Accumulation of adipose tissue in lower body lowers risk of cardiovascular and metabolic disorders. The molecular basis of this protective effect of gluteofemoral depot is not clear. The aim of this study was to compare the profile of expression of inflammation-related genes in su bcutaneous gluteal (sGAT) and abdominal (sAAT) adipose tissue at baseline and in response to multiphase weight-reducing dietary intervention (DI). 14 premenopausal healthy obese women underwent a 6 months’ DI consisting of 1 month very-low-calorie-diet (VLCD), subsequent 2 months’ low-calori e-diet and 3 months’ weight maintenance diet (WM). Paired samples of sGAT and sAAT were obtained before and at the end of VLCD and WM periods. mRNA expression of 17 genes (macrophage markers, cytokines) was measured using RT-qPCR on chip-platform. At baseline, there were no differences in gene expression of macrophage markers and cytokines between sGAT and sAAT. The dynamic changes induced by DI were similar in both depots for all genes except for three cytokines (IL6, IL10, CCL2) that differed in their response during weight maintenance phase. The results show that, in obese women, there are no major differences between sGAT and sAAT in expression of inflammation-related genes at baseline conditions and in response to the weight-reducing DI., L. Mališová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
First intron variability of the fat mass and obesity associated gene (FTO) has strong impact on adiposity. We focused on lean women carrying the most “obesity-risk” haplotype to study their anthropometric parameters and hormonal and metabolic profile. Genotype-phenotype correlation was performed in a group of 172 lean women (body mass index (BMI) ≥18.5 and <25 kg/m2; age 26.8±7.26 years), 77 of them used hormonal contraceptives. Even in lean women the association of the risk haplotype CAGA with BMI was confirmed but it did not influence the anthropometric indices of body composition. CAGA carriers compared to non-carriers had significantly higher both fasting (p=0.016) and post glucose load (p<0.001) levels of growth hormone (GH), significantly higher glucose, insulin and C-peptide levels in the late phase of oGTT and lower fasting concentration of total cholesterol and LDL-cholesterol. Administration of hormonal contraceptives further increased observed hormonal and metabolic effects in CAGA carriers. We conclude that higher levels of GH in lean women carrying the FTO “obesity risk” haplotype could protect them from the development of obesity. The relation between the FTO gene variability and GH secretion has to be elucidated. This is the first study demonstrating the interaction of FTO genotype with hormonal contraception., P. Lukášová, M. Vaňková, J. Včelák, D. Vejražková, O. Bradnová, S. Stanická, V. Hainer, B. Bendlová., and Obsahuje bibliografii
Bariatric surgery is the most effective method in the treatment of obesity and type 2 diabetes (T2DM). The aim of this study was to evaluate the effects of different types of bariatric procedures on remission of T2DM and on the fatty acid composition in subcutaneous adipose tissue. Patients included obese diabetic women who underwent bariatric surgery: biliopancreatic diversion (BPD), n=8, laparoscopic gastric banding (LAGB), n=9 or laparoscopic greater curvature plication (LGCP), n=12. Anthropometric characteristics and fatty acid composition of adipose tissue (FA AT) were analyzed before surgery, then 6 months and 2 years after surgery. FA AT was analyzed by gas chromatography. Diabetes remission was estimated. BPD was most efficient in inducing a remission of diabetes (p=0.004). Significantly higher increases in lauric (12:0), myristoleic (14:1n-5) and palmitoleic (16:1n-7) acids and delta-9 desaturase were found two years after BPD, suggesting higher lipogenesis in adipose tissue. Docosatetraenoic acid (22:4n-6) increased significantly after BPD, while docosapentaenoic acid (22:5n-3) decreased 6 months after BPD and increased after 2 years. No changes were found after LAGB and LGCP after 2 years. Bariatric surgery led to significant changes in the fatty acid composition of subcutaneous adipose tissue in severely obese diabetic women after six months and two years, and was partly influenced by the type of surgery used., M. Kunešová, B. Sedláčková, O. Bradnová, E. Tvrzická, B. Staňková, P. Šrámková, K. Dolešalová, P. Kalousková, P. Hlavatý, M. Hill, B. Bendlová, M. Fried, V. Hainer, J. Vrbíková., and Obsahuje bibliografii
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
To investigate the relationship between early nutritional experience, ontogeny of the small intestinal functions and predisposition to obesity development, the following experimental models of male Sprague-Dawley rats were used: 1) rats in which the quantity of nutrition was manipulated from birth to weaning (day 30) by adjusting the number of pups in the nest to 4 (SL), 10 (NL) and 16 pups (LL) and 2) littermates of SL, NL and LL rats fed either a standard or a hypercaloric diet from days 80 to 135 of age. The overfed SL pups were overweight after day 15 and became permanently obese, whereas the underfed smaller LL pups, due to accelerated growth and enhanced food intake from day 30 to day 35, attained a body fat level that did not differ from normally fed NL rats. Moreover, a significantly increased duodenal and jejunal alkaline phosphatase (AP) activity was found in SL and LL rats and these acquired somatic and intestinal characteristics persisted from weaning throughout life. Eight weeks of high-energy diet feeding elicited a similar pattern of intestinal response in SL and LL rats that was clearly different from NL rats. Despite energy overconsumption in these three groups, both SL and LL rats still displayed enhanced AP activity and showed a significant increase in protein/DNA ratio accompanied with a significant body fat accretion. These results indicate that the postnatally acquired small intestinal changes induced by over- and undernutrition could be involved in the similar predisposition to obesity risk in later life when caloric density of the diet is raised., Š. Možeš, Z. Šefčíková, Ľ. Lenhardt., and Obsahuje bibliografii a bibliografické odkazy
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