Visfatin Gene Expression Research Articles

Analysis of Changes in Serum Levels and Gene Expression Profiles of Novel Adipocytokines (Omentin, Vaspin, Irisin and Visfatin) and Their Correlation with Serum C-reactive Protein Levels in Women Diagnosed with Endometriosis

This study aimed to investigate the role of new adipocytokines (omentin, vaspin, irisin and visfatin) in the development of endometriosis and the relationship of these adipocytokines with the inflammatory marker, C-reactive protein (CRP) levels in serum. In this study, endometriosis (n=16) and control groups (n=14) were determined via ultrasound. Serum omentin, vaspin and irisin levels were measured by ELISA method. CRP levels in serum and the gene expression of visfatin and vaspin in whole blood samples were determined by clinical analyzer and the real-time polymerase chain reaction, respectively. Serum irisin and CRP levels in the endometriosis group were significantly higher than in the control group. Irisin protein levels demonstrated a positive correlation with body mass index and CRP in women diagnosed with endometriosis. No statistically significant difference was found in serum omentin and vaspin levels between groups. The visfatin and vaspin gene expression in whole blood samples from the endometriosis group was found to be significantly lower than the control group. Increased levels of serum irisin and decreased visfatin and vaspin gene expressions in blood may be considered as a potential biomarker in endometriosis. The identification of new adipocytokines, which demonstrate an alteration in the presence of endometriosis and the relationship between these adipocytokines and inflammation will facilitate the detection of mechanisms involved in endometriosis and will lead to the development of targeted therapy.

PHARMACOLOGICAL EFFECT OF METFORMIN AND PIOGLITAZONE ON VISFATIN DERIVED FROM ADIPOCYTES IN PATHOGENESIS OF TYPE 2 DIABETES

Adipocytes secreate many adipocytokines including visfatin. Many evidence either in direct relation or in in vitro showed that visfatin alters the state of type 2 diabetes (T2DM).To unfold the role of visfatin in response to metformin and pioglitazone we have investigated the lipid profile and levels of visfatin along with its mRNA expression in response to antidiabetic drugs metformin and pioglitazone in vitro adipocytes.Adipocytes were cultured for the estimation of lipid profile and secreted visfatin using ELISA and the response of mRNA visfatin gene expression by the use of metformin hydrochloride and pioglitazone hydrochloride and combination of both.The determination was performed by RT- PCR quantification. Differences were considered significant when P values were ≤0.05 calculated using SPSS software (ver. 19).In Glucose treated adipocytes the lipid profile showed significant change in HDL while highly significant change in other lipoproteins.However,the released level of visfatin also showed significant change in glucose treated adipocytes as compared to normal control adipocytes. No significant change was observed in metformin hydrochloride while pioglitazone hydrochloride showed significant change as concurred by mRNA level estimation. The present report examined whether visfatin is regulated by anti-diabetic drugs metformin and pioglitazone in glucose feed adipocytes mimicking the state of T2DM along with effect of these drugs in secreted lipid profile. Pioglitazone treatment showed highly significant association at higher concentration. Our finding suggest that the treatment with pioglitazone in glucose treated adipocytes could play a role in the regulation of visfatin in adipocytes

Inflammatory Gene Expression in Neck Perivascular and Subcutaneous Adipose Tissue in Men With Carotid Stenosis.

The inflammatory phenotype of neck adipose tissue (NAT) might reflect its involvement in the pathogenesis of carotid atherosclerosis. We investigated inflammatory gene expression in the subcutaneous and the perivascular (pericarotid) adipose tissue from patients with carotid stenosis (CS) undergoing endarterectomy and a control group of patients without significant carotid atherosclerosis undergoing thyroid surgery. Only male patients were included (n = 13 in each study group). Clinical and biochemical data along with serum leptin, adiponectin, and monocyte chemoattractant protein 1 (MCP-1) were collected. Adipose tissue samples were obtained from both the subcutaneous and pericarotid compartments. Real-time polymerase chain reaction was used to measure gene expression of macrophage markers and adipokines. The CS group had higher subcutaneous and pericarotid visfatin gene expression and higher pericarotid expression of MCP-1 and CD68 genes. The ratio between pericarotid CD206 and CD68 gene expression was similar between study groups. Adiponectin gene expression in both NAT compartments did not differ between groups, but it was negatively associated with body weight. These observations suggest that NAT, and especially the pericarotid compartment, express enhanced inflammatory properties in patients with CS, but the proportion of anti-inflammatory macrophages in advanced atherosclerosis seems to be maintained.

Plasma level and expression of visfatin in the porcine hypothalamus during the estrous cycle and early pregnancy

Visfatin appears to be an energy sensor involved in the regulation of female fertility, which creates a hormonal link integrating the control of energy homeostasis and reproduction. This study evaluates the expression levels of visfatin gene and protein in selected areas of the porcine hypothalamus responsible for gonadotropin-releasing hormone synthesis: the mediobasal hypothalamus (MBH) and preoptic area (POA), and visfatin concentrations in the blood plasma. The tissue samples were harvested from gilts on days 2–3, 10–12, 14–16, and 17–19 of the estrous cycle, and on days 10–11, 12–13, 15–16, 27–28 of pregnancy. Visfatin was localized in the cytoplasm and nucleus of cells creating both studied hypothalamic structures. The study demonstrated that visfatin gene and protein expression in MBH and POA depends on hormonal status related to the phase of the estrous cycle or early pregnancy. Blood plasma concentrations of visfatin during the estrous cycle were higher on days 2–3 in relation to other studied phases of the cycle, while during early pregnancy, the highest visfatin contents were observed on days 12–13. This study demonstrated visfatin expression in the porcine hypothalamus and its dependence on the hormonal milieu related to the estrous cycle and early pregnancy.

Association of serum visfatin and its mRNA expression levels with cognitive function and idiopathic intracranial hypertension in obese Egyptian women

BackgroundAn epidemic of obesity has spread across the globe. Obesity has numerous comorbidities, including airway disease, insulin resistance, type 2 diabetes, cardiovascular disease, atherosclerosis, degenerative neurological disease, cognitive dysfunction, and cancer. Inflammatory cytokine is suggested to play a role in obesity and its complications. The current study aimed to estimate the expression and serum visfatin concentrations in obese Egyptian women. Moreover, we aimed to evaluate the possible association of visfatin gene expression and its serum levels with idiopathic intracranial hypertension (IIH) and cognitive dysfunctionParticipants and methodsThis cross-sectional study enrolled 60 obese women and 40 lean healthy women as controls. Obese women were classified according to grades of obesity into three groups. All participants underwent full clinical, neurological, and psychiatric examination. IIH group included patients with intracranial pressure greater than 25 cm H2O (opening pressure measured during lumber puncture in lateral decubitus position). Cognitive function was evaluated by using Montreal Cognitive Assessment scale (MoCA), Arabic version. Estimation of visfatin expression levels was determined by real-time PCR, and serum visfatin concentrations were measured using enzyme-linked immunosorbent assay.ResultsOur results revealed that obese women had higher values of visfatin expression (1.44±0.29) and serum levels (124.1±) compared with lean women (1.01±0.3 and 46.1±33.8, respectively). The visfatin expression and serum levels were significantly positively correlated with obesity indices, metabolic risks, MoCA, cerebrospinal fluid opening pressure, and cognitive dysfunction. Linear regression test showed that BMI, cerebrospinal fluid opening pressure, and MoCA were the main predictors of both serum and expression levels of visfatin in obese women. The receiver operating characteristic curve analysis revealed that the power of serum visfatin levels was higher than visfatin expression in differentiating obese women from lean ones.ConclusionThere was a strong independent association between both higher visfatin expression and serum levels and obesity indices, metabolic risks, IIH, and cognitive dysfunction in obese Egyptian women.

Hormonal regulation of visfatin gene in avian Leghorn male hepatoma (LMH) cells

Visfain has been extensively studied in mammals and has been shown to play an important role in obesity and insulin resistance. However, there is a paucity of information on visfatin regulation in non-mammalian species. After characterization of chicken visfatin gene, we undertook this study to determine its hormonal regulation in avian (non-mammalian) liver cells. Addition of 5 ng/mL TNFα, 100 ng/mL leptin, 1, 3, 10 or 100 ng/mL T3 for 24 h upregulated visfatin gene expression by 1.2, 1.8, 1.95, 1.75, 1.80, and 2.45 folds (P < .05), respectively, compared to untreated LMH cells. Administration of 10 ng/mL of orexin A significantly down regulated visfatin gene expression by 1.35 folds compared to control cells. In contrast, treatment with IL-6 or orexin B for 24 h did not influence visfatin mRNA abundance. These pro-inflammatory cytokines and obesity-related hormones modulate the expression of CRP, INSIG2, and nuclear orphan receptors. Hepatic CRP gene expression was significantly upregulated by IL-6, TNFα, orexin B, and T3 and down regulated by leptin and orexin A. LXR mRNA abundances were increased by orexin A, decreased by orexin B, and T3, and did not affected by IL6, TNFα, or leptin. The expression of FXR gene was induced by IL-6, leptin, and T3, but it was not influenced by TNFα, orexin A or B. CXR gene expression was up regulated by TNFα, leptin, orexin B, and T3, down regulated by 5 ng/mL orexin A, and did not affected by IL-6. INSIG2 mRNA levels were increased by TNFα (5 ng/mL), leptin (100 ng/mL), and T3 (1, 3, 10, and 100 ng/mL), decreased by orexin A, and remained unchanged with IL-6 or orexin B treatment.Together, this is the first report showing hormonal regulation of visfatin in avian hepatocyte cells and suggesting a potential role of CRP, INSIG2, and nuclear orphan receptor LXR, FXR, and CXR in mediating these hormonal effects.

Effect of glucagon-like peptide-1 analogue; Exendin-4, on cognitive functions in type 2 diabetes mellitus; possible modulation of brain derived neurotrophic factor and brain Visfatin

BackgroundBrain derived neurotrophic factor (BDNF) is one of the most essential neurotrophic factors in the brain. BDNF is involved in learning, memory and locomotion suggesting it as a target in type 2 diabetes mellitus (T2DM) associated cognitive changes. Visfatin; an adipokine discovered to be expressed in the brain; was found to have multiple effects including its participation in keeping energy supply to the cell and is consequentially involved in cell survival. Its role in cognitive functions in T2DM was not studied before. Recent studies point to the possible neuro-protective mechanisms of glucagon-like peptide 1 analogue: Exendin-4 (Ex-4) in many cognitive disorders, but whether BDNF or Visfatin are involved or not in its neuro-protective mechanisms; is still unknown. Aimsto study the changes in cognitive functions in T2DM, either not treated or treated with Glucagon-like peptide 1 (GLP-1) analogue: Ex-4, and to identify the possible underlying mechanisms of these changes and whether BDNF and brain Visfatin are involved. MethodsA total of 36 adult male wistar albino rats were divided into 4 groups; Control, Exendin-4 control, Diabetic and Exendin-4 treated groups. At the end of the study, Y-maze and open field tests were done the day before scarification to assess spatial working memory and locomotion, respectively. Fasting glucose and insulin, lipid profile and tumor necrosis factor- alpha (TNF-α) were measured in the serum. Homeostasis model assessment insulin resistance was calculated. In the brain tissue, malondialdehyde (MDA) level, gene expression and protein levels of BDNF and Visfatin, area of degenerated neurons, area of glial cells and area % of synaptophysin immunoexpression were assessed. ResultsCompared with the control, the untreated diabetic rats showed insulin resistance, dyslipidemia and elevation of serum TNF-α. The brain tissue showed down-regulation of BDNF gene expression and reduction of its protein level, up-regulation of Visfatin gene expression and elevation of its protein level, increase in MDA, area of degenerated neurons and area of glial cells and reduction in area % of synaptophysin immunoexpression. These changes were paralleled with significant deterioration in spatial working memory and locomotion. Treatment of diabetic rats with Ex-4 reversed all these changes. ConclusionT2DM has a negative impact on cognitive functions through different pathological and subcellular mechanisms. The current study provides evidence for involvement of BDNF and brain Visfatin in T2DM- associated cognitive dysfunction. BDNF and brain Visfatin were also found to contribute to the neuro-protective effect of Ex-4 via modulation of inflammation, oxidative stress, neuro-degeneration and synaptic function.

Visfatin gene expression and oxidative stress in pregnancy induced hypertension

Preeclampsia, a hypertensive disorder of pregnancy, was related to hypertension, diabetes, oxidative stress, obesity, in addition to polycystic ovarian diseases. Visfatin, potentially a new adipokine has emerged having high contribution in pathogenesis of preeclampsia. Oxidative stress was increased lipid peroxidation and caused vascular endothelial damage. This study was conducted with the aim of evaluating the level of visfatin gene expression in placenta and measuring some oxidative stress parameters. Eighty Egyptian patients of newly diagnosed pregnant hypertensive disorder were selected for the study which was recruited from Mansoura University Hospital, Department of Obstetrics and Gynecology and also normotensive pregnant women were collected. The pregnant women groups were classified into four groups: gestational hypertension (n = 20), mild preeclampsia (n = 16), severe preeclampsia (n = 25), chronic hypertension with superimposed preeclampsia (n = 19) and compared with normotensive pregnant women (n = 10) as control group. Visfatin gene expression level was decreased in placenta of pregnant hypertensive disorder women groups with mean 1.28 ± 0.42, 1.01 ± 0.24, 0.40 ± 0.14 and 0.32 ± 0.11 respectively when compared to normotensive pregnant women with mean 1.56 ± 0.69. Additionally, catalase activity, total antioxidant capacity and reduced glutathione levels were decreased in hypertensive pregnant women groups compared with normotensive ones. On the other hand malondialdhyde level was increased in preeclampsia groups when compared with normalized pregnant women. Decreased visfatin level has an important pathophysiology of preeclampsia and suggests the complication in pregnancy. Also the imbalance between oxidant and antioxidant has an important causative factor in the pathogenesis of preeclampsia.

Characterization of the visfatin gene and its expression pattern and effect on 3T3-L1 adipocyte differentiation in chickens

Visfatin is a newly identified adipocytokine that plays an important role in the determination of fat traits. In this study, we investigated the characterization of visfatin and the relationship between gene expression and chicken development to provide a theoretical basis for studying visfatin functions. The main results are summarized as follows: The 1482-bp full coding sequence of the visfatin gene of silky fowl was obtained and found to encode 493 amino acids. This gene contains 26 phosphorylation sites and a conserved domain of the NAPRTase family but no signal peptide sequence. It exhibits six functional motifs, including an amidation site. In chickens, visfatin is a highly conserved protein. The highest expression of visfatin was found in breast muscle and the lowest in bone marrow. There was no difference in expression between visceral fat and subcutaneous fat. However, the expression of visfatin in the bone marrow, liver, kidneys, and subcutaneous and visceral fat of broiler chickens was significantly higher than that in silky fowl (P<0.05). Visfatin mRNA levels in the bone marrow decreased with development (P<0.05) but increased in the liver and leg muscle. Visfatin gene expression in the liver, heart and bone marrow did not differ in silky fowl according to sex. A visfatin fusion protein caused a significant increase in the expression of adipocyte differentiation markers (PPARγ, aP2, C/EBPα, and FAS) compared with the control group and a decrease compared with the insulin group. Taken together, the results of the present study contribute to a better understanding of the expression and role of the visfatin gene in chickens.

Association of leptin, visfatin, apelin, resistin and adiponectin with clear cell renal cell carcinoma.

Although an association between obesity and the occurrence of renal cell carcinoma (RCC) has been identified, the mechanism by which obesity functions to increase this risk of cancer remains unclear. Leptin, visfatin, apelin, resistin and adiponectin are peptide hormones secreted by adipocytes; it is considered that these may affect RCC development by exerting effects on proliferation, cell growth and inflammation. The aim of the present study was to investigate the association between the aforementioned adipokine genes and clear cell RCC (CC-RCC). The GSE6344 dataset was downloaded from the Gene Expression Omnibus database, and the relative expression levels of the adipokine genes were analyzed. To verify the results of the mRNA microarray, 77 paired samples of CC-RCC and corresponding adjacent normal tissue were allocated into two groups. The extraction of total RNA was conducted, and the mRNA expression of adipokine genes was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The data from the GSE6344 dataset indicated that the expression of visfatin and apelin was upregulated (P<0.0001 and P<0.01, respectively), and adiponectin was downregulated (P<0.001) in the CC-RCC tissues compared with the adjacent normal tissues. The data from RT-qPCR demonstrated that visfatin and resistin gene expression was increased (P<0.01 and P<0.05, respectively) in the CC-RCC tissues. Furthermore, the mRNA expression level of leptin and adiponectin in the adjacent normal tissue was higher than those in the cancer tissue (P<0.01). The current study verifies that visfatin and adiponectin are associated with an increased risk of CC-RCC, which presents further insights into the molecular mechanisms of CC-RCC tumorigenesis.

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

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.

The mRNA Expression and Circulating Levels of Visfatin and Their Correlation with Coronary Artery Disease Severity and 25-Hydroxyvitamin D.

It is evident that coronary artery disease (CAD) is closely associated with abnormal glucose and lipid metabolism. Notably, dysregulation of inflammatory pathways and immune system also contribute to CAD development. Recently, it has been suggested that visfatin, a proinflammatory adipocytokine, may be involved in several inflammatory and metabolic diseases. In this study, we evaluated the serum visfatin levels and its mRNA expression in peripheral blood mononuclear cells (PBMCs) from CAD patients compared with control subjects. We also studied the correlation between visfatin gene expression and serum levels with clinical and metabolic parameters. This study was conducted on 56 male patients with CAD confirmed by angiography and 30 healthy men as controls. CAD severity was determined based on the number of vessels. Study of gene expression in PBMCs was performed using real time-PCR, and serum levels of visfatin and 25-hydroxyvitamin D were measured by ELISA. We found that serum visfatin levels and its gene expression in PBMCs were increased in patients with CAD compared with the control group (p=0.027 and p=0.016, respectively). Also, visfatin gene expression was positively correlated with visfatin levels and both these variables had a strong positive correlation with the severity of CAD. It appears that elevated mRNA expression and circulating level of visfatin might be of relevance to the pathogenesis and severity of CAD. However, further studies are necessary to better clarify the associations between visfatin and CAD.

Resveratrol attenuates visfatin and vaspin genes expression in adipose tissue of rats with type 2 diabetes.

Visfatin and vaspin are secreted by adipose tissue and play key roles in glucose homeostasis and subsequently are potential targets for diabetes treatment. Resveratrol (RVS) corrects insulin secretion and improves insulin sensitivity. We investigated the RVS effects on serum antioxidants, insulin and glucose levels, also visfatin and vaspin genes expression in adipose tissue of streptozotocin-nicotinamide (STZ-NA) induced type 2 diabetic rats. Diabetes was induced in Wistar rats (n=32) using STZ (60 mg/kg body weight) and NA (120 mg/kg body weight); rats were divided into 4 groups (n=8). Eight untreated normal rats were used as control group; four diabetic rat groups (2-5) were treated with 0, 1, 5 and 10 mg/kg body weight of RVS, respectively for 30 days. After treatment blood and adipose tissue were prepared from all animals. Serum glucose, insulin, HOMA index, total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured. Visfatin and vaspin genes expression in adipose tissue were evaluated using real-time PCR. RVS reduced blood glucose significantly and increased insulin level, resulting in insulin sensitivity improvement. Furthermore RVS increased weight and TAC, while reducing serum MDA in the diabetic groups. Visfatin gene expression increased in the diabetic group, and RVS treatment reduced it. Vaspin gene expression was reduced in RVS receiving diabetic groups. The results indicated that RVS has potential hypoglycemic effect, probably by increasing insulin level and changing gene expression of visfatin and vaspin. Moreover RVS showed antioxidant effects through reduction in peroxidiation products and augmented antioxidant capacity.

Adipokine gene expression in peripheral blood of adult and juvenile dermatomyositis patients and their relation to clinical parameters and disease activity measures.

ObjectiveRecently adipokines have been implicated in the regulation of immune and inflammatory responses in autoimmune disease. To investigate the role of adipokines in adult and pediatric patients with newly diagnosed dermatomyositis (DM), we analyzed peripheral blood and skeletal muscle gene expression of four adipokines: visfatin, leptin, adiponectin and resistin.MethodsPeripheral blood mononuclear cells (PBMCs) were collected for 21 adult DM, 26 juvenile DM, 5 non-disease adult controls, and 6 non-disease pediatric controls at two time points: baseline and 6 months. Muscle biopsies from 5 adult DM patients and 5 non-disease adult controls were collected at baseline. Similarly, muscle biopsies from 7 juvenile DM patients and 5 non-disease pediatric controls were collected at baseline. The gene expression levels of leptin, adiponectin, resistin, visfatin and related inflammatory cytokines, IL-6, TNF- α, and housekeeping genes GAPDH, B2M, and ACTB were generated using a custom RT2 Profiler PCR Array.ResultsVisfatin gene expression levels in peripheral blood were significantly higher in newly diagnosed adult DM cases compared to non-disease controls (P = 0.004) and these levels correlated with baseline clinical parameters such as age (r = 0.34, P = 0.020), male sex (r = −0.35, P = 0.017), prednisone use (r = −0.42, P = 0.006), and DMARD use (r = 0.35, P = 0.025). No significant association was found between change in visfatin gene expression levels and change in disease activity measures. While visfatin gene expression was significantly up-regulated in muscle tissue of juvenile DM patients (P = 0.028), in adult DM patients only a trend towards significance was observed (P = 0.08). Also, muscle gene expression levels of resistin were significantly elevated in both adult and juvenile DM patients compared respectively to non-disease adult and pediatric controls. Furthermore, an association between peripheral blood resistin gene expression and DM disease activity, including global, muscle, and extra-skeletal disease activity was also observed.ConclusionPeripheral blood visfatin gene expression and muscle resistin gene expression are significantly increased in newly diagnosed adult DM patients. Further longitudinal studies should explore the possibility of using gene expression levels of adipokines such as visfatin and resistin as novel clinical diagnostic biomarkers in DM.

The Effect of Acute Aerobic Bout on Adipose Tissue Visfatin Gene Expression in Diabetic Rats

The Effect of Acute Aerobic Bout on Adipose Tissue Visfatin Gene Expression in Diabetic Rats

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.

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.

FRI0039 VISFATIN/PBEF in bone remodelling of rheumatoid arthritis

ObjectivesRheumatoid arthritis (RA) is associated with increased production of adipocytokines, which are cytokine-like mediators. Increased levels of the adipokine visfatin were found in synovial fluid and tissue of RA patients....

Glucose Intolerance and Lipid Metabolic Adaptations in Response to Intrauterine and Postnatal Calorie Restriction in Male Adult Rats

Enhanced de novo lipogenesis (DNL), an adult hepatic adaption, is seen with high carbohydrate or low-fat diets. We hypothesized that ad libitum intake after prenatal calorie restriction will result in adult-onset glucose intolerance and enhanced DNL with modified lipid metabolic gene expression profile. Stable isotopes were used in 15-month-old adult male rat offspring exposed to prenatal (IUGR), pre- and postnatal (IPGR), or postnatal (PNGR) caloric restriction vs. controls (CON). IUGR vs. CON were heavier with hepatomegaly but unchanged visceral white adipose tissue (WAT), glucose intolerant with reduced glucose-stimulated insulin secretion (GSIS), pancreatic β-cell mass, and total glucose clearance rate but unsuppressed hepatic glucose production. Liver glucose transporter (Glut) 1 and DNL increased with decreased hepatic acetyl-CoA carboxylase (ACC) and fatty acid synthase but increased WAT fatty acid transport protein-1 and peroxisomal proliferator-activated receptor-γ, resistin, and visfatin gene expression. In contrast, PNGR and IPGR were lighter, had reduced visceral WAT, and were glucose tolerant with unchanged hepatic glucose production but with increased GSIS, β-cell mass, glucose clearance rate, and WAT insulin receptor. Hepatic Glut1 and DNL were also increased in lean IPGR and PNGR with increased hepatic ACC, phosphorylated ACC, and pAMPK and reduced WAT fatty acid transport protein-1, peroxisomal proliferator-activated receptor-γ, and ACCα. We conclude the following: 1) the heavy, glucose-intolerant and insulin-resistant IUGR adult phenotype is ameliorated by postnatal caloric restriction; 2) increased DNL paralleling hepatic Glut1 is a biomarker of exposure to early caloric restriction rather than the adult metabolic status; 3) hepatic lipid enzyme expression reflects GSIS rather than DNL; and 4) WAT gene expression reflects an obesogenic vs. lean phenotype.

Plasma visfatin levels and gene expression in morbidly obese women with associated fatty liver disease

ObjectivesThe few studies on the physiopathological role of visfatin in morbid obesity and the related metabolic diseases have led us to examine visfatin levels and its liver gene expression in morbidly obese women with non-alcoholic fatty liver disease (NAFLD). Design and methodsWe examined the circulating levels of visfatin by ELISA in serum samples from 95 morbidly obese women (MO) (BMI>40kg/m2) who underwent bariatric surgery and 38 normal weight control women (BMI<25kg/m2). We analysed visfatin liver and adipose tissue mRNA expression by RT-PCR. We evaluated the circulating levels and gene expression of adiponectin, resistin, RBP4, TNFα, IL6 and CRP. ResultsSerum visfatin was significantly higher in MO compared with controls, and also in MO with NAFLD was significantly higher than MO with normal liver. We found that NAFLD diabetic patients presented similar serum visfatin levels than non-diabetic. Serum visfatin correlated with IL6 (r=0.496; p<0.001) and CRP levels (r=0.241; p=0.049).Liver visfatin expression was significantly higher in MO compared to controls and was also significantly higher in MO with NAFLD than in MO with normal liver. Visfatin liver expression correlated positively with resistin (r=0.436, p=0.018) and TNFα expression (r=0.328, p=0.028).Visfatin expression in adipose tissues was similar among the MO groups analysed. ConclusionSerum visfatin and its liver expression are higher in MO women with NAFLD, irrespective of the presence of diabetes. Serum visfatin and its liver expression correlate positively with pro-inflammatory factors. These findings suggest that visfatin may be a molecule related with fat inflammation in morbid obesity and fatty liver disease.

Increased levels and adipose tissue expression of visfatin in morbidly obese women: the relationship with pro‐inflammatory cytokines

The controversial results on the physiopathological role of visfatin led us to examine both circulating visfatin levels and gene expression in visceral (VAT) and subcutaneous fat (SAT) in a homogeneous group of morbidly obese women. We analysed circulating levels of several adipo/cytokines in 133 Spanish women: 40 lean (C) [body mass index (BMI) < 25 kg/m(2) ] and 93 morbidly obese (MO) (BMI > 40 kg/m(2) ). In the MO group, we found 31 diabetic and 62 nondiabetic subjects. We obtained follow-up blood samples at 6 and 12 months after bariatric surgery from 30 MO patients. We determined the circulating levels of visfatin, adiponectin, interleukin-6 (IL6), C-reactive protein (CRP), resistin and tumour necrosis factor-α (TNFα) by ELISA, and visfatin, adiponectin, IL6, resistin and TNFα gene expression in SAT and VAT by real-time RT-PCR. Circulating visfatin levels were higher in MO women compared with lean controls (C = 1·43 ± 0·14 μg/l, MO = 3·60 ± 0·29 μg/l, P < 0·001). After bariatric surgery-induced weight loss, visfatin levels were reduced significantly over 12 months. Visfatin expression in SAT and VAT was similar, but significantly higher in MO compared to C and independent of the presence of diabetes mellitus. Circulating visfatin levels were positively related to IL6 and CRP levels. Visfatin gene expression in VAT and SAT was strongly related to IL6 and TNFα expression. In a homogeneous cohort of morbidly obese women, our findings show that visfatin has a strong relationship with pro-inflammatory factors in severe obesity.