Both, common gene variants and human adenovirus 36 (Adv36) are involved in the pathogenesis of obesity. The potential relationship between these two pathogenic factors has not yet been investigated. The aim of our study was to examine the association of obesity susceptibility loci with Adv36 status. Genotyping of ten gene variants (in/near TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, FTO) and analysis of Adv36 antibodies was performed in 1,027 Czech adolescents aged 13.0-17.9 years. Variants of two genes (PCSK1 and BDNF) were associated with Adv36 seropositivity. A higher prevalence of Adv36 antibody positivity was observed in obesity risk allele carriers of PCSK1 rs6232, rs6235 and BDNF rs4923461 vs. noncarriers (χ2=6.59, p=0.010; χ2=7.56, p=0.023 and χ2=6.84, p=0.033, respectively). The increased risk of Adv36 positivity was also found in PCSK1 variants: rs6232 (OR=1.67, 95 % CI 1.11-2.49, p=0.016) and rs6235 (OR=1.34, 95 % CI 1.08-1.67, p=0.010). PCSK1 rs6232 and BDNF rs925946 variants were closely associated with Adv36 status in boys and girls, respectively (χ2=5.09, p=0.024; χ2=7.29, p=0.026). Furthermore, PCSK1 rs6235 risk allele was related to Adv36 seropositivity (χ2=6.85, p=0.033) in overweight/obese subgroup. In conclusion, our results suggest that obesity risk variants of PCSK1 and BDNF genes may be related to Adv36 infection., L. Dušátková, H. Zamrazilová, I. Aldhoon Hainerová, R. L. Atkinson, B. Sedláčková, Z. P. Lee, J. Včelák, B. Bendlová, M. Kunešová, V. Hainer., and Obsahuje bibliografii
This study aimed to examine relationships between DHEA(S), anthropometric parameters, oral glucose tolerance test derived data and lipid spectra in a Czech non-diabetic population. 380 healthy volunteers both with and without a family history of diabetes type 2 (DM2) were en rolled into the study (women: n=235, age 28.9±9.4 years, BMI 22.3±4.5 kg/m2, men: n=145, age 32.3±10.0 years, BMI 24.7±3.6 kg/m2). Spearman’s correlations (both without and with the adjustment for age, age and BMI), as well as ANCOVA were used. Non-adjusted data showed many “beneficial” correlations between DHEA(S) and both anthropometric and metabolic variables. Statistical analysis revealed that almost all correlations of DHEA(S) to adiposity and fat distribution in men as well as in women disappeared after the adjustment. There are, however, differences between men and women in the correlation of DHEA(S) to insulin sensitivity and lipid levels. The use of hormonal contraceptives (COC) is also an important factor in this relationship. In men and also in women using COC, DHEA-S after adjustment correlated positively with fasting and stimulated glucose, insulin and C-peptide, and negatively with insulin sensitivity. In this respect, the benefit of DHEA(S) supplementation seems - at least in terms of its alleged antiobesity and antidiabetogenic effects - to be more than controversial., B. Bendlová, J. Vrbíková, M. Hill, M. Vaňková, P. Lukášová, J. Včelák, D. Vejražková, K. Dvořáková, R. Hampl, K. Vondra, L. Stárka., and Obsahuje bibliografii a bibliografické odkazy
Gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS) are distinct pathologies with impaired insulin sensitivity as a common feature. The aim of this study was to evaluate the response of fat tissue adipokines and gastrointestinal incretins to glucose load in patients diagnosed with one of the two disorders and to compare it with healthy controls. Oral glucose tolerance test (oGTT) was performed in 77 lean young women: 22 had positive history of GDM, 19 were PCOS patients, and 36 were healthy controls. Hormones were evaluated in fasting and in 60 min intervals during the 3 h oGTT using Bio-Plex ProHuman Diabetes 10-Plex Assay for C-peptide, ghrelin, GIP, GLP1, glucagon, insulin, leptin, total PAI1, resistin, visfatin and Bio-Plex ProHuman Diabetes Adipsin and Adiponectin Assays (Bio-Rad). Despite lean body composition, both PCOS and GDM women were more insulin resistant than controls. Significant postchallenge differences between the GDM and PCOS groups were observed in secretion of adipsin, leptin, glucagon, visfatin, ghrelin, GIP, and also GLP1 with higher levels in GDM. Conversely, PCOS was associated with the highest resistin, C-peptide, and PAI1 levels. Our data suggest that decreased insulin sensitivity observed in lean women with GDM and PCOS is associated with distinct hormonal response of fat and gastrointestinal tissue to glucose load., D. Vejrazkova, O. Lischkova, M. Vankova, S. Stanicka, J. Vrbikova, P. Lukasova, J. Vcelak, G. Vacinova, B. Bendlova., and Obsahuje bibliografii
Nucleoside diphosphate kinase 7, non-metastatic cells 7 (NME7) is an acknowledged member of ciliome and is involved in the biogenesis or function of cilia. As obesity and diabetes are common in several ciliopathies, we aimed to analyze changes of gene expression within Nme7 interactome in genetically designed rat models of metabolic syndrome. We assessed the liver transcriptome by Affymetrix microarrays in adult males of 14 PXO recombinant inbred rat strains and their two progenitor strains, SHR-Lx and BXH2. In the strains with the lowest expression of Nme7, we have identified significant enrichment of transcripts belonging to Nme7 interactome. In the subsequent network analysis, we have identified three major upstream regulators - Hnf4a , Ppara and Nr1h4 and liver steatosis (p=0.0001) and liver necrosis/cell death (apoptosis of liver cells, p=0.0003) among the most enriched Tox categories. The mechanistic network reaching the top score showed substantial overlap with Assembly of non-motile cilium and Glucose metabolism disorder gene lists. In summary, we show in a genetic model of metabolic syndrome that rat strains with the lowest expression of Nme7 present gene expression shifts of Nme7 interactome that are perturbing networks relevant for carbohydrate and lipid metabolism as well as ciliogenesis., L. Šedová, E. Školníková, M. Hodúlová, J. Včelák, O. Šeda, B. Bendlová., and Obsahuje bibliografii
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
Metabolic disorders such as obesity, insulin resistance and other components of metabolic syndrome (MetS) are connected with birth weight. Low and high birth weight is associated with a higher risk of developing type 2 diabetes mellitus, the mechanism is not clear. In this study, we evaluated the association between birth weight and anthropometric as well as biochemical components of MetS in women with a history of gestational diabetes mellitus (GDM) in comparison with control women. In part of the GDM group, we re-evaluated metabolic changes over 5-8 years. Anthropometry, blood pressure, glucose metabolism during the 3-h oGTT, lipid profile, uric acid, thyroid hormones, and liver enzymes were assessed. From the analyzed components of MetS in adult women we proved the association of low birth weight (birth weight <25th percentile) with glucose processing, in particular among women with a history of GDM. Low birth weight GDM women revealed significantly higher postchallenge insulin secretion and lower peripheral insulin sensitivity. Re-examinations indicate this association persists long after delivery., D. Vejrazkova, P. Lukasova, M. Vankova, O. Bradnova, G. Vacinova, J. Vcelak, V. Cirmanova, K. Andelova, H. Krejci, B. Bendlova., and Obsahuje bibliografii
The cyclical effects of hormones during the menstrual cycle (MC) are not just responsible for driving ovulation, but also have significant influence on dietary intake and appetite, as well as psychological and behavioral changes. The aim of our study was to describe changes and relationships between the MC and selected steroids, adipokines and food intake-related hormones. Twenty-seven women with regular menstrual cycles were included in the study, and their hormonal spectrum was measured in regular intervals starting from the first day of their cycle. Classical changes in gonadotropins, estrogens and progesterone during the menstrual cycle are accompanied by less striking but significant changes in 17-hydroxyprogesterone and testosterone. No significant changes show dehydroepiandrosterone and its 7-oxygenated metabolites. Adipokines show a tendency to increase during ovulation, while ghrelin and resistin decrease. There is also a remarkable association of sex hormone-binding globulin on the day of the cycle. Our results demonstrate that changes to adipokines during the menstrual cycle are not substantial, but nonetheless can play a role in the changes of food intake described in the literature. Precise descriptions of physiological changes in healthy women are important in helping us understand the significance of the changes accompanying various pathological states., M. Šrámková, M. Dušková, J. Vítků, J. Včelák, P. Matucha, O. Bradnová, J. de Cordeiro, L. Stárka., 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
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
Free fatty acids (FFAs) are natural ligands of the PPARγ2 receptor. FFA plasma concentration and composition may represent one of the factors accounting for high heterogeneity of conclusions concerning the effect of the Pro12Ala on BMI, insulin sensitivity or diabetes type 2 (DM2) susceptibility. Our objective was to investigate the relation and possible interactions between the Pro12Ala polymorphism and FFA status, metabolic markers, and body composition in 324 lean nondiabetic subjects (M/F: 99/225; age 32±11 years; BMI 23.9±4.0 kg/m2) with and without family history of DM2. Family history of DM2 was associated with lower % PUFA and slightly higher % MUFA. The presence of Pro12Ala polymorphism was not associated with fasting plasma FFA concentration or composition, anthropometric or metabolic markers of glucose and lipid metabolism in tested population. However, the interaction of carriership status with FFA levels influenced the basal glucose levels, insulin sensitivity and disposition indices, triglycerides, HDL-cholesterol and leptin levels, especially in women. The metabolic effects of 12Ala carriership were influenced by FFA levels – the beneficial role of 12Ala was seen only in the presence of low concentration of plasma FFA. Surprisingly, a high PUFA/SFA ratio was associated with lower insulin sensitivity, the protective effect of 12Ala allele was apparent in subjects with family history of DM2. On the basis of our findings and published data we recommend the genotyping of diabetic patients for Pro12Ala polymorphism of the PPARγ2 gene before treatment with thiazolidinediones and education of subjects regarding diet and physical activity, which modulate metabolic outcomes., B. Bendlová, D. Vejražková, J. Včelák, P. Lukášová, D. Burkoňová, M. Kunešová, J. Vrbíková, K. Dvořáková, K. Vondra, M. Vaňková., and Obsahuje bibliografii a bibliografické odkazy