CD163 is a marker of macrophages with anti-inflammatory properties and its soluble form (sCD163) is considered a prognostic predictor of several diseases including type 2 diabetes mellitus (T2DM). We explored sCD163 levels at baseline and after very low-calorie diet (VLCD) or bariatric surgery in 32 patients with obesity (20 undergoing VLCD and 12 bariatric surgery), 32 obese patients with T2DM (22 undergoing VLCD and 10 bariatric surgery), and 19 control subjects. We also assessed the changes of CD163 positive cells of monocyte-macrophage lineage in peripheral blood and subcutaneous adipose tissue (SAT) in subset of patients. Plasma sCD163 levels were increased in obese and T2DM subjects relative to control subjects (467.2±40.2 and 513.8±37.0 vs. 334.4±24.8 ng/ml, p=0.001) and decreased after both interventions. Obesity decreased percentage of CD163+CD14+ monocytes in peripheral blood compared to controls (78.9±1.48 vs. 86.2±1.31 %, p=0.003) and bariatric surgery decreased CD163+CD14+HLA-DR+ macrophages in SAT (19.4±2.32 vs. 11.3±0.90 %, p=0.004). Our data suggest that increased basal sCD163 levels are related to obesity and its metabolic complications. On the contrary, sCD163 or CD163 positive cell changes do not precisely reflect metabolic improvements after weight loss., A. Cinkajzlová, Z. Lacinová, J. Kloučková, P. Kaválková, P. Trachta, M. Kosák, J. Krátký, M. Kasalický, K. Doležalová, M. Mráz, M. Haluzík., and Obsahuje bibliografii
Adipocyte fatty acid binding protein (A-FABP) is a novel adipokine involved in the regulation of lipid and glucose metabolism and inflammation. To evaluate its potential role in the development of postoperative hyperglycemia and insulin resistance we assessed A-FABP serum concentrations and mRNA expression in skeletal and myocardial muscle, subcutan eous and epicardial adipose tissue and peripheral monocytes in 11 diabetic and 20 age- and sex-matched non-diabetic patients undergoing elective cardiac surgery. Baseline serum A-FABP did not differ between the groups (31.1±5.1 vs. 25.9±4.6 ng /ml, p=0.175). Cardiac surgery markedly increased serum A-FABP in both groups with a rapid peak at the end of surgery foll owed by a gradual decrease to baseline values during the next 48 h with no significant difference between the groups at any timepoint. These trends were analogous to postoperative excursions of plasma glucose, insulin and selected proinflammatory markers. Cardiac surgery increased A-FABP mRNA expression in peripheral monocytes, while no effect was observed in adipose tissue or muscle. Our data suggest that circulating A-FABP might be involved in the development of acute perioperative stress response, insulin resistance and hyperglycemia of critically ill irrespectively of the presence of diab etes mellitus., T. Kotulak ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Patients with obesity and type 2 diabetes often display high levels of the anti-diabetic factor fibroblast growth factor-21 (FGF21), suggesting that the overproduction of FGF21 may result from increased adiposity in an attempt by white adipose tissue (WAT) to counteract insulin resistance. However, the production of FGF21 diabetes in the absence of WAT has not been examined. In this study, we investigated the effects of lipodystrophy in A-ZIP F-1 mice on FGF21 production in relation to diabetes. A-ZIP F-1 mice displayed high FGF21 plasma levels resulting from enhanced FGF21 mRNA expression in the liver. Concomitant enhancement of FGF21 receptor (FGFR1) and glucose transporter 1 (GLUT-1) mRNA expression was observed in the muscles of A-ZIP F-1 mice. Furthermore, the activation of hypothalamic NPY and AgRP mRNA expression positively correlated with plasma levels of FGF21 but not active ghrelin. Our study demonstrates that an increased FGF21 plasma level in lipodystrophic A-ZIP F-1 mice results mainly from up-regulated liver production but does not suffice to overcome the lipodystrophy-induced severe type 2-diabetes and insulin resistance in the liver linked to the augmented liver fat deposition., A. Špolcová, M. Holubová, B. Mikulášková, V. Nagelová, A. Štofková, Z. Lacinová, J. Jurčovičová, M. Haluzík, L. Maletínská, B. Železná., and Obsahuje bibliografii
Thiazolidinediones are insulin-sensitizing drugs acting through peroxisome proliferator- activated receptor (PPAR)-γ. The aim of our study was to evaluate the effect of 5-month treatment with PPAR-γ agonist – rosiglitazone (4 mg/day), on the circulating markers of endothelial dysfunction and to evaluate the role of changes in endocrine function of adipose tissue in this process. Biochemical and metabolic parameters, circulating adiponectin, resistin, ICAM-1, VCAM-1, E-selectin, P-selectin, PAI-1, myeloperoxidase (MPO), and matrix metalloproteinase-9 (MMP-9) concentrations were assessed in 10 women with type 2 DM before and after rosiglitazone treatment and in a control group of healthy women. At baseline, diabetic group had significantly higher serum concentrations of glucose, glycated hemoglobin, V-CAM and PAI-1 compared to control group. Adiponectin levels tended to be lower in diabetic group, while resistin concentrations did not differ from control group. Rosiglitazone treatment improved diabetes compensation, significantly reduced VCAM-1, PAI-1 and E-selectin concentrations and increased adiponectin levels, while it did not affect serum resistin concentrations. Adiponectin concentrations at baseline were inversely related to E-selectin and MPO levels, this correlation disappeared after rosiglitazone treatment. We conclude that 5-month rosiglitazone treatment significantly reduced several markers of endothelial dysfunction. This effect could be at least in part attributable to marked increase of circulating adiponectin levels., R. Doležalová, M. M. Haluzík, L. Bošanská, Z. Lacinová, Z. Kasalová, T. Štulc, M. Haluzík., and Obsahuje bibliografii a bibliografické odkazy
Hepcidin, a key regulator of iron metabolism, plays a crucial role in the pathogenesis of anemia of chronic disease. Although it is produced mainly in the liver, its recently described expression in adipose tissue has been shown to be enhanced in massive obesity due to chronic low-grade inflammation. Our objective was to study the changes in hepcidin expression in adipose tissue during acute-phase reaction. We measured hepcidin mRNA expression from isolated subcutaneous and epicardial adipose tissue at the beginning and at the end of the surgery. The expression of mRNAs for hepcidin and other iron-related genes (transferrin receptor 1, divalent metal transporter 1, ferritin, ferroportin) were measured by real-time RT-PCR. Hepcidin expression significantly increased at the end of the surgery in subcutaneous but not in epicardial adipose tissue. Apart from the increased levels of cytokines, the parameters of iron metabolism showed typical inflammation-induced changes. We suggest that acute inflammatory changes could affect the regulation of hepcidin expression in subcutaneous adipose tissue and thus possibly contribute to inflammation-induced systemic changes of iron metabolism., M. Vokurka ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
We studied the changes in seru m fibroblast growth factor-21 (FGF-21) concentrations, its mR NA, and protein expression in skeletal muscle and adipose tissue of 15 patients undergoing cardiac surgery. Blood samples were obtained: prior to initiation of anesthesia, prior to the start of extracorporeal circulation, upon completion of the surger y, and 6, 24, 48, and 96 hours after the end of the surgery. Tissue sampling was performed at the start and end of surgery. The mean baseline serum FGF-21 concentration was 63.1 (43.03-113. 95) pg/ml and it increased during surgery with peak 6 ho urs after its end [385.5 (274.55-761.65) pg/ml, p<0.001], and return ed to baseline value [41.4 (29.15-142.83) pg/ml] 96 hours afte r the end of the surgery. Serum glucose, insulin, CRP, IL-6, IL-8, MCP-1, and TNF-alpha concentrations significantly increased during the surgery. Baseline FGF-21 mRNA expression in skeletal muscle was higher than in both adipose tissue depots and it was not affected by the surgery. Epicardial fat FGF-21 mRNA increased after surgery. Muscle FGF-21 mRNA positively correlated with blood glucose levels at the end of the surgery. Our data suggest a possible role of FGF-21 in the regulation of glucose metabolism and insulin sensitivity in surgery-related stress., T. Kotulák ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Paraoxonase 1 (PON1), an antioxidant enzyme closely associated with HDL (high-density lipoproteins), preserves LDL (low-density lipoproteins) against oxidation. Less protection may be therefore supposed by decreased PON1 activity. This study was undertaken to investigate the association of PON1 gene polymorphisms with diabetic angiopathy and to evaluate the relationship of these polymorphisms with PON1 activity. Total of 86 Type 1 (T1DM) and 246 Type 2 (T2DM) diabetic patients together with 110 healthy subjects were examined. DNA isolated from leukocytes was amplified with polymerase chain reaction (PCR) followed by restriction enzyme digestion. The products were analyzed for L55M and Q192R polymorphisms in coding region and for –107 C/T and –907 G/C in promotor sequence of PON1. Serum enzyme activity was measured spectrophotometrically. Significant differences were found between T1DM or T2DM and control persons in L55M polymorphism (allele M more frequent in T1DM and T2DM vs. controls, p<0.05) and Q192R polymorphism (R allele less frequent in T1DM and T2DM vs. controls, p<0.01) of the PON1 gene. Serum PON1 activity was significantly decreased in T1DM (110±68 nmol/ml/min) and T2DM patients (118±69 nmol/ml/min) compared to the control persons (203±58 nmol/ml/min), both p<0.01. The presence of MM and QQ genotypes was accompanied by lower PON1 activity than of LL and RR genotypes (p<0.05), respectively. Better diabetes control was found in patients with LL than with MM genotypes and similarly in RR genotype than QQ genotype with p<0.05. Significantly different allele frequencies were found in diabetic patients with macroangiopathy than in those without it (M: 0.59 vs. 0.44. R: 0.12 vs. 0.19, p<0.01). The association of PON1 polymorphisms, lower PON1 activity and poorer diabetes control found in patients with macroangiopathy further support the idea of genetic factors contributing to the development of vascular disorders in diabetes., M. Flekač, J. Škrha, K. Zídková, Z, Lacinová, J. Hilgertová., and Obsahuje bibliografii a biblografické odkazy
Clusterin is a heterodimeric glycoprotein with wide range of functions. To further explore its possible regulatory role in energy homeostasis and in adipose tissue, we measured plasma clusterin and its mRNA expression in subcutaneous adipose tissue (SCAT) of 15 healthy lean women, 15 obese women (OB) and 15 obese women with type 2 diabetes mellitus (T2DM) who underwent a 2-week very low-calorie diet (VLCD), 10 obese women without T2DM who underwent laparoscopic sleeve gastrectomy (LSG) and 8 patients with T2DM, 8 patients with impaired glucose tolerance (IGT) and 8 normoglycemic patients who underwent hyperinsulinemic euglycemic clamp (HEC). VLCD decreased plasma clusterin in OB but not in T2DM patients while LSG and HEC had no effect. Clusterin mRNA expression in SCAT at baseline was increased in OB and T2DM patients compared with controls. Clusterin mRNA expression decreased 6 months after LSG and remained decreased 12 months after LSG. mRNA expression of clusterin was elevated at the end of HE C compared with baseline only in normoglycemic but not in IGT or T2DM patients. In summary, our data suggest a possible local regulatory role for clusterin in the adipose tissue rather than its systemic involvement in the regulation of energy homeostasis., J. Kloučková, Z. Lacinová, P. Kaválková, P. Trachta, M. Kasalický, D. Haluzíková, M. Mráz, M. Haluzík., and Obsahuje bibliografii
Serum adipocyte fatty acid-binding protein (FABP-4) concentrations are linked to human obesity and other features of metabolic syndrome. Patients with Cushing's syndrome (CS) develop numerous features of metabolic syndrome due to chronic cortisol excess. Here we tested the hypothesis that chronically increased cortisol levels in CS patients may alter circulating levels of FABP-4. Fourteen patients with CS, 19 patients with simple obesity (OB) and 36 healthy control subjects (C) were included in the study. Serum FABP-4 concentrations were significantly higher in both CS and OB patients relati ve to C group, but they did not differ between CS and OB groups. In a combined population of all groups, serum FABP-4 levels correlated positively with BMI, body fat content, serum glucose, triglycerides, HbA1c and HOMA index and were inversely relate d to HDL-cholesterol, resting energy expenditure and freeT3 levels. We conclude that FABP-4 levels are significantly increased in both patients with simple obesity and obese patients with Cushing's syndrome. We suggest that increased FABP-4 concentrations in CS patients are rather due to their excessive fat accumulation and related metabolic abnormalities than due to a direct effect of cortisol on FABP-4 production., V. Ďurovcová, J. Marek, V. Hána, M. Matoulek, V. Zikán, D. Haluzíková, P. Kaválková, Z. Lacinová, M. Kršek, M. Haluzík., and Obsahuje bibliografii
The objective of this study was to measure plasma fibroblast growth factor 21 and 19 (FGF21 and FGF19) levels in patients with Cushing's syndrome (CS) and to compare it with those of lean control subjects (C) and patients with obesity (OB). Fourteen untreated patients with CS, 19 patients with OB and 36 controls were included in the study. Plasma FGF21 and FGF19 levels were measured by ELISA kits, other hormonal and biochemical parameters were measured by standard laboratory methods. Plasma FGF19 did not significantly differ among the studied groups. Plasma FGF21 levels were significantly higher in both CS and OB groups relative to C group but they did not differ between CS and OB groups. In a combined population of all three groups FGF21 levels positively correlated with BMI, waist circumference and percentage of total and truncal fat mass. Less prominent inverse relationship with these parameters was found for FGF19. Neither FGF21 nor FGF19 were significantly related to cortisol concentrations. Increased FGF21 concentrations in both patients with CS and OB relative to lean subjects suggest that excessive body fat and/or related metabolic abnormalities rather than direct effects of cortisol are responsible. In contrast neither obesity nor hypercortisolism significantly affected FGF19 concentrations., V. Ďurovcová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy