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Local metabolism of glucocorticoids in female Prague hereditary hypertriglyceridemic rats
Klusoňová, Petra ; Pácha, Jiří (advisor) ; Kopecký, Jan (referee) ; Haluzík, Martin (referee)
11-hydroxysteroid dehydrogenase (11HSD1) is an oxidoreductase which catalyzes conversion of inactive 11-oxo steroid derivatives into active 11-hydroxy forms. 11HSD1 elevates intracellular level of active glucocorticoid (GC) hormones: cortisol in human tissues and corticosterone in rodents, therefore local level of active GCs can be set independently from systemic secretion driven by hypothalamo-pituitary-adrenal axis (HPA axis). Chronic systemic excess of GCs results in development of Cushing's syndrome which is characterised by central obesity and other metabolic disturbances. Despite normal serum levels of GCs, the patients with idiopathic obesity also develop metabolic syndrome. It was suggested that GCs could be elevated locally in target tissues due to enhanced 11HSD1 activity. This hypothesis was confirmed in transgenic rodent models. Prague hereditary hypertriglyceridemic (HHTg) rats represent a non-obese model of metabolic syndrome without genetic manipulations or specific mutations. The strain was bred by cross-mating of Wistar rat individuals with elevated serum levels of triglycerides (TGs). The strain exhibit hypertriglyceridemia and hypertension. When kept on high carbohydrate diet HHTg rats exhibit alterations in glucose homeostasis. Since there are no data that would describe...
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Evaluation of Selected Biochemical Markers of Metabolic Syndrome and Adipose Tissue After Bariatric Surgery
Horká, Veronika ; Bužga, Marek (advisor) ; Holéczy, Pavol (referee)
The diploma thesis deals the problematics of weight reduction with the using of bariatric- metabolic surgery and focuses on the changing risk components of the metabolic syndrome during one year long observation of 45 probands who have undergone Partial Jejuno-Ileal Diversion, Laparoscopic Sleeve Gastrectomy or Laparoscopic Gastric Plication. The main aim of the diploma thesis is to evaluate the changing risk components of the metabolic syndrome during weight reduction after undergoing bariatric surgery. The thesis shows that in the studied sample of bariatric patients it is an effective method of weight reduction (in PJID the success rate was 48 % EWL, in LGCP 51 % EWL and the most successful was LSG with 76 % EWL) with metabolic effect such as for example observed positive changes in risk components of the metabolic syndrome - reduction of morning glucose levels, increase of HDL cholesterol and decrease of triacylglycerols in the blood, decrease of waist circumferences and decrease of blood pressure or elimination of metabolic syndrome. Up to 68.9 % of the monitored probands showed signs of metabolic syndrome when evaluating the initial measurement before bariatric surgery, the remaining 22.2 % of the probands showed the signs after the year's observation. As part of the risk assessment for the...
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Surgical models of the study of the pro-inflammatory effect of adipose tissue in the development of atherosclerosis
Thieme, Filip ; Froněk, Jiří (advisor) ; Vrablík, Michal (referee) ; Broďák, Miloš (referee)
Univerzita Karlova v Praze 1. lékařská fakulta Doktorský studijní program Studijní obor: Experimentální chirurgie MUDr. Filip Thieme Název závěrečné práce Chirurgické modely studia proinflamačního vlivu tukové tkáně v rozvoji aterosklerózy Title Surgical models of the study of the pro-inflammatory effect of adipose tissue in the development of atherosclerosis Typ závěrečné práce Disertační Školitel: doc. MUDr. Jiří Froněk, Ph.D., FRSC Konzultant doc. MUDr. Libor Janoušek, Ph.D. Klinika transplantační chirurgie, IKEM Praha, 2021 Abstract Background: Atherosclerosis is a serious inflammatory systemic disease. Surgery mainly addresses its vascular complications. Conversely, surgery may also lead to the development and acceleration of atherosclerosis, e.g., in a living kidney donor. This would especially be the case in a donor who meets internationally recognized donation criteria but suffers from metabolic syndrome. The effort to refine assessments of living kidney donors in terms of eliminating the risk of developing atherosclerosis is a long-term project. Our aim is to determine risk factors for living kidney donors and to prevent long-term complications after donation. Collecting tissue from a living donor involves not oly subcutaneous tissue (SCAT) but also visceral (VAT) and perivascular tissue (PVAT),...
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Activity of antioxidant enzymes in different pathophysilogical states.
Vávrová, Lucie
Background: Oxidative stress is supposed to be implicated in the pathogenesis of several diseases which are connected with increased formation of reactive oxygen and nitrogen species (RONS). Oxidative stress could play an important role in the pathogenesis of inflammation and sepsis, acute and chronic pancreatitis or in the development of cancer. Organisms are protected against RONS from antioxidant system that is composed of antioxidant enzymes and non-enzymatic antioxidants. To the most important antioxidant enzymes belong superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase, glutathione reductase and paraoxonase (PON). The aim of this Doctoral Thesis was to investigate the behaviour of three of these antioxidant enzymes - CuZnSOD, CAT and PON1 in different pathophysiological states. Materials and methods: The activities of CuZnSOD, CAT and PON1 were measured in six different pathophysiological states. Forty patients with metabolic syndrome (MetS), 35 women with depressive disorder (DD), 30 septic patients (SP), 50 patients with pancreatic cancer (PC), 50 patients with chronic pancreatitis (CP) and 13 patients with acute pancreatitis (AP) were included in different studies together with sex- and age-matched healthy controls (CON). Patients with AP and SP were observed in the course...
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Effects of n-3 polyunsaturated fatty acids on development of non-alcoholic fatty liver disease in experiment, prevalence in patients with type 2 diabetes mellitus and metabolic syndrome, non-invasive diagnostics
Dvořák, Karel ; Brůha, Radan (advisor) ; Ehrmann, Jiří (referee) ; Lotková, Halka (referee)
This thesis focuses on the effects of n-3 polyunsaturated fatty acids (n-3 PUFA) on development of non-alcoholic fatty liver disease (NAFLD) in experiment, on prevalence of this condition in patients with type 2 diabetes mellitus and metabolic syndrome and also on non-invasive diagnostics. The aim was to study the effect of n-3 PUFA on NAFLD development in an experimental model and based on analysis of a group of patients with type 2 diabetes and metabolic syndrome to assess the prevalence of this condition. Lastly we aimed to evaluate non-invasive diagnostic methods of liver fibrosis and NASH. We demonstrated beneficial effects of n-3 PUFA administration on NAFLD development in a C57/Bl6 mice high fat methionin-cholin defficient dietary model of NAFLD. n-3 PUFA administration led to biochemical improvement, decrease of lipid accumulation in the liver as well as improvement of histology. These effects are determined by complex modulation of lipid metabolism, mainly due to decrease in availability of fatty acids for triglyceride synthesis in the liver, changes of adipokine levels and amelioration of proinflammatory status in the liver. In a group of type 2 diabetics we found NAFLD prevalence of almost 80%, 14% of these patients had also signs of liver fibrosis or cirrhosis. Non-invasive methods...
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Functional genomic and pharmacogenomic analysis of metabolic syndrome aspects
Krupková, Michaela ; Šeda, Ondřej (advisor) ; Haluzík, Martin (referee) ; Polák, Jan (referee)
Metabolic syndrome is a prevalent disease characterized by concurrent manifestation of insulin resistance, obesity, dyslipidemia, hypertension and other hemodynamic and metabolic disorders. It has multifactorial type of inheritance and its resultant phenotype is determined by both environmental and genetic factors as well as their interactions. That is the main reason why comprehensive analysis of the genetic component of this syndrome is complicated in human population. Genetically designed experimental animal models are significant tools for analysis of genetic architecture of human complex conditions including the metabolic syndrome. The aim of this Thesis is utilization of functional and comparative genomic tools to uncover pathogenesis of metabolic syndrome aspects and their genetic determinants. We also studied pharmacogenetic interactions of these genetic determinants with drugs affecting particular components of the metabolic syndrome. Establishing and utilizing several genetically designed congenic rat strains, we undertook four different research projects focusing on pharmacogenetic interaction of all-trans retinoic acid and ondansetron with differential segment of rat chromosome 8, pharmacogenetic interaction of differential segment of rat chromosome 4 and dexamethasone, determining Plzf...
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Effect of fatty acids on lipid metabolism and weight reduction
Hlavatý, Petr ; Kunešová, Marie (advisor) ; Müllerová, Dana (referee) ; Flachs, Pavel (referee)
Fat tissue plays a main role in the development of the metabolic syndrome. Many components of the metabolic syndrome may be improved by dietary arrangements, including an increased intake of n-3 PUFA. In addition to the positive effect of n-3 PUFA, a possible effect of a higher calcium intake on influencing weight loss and energy metabolism has also been discussed for a long time. In addition to nutritional factors, genetic factors significantly contribute to influencing weight and lipid and glucose metabolism. In study A, 40 obese women were observed during three weeks of weight reduction management. Women were randomly divided into two groups. The first group received yogurt enriched with n-3 PUFA, and the second group consumed yoghurt without the supplementation. The results show that low-dose supplementation with n-3 PUFA in yogurt in combination with a reduced energy intake increases n-3 PUFA content in serum lipids and prevents adverse changes in the composition of FA in serum after a short-term low-calorie diet. In study B, we monitored the influence of n-3 PUFA supplementation on short-term weight management with VLCD in 20 women with severe obesity, who were randomly divided into two groups. The first group received VLCD enriched with n-3 PUFA, the second group VLCD with a placebo. The addition of...
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Glutathione and glutathione-dependent enzymes in various pathophysiological states.
Kodydková, Jana
Backround: Oxidative stress (OS) has been implicated in pathogenesis of human disorders such as depressive disorder, sepsis, cardiovascular disease, acute and chronic pancreatitis, and cancer. Increased OS is result of imbalance between increased reactive oxygen and nitrogen species (RONS) production and / or insufficient activity of antioxidant defence system. Antioxidant system, which is composed of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidases (GPX), glutathione reductase (GR) and non- enzymatic antioxidant reduced glutathione (GSH) plays an important role in the protection of cells against enhanced OS. The aim of this study was to assess the OS markers and antioxidant enzymes in different pathophysiological states. Materials and methods: Activities of erythrocyte glutathione peroxidase (GPX1), GR and concentration of GSH as well as levels of OS markers were analysed in six different pathophysiologic states. These parameters were measured in 35 women with depressive disorder (DD), 40 patients with metabolic syndrome (MetS), 30 septic patients (S) followed up in the course of sepsis; 15 non-septic critically ill patients (NC), 13 patients with acute pancreatitis (AP), 50 with chronic pancreatitis (CP) and 50 patients with pancreatic cancer (PC), compared to...
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Study of genetic and infectious risk factors in the pathogenesis of obesity in Czech adolescents.
Elblová, Lenka
4 Abstract The prevalence of obesity and its related cardiometabolic complications in children remains high across the world. Obesity is a multifactorial disease caused by interaction between genes and environmental factors. Genome-wide association studies have discovered several single nucleotide polymorphisms associated with obesity. A causal role of infection in the pathogenesis of obesity has also been considered, particularly the role of adenovirus 36 (Adv36). The aim of the Ph.D. thesis was to investigate the associations of obesity susceptibility loci (TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, FTO) and Adv36 infection with obesity-related characteristics and complications in the Czech adolescent population. The results are described in eight publications, of which six are original papers and two are reviews. Studies were performed on a cohort of Czech adolescents recruited either from the general population (1,533 individuals from the epidemiological study) and from in-patient or outpatient weight management clinics (562 overweight/obese individuals underwent an intervention). The results demonstrated an association of TMEM18, SEC16B and FTO gene variants with obesity. Some variants of the genes involved in hypothalamic regulation of energy homeostasis − MC4R, BDNF, PCSK1 − were related to...
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