The prevalence of obesity is increasing worldwide at an alarming rate in both developed and developing countries. Obesity is a chronic complex disease of multifactorial origin resulting from a long-term positive energy balance, in which both genetic and environmental factors are involved. Genetically prone individuals are the first to accumulate fat in the present obesogenic environment. Obesity increases the risks of type 2 diabetes, hypertension, cardiovascular disease, dyslipidemia, arthritis, and several cancers and reduces the average life expectancy. Implementation of effective strategies in prevention and management of obesity should be come an important target in health care systems. Weight changes throughout life depend on the interaction of behavioral, genetic and environmental factors. Weight loss in response to weight management shows a wide range of interindividual variation which is largely influenced by genetic determinants. The strong control of weight loss by genotype was confirmed by twin and family studies. Recently, special attention has been paid to nutritional, hormonal, psychobehavioral and genetic factors which can predict the response to weight reduction programme. In this article currently available data on the role of obesity candidate gene polymorphisms in weight loss and maintenance are reviewed. It is believed that an elucidation of the genetic component in the prognosis of weight management could assist in the development of more effective and individually tailored therapeutic strategies., V. Hainer, H. Zamrazilová, J. Spálová, I. Hainerová, M. Kunešová, B. Aldhoon, B. Bendlová., and Obsahuje bibliografii a bibliografické odkazy
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
Omentin is a novel adipokine with insulin-sensitizing effects expressed predominantly in visceral fat. We investigated serum omentin levels and its mRNA expression in subcutaneous adipose tissue (SCAT) of 11 women with type 2 diabetes mellitus (T2DM), 37 obese non-diabetic women (OB) and 26 healthy lean women (C) before and after various weight loss interventions: 2-week very-low-calorie diet (VLCD), 3-month regular exercise and laparoscopic sleeve gastrectomy (LSG). At baseline, both T2DM and OB groups had decreased serum omentin concentrations compared with C group while omen tin mRNA expression in SCAT did not significantly differ among the groups. Neither VLCD nor exercise significantly affected serum omentin concentrations and its mRNA expression in SCAT of OB or T2DM group. LSG significantly increased serum omen tin levels in OB group. In contrast, omentin mRNA expression in SCAT was significantly reduced after LSG. Baseline fasting serum omentin levels in a combined group of the studied subjects (C, OB, T2DM) negatively correlated with BMI, CRP, insulin, LDL-cholesterol, triglycerides and leptin and we re positively related to HDL- cholesterol. Reduced circulating omentin levels could play a role in the etiopathogenesis of obesity and T2DM. The increase in circulating omentin levels and the decrease in omentin mRNA expression in SCAT of obese women after LSG might contribute to surgery-induced metabolic improvements and sustained reduction of body weight., M. Urbanová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The aim of our study was to measure serum concentrations of fibroblast growth factor 19 (FGF-19) in patients with obesity (OB), obesity and type 2 diabetes mellitus (T2DM) and healthy subjects (C) at baseline and after selected interventions. We measured serum FGF-19 levels and other biochemical and hormonal parameters in 29 OB and 19 T2DM females and 30 sex- and age-matched control subjects. The interventions were acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp (n=11 for T2DM and 10 for C), very-low calorie diet (VLCD, n=12 for OB) and 3 months treatment with PPAR- α agonist fenofibrate (n=11 for T2DM). Baseline serum FGF-19 levels were significantly lower in OB relative to C group (132.1±12.7 vs. 202.2±16.7 pg/ml, p<0.05), while no significant difference was observed between T2DM and OB or control group. Acute hyperinsulinemia tended to decrease FGF-19 levels in both healthy and T2DM subjects. Three weeks of VLCD in OB group had no significant effect on FGF-19, whereas three months of fenofibrate treatment markedly reduced FGF-19 levels in T2DM patients (194.58±26.2 vs. 107.47±25.0 pg/ml, p<0.05). We conclude that FGF-19 levels in our study were at least partially dependent upon nutritional status, but were not related to parameters of glucose metabolism or insulin sensitivity., M. Mráz ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Ghrelin is a new endogenous ligand for the growth hormone secretagogue receptor. It activates the release of growth hormone from the pituitary and it also participates in the regulation of energy homeostasis. The aim of the study was to characterize changes in serum ghrelin levels in obese subjects and their relationship to the serum levels of leptin and soluble leptin receptor. Eight obese patients (6 women and 2 men) with body mass index (BMI) 40.313.4 kg.m-2 and eight healthy controls (5 women and 3 men) with BMI 22.7±1.3 kg.m-2 were examined. The ghrelin serum levels (165.0±58.1 vs. 343.37±81.96; p<0.001) and soluble leptin receptor serum levels (7.25±3.44 vs. 21.80±4.99; p<0.0001) were significantly lower in obese patients. The leptin serum levels (23.45±12.90 vs. 6.41±2.96; p<0.005) were significantly higher compared to the lean subject group. In both measured groups the levels of serum leptin significantly positively correlated with BMI. We proved a significantly lower serum ghrelin levels in the group of obese patients in comparison with the control group., M. Rosická, M. Kršek, M. Matoulek, Z. Jarkovská, J. Marek, V. Justová, Z. Lacinová., and Obsahuje bibliografii
It is believed that omentin is secreted by stromal cells of adipose tissue and modulates insulin se nsitivity. Data from a few studies have shown lower serum omentin in obese children and higher in anorexia nervosa. However, to date, there is lack of research on serum omentin concentrations in adolescent patients in a wide range of body mass index (BMI) and insulin resistance. In this cross -sectional study omentin -1 serum concentrations were evaluated using commercially available ELISA kit in 47 Polish girls with restrictive anorexia nervosa (AN), 50 with simple obesity (OB) and 39 healthy controls (C). T he mean serum omentin -1 concentration in girls with AN was statistically significantly higher than that of C and OB girls. Statistically significant (P<0.0001) negative correlations between the serum concentrations of omentin- 1 and body weight (r= - 0.73), BMI (r= - 0.75), standard deviation score for body mass index (BMI -SDS) (r= - 0.75), insulin (r= - 0.81) and HOMA -IR index (r= - 0.82) were seen in the entire examined population. We conclude, that omentin -1 is the nutritional marker reflecting body weight and insulin resistance. Our findings support the hypothesized role of omentin in maintenance of body weight and regulation of appetite and suggest the adaptation of its secretion to body weight and glucose metabolism., J. Oświęcimska, A. Suwała, E. Świętochowska, Z. Ostrowska, P. Gorczyca, K. Ziora-Jakutowicz, E. Machura, M. Szczepańska, M. Kukla, M. Stojewska, D. Ziora, K. Ziora., and Obsahuje bibliografii
The local concentration of glucocorticoids is intensively regulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD 1). Human 11β-HSD 1 also reversibly catalyzes the inter-conversion of 7α-hydroxy- and 7β-hydroxy-dehydroepiandrosterone (DHEA) into 7-oxo-DHEA. The cohort of 282 obese adolescents, 154 girls (median age 15.31 years, range 14.17-16.68 years) and 128 boys (median age 14.95 years, range 13.87-16.16 years), BMI (Body Mass Index) >90th percentile was examined. In samples collected before and after one month of reductive diet therapy, circulating levels of steroids were analyzed by liquid chromatography-tandem mass spectrometry and radioimmunoassay methods. The model of the treatment efficacy prediction was calculated. A significant reduction in circulating levels of cortisone, E2 and increased levels of 7β-hydroxy-DHEA after the reductive treatment was observed. Levels of cortisol, DHEA, DHT sustained without any significant change. The predictive Orthogonal Projections to Latent Structures (OPLS) model explained 20.1 % of variability of BMI, z-score change by the basal levels of 7α-hydroxy-DHEA, DHEA, cortisol and E2 as the strongest predictors. Reduced levels of circulating cortisone and reduced ratios of oxygenated/reduced metabolites reflect increased reductase activity of 11β-HSD 1 with reduced BMI, z-score. We hypothesize whether these changes can be attributed to the altered activity of 11β-HSD 1 in the liver., L. Máčová, L. Sosvorová, J. Vítků, M. Bičíková, M. Hill, H. Zamrazilová, B. Sedláčková, L. Stárka /., and Obsahuje bibliografii
The gene for connexin 37 (Cx37) is considered to be one of the candidate genes for cardiovascul ar disease. We evaluated the association between Cx37 (1019C>T) gene polymorphism (Pro319Ser) and ankle brachial blood pressure index (ABI) in women with type 1 (n=178) and ty pe 2 (n=111) diabetes, and in women from general population (n=862). All women were genotyped for Cx37 polymorphism. In addition to traditional cardiovascular risk factors, ABI was analyzed. In women with type 1 diabetes, ABI significantly decreased from TT to CC carriers (p for trend= 0.008). A similar trend was seen in women with type 2 diabetes (p=0.050) and in women with waist circumference above 75 th percentile (94 cm; n=208) of the general population (p=0.049). The gene for Cx37 was associated with subclinical atherosclerosis in women with type 1 and 2 diabetes and in women with advanced central obesity. The presence of C allele indicated increased risk., J. Piťha, J. A. Hubáček, P. Piťhová., and Obsahuje bibliografii
a1_Renal transplantation is associated with a large number of risk factors that can have an influe nce on early renal graft function (ERGF). One of these factors could be the increasing number of obese kidney donors. The mechanisms of reduced ERGF in obese kidney donors are still poorly understood. To that end, w e compared ERGF in recipients with body mass index (BMI), perivascular fat and plasma inflammation markers of live kidney donors. We hypothesi zed that the BMI of donors would negatively correlate with an average increase of glomerular filtration rate (GFR ) and that it would also be associated wi th increased perivascular and plasma inflammation markers in the first seven days after transplantation. Between January 2013 and December 2014, some 58 living kidney transplantation pairs were included in the study. Donor and recipient demographic data, preoperative BMI, blood C -reactive protein (CRP) and adiponectin levels, perivascular adipose tissue (PAT) samples and recipient blood creatinine levels were analy zed. The median CRP of donors was 0.68 mg/l (max: 8.66 mg/l, min: 0.33 mg/l), the median of M1 macrophages (CD14+CD16+) in one gram of PAT was 5940 (max: 41 100, min: 248) and the median of adiponectin was 411 930 pg/ml (max: 14 217 000, min: 167 300) in plasma. We did not find any association between early renal graft function and the percentage o f M1 macrophages in donor perirenal adipose tissue (p=0.83, r=0.03, n=58), adiponectin (p=0.65, r=0.06, n=58) or CRP (p=0.16, r=0.2, n=58) in plasma. The obesity level of donors, expressed as BMI, did not correlate with early renal graft function in the first seven days after transplantation. The associations between ERGF and plasma and perivascular fat inflammation markers were not significant., a2_We confirmed a negative correlation between the BMI of recipients and an average increase of GFR in the first sev en days after transplantation (p<0.02, r= -0.325, N=58). We confirmed a negative correlation of adiponectin plasma concentration to the BMI of donors., F. Thieme, L. Janousek, J. Fronek, A. Kralova, S. Cejkova, I. Kralova Lesna, R. Poledne., and Obsahuje bibliografii
Type 2 diabetes (T2D) as well as cardiovascular disease (CVD) represent major complications of obesity and associated metabolic disorders (metabolic sy ndrome). This review focuses on the effects of long-chain n-3 polyunsaturated fatty acids (omega-3) on insulin sensitivity and glucose homeostasis, which are improved by omega-3 in many animal models of metabolic syndrome, but remain frequently unaffected in humans. Here we focus on: (i) mechanistic aspects of omega-3 action, reflecting also our experiments in dietar y obese mice; and (ii) recent studies analysing omega-3’s effects in various categories of human subjects. Most animal experiments document beneficial effects of omega-3 on insulin sensitivity and glucose metabolism even under conditions of established obesity and insulin resistance. Besides positive results obtained in both cross- sectional and prospective cohort studies on healthy human populations, also some intervention studies in prediabetic subjects document amelioration of impaired glucose homeostasis by omega-3. However, the use of omega-3 to reduce a risk of new-onset diabetes in prediabetic subjects still remains to be further characterized. The results of a majority of clinical trials performed in T2D patients suggest that omega-3 have none or marginal effects on metabolic control, while effectively reducing hypertriglyceridemia in these pati ents. Despite most of the recent randomized clinical trials do not support the role of omega-3 in secondary prevention of CVD, this issue remains still controversial. Combined interventions using omega-3 and antidiabetic or hypolipidemic drugs should be further explored and considered for treatment of patients with T2D and other diseases., P. Flachs, M. Rossmeisl, J. Kopecky., and Obsahuje bibliografii a bibliografické odkazy