Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator produced primarily by the liver that exerts potent antidiabetic and lipid-lowering effects in animal models of obesity and type 2 diabetes mellitus. This hormone contributes to body weight regulation and is strongly involved in the response to nutritional deprivation and ketogenic state in mice. The principal sites of metabolic actions of FGF21 are adipose tissue, liver and pancreas. Experimental studies have shown marked improvements in diabetes compensation and dyslipidemia after FGF21 administration in diabetic mice and primates. Positive metabolic actions of FGF21 without the presence of apparent side effects make this factor a hot candidate to treat type 2 diabetes and accompanying metabolic diseases. The aim of this review is to summarize the current knowledge about the metabolic effects of FGF21 including some preliminary data on changes of its levels in humans with a special emphasis on its therapeutic potential in type 2 diabetes mellitus., I. Dostálová, D. Haluzíková, M. Haluzík., and Obsahuje seznam literatury
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
Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-α and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-α (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71- 1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35±1.42 vs. 5.97±1.29 109 l); APA vs. IHA: TNF-α (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63- 1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37±1.41 vs. 5.71±1.21 109 l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] μg/l, p≤0.003). No differences in inflammatory markers were observed between the followed groups, we confirmed higher levels of PINP in patients with PA., Z. Šomlóová, O. Petrák, J. Rosa, B. Štrauch, T. Indra, T. Zelinka, M. Haluzík, V. Zikán, R. Holaj, J. Widimský Jr., and Obsahuje bibliografii
Recent studies have demonstrated that adipocyte fatty acid binding proteins (FABP) may play a role in the etiopathogenesis of insulin resistance. The aim of our study was to assess serum FABP levels in obese patients with type 2 diabetes mellitus (T2DM) before and after 3 months of treatment with PPAR-α agonist fenofibrate (F) and to explore the relationship of FABP to biochemical parameters and measures of insulin sensitivity assessed by hyperinsulinemic-isoglycemic clamp. We measured biochemical parameters by standard laboratory methods, insulin sensitivity by hyperinsulinemic-isoglycemic clamp and serum concentrations of FABP by commercial ELISA kit in 11 obese females with T2DM before and after three months of treatment with PPAR-α agonist fenofibrate and in 10 lean healthy control women (C). Serum FABP levels were 2.5-fold higher in T2DM group relative to C and were not affected by fenofibrate treatment (C: 20.6±2.1 μg/l, T2DM before F: 55.6±5.7 μg/l, T2DM after F: 54.2±5.4 μg/l, p<0.0001 for C vs. T2DM before F). Hyperinsulinemia during the clamp significantly suppressed FABP levels in both C and T2DM group. FABP levels positively correlated with BMI, triglyceride levels, blood glucose, glycated hemoglobin, atherogenic index and insulin levels. An inverse relationship was found between FABP and HDL levels, metabolic clearance rate of glucose, M/I and MCRglc/I sensitivity indexes. We conclude that FABP levels are closely related to BMI, parameters of insulin sensitivity, HDL levels and measures of diabetes compensation. This combination makes FABP a valuable marker of metabolic disturbances in patients with type 2 diabetes mellitus., M. M. Haluzík ... [et al.]., and Obsahuje seznam literatury
Visfatin is an adipose tissue-derived hormone shown to correlate with visceral fat mass in patients with obesity. Its possible role in patients with different types of eating disorders is unknown. We measured fasting serum levels of visfatin and leptin and surrogate measures of insulin sensitivity in 10 untreated patients with anorexia nervosa (AN), 10 untreated patients with bulimia nervosa (BN) and 20 age-matched healthy women (C) to study the possible role of visfatin in these disorders. Patients with AN had severely decreased body mass index (BMI) and body fat content. BMI of BN group did not significantly differ from that of C group, whereas body fat content of BN group was significantly lower compared to C and higher compared to AN group, respectively. Serum glucose levels did not significantly differ among the groups studied, whereas serum insulin and leptin levels and HOMA index were significantly decreased in AN group relative to both C and BN group. In contrast, serum visfatin levels in both patients with AN and BN did not differ from those of C group. We conclude that circulating visfatin levels are not affected by the presence of chronic malnutrition in AN or binge/purge eating behavior in BN., I. Dostálová ...[et al.]., and Obsahuje seznam literatury
The aim of our study was to evaluate the influence of surgical removal of pheochromocytoma on the endocrine function of adipose tissue and subclinical inflammation as measured by circulating C-reactive protein (CRP) levels. Eighteen patients with newly diagnosed pheochromocytoma were included into study. Anthropometric measures, biochemical parameters, serum CRP, leptin, adiponectin and resistin levels were measured at the time of diagnosis and six months after surgical removal of pheochromocytoma. Surgical removal of pheochromocytoma significantly increased body weight, decreased both systolic and diastolic blood pressure, fasting blood glucose and glycated hemoglobin levels. Serum CRP levels were decreased by 50 % six months after surgical removal of pheochromocytoma (0.49±0.12 vs. 0.23±0.05 mg/l, p<0.05) despite a significant increase in body weight. Serum leptin, adiponectin and resistin levels were not affected by the surgery. We conclude that increased body weight in patients after surgical removal of pheochromocytoma is accompanied by an attenuation of subclinical inflammation probably due to catecholamine normalization. We failed to demonstrate an involvement of the changes in circulating leptin, adiponectin or resistin levels in this process., L. Bošanská ... [et al.]., and Obsahuje seznam literatury
Gastrointestinal hormones play an important role in the neuroendocrine regulation of food intake and postprandial satiety. Ghrelin is a 28-amino acid orexigenic peptide produced mainly by the stomach that is involved in both the long-term regulation of body weight and the short-term regulation of postprandial satiety. Impairments in ghrelin secretion may in concert with other factors play an important role in the development of both obesity and anorexia nervosa. Despite an intensive research the critical factors regulating physiological postprandial ghrelin response in healthy individuals and its modification by the presence of obesity and anorexia nervosa are only partially understood. The potential contribution of ghrelin to the differences of diet- vs. surgical-induced weight losses in morbidly obese patients is now also being recognized. The aim of this review is to summarize the current knowledge about the physiology and pathophysiology of ghrelin and to discuss its potential in the prevention and/or treatment of obesity and anorexia nervosa., I. Dostálová, M. Haluzík., and Obsahuje seznam literatury