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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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Nutrigenomic analysis of diet influence in prenatal and early development on metabolic syndrome aspects manifestation in adulthood.
Školníková, Elena ; Šeda, Ondřej (advisor) ; Černá, Marie (referee) ; Malínská, Hana (referee)
16 Abstract The rising prevalence in noncommunicable diseases worldwide calls for the effort to determine their underlying causes. Common metabolic disorders in particular overwhelm the healthcare systems and are a one of the leading causes of poor quality of life of patients. Metabolic syndrome is represented by concurrence of several conditions - dyslipidaemia, obesity, hypertension or impaired glucose tolerance - altered metabolic phenotypes related to genetic and environmental factors. Recent studies suggest that early-life exposure to certain environmental stimuli is particularly capable of changing the mammalian phenotypes. Nutrition, as one of the major factors influencing health, is naturally a focus of research, which studies the link between parental diets and phenotypic alterations in offspring. The developmental origins of health and disease were historically more focused on maternal undernutrition, it is, however, more important to focus on surplus of macronutrients considering the westernization of modern diets. We propose the relevancy of not only the amount of macronutrients in maternal diet, but also their sources, as they may increase disease risk in offspring. Here we report, that sucrose as an alternative carbohydrate in maternal diet, has a marked impact on metabolism of the offspring...
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Nutrigenetic analysis of metabolic syndrome: the role of spontaneously hypertensive rat chromosome 4
Petrů, Karolína ; Šeda, Ondřej (advisor) ; Malínská, Hana (referee)
Metabolic syndrome (MetS) is a complex condition with a number of interacting genes, epigenetic and environmental factors underlying its pathogenesis. The analysis of genetic component of MetS showed that number of defining parameters of the syndrome is linked to regions of rat chromosome 4. In order to verify these quantitative trait loci (QTL), a double congenic strain was derived with parts of chromosome 4 of spontaneously hypertensive rat (SHR, an inbred MetS model) origin introgressed onto genomic background of congenic Brown Norway strain (BN-Lx). The aim of the proposed thesis is comprise detail genetic mapping of differential segments of the above mentioned double congenic strain BN-Lx.SHR4 and comparison of its metabolic profile under different dietary conditions with varying carbohydrate and fat content. Utilizing DNA sequence and gene expression comparisons, candidate genes or polymorphisms for the MetS aspects and potential nutrigenetic interactions will be identified. Key words: nutrigenetics, experimental models, metabolic syndrome, congenic strain, genotyping, rat
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Remission of type 2 diabetes in patients on various dietary regimens
Kábelová, Adéla ; Krejčí, Hana (advisor) ; Šeda, Ondřej (referee)
Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder linked with the development of specific complications and comorbidities that negatively affect life quality and greatly increase the risk of an early death. The main goal of T2D treatment, which in common clinical practice comprises lifestyle changes and pharmacotherapy, is to delay onset of these complications. Evidence from many recent studies shows the ability of some interventional methods to induce remission of T2D, meaning a major improvement or complete disappearance of T2D symptoms. Besides bariatric surgery procedures, some dietary regimens such as low-energy diet, low-carbohydrate diet and intermittent fasting, can also lead to T2D remission. Attributes of these dietary regimens, especially their effect in T2D treatment, is summarized in the theoretical part of this theses. The aim of the practical part of this thesis was to assess the effect of the dietary regimens mentioned above on morphometric and biochemical parameters associated with T2D by clinical and survey research. In most of the subjects with T2D, the individual dietary regimens, more precisely low-energy diet and low-carbohydrate diet, decreased body weight, where the weight loss induced by low-carbohydrate diet was caused by major decrease in the amount...
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Berkova Residence
Seďa, Ondřej ; Šubrt, Jan (referee) ; Dulenčín, Juraj (advisor) ; Jelínek, Petr (advisor)
The topic of the bachelor thesis is a design of Berkova Residence. The building plot is situated in the corner of the streets Berkova and Bulharská in Královo Pole. The residence has 6 storeys. In the residence there is a big variety of flats, 2 maisonettes, common areas – an underground garage, the cellar cubicles, garden, a place for storage bikes, baby carriages and wheelchairs, an exterior entrance hall with mailboxes and staircase core with a design facade.
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Nutrigenetic interactions of dietary intake of carbohydrates in pathogenesis of type 2 diabetes
Turková, Michaela ; Šeda, Ondřej (advisor) ; Malínská, Hana (referee)
Type 2 diabetes is the most common metabolic condition caused by multiple factors comprising genetic predispositions, lifestyle including diet quality and quantity, environmental factors and others. Particular alleles of numerous genes taking part in pathogenesis of type 2 diabetes interact with dietary intake of specific carbohydrate or distinct ratio of carbohydrates and other macronutrients. The aim of this Bachelor thesis is to summarize the currently available data on nutrigenetic interactions involving carbohydrate intake and, at the same time, affecting risk of type 2 diabetes manifestation.
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Mechanisms of apoptosis induction and inhibition by fatty acids in pancreatic β-cells
Šrámek, Jan ; Kovář, Jan (advisor) ; Brunerová, Ludmila (referee) ; Šeda, Ondřej (referee)
Recently, diabetes mellitus type 2 (DMT2) represents one of the most important metabolic diseases according to its incidence and economic impacts. One of the main reasons of this diesease is loss of function and viability of pancreatic β-cells due to the effect of increased levels of saturated fatty acids (FAs). Unsaturated FAs are better tolerated by β-cells. They are even capable of inhibiting detrimental effects of saturated FAs. Molecular mechanisms of apoptosis induction in pancreatic β-cells by saturated FAs as well as mechanisms of inhibition of this induction by unsaturated FAs are not completely elucidated. The main aim of this study was to contribute to elucidation of these mechanisms. Concerning human pancreatic β-cell line NES2Y we demonstarted: (1) Activation of caspase-2 by stearic acid (SA), in apoptosis inducing concentration (1 mM), is not crucial for the process of apoptosis induction. However, this caspase modulates SA-induced endoplasmic reticulum (ER) stress pathways. (2) SA (1 mM) activates the p38 MAPK signaling pathway and inhibits the ERK signaling pathway. Inhibition of the ERK signaling pathway is probably a consequance of the p38 MAPK pathway activation. However, p38 MAPK is not very likely crutial for the apoptosis induction by SA. Unsaturated oleic acid (OA, 0.2 mM) is able to...
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Low carbohydrate diet in type 2 diabetes mellitus therapy
Kábelová, Adéla ; Krejčí, Hana (advisor) ; Šeda, Ondřej (referee)
Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder, which substantially affects quality of patients' lives and simultaneously increases the risk of early death due to development of its specific complications. Current T2D therapy comprises mainly pharmacotherapy, however, lifestyle changes, particularly modification of dietary habits, also assume an important role in the process. While conventional dietotherapy of T2D primarily concerns reduction of dietary fat intake aiming to achieve caloric restriction, the low carbohydrate diet (LCD), recently often discussed in relation to T2D therapy, is based on the reduction of dietary carbohydrates, whereas fats and/or proteins are increased. The positive effects of LCD in T2D therapy and its comorbidities are summarized in the theoretical part of this thesis. The aim of the practical part of the bachelor thesis was to asses the effect of LCD on health parameters associated with T2D as well as the subjective sense of respondents' satisfaction with this diet together with their adherence and compliance. The results of the survey showed that LCD led to weight loss, decreased waist circumference, glycaemia and levels of glycated haemoglobin and led, in a number of cases, to medication reduction. The level of satisfaction with LCD in the...
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Interaction of PPARG gene polymorphisms with diet components in pathogenesis of type 2 diabetes
Petrů, Karolína ; Šeda, Ondřej (advisor) ; Schierová, Michaela (referee)
Type 2 diabetes is a multifactorial trait as interactions between genetic predispositions and environmental factors contribute to its pathogenesis. Nuclear receptor PPARG (peroxisome proliferator-activated receptor gamma) belongs among genes with substantial impact on pathophysiological processes leading to manifestation of type 2 diabetes. Metaanalyses of human studies showed that several common polymorphisms of this gene are involved in interactions with environmental factors, particularly diet, physical activity and medication. The aim of this Bachelor thesis is to summarize current knowledge on nutrigenetic interactions comprising polymorphisms of PPARG gene and specific qualitative and quantitative parameters of the diet in relation to pathogenesis of type 2 diabetes.
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Pharmacogenetics of statins and metabolic syndrome
Kučera, Miroslav ; Šeda, Ondřej (advisor) ; Schierová, Michaela (referee)
Metabolic syndrome is one of the most prevalent conditions in our population. Among components of the syndrome is a major risk factor of cardiovascular diseases - a change in blood lipid profile presented by alterations in cholesterol and triacylglycerol levels. Statins are currently the drug of choice for therapy of dyslipidemia. This group of drugs is characterized by inhibition of cholesterol synthesis in liver. Pharmacogenetics is a progressive field studying interactions between drugs and genetic background of a patient. There has been described a large amount of genetic variants affecting pharmacokinetic and pharmacodynamic aspects of statin effects. These variants were shown to be important for course of treatment and development of side effects such as statin myopathy. First, this work characterizes pharmacogenetics, metabolic syndrome and statins. Second, it provides a comprehensive summary of genetic polymorphisms underlying important pharmacogenetic interactions with statins.
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