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
Moderately elevated plasma/serum triglycerides (2 -10 m mol/l) signalize increased risk for cardiovascular disease or presence of non- alcoholic steatohepatitis. Extremely elevated triglycerides (more than 10 mmol/l) signalize increased risk for pancreatitis and lipemia retinalis. The concentration of triglycerides is regulated by many genetic and nongenetic factors. Extremely elevated triglycerides not provoked by nutritional factors, especially inappropriate alcohol intake are more likely to have a monogenic cause. On the contrary, mildly to moderately elevated triglycerides are often caused by polygenic disorders; these could be also associated with central obesity, insulin resistance, and diabetes mellitus. Concentration of triglycerides is also closely interconnected with presence of atherogenic remnant lipop roteins, impaired reverse cholesterol transport and more atherogenic small LDL particles. In general, there is tight association between triglycerides and many other metabolic factors including intermediate products of lipoprotein metabolism which are freq uently atherogenic. Therefore, reliable evaluation of the independent role of triglycerides especially in atherosclerosis and cardiovascular disease is difficult. In individual cases values of HDL cholesterol, non -HDL cholesterol (total minus HDL cholester ol), non -HDL/nonLDL cholesterol (total minus HDL minus LDL cholesterol, especially in nonfasting status), atherogenic index of plasma and/or apolipoprotein B could help in decisions regarding a ggressiv eness of treatment., J. Piťha, J. Kovář, T. Blahová., 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
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
The issue of plasma triglyceride levels relative to the risk of development of cardiovascular disease, as well as overall mortality, has been actively discussed for many years. Like other cardiovascular disease risk factors, final plasma TG values have environmental influences (primarily dietary habits, physical activity, and smoking), and a genetic predisposition. Rare mutations (mainly in the lipoprotein lipase and apolipoprotein C2) along with common polymorph isms (within apolipoprotein A5, glucokinase regulatory protein, apolipoprotein B, apolipo - protein E, cAMP responsive element binding protein 3 -like 3 , glycosylphosphatidylinositol- anchored HDL -binding protein 1) play an important role in determining plasma TG levels., L. Schwarzova, J. A. Hubacek, M. Vrablik., 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 aims were to explore the effect of head-up tilt (HUT) to 30 and 60 degrees on hemodynamics and tissue oxygenation in anesthetized healthy swine. The data serve as a reference for a study of resuscitation efficacy at HUT such as during transport. Nine healthy swine (49±4 kg) were anesthetized and multiple sensors including myocardial pressure-volume loops catheter, carotid flow probe, blood pressure catheters, near infrared spectroscopy (NIRS) tissue oximetry and mixed venous oximetry (SVO2) catheter were introduced and parameters continuously recorded. Experimental protocol consisted of baseline in supine position (15 min), 30 degrees HUT (15 min), recovery at supine position (15 min) and 60 degrees HUT (5 min). Vacuum mattress was used for body fixation during tilts. We found that 30 and 60 degrees inclination led to significant immediate reduction in hemodynamic and oximetry parameters. Mean arterial pressure (mm Hg) decreased from 98 at baseline to 53 and 39, respectively. Carotid blood flow dropped to 47 % and 22 % of baseline values, end diastolic volume to 49 % and 53 % and stroke volume to 47 % and 45 % of baseline. SVO2 and tissue oximetry decreased by 17 and 21 percentage points. The values are means. In conclusions, within minutes, both 30 and 60 degrees head-up tilting is poorly tolerated in anesthetized swine. Significant differences among individual animals exist., M. Mlcek, J. Belohlavek, M. Huptych, T. Boucek, T. Belza, S. Lacko, P. Krupickova, M. Hrachovina, M. Popkova, P. Neuzil, O. Kittnar., and Obsahuje bibliografii
The aim of the study was to evaluate short-term heart rate variability (HRV) as an index of cardiac autonomic control in rats with lipopolysaccharide (LPS)-induced endotoxemia. Animals were injected intraperitoneally with LPS (100 μg/kg b.w.) and control group with an equivalent volume of saline. ECG recordings were done before (base) and 60, 120, 180, 240 and 300 min after LPS or saline administration. HRV magnitude was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD, spectral powers in low (LF) and high frequency (HF) bands. Heart tissue homogenates and plasma were analyzed to determine interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and oxidative stress level (TBARS). Administration of lipopolysaccharide was followed by continuous rise in colonic body temperature compared to saline-treated controls. Endotoxemia in rats was accompanied by significant decrease in HRV spectral activity in high-frequency range at maximal body temperature (logHFpower: 1.2±0.5 vs. 1.9± 0.6 ms2, P<0.01). Increased IL-6 was found in heart tissue homogenates of LPS rats (8.0±0.6 vs. 26.4±4.8 pg/ml, (P<0.05). In conclusions, reduced HRV in HF band may indicate a decreased parasympathetic activity in LPS-induced endotoxemia as basic characteristics of altered cardiac control during response to endotoxemia., I. Zila, D. Mokra, J. Kopincova, M. Kolomaznik, M. Javorka, A. Calkovska., and Obsahuje bibliografii
Heart rate (HR) and heart rate variability (HRV) in newborns is influenced by genetic determinants, gestational and postnatal age, and other variables. Premature infants have a reduced HRV. In neonatal HRV evaluated by spectral analysis, a dominant activity can be found in low frequency (LF) band (combined parasympathetic and sympathetic component). During the first postnatal days the activity in the high frequency (HF) band (parasympat hetic component) rises, together with an increase in LF band and total HRV. Hypotrophy in newborn can cause less mature autonomic cardiac control with a higher contribution of sympathetic activity to HRV as demonstrated by sequence plot analysis. During quiet sleep (QS) in newborns HF oscillations increase - a phenomenon less expressed or missing in premature infants. In active sleep (AS), HRV is enhanced in contrast to reduced activity in HF band due to the rise of spectral activity in LF band. Comparison of the HR and HRV in newborns born by physiological vaginal delivery, without (VD) and with epidural anesthesia (EDA) and via sectio cesarea (SC) showed no significant differences in HR and in HRV time domain parameters. Analysis in the frequency domain re vealed, that the lowest sympathetic activity in chronotropic cardiac chronotropic regulation is in the VD group. Different neonatal pathological states can be associated with a reduction of HRV and an improvement in the health conditions is followed by ch anges in HRV what can be use as a possible prognostic marker. Examination of heart rate variability in neonatology can provide information on the maturity of the cardiac chronotropic regulation in early postnatal life, on postnatal adaptation and in pathological conditions about the potential dysregulation of cardiac function in newborns, especially in preterm infants., K. Javorka, Z. Lehotska, M. Kozar, Z. Uhrikova, B. Kolarovszki, M. Javorka, M. Zibolen., and Obsahuje bibliografii