obtained prior to the procedure. Pulmonary vein isolation was performed in all patients through point-by point radiofrequency ablation guided by 3D electroanatomical mapping system. Patients were followed for 12 months for AF recurrence. Forty-one (35%) patients developed AF recurrence. Those patients were significantly older, had significantly higher BMI, lower ejection fraction, and wider maximal left atrial diameter (LAD). Serum hs-CRP, IL-6, TNF-α, visfatin, and adiponectin levels were significantly higher compared to those who did not develop AF recurrence. Correlation analysis showed positive correlations between the incidence of RAF and patients’ age, BMI, and maximum LAD and elevated cytokine levels and maximal LAD showed significant correlations with the type of AF and elevated serum TNF-α, visfatin, and adiponectin. Statistical analyses defined elevated serum levels of TNF-α, visfatin, and adiponectin as positive predictors for RAF, and automatic linear modeling analysis showed that elevated serum visfatin, TNF-α, and adiponectin can predict RAF by accuracy rates of 50%, 34%, and 16%, respectively.ConclusionsRAF is most probably an outcome of the interplay between patients' clinical data, obesity, and inflammation. Pre-procedural estimation of serum levels of visfatin and TNF-α might determine patients with probability for RAF.

Relationship Between Visfatin Level and Cardiovascular Changes in Hemodialysis Patients.

Background: Cardiovascular alterations include atherosclerosis, calcification, heart failure, diastolic and systolic dysfunction, and stroke are a primary cause of mortality in people with CKD and ESRD. Individuals with CKD have been demonstrated to have increased serum levels of visfatin. A new study suggests that high visfatin levels in individuals with chronic kidney disease accurately predict cardiovascular abnormalities. Chronic renal failure, atherosclerosis, and calcification in the carotid arteries vary in individuals. The researchers set out to look at correlation of visfatin level and cardiovascular abnormalities in CKD patients. In this case-control comparative study, conventional Echocardiogram and carotid duplex assessment were used to evaluate the differences between 40 patients with stage III or stage IV CKD receiving conservative treatment, 40 ESRD patients receiving regular hemodialysis, and 20 subjects as a control group. Results: Hemodialysis-dependent Carotid atherosclerosis, systolic and diastolic dysfunction, and calcifications are more common in ESRD patients compared to non-hemodialysis-dependent individuals that significantly correlated with high serum Visfatin levels compared to healthy control participants. Carotid atherosclerosis, diastolic dysfunction, and systolic dysfunction are all more likely to occur in those with CKD who had increased CIMT p-value (0.036) of carotid doppler, decreased EF % p-value (0.032), increased LVMI p-value (0.004) and reversed E/A ratio p-value (0.003) demonstrated by Echocardiographic and carotid Doppler assessment. Patients with an elevated visfatin level had increased cardiovascular morbidity and mortality and atherosclerosis of the carotid arteries with a high risk of ischemic stroke.

Correlation of Serum Visfatin Level in Non-obese Women with Polycystic Ovary Syndrome and Matched Control.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy affecting reproductive-age women. Visfatin, an adipocytokine, and insulin resistance (IR) marker in diabetes since PCOS and diabetes share insulin resistance as an etiological factor, this study aimed to investigate visfatin as a predictive marker for IR and hyperandrogenemia in non-obese PCOS women and test its correlation to other parameters. A cross-sectional study conducted at the University Hospital recruited 140 women, divided into two groups. Group I (70/140, study group) was PCOS patients' diagnosis based on 2003 Rotterdam criteria and Group II (70/140, healthy controls). Both were aged, and body mass index (BMI) matched. After a detailed history and general examination, the clinical, demographic, biochemical, hormonal, and metabolic parameters were taken for comparison's sake. PCOS patients were subdivided according to the clinical or hormonal evidence of hyperandrogenemia into two groups: those with hyperandrogenemia and those without. Higher serum visfatin was estimated in the PCOS group (4.4 ± 1.7) versus healthy controls (3.1 ± 0.7) ng/mL, P < 0.0001. Significantly higher visfatin was confirmed in hyperandrogenic PCOS versus non-hyperandrogenic PCOS women (5.69 ± 1.1 vs. 2.76 ± 0.51ng/mL). A strong correlation was found between visfatin versus hemoglobin A1c and free androgen index (FAI); r = 0.784 and 0.624, respectively. BMI and free testosterone scored a modest correlation. BMI centiles' correlation with serum visfatin revealed no significant effect on serum visfatin, P = 0.62. The ROC calculated visfatin cut-off value; 4.34ng/mL with 51.4% sensitivity and 100% specificity, and a P-value < 0.001 in discriminating PCOS cases. In conclusion, a strong positive correlation of visfatin with insulin resistance, followed by FAI in PCOS cases irrespective of BMI, suggests the intimate relation of visfatin in PCOS pathophysiology among non-obese women. Further research is warranted to explore this association's therapeutic and prognostic value.

Serum visfatin as a metabolic biomarker in obese patients with gestational diabetes mellitus.

Visfatin is an adipokine produced and secreted by the adipose tissue. It exerts an insulin-like effect by the insulin receptor-1 and has a hypoglycemic effect. We aimed to investigate how serum visfatin changes in women with gestational diabetes mellitus (GDM), and whether it is predictive of neonatal outcomes. Visfatin levels were prospectively measured in peripheral blood serum by enzyme immunoassay in 210 pregnant women, 156 of which were diagnosed with GDM, 18 of which suffered from pregnancy-induced hypertension (PIH) and 36 healthy controls. Patients with obesity class II (median=2.562 ng/mL) and class III (median=6.2940 ng/mL) had higher serum visfatin than overweight patients (median=0.735 ng/mL); (Mann-Whitney U test, P=0.037 and P=0.023, respectively). In GDM patients with BMI above 30, serum visfatin was associated to glycosylated hemoglobin (Spearman correlation test, R=0.26, P=0.045). Women with BMI above 25 treated with insulin had lower serum visfatin levels than those treated with diet only (Mann-Whitney U test, P=0.045). No correlation was found between visfatin and parameters of lipid profile such as HDL, LDL, or triglycerides (Spearman correlation tests, R=-0.051, -0.1, 0.0019; P=0.54, 0.29, 0.98, respectively). We observed that visfatin was not associated with birth weight (Spearman correlation test, R=-0.014, P=0.86) or adverse neonatal outcome as measured by umbilical artery pH below 7.25 (Mann-Whitney U test, P=0.55) or Apgar score below 10 (Mann-Whitney U test, P=0.21). In GDM patients with higher BMI, serum visfatin was elevated, correlated positively with glycosylated hemoglobin, and decreased upon treatment with insulin therapy.

SERUM VISFATIN RELATIONSHIP WITH GLYCEMIC CONTROL AND ADIPOSITY INDICES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

OBJECTIVE: To assess and compare serum visfatin levels with body composition adiposity indices and glycemic control in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: This observational case-control study was conducted at the Department of Physiology, College of Medicine and King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia from April 2018 to March 2019. We studied sixty three individuals (33 T2DM and 30 controls) who were recruited from diabetes care clinics. Anthropometric, demographic and clinical characteristics were recorded from all participants and they were matched for age and gender. Venous blood samples were collected to measure visfatin and glycosylated hemoglobin (HbA1c). Adiposity indices were analyzed by Bio Impedance Analyzer (BIA). RESULTS: Serum visfatin levels were 7.01±3.79 ng/ml in subjects with T2DM and 4.02±2.74 ng/ml in healthy subjects (p=0.046). Body composition indices including BMI, BMR, body fat percentage [BF%], body fat mass [BFM], truncal fat [TF], truncal fat mass [TFM] and visceral fat [VF] differences were not statistically significant between two groups. Serum visfatin levels were 9.29±3.44 ng/ml in T2DM with poor glycemic control (HbA1c >7.5%) as compared to 4.24±1.87 ng/ml in diabetic patients with good glycemic control (HbA1c <7.5%) [p=0.001]. Visfatin positively correlated with BMI (r=0.284, p<0.05), BF% (r=0.302, p<0.05), BFM (r=0.280, p<0.05), VF (r=0.263, p<0.05) and HbA1c (r=0.394, p<0.01). CONCLUSION: The results of this study show that T2DM patients have high serum visfatin levels. Moreover, higher levels of visfatin are observed with poor glycemic control and increasing body adiposity indices.

Placental expressions and serum levels of adiponectin, visfatin, and omentin in GDM.

Adiponectin, visfatin, and omentin have been shown to be associated with insulin sensitivity and might have a role in the pathophysiology of gestational diabetes mellitus (GDM). This study aimed to (1) compare adiponectin, visfatin, and omentin mRNA expressions in placenta and their serum levels between normal pregnancy (NP) and GDM class A1 (GDMA1) pregnancy and (2) determine correlations between placental gene expressions as well as serum levels with maternal and neonatal clinical parameters in all, NP, and GDM subjects. NP subjects (n = 37), who had normal medical history during their pregnancies without diagnosis of any abnormalities and GDMA1 subjects (n = 37), who were diagnosed since they had antenatal care, were recruited when they were in labor with a gestational age of at least 34weeks. Clinical parameters and serum adiponectin, visfatin, and omentin levels were measured in the delivery room. GDMA1 subjects had higher serum visfatin and plasma glucose levels, but lower serum omentin levels (p <0.05 all) compared to controls, with comparable levels of placental adiponectin, visfatin, and omentin expressions, plasma insulin, and indices of insulin sensitivity and insulin resistance. Serum visfatin was negatively correlated with neonatal weight and length in the GDM group (p <0.05 all). Serum omentin was negatively correlated with pre-pregnancy body mass index and waist circumference only in the NP group (p <0.05 all). Serum adiponectin was negatively correlated with maternal age and HOMA-IR in the NP group (p <0.05 all) and with placental weight and serum omentin in the GDM group (p <0.05 all). In conclusion, in GDMA1, increased serum visfatin, which has insulin-mimetic effect, might be associated with a compensatory mechanism that improves the impaired insulin function. Decreased serum omentin in GDMA1, which is normally found in visceral obesity, might lead to insulin resistance and contribute to the pathophysiology of GDM.

Extracellular Visfatin-Promoted Malignant Behavior in Breast Cancer Is Mediated Through c-Abl and STAT3 Activation.

Visfatin is an adipocytokine involved in cellular metabolism, inflammation, and cancer. This study investigated the roles of extracellular visfatin in breast cancer, and explored underlying mechanisms in clinical and experimental settings. Associations of serum visfatin with clinicopathologic characteristics and patient survival were assessed with Cox regression models and Kaplan-Meier analyses. Effects of extracellular visfatin on cultured breast cancer cells were examined, followed by in vivo investigation of tumor growth and metastasis in xenograft animal models. Imatinib and Stattic were used to inhibit c-Abl and STAT3 activation, respectively. Breast cancer patients with high serum visfatin levels were associated with advanced tumor stage, increased tumor size and lymph node metastasis, and poor survival. Elevated phosphorylation of c-Abl and STAT3 in breast tumor tissues were correlated with high serum visfatin levels in patients. Visfatin-promoted in vitro cell viability and metastatic capability were suppressed by imatinib (c-Abl inhibitor) and Stattic (STAT3 inhibitor). Increased in vivo cell invasiveness was observed in zebrafish xenografted with visfatin-pretreated breast cancer cells. Tumor growth and lung metastasis occurred in visfatin-administered mice xenografted with breast cancer cells. Tail vein-injected mice with visfatin-pretreated breast cancer cells showed increased lung metastasis, which was suppressed by imatinib. Serum visfatin levels in breast cancer patients reveal potential prognostic values, and our findings that visfatin promoted breast cancer through activation of c-Abl and STAT3 may provide an important molecular basis for future design of targeted therapies that take into account different serum visfatin levels in breast cancer. Clin Cancer Res; 22(17); 4478-90. ©2016 AACR.

Expression of serum visfatin in 58 patients with hepatocellular carcinoma and its effects on long time survival

Objective To explore the expression and significance of serum visfatin level in patients with hepatocellular carcinoma(HCC). Methods A total of 58 patients with primary HCC were collected. The gender, age and body mass index (BMI), matched healthy individuals were also collected. Serum were obtained for visfatin, pre-albumin and high sensitivity C-reaction protein (hs-CRP) detecting. Condition of nutrition was also evaluated. According to low, normal and high BMI (<18.5, 18.5 to 23.9, 24.0 to 27.9 kg/m2), patients with HCC were further divided. Non normal distribution of measurement data was indicated by median(interquartile range)[M(QR)]. Mann-Whitney U test and Kruskal-Wallis H test were performed for comparison between groups. Spearman correlation analysis was used for correlation analysis between visfatin and various factors. Cox regression analysis was used for analysis the risk factors of death. Results Serum visfatin level of HCC group was significantly higher than that of control group (127.65(200.66) μg/L vs 9.32(9.02) μg/L, U=-7.706, P<0.01). There was no significant difference in the visfatin level of HCC group between male and female patients (125.49(122.08) μg/L vs 133.64(212.20) μg/L, U=-1.432, P=0.152). Visfatin level of HCC group with low BMI, normal BMI and high BMI gradually increased (11.01(7.08) μg/L, 135.28(80.06) μg/L and 253.04(73.29) μg/L, H=42.034, P<0.01). There was no significant difference in serum visfatin between normal nutrition group and poor nutrition group of HCC patients (130.65(132.71) μg/L vs 118.76(160.30) μg/L, U=-0.960, P=0.337). Visfatin levels of HCC group with TNM stage Ⅰ to Ⅵ were 10.46(5.12) μg/L; 67.29(55.54) μg/L, 135.90(140.32) μg/L and 261.73(151.28) μg/L, respectively. Therein stage Ⅱ、Ⅲ and Ⅳ were significant highly than that of control group (U=-4.808、-7.221、-4.440, all P<0.01). When excluded form the effect of BMI, the increasing visfatin level was still correlated with TNM stage of HCC (r=0.735, P<0.01). In HCC group, the visfatin level was positively correlated with age, sex, BMI, waist/hip ratio, body fat content and hs-CRP (r=0.545, 0.133, 0.738, 0.495, 0.514 and 0.766, all P<0.05), and was negatively correlated with pre-albumin (r=-0.270, P=0.040). The mean follow-up time was 421 days, and 23 cases were dead. High serum visfatin level (relative risk (RR)=2.016, 95% confidence interval (CI) 1.159-2.932, P=0.002) and TNM stage (RR=2.181, 95%CI 1.342-3.674, P=0.001) were independent risk factors of patient death prediction. Conclusions The increasing serum visfatin level of HCC patients is correlated with nutrition status and TNM stage. High serum visfatin level is an independent risk factor of patient death prediction. Key words: Visfatin; Nutrition assessment; Liver neoplasms; Survival analysis

Abstract 434: Circulating visfatin promotes malignant cancer behavior through activation of STAT3 signaling in breast cancer

Abstract Adipocytokines are adipocyte-derived hormones which have been shown potentially associated with carcinogenesis. In this study, the role of circulating visfatin, a recently discovered adipocytokine involving in breast cancer progression, was investigated. Our data showed that the levels of serum visfatin in breast cancer patients were closely correlated with several clinicopathological characteristics including tumor stages, tumor size, and lymph node (LN) metastasis. In addition, differential association of disease recurrence and patients survival with hormone receptors such as estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (Her2/Neu) were observed. Patients with high serum visfatin, especially in combination with ER- status, showed the lowest survival rate. Furthermore, high serum visfatin patients had a lower recurrence risk and better patient survival after adjuvant hormone therapy. Notably, serum visfatin was positively associated with STAT3 activation through tyrosine phosphorylation in breast cancer tissues. In agreement with the clinical observation, our in vitro data revealed that breast cancer cells treated with visfatin not only enhanced cell proliferation but also activated STAT3 and its upstream regulator, JAK1. Moreover, inhibition of STAT3 resulted in the reduced cell proliferation and invasive ability of breast cancer cells. In conclusion, we propose that high levels of circulating visfatin, probably via activation of STAT3 signaling pathway, lead to a malignant cancer progression and poor survival of breast cancer patients. Therefore, the visfatin/STAT3 pathway may constitute a valuable prognostic system for breast cancer patients. In addition, interference of the visfatin/STAT3 signaling may represent a novel therapeutic potential in the treatment of breast cancer. Table 1. Univariate and multivariable analysis of overall survival for breast cancerVariablesItemUnivariateMultivariable†Hazard Rate Ratio95% Confidence intervalP valueHazard Rate Ratio95% Confidence intervalP valueTumor size (cm)&amp;gt;54.36(1.69,11.27)0.0022.13(0.79,5.74)0.1362-52.47(1.05,5.81)0.0391.68(0.70,4.05)0.245&amp;lt;21.001.00LN Metastasis≥23.34(1.75,6.37)&amp;lt;0.0012.43(1.25,4.72)0.0090-11.001.00GradeIII2.47(0.81,7.53)0.112---II1.56(0.53,4.55)0.419--I1.00-Age(y)&amp;gt;501.49(0.81,2.73)0.197---≤501.00-BMI(kg/m2)&amp;lt;241.14(0.60,2.14)0.690---≥241.00-Her2/NeuPositive1.14(0.60,2.17)0.699---Negative1.00-RadiotherapyYes1.11(0.60,2.03)0.744---No1.00-ChemotherapyYes0.89(0.41,1.93)0.774---No1.00-HormoneTherapyYes0.36(0.20,0.66)0.0010.46(0.24,0.87)0.017No1.001.00VisfatinHigh5.67(2.01,15.98)0.0013.55(1.22,10.36)0.020Low1.001.00† Variables with P values greater than 0.10 in the univariate analysis were excluded from multivariable analysis. Citation Format: Shyng-Shiou F. Yuan, Amos C. Hung, Ming-Feng Hou. Circulating visfatin promotes malignant cancer behavior through activation of STAT3 signaling in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 434. doi:10.1158/1538-7445.AM2014-434

Increased serum visfatin as a risk factor for atherosclerosis in patients with ischaemic cerebrovascular disease.

The present study aimed to investigate the possible associations between serum levels of visfatin, an adipokine, and atherosclerosis in patients with ischaemic cerebrovascular disease. A total of 95 participants were recruited for this study. Group A comprised 35 individuals with no history of cerebrovascular disease (control group) and Group B comprised 60 patients with ischaemic cerebrovascular disease. Group B was further categorised into two subgroups based on the ultrasonographic findings of the common carotid artery intima‑media thickness (CCA‑IMT) - Group B1 consisted of 21 patients with no atherosclerosis (i.e. CCA‑IMT ≤ 0.9 mm) and Group B2 consisted of 39 patients with atherosclerosis (i.e. CCA‑IMT > 0.9 mm). The body mass index, fasting blood total cholesterol, triglycerides, high‑density lipoprotein cholesterol, low‑density lipoprotein cholesterol and glucose levels of each patient were measured. Serum visfatin levels were determined using enzyme‑linked immunosorbent assays. Visfatin levels were compared between groups, and stepwise logistic regression analysis was used to identify risk factors for atherosclerosis, including visfatin levels. The mean serum visfatin level of the patients in Group B was higher than that in Group A (75.5 ± 77.80 ng/mL vs. 8.6 ± 4.69 ng/mL; p < 0.05) and the level was higher in patients from Group B2 than those from Group B1 (89.0 ± 80.68 ng/mL vs. 50.4 ± 72.44 ng/mL; p < 0.05). Multivariate regression analysis showed that CCA‑IMT values were not significantly associated with visfatin levels. However, logistic regression analysis showed that serum visfatin was an independent risk factor for atherosclerosis (odds ratio 37.80; p = 0.004). Serum visfatin may be an independent risk factor for cerebral infarction, as high serum visfatin levels are positively associated with the underlying pathogenic mechanisms of ischaemic cerebrovascular disease.

Preoperative serum visfatin levels and prognosis of breast cancer among Chinese women

Visfatin is identified a pro-inflammatory cytokine and its serum level is increased in various cancers. This study aimed to evaluate the prognostic value of preoperative serum visfatin level in breast cancers. Preoperative serum visfatin levels of 248 patients with breast cancer and serum visfatin levels of 100 healthy individuals and 100 benign women controls were determined using enzyme-linked immunosorbent assay. Unfavorable outcome was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause. Disease-free survival was defined as the time between surgery and the date of unfavorable outcome whichever appeared first. Overall survival was defined from surgery to death for any cause. The association of serum visfatin level with outcomes including mortality, unfavorable outcome, disease-free survival and overall survival was investigated by univariate and multivariate analyses. Preoperative serum visfatin level was substantially higher in patients than in healthy subjects and benign controls respectively. Elevated preoperative serum level of visfatin was identified an independent predictor of mortality, unfavorable outcome, disease-free survival and overall survival. Receiver operating characteristic curve analysis showed that serum level visfatin had high predictive value for mortality and unfavorable outcome. Thus, our results suggest that high preoperative serum visfatin level is associated with poor patient outcomes as well as may play a role as prognostic biomarker in breast cancer survival.

Diet-induced obesity promotes murine gastric cancer growth through a nampt/sirt1/c-myc positive feedback loop

Obesity increases the risk of gastric cancer and may promote its growth, as was recently demonstrated by our novel invivo mouse model. However, the underlying mechanisms of this correlation remain unclear. The purpose of this study was to investigate the precise effects of obesity on gastric cancer growth and to elucidate the potential molecular mechanisms. Diet-induced obese mice were insulin-resistant, glucose-intolerant and had high serum visfatin concentration. In the subcutaneous mouse model, tumors were more aggressive in diet-induced obese mice compared with lean mice. Tumor weights showed a significant positive correlation with mouse body weights, as well as serum insulin and visfatin concentrations. Immunohistochemical staining showed that the expression levels of iNampt, Sirt1 and c-MYC proteins were upregulated in the subcutaneous tumors from obese mice compared to those from lean animals. Furthermore, obesity not only prompted significantly murine forestomach carcinoma cell migration, proliferation, but also affected cellular apoptosis and cell cycle by endocrine mechanisms. These were associated with increased expression of the pro-survival nampt/sirt1/c-myc positive feedback loop confirmed by RT-PCR and western blotting. These results suggested that diet-induced obesity could promote murine gastric cancer growth by upregulating the expression of the nampt, sirt1 and c-myc genes.

Abstract 1933: Visfatin promotes malignant breast cancer behavior through activation of STAT3.

Abstract Background. Obesity-associated adipocyte dysfunction and adipocytokine imbalance has become a major focus in breast cancer research. In this study, the role of circulating visfatin, a recently discovered adipocytokine, in breast cancer was explored. Methods. Serum visfatin was analyzed by enzyme-linked immunosorbent assay and correlated with clinicopathological characteristics and survival, while the expression of phosphorylated and activated STAT3 in breast cancer tissue was analyzed by immunohistochemistry. The biologic activity of visfatin as well as the underlying mechanisms was analyzed by using XTT cell proliferation assay, flow cytometry and immunoblotting analysis in human breast cancer cells. Results. Serum visfatin was substantially elevated in breast cancer patients. It was positively associated with tumor stage and lymph node metastasis, but negatively associated with estrogen receptor (ER) and progesterone receptor (PR) status. Breast cancer patients with high serum visfatin, especially in combination with ER− and PR− status, had a poor patient survival. On the other hand, patients with high serum visfatin had a lower incidence of disease recurrence and a better patient survival after adjuvant hormone therapy. Serum visfatin was positively associated with STAT3 tyrosine phosphorylation in breast cancer tissues. In agreement with the clinical observation, visfatin treatment in breast cancer cells activated JAK1 and SRC as well as their downstream molecule STAT3, followed by an enhanced G1/S progression and cell proliferation. Conclusion. Serum visfatin, through activation of STAT3, leads to a malignant cancer behavior and poor survival in breast cancer patients. Key words: visfatin, adipocytokine, breast cancer, STAT3 Citation Format: Shyng-Shiou F. Yuan, Yun-Ju Chen, Yi-Chen Lee, Ming-Feng Hou. Visfatin promotes malignant breast cancer behavior through activation of STAT3. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1933. doi:10.1158/1538-7445.AM2013-1933 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

Visfatin and its genetic variants are associated with obesity‐related morbidities and cardiometabolic risk in severely obese children

Visfatin is an adipokine, associated with obesity and possibly glucose regulation. The aim of this study was to examine the association of visfatin and its genetic variants with adiposity, cardiometabolic risk factors and obesity-related morbidities in obese children. Anthropometric measurements, dual energy X-ray absorptiometry scan, fasting blood samples and oral glucose tolerance tests were performed for 243 obese children. We screened the visfatin gene of 24 obese subjects and then performed genotyping of identified genetic variants in other 219 obese children through direct DNA sequencing. Fasting serum visfatin correlated with measures of obesity and liver enzymes and was elevated in obese children with abnormal glucose tolerance and non-alcoholic fatty liver disease. The two upstream single nucleotide polymorphisms, -3187G>A (rs11977021) and -1537C>T (rs61330082), were at complete linkage disequilibrium. The AA genotype of -3187G>A was associated with higher serum visfatin (6.17 ± 0.76 ng mL(-1) vs. 3.92 ± 0.44 ng mL(-1)) and higher triglyceride (1.39 ± 0.08 mmol L(-1) vs. 1.19 ± 0.07 mmol L(-1)) as compared with the GG genotype. There was also a significant linear increase in serum visfatin across GG to GA to AA genotype of -3187G>A, indicating possible additive effect of A allele. The dominant GA + AA genotype model of +21426G>A (rs2302559) was associated with lower serum visfatin (3.83 ± 0.56 ng mL(-1) vs. 5.13 ± 0.34 ng mL(-1)) and lower plasma glucose (4.37 ± 0.08 mmol L(-1) vs. 4.77 ± 0.12 mmol L(-1)) as compared with the GG genotype. Visfatin and its genetic variants were associated with adiposity, obesity-related morbidities and adverse cardiometabolic parameters. This supported our hypothesis that visfatin plays a significant role in the development of obesity-related morbidities and cardiometabolic risk.

Serum visfatin in Asian women with polycystic ovary syndrome

Objective. To determine serum visfatin levels in Asian polycystic ovary syndrome (PCOS) women and its correlations with various parameters.Study design. Case–control study.Setting. University hospital.Subjects. Eighty women were enrolled in this study. Of these, 40 women were PCOS and 40 age-matched subjects with regular menstrual cycles were controls.Intervention. Seventy-five gram oral glucose tolerance tests were performed in all women. Fasting venous blood samples for serum visfatin, insulin and androgen levels were obtained both from the PCOS and the control women.Main outcome measures. Serum concentrations of visfatin, fasting insulin (FI), fasting glucose, 2-h post-load glucose (2hPG), homeostasis model assessment insulin resistance, homeostasis model assessment beta cell function, total testosterone, free testosterone, androstenedione and dehydroepiandrosterone sulfate were measured in both groups.Results. Women with PCOS had significantly higher serum visfatin levels than the healthy controls [100.39 ± 41.90 vs. 45.09 ± 28.24 mg/ml, p < 0.01]. PCOS women also had significantly higher concentrations of all androgens (p < 0.01). Insulin resistance seemed to be greater in the PCOS than the control groups, but did not reach a statistically significant level. In the PCOS group, serum visfatin levels were positively correlated with 2hPG, and systolic blood pressure and diastolic blood pressure. Serum visfatin levels were negatively associated with FI (r = −0.80, p = 0.03) and positively associated with systolic and diastolic blood pressure (r = 0.77, p = 0.04, r = 0.79, p = 0.03, respectively) in the sub-group of PCOS women with abnormal glucose tolerance (AGT).Conclusions. Asian PCOS women had significantly higher serum visfatin levels than age-matched healthy controls. Their levels were significantly correlated with 2hPG and blood pressure in PCOS women, and with FI and blood pressure in PCOS women with AGT.

Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome

Visfatin, a protein secreted by adipose tissue, is suggested to play a role in pathogenesis of insulin resistance. In polycystic ovary syndrome (PCOS), insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the study was to asses the relation between serum visfatin concentration and insulin sensitivity and markers of hyperandrogenism in lean and obese PCOS patients. The study group consisted of 70 women with PCOS (23 lean and 47 obese) and 45 healthy women (25 lean and 20 obese). Euglycemic hyperinsulinemic clamp and the measurements of serum visfatin, sex hormones were performed. The PCOS group had lower insulin sensitivity (P=0.00049) and higher serum visfatin (P=0.047) in comparison to the control group. The decrease in insulin sensitivity was present in both the lean (P=0.019) and obese (P=0.0077) PCOS subjects, whereas increase in serum visfatin was observed only in lean PCOS subjects (P=0.012). In the whole group, serum visfatin was negatively correlated with insulin sensitivity (r=-0.27, P=0.004). This relationship was also observed in the subgroup of lean (r=-0.30, P=0.038), but not obese women. Additionally, in lean women, visfatin was associated with serum testosterone (r=0.47, P=0.002) and free androgen index (r=0.48, P=0.002), independently of other potential confounding factors. Visfatin is associated with insulin resistance and markers of hyperandrogenism in lean PCOS patients.