Adiponectin (APN), an adipose tissue-excreted adipokine, plays protective roles in metabolic and cardiovascular diseases. In this study, the effects and mechanisms of APN on biological functions of rat vascular endothelial progenitor cells (VEPCs) were investigated in vitro . After administrating APN in rat VEPCs, the proliferation was measured by methyl thiazolyl tetrazolium (MTT) method, the apoptotic rate was test by Flow cytometry assay, mRNA expression of B-cell lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression of mechanistic target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 (pSTAT3) was analyzed by Western blot. It was suggested that APN promoted the optical density (OD) value of VEPCs, enhanced mRNA expression of Bcl-2 and VEGF, and inhibited cell apoptotic rate. Furthermore, protein expression of pSTAT3 was also increased in the presence of APN. Moreover, APN changed-proliferation, apoptosis and VEGF expression of VEPCs were partially suppressed after blocking the mTOR-STAT3 signaling pathway by the mTOR inhibitor XL388. It was indicated that APN promoted biological functions of VEPCs through targeting the mTOR-STAT3 signaling pathway., Xiaoying Dong, Xia Yan, Wei Zhang, Shengqiu Tang., and Obsahuje bibliografii
Adiponectin acts as an endogenous antithrombotic factor. However, the mechanisms underlying the inhibition of platelet aggregation by adiponectin still remain elusive. The present study was designed to test whether adiponectin inhibits platelet aggregation by attenuation of oxidative/nitrative stress. Adult rats were fed a regular or high-fat diet for 14 weeks. The platelet was immediately separated and stimulated with recombinant full-length adiponectin (rAPN) or not. The platelet aggregation, nitric oxide (NO) and superoxide production, endothelial nitric oxide synthase (eNOS)/inducible NOS (iNOS) expression, and antioxidant capacity were determined. Treatment with rAPN inhibited hyperlipidemia- induced platelet aggregation (P<0.05). Interestingly, total NO, a crucial molecule depressing platelet aggregation and thrombus formation , was significantly reduced, rather than increased in rAPN-treated platelets. Treatment with rAPN markedly decreased superoxide production (-62 %, P<0.05) and enhanced antioxidant capacity (+38 %, P<0.05) in hyperlipidemic platelets. Hyperlipidemia-induced reduced eNOS phosphorylation and increased iNOS expression were significantly reversed following rAPN treatment (P<0.05, P<0.01, respectively). Taken together, these data suggest that adiponectin is an adipokine that suppresses platelet aggregation by enhancing eNOS activation and attenuating oxidative/nitrative stress including blocking iNOS expression and superoxide production., W.-Q. Wang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Adiponectin is an adipokine increasing glucose and fatty acid metabolism and improving insulin sensitivity. The aim of this study was to investigate the role of adiponectin in the regulation of adipocyte lipolysis. Human adipocytes isolated from biopsies obtained during surgical operations from 16 non-obese and 17 obese subjects were incubated with 1) human adiponectin (20 μg/ml) or 2) 0.5 mM AICAR - activator of AMPK (adenosine monophosphate activated protein kinase). Following these incubations, isoprenaline was added (10-6 M) to investigate the influence of adiponectin and AICAR on catecholamine-induced lipolysis. Glycerol concentration was measured as lipolysis marker. We observed that adiponectin suppressed spontaneous lipolysis by 21 % and isoprenaline-induced lipolysis by 14 % in non-obese subjects. These effects were not detectable in obese individuals, but statistically significant differences in the effect of adiponectin between ob ese and non-obese were not revealed by two way ANOVA test. The inhibitory effect of AICAR and adiponectin on lipolysis was reversed by Compound C. Our results suggest, that adiponectin in physiological concentrations inhibits spontaneous as well as catecholamine-induced lipolysis. This effect might be lower in obese individuals and this regulation seems to involve AMPK., Z. Wedellová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Increases in resting energy expenditure (REE) likely contribute to weight loss in various chronic diseases. In chronic obstructive pulmonary disease (COPD), relationships between the ventilatory impairment and increased REE, and between disturbances in adipokines and weight loss were previously described. Therefore, we investigated serum levels and adipose tissue expression of leptin and adiponectin, and their relationships to REE in patients with COPD. In 44 patients with stable COPD (38 male; age 62.3±7.2 years), REE was assessed using indirect calorimetry. Subcutaneous adipose tissue samples were analyzed using realtime PCR. From underweight [n=9; body mass index (BMI) <20.0 kg.m−2 ], to normal weight-overweight (n=24, BMI=20.0- 29.9 kg.m−2 ) and obese patients (n=11; BMI≥30 kg.m−2 ), REE adjusted for body weight decreased (32.9±6.1 vs. 26.2±5.8 vs. 23.9±6.6 kcal.kg−1 .24 h−1 , p=0.006), serum levels and adipose tissue expression of leptin increased (p<0.001 for both), and serum and adipose tissue adiponectin decreased (p<0.001; p=0.004, respectively). REE was inversely related to serum and adipose tissue leptin (R=−0.547, p<0.001; R=−0.458, p=0.002), and directly to serum adiponectin (R=0.316, p=0.039). Underweight patients had increased REE compared to normal weight-overweight patients, in association with reductions in serum and adipose tissue leptin, and increased serum adiponectin, suggesting a role of adipokines in energy imbalance in COPD-related cachexia, M. Brúsik ... [et al.]., and Obsahuje seznam literatury
The aim of this study was to explore the changes in the adipokines leptin and adiponectin in obese patients with type 1 diabetes mellitus (T1DM) who underwent seven days of fasting and 21 days of low-calorie diet (LCD). The plasma leptin and adiponectin concentrations were measured in 14 obese patients with T1DM at baseline, immediately after 7 days of fasting, and after 21 days of LCD. 13 non-obese patients with T1DM were studied only after an overnight fasting. Bioimpedance technique was used for determination of body composition. Obese T1DM patients lost 6.0 kg (6.0; 6.8) (median, 25 %; 75 %) and decreased their fat tissue after fasting and LCD. Plasma leptin in obese T1DM was significantly higher than in non-obese T1DM patients: 9.10 (5.06; 25.89) vs. 1.71 (1.12; 7.08) μg ∙ l-1 and transiently decreased immediately after fasting: 3.45 μg ∙ l-1 (1.47; 7.00), (P<0.05). Adiponectin/leptin ratio in obese T1DM was significantly lower than in non-obese T1DM patients: 0.67 (0.57; 1.49) vs. 3.50 (2.46; 6.30) ∙ 103 and transiently increased immediately after fasting: 2.22 (1.26; 3.24) ∙ 103, (P<0.05). We conclude that obese patients with T1DM are characterized by hyperleptinemia that is reduced by prolonged fasting, but only slightly affected by low calorie diet., F. Musil, V. Blaha, A. Ticha, R. Hyspler, M. Haluzik, J. Lesna, A. Smahelova, L. Sobotka., and Obsahuje bibliografii
Critical illness induces among other events production of proinflammatory cytokines that in turn interfere with insulin signaling cascade and induce insulin resistance on a postreceptor level. Recently, local renin-angiotensin system of adipose tissue has been suggested as a possible contributor to the development of insulin resistance in patients with obesity. The aim of our study was to determine local changes of the renin-angiotensin system of subcutaneous and epicardial adipose tissue during a major cardiac surgery, which may serve as a model of an acute stress potentially affecting endocrine function of adipose tissue. Ten patients undergoing elective cardiac surgery were included into the study. Blood samples and samples of subcutaneous and epicardial adipose tissue were collected at the beginning and at the end of the surgery. Blood glucose, serum insulin and adiponectin levels were measured and mRNA for angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1 receptor were determined in adipose tissue samples using RT PCR. Cardiac surgery significantly increased both insulin and blood glucose levels suggesting the development of insulin resistance, while serum adiponectin levels did not change. Expression of angiotensinogen mRNA significantly increased in epicardial adipose tissue at the end of surgery relative to baseline but remained unchanged in subcutaneous adipose tissue. Fat expression of angiotensin-converting enzyme and type 1 receptor for angiotensin II were not affected by surgery. Our study suggests that increased angiotensinogen production in epicardial adipose tissue may contribute to the development of postoperative insulin resistance., T. Roubíček, M. Dolinková, J. Bláha, D. Haluzíková, L. Bošanská, M. Mráz, J. Křemen, M. Haluzík., and Obsahuje bibliografii a bibliografické odkazy
PPAR-α agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-α agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-α agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-α expression in human liver and muscle., K. Anderlová, R. Doležalová, J. Housová, L. Bošanská, D. Haluzíková, J. Křemen, J. Škrha, M. Haluzík., and Obsahuje bibliografii a bibiografické odkazy
Secondary hyperparathyroidism (SHPT) may contribute to the systemic illness that accompanies chronic heart failure (CHF). Healthy elderly with vitamin D deficiency who did not develop hyperparathyroidism (functional hypoparathyroidism, FHPT) had lower mortality than those who di d. This study was designed to examine determinants of the PTH response in the vitamin D insufficient CHF patients. Sixty five vitamin D insufficient males with NYHA class II and III and 20 control subjects age ≥ 55 years were recruited. Echocardiography, physical performance, NT-pro-BNP, PTH, 25-hydroxyvitamin D (25(OH)D), adiponectin and bone activity surrogat e markers (OPG, RANKL, OC, β-CTx) were assessed. Increased NYHA cl ass was associated with SHPT, while physical performance was inferior compared to FHPT. SHPT was associated with lower left ventricular ejection fraction (LVEF) and flow mediated dilatation, but with higher left heart dimensions, left ventricular mass index and right ventricular systolic pressure. CHF patients with SHPT had increased NT-pro-BNP, adiponectin and bone markers, but decreased 25(OH)D compared to those with FHPT. Independent determinants for SHPT in CHF patients with vitamin D insufficiency were LVEF, adiponectin and β-CTx, irrespective of renal function and serum vitamin D levels. In conclusion, increased PTH levels, but not low vitamin D, demonstrated close relation to CHF severity., B. Bozic ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Peripheral insulin resistance is associated with decreasing adiponectin and increasing leptin plasma levels, and also with cognitive decline. The effects of adipokines on brain function have been published from both animal and human studies. In particular, the influence of leptin and adiponectin on the development of Alzheimer’s disease (AD) has been extensively investigated. However, the association between adipsin and AD is as yet unknown. In 37 patients with AD and 65 controls that followed the same study protocol, we tested whether adiponectin, leptin, and adipsin could be used as biomarkers in the early stages of AD. In contrast with conclusions of cognition studies in insulin resistant states, our study found a correlation of impaired neuropsychological performance with increasing adiponectin and decreasing leptin in AD patients. Nevertheless, no significant differences between patients and controls were found. AD women had significantly increased adipsin compared to controls, and there was a positive correlation of adipsin with age and disease duration. Although adipokines do not appear to be suitable biomarkers for early AD diagnosis, they certainly play a role in the pathogenesis of AD. Further studies will be needed to explain the cause of the adipokine “breaking point” that leads to the pathogenesis of overt AD., Markéta Vaňková, Gabriela Vacínová, Josef Včelák, Daniela Vejražková, Petra Lukášová, Robert Rusina, Iva Holmerová, Eva Jarolímová, Hana Vaňková, Běla Bendlová., and Obsahuje bibliografii
Our aim was to assess the reaction of TNFα, resistin, leptin and adiponectin to lipid infusion. Eight healthy subjects underwent a 24-hour lasting infusion of lipid emulsion. Plasma concentrations and expressions of selected cytokines in subcutaneous fat were measured. TNFα plasma concentration did not change during the first 4 hours of hypertriglyceridemia, but a significant increase after 24 hours was detected (p<0.001 for 0; 30; 240 min vs. 24 h). Plasma concentration of resistin significantly increased at 30 min of infusion and remained elevated (p<0.01 for 0 min vs. 30; 240 min; p<0.001 for 0 min vs. 24 h). Plasma concentrations of leptin and adiponectin did not show any significant changes. Although the expression of resistin in the subcutaneous adipose tissue tended to increase, the change was not significant. Expressions of TNFα, leptin and adiponectin were unaffected. In conclusions, our results indicate that acutely induced hyperlipidemia could influence the secretion of TNFα and resistin., J. Kopecký ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy