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
Among the factors influencing weight loss and maintenance, psychobehavioral, nutritional, metabolic, hormonal and hereditary predictors play an important role. Psychobehavioral factors influence adherence to lifestyle changes and thus weight loss maintenance. The outcome of short-term weight reduction treatment is mainly affected by changes in energy and nutrient intake and physical activity and thus the impact of hormones can possibly be obscured. In order to reveal hormonal determinants of weight loss, a 4-week in-patient comprehensive weight reduction program was introduced in which food intake and physical activity were under the strict control. Women (n = 67, BMI: 32.4 ± 4.4 kg; age: 48.7 ± 12.2 years) who exhibited stable weight on a 7 MJ/day diet during the first week of weight management were given a hypocaloric diet yielding daily energy deficit 2.5 MJ over the subsequent 3-week period. This treatment resulted in a mean weight lo ss of 3.80 ± 1.64 kg. Correlation analysis revealed that baseline concentrations of several hormones were significantly associated either with a higher (free triiodothyronine, C-peptide, growth hormone, pancreatic polypeptide) or with a lower (insulin-like growth factor-I, cortisol, adiponectin, neuropeptide Y) reduction of anthropometric parameters in response to weight management. In a backward stepwise regression model age, initial BMI together with baseline levels of growth hormone, peptide YY, neuropetide Y and C-reactive protein predicted 49.8 % of the variability in weight loss. Psychobehavioral factors (items of the Eating Inventory, Beck Depression score) did not contribute to weight change induced by a well-controlled short-term weight reduction program., V. Hainer, K. Hlavatá, M. Gojová, M. Kunešová, M. Wagenknecht, V. Kopský, J. Pařízková, M. Hill, J. Nedvídková., and Obsahuje bibliografii a bibliografické údaje
Chronic inflammation of adipose tissue is associated with the pathogenesis of cardiovascular diseases. Mast cells represent an important component of the innate defense system of the organism. In our work, we quantified mast cell number in epicardial adipose tissue (EAT), subcutaneous adipose tissue (SAT), and right atrial myocardium (RA) in patients undergoing open heart surgery (n=57). Bioptic samples of EAT (n=44), SAT (n=42) and RA (n=17) were fixed by 4 % paraformaldehyde and embedded into paraffin. An anti-mast cell tryptase antibody was used for immunohistochemical detection and quantification of mast cells. We also demonstrated immunohistochemically the expression of CD117 and chymase markers. In EAT of patients with coronary artery disease (CAD), higher incidence of mast cells has been found compared to patients without CAD (3.7±2.6 vs. 2.1±1.2 cells/mm2 ). In SAT and RA, there was no difference in the number of mast cells in CAD and non-CAD patients. Mast cells in SAT, EAT and RA expressed CD117 and chymase. An increased incidence of mast cells in EAT of CAD patients may indicate the specific role of these inflammatory cells in relation to EAT and coronary arteries affected by atherosclerosis., Karolína Rozsívalová, Aneta Pierzynová, Helena Kratochvílová, Jaroslav Lindner, Michal Lipš, Tomáš Kotulák, Peter Ivák, Ivan Netuka, Martin Haluzík, Tomáš Kučera., and Obsahuje bibliografii
Obesity in children is accompanied by increased circulating leptin concentrations. Girls have higher leptin concentrations than boys. The aim of our study was to compare serum leptin levels before and after a five-week weight reduction program and to study the relationship of leptin levels, serum total cholesterol, and androgens (testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate) in 33 obese boys (age: 12.71.97 years, BMI: 30.46±4.54) and 66 obese girls (age: 12.7±2.51 years, BMI: 29.31±4.62). We found that serum leptin concentrations in obese children were significantly decreased after a weight reduction program (before 20.79±9.61 ng/ml, after 13.50±8.65 ng/ml in girls; before 12.25±10.09 ng/ml and after 5.18±3.56 ng/ml in boys, p<0.0001 in both genders). Leptin levels correlated positively with the body mass index before and after weight reduction. There was a positive association in obese boys and a negative one in obese girls between leptin levels and the WHR (waist to hip circumference ratio). Serum leptin also shows a strong relationship to fat distribution (p = 0.02 in boys, p<0.0001 in girls). No significant correlation was found between leptin concentrations and total cholesterol or androgens. We confirmed that leptin is a sensitive parameter of body composition and weight reduction in obese children., R. Pilcová, J. Šulcová, M. Hill, P. Bláha, L. Lisá., and Obsahuje bibliografii
Obesity is linked to a low-level chronic inflammatory state that may contribute to the development of associated metabolic complications. Retinol-binding protein 4 (RBP4) is an adipokine associated with parameters of obesity including insulin resistance indices, body mass index, waist circumference, lipid profile, and recently, with circulating inflammatory factors. Due to the infiltration of adipose tissue in obesity by macrophages derived from circulating monocytes and, on the other hand, the existence of a close genetic relationship between adipocytes and macrophages, we decided to examine if RBP4 is expressed in monocytes and/or primary human macrophages. While we did not detect expression of RBP4 in undifferentiated monocytes, RBP4 expression became evident during the differentiation of monocytes into macrophages and was highest in differentiated macrophages. Once we demonstrated the expression of RBP4 in macrophages, we checked if RBP4 expression could be regulated by inflammatory stimuli such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), or the endotoxin lipopolysaccharide (LPS). We observed that while RBP4 expression was strongly inhibited by TNF-α and LPS, it was not affected by IL-6. Our results highlight the complexity behind the regulation of this adipokine and demonstrate that RBP4 expression in macrophages could be modulated by inflammatory stimuli., M. Broch ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Leptin-melanocortin pathway plays an essential role in the body weight regulation. Enhanced melanocortin signaling in the hypothalamus results in both decreased food intake and increased energy expenditure. The discovery of monogenic obesities with dysfunction of melanocortin-4 receptor (MC4R) greatly contributed to understanding of energy balance regulation. This review presents phenotypical characterization and prevalence of the MC4R gene mutations. Genome-wide association studies revealed that MC4R gene is significantly related not only to monogenic obesities but also to common obesity. An interaction of variants in the MC4R gene with fat mass and obesity associated (FTO) gene significantly increases the risk for obesity, particularly in adolescence. On the other hand, about 15 % of the MC4R gene variants result in a gain of function that protects against obesity and is associated with favorable metabolic profile. Long-term attempts to activate the MC4R have recently been finalized by a discovery of setmelanotide, a novel specific MC4R agonist that is devoid of untoward cardiovascular side-effects. The employment of specific MC4R agonists may open new horizons not only in the treatment of rare monogenic obesities but also in some common obesities where stimulation of MC4R could be achieved., Vojtěch Hainer, Irena Aldhoon Hainerová, Marie Kunešová, Radka Taxová Braunerová, Hana Zamrazilová, Běla Bendlová., and Obsahuje bibliografii
The most common etiology of non- syndromic monogenic obesity are mutations in gene for the Melanocortin -4 receptor ( MC485 ) with variable prevalence in different countries (1.2 -6.3 % of obese children). The aim of our study was 1 ) to search for MC4R mutations in obese children in Slovakia and compare their prevalence with other European countries, and 2 ) to describe the phenotype of the mutation carriers. DNA analysis by direct Sanger sequencing of the coding exons and intron/exon boundaries of the MC4R gene was performed in 268 unrelated Slovak children and adolescents with body mass index above the 97 th percentile for age and sex and obesity onset up to 11 years (mean 4.3±2.8 years). Two different previously described heterozygous loss of function MC4R variants (i.e. p.Ser19Alafs*34, p.Ser127Leu) were identified in two obese probands, and one obese (p.Ser19Alafs*34), and one lean (p.Ser127Leu) adult family relatives. No loss of function variants were found in lean controls. The prevalence of loss -of-function MC4R variants in obese Slovak children was 0.7 %, what is one of the lowest frequencies in Europe., D. Stanikova, M. Surova, L. Ticha, M. Petrasova, D. Virgova, M. Huckova, M. Skopkova, D. Lobotkova, L. Valentinova, M. Mokan, J. Stanik, I. Klimes, D. Gasperikova., and Obsahuje bibliografii
Although the mutations in MC4R gene became known as the most common genetic cause of human obesity, the effect of rs12970134 A/G near MC4R gene on insulin resistance has been described. The aim of this study was to determine the effect of rs12970134 on obesity, hormone levels, and glucose metabolism in a cohort of women varying in glucose tolerance: 850 normoglycemic women, 423 diagnosed with polycystic ovary syndrome (PCOS), 402 gestational diabetics (GDM), and 250 type 2 diabetic (T2D) women. We did not confirm the explicit effect of rs12970134 on obesity. However, the influence of the A-allele on body adiposity index was observed in a cohort of women diagnosed with PCOS. In normoglycemic women, the A-allele carriership was associated with lower fasting levels of glucose, insulin, C-peptide, and index of insulin resistance. Furthermore, higher levels of growth hormone, leptin and SHBG, and lower levels of fT3, testosterone, and androstenedione were recorded in normoglycemic A-allele carriers. In conclusion, the study presents the evidence of the impact of rs12970134 on complex hypothalamic regulations., O. Bradnová, D. Vejražková, M. Vaňková, P. Lukášová, J. Včelák, S. stanická, K. Dvořáková, B. Bendlová., and Obsahuje bibliografii
Adipose tissue is an important target for thyroid hormones (TH). However, the metabolism of TH in white adipose tissue is poorly characterized. Our objective was to describe possible changes in activities of TH-metabolizing enzymes in white adipose tissue, and the role of TH metabolism in the tissue during obesogenic treatment, caloric restriction and in response to leptin in mice. Activity of type I iodothyronine 5’-deiodinase (D1) in white fat was stimulated by a high-fat diet, which also increased plasma leptin levels, while brown adipose tissue D1 activity did not change. Caloric restriction decreased the activity of D1 in white fat (but not in the liver), reduced leptin levels, and increased the expression of stearoyl CoA desaturase 1 (SCD-1), a marker and mediator of the effect of leptin on tissue metabolism. Leptin injections increased D1 activity and down-regulated SCD-1 in white fat. Our results demonstrate changes in D1 activity in white adipose tissue under the conditions of changing adiposity, and a stimulatory effect of leptin on D1 activity in the tissue. These results suggest a functional role for D1 in white adipose tissue, with D1 possibly being involved in the control of adipose tissue metabolism and/or accumulation of the tissue., Z. Macek Jílková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Neuromedin beta (NMB) is a member of the bombesin-like peptide family expressed in brain, gastroin testinal tract, pancreas, adrenals and adipose tissue. The aim of our study was to compare the frequency of P73T polymorphism in overweight and obese patients (37 men: age 50.6±11.7 years, BMI 41.1±7.8 kg/m2; 255 women: age 49.0±11.9 years, BMI 37.9±6.8 kg/m2) with that of healthy normal weight subjects (51 men: age 28.2±7.1 years, BMI 22.3±2.0 kg/m2; 104 women: age 29.1±9.1 years, BMI 21.5±1.9 kg/m2) and to investigate the polymorphism’s influence on anthropometric, nutritional and psychobehavioral parameters in overweight/obese patients both at the baseline examination and at a control visit carried out 2.5 years later, regardless of the patient́s compliance with the weight reduction program. No significant differences in the genotype distribution were demonstrated between normal weight and overweight/obese subjects. Male T allele non-carriers compared to T allele carriers had higher energy (p=0.009), protein (p=0.018) and fat (p=0.002) intakes and hunger score (p=0.015) at the beginning of treatment. Male T allele non-carriers had a more favorable response to weight management at the follow-up, as they exhibited a significant reduction in waist circumference, energy intake and depression score as well as a significant increase in dietary restraint. No significant differences between carriers and non-carriers were demonstrated in women at the baseline examination. Both female T allele carriers and non-carriers demonstrated similar significant changes in nutritional parameters and in restraint score at the follow-up. Nevertheless, only female non-carriers showed a significant decrease in the hunger score., J. Spálová, H. Zamrazilová, J. Včelák, M. Vaňková, P. Lukášová, M. Hill, K. Hlavatá, P. Šrámková, M. Fried, B. Aldhoon, M. Kunešová, B. Bendlová, V. Hainer., and Obsahuje bibliografii a bibliografické odkazy