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Genetic factors responsible for development of metabolic syndrome
Mirchi, Lukáš Farhád ; Liška, František (advisor) ; Černá, Marie (referee) ; Mlejnek, Petr (referee)
Metabolic syndrome (MetS) is a worldwide highly prevalent disease defined as a clustering of at least three of the following conditions: central obesity, hypertension, diabetes, high level of low-density lipoproteins, low level of high-density lipoprotein or high level cholesterol. MetS is a multifactorial disease which is caused by both environmental factors and a heritable component. Unfortunately, because of its ever rising worldwide incidence MetS emerges as a worldwide epidemic and a heavy socioeconomic burden. In order to effectively fight the MetS pandemic, it is vital to dissect the genetic background and mechanisms that underlie MetS and its individual components, a goal that is profoundly benefitted by physiological and genetic studies in animal models of MetS. The aim of this thesis was to dissect the genetic background of metabolic syndrome by using comparative transcriptomic analysis in relevant organs obtained from genetically defined rodent models. Each of our genetically defined rat strains is phenotypically distinct in terms of manifesting individual components of MetS. We present three separate transcriptomic experiments in order to unravel the genetic background of MetS. First, we performed the global comparative transcriptomic analysis of left ventricular tissue from SHR and...
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Effect of mitochondrially targeted senolytic agents on the development of respiratory diseases
Rennerová, Michaela ; Štemberková-Hubáčková, Soňa (advisor) ; Neckář, Jan (referee)
Aging is a complex biological process characterized by gradual decline in the physiological functions of cells and tissues, leading to the activation of a process known as cellular senescence. This results in the development of structural and functional changes in the organism accompanied by an increased risk of various diseases. Respiratory diseases are among the most common chronic conditions associated with the accumulation of senescent cells in the body. Current treatment for chronic respiratory diseases primarily focuses on symptom relief rather than addressing the primary cause of these conditions. Given that senescent cells play a significant role in the pathogenesis of respiratory diseases, the future of therapies lies in their elimination using senolytic agents. Despite promising results from some studies, current research is limited by the heterogeneity of senescent cells, which is reflected in their sensitivity to senolytic agents and the variability of therapeutic responses. Mitochondria play a central role in the development and maintenance of the senescent cell phenotype by regulating key processes such as energy metabolism and cellular signaling, regardless of the type of senescent cell. Thus, targeting mitochondria in senescent cells may represent a promising therapeutic strategy...
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Importance of physical activity in patients with diabetes
Kozáková, Eva ; Škrha, Jan (advisor) ; Pehr, Martin (referee)
Aim of the thesis: The research aimed to evaluate the importance of long-term regular physical activity in patients with diabetes. Methods: In total, 53 patients with diagnosed diabetes from the Third Department of Internal Medicine of the General University Hospital in Prague were selected for the research. In order to achieve the aim of the study, a combination of data collection in the form of an anonymous questionnaire survey of own design and laboratory results from the medical records in the hospital's information system Medea was used. During the completion of the questionnaire, the patients were consulted in detail and they had the opportunity to ask their own questions and receive a short education on the subject. All data were recorded in tables and subsequently processed into graphs in the computer program Microsoft Office Excel. Statistical evaluation was performed using Tibco Statistica 14.0 software. Results: Regular physical activity is associated with more favourable laboratory results. The most important parameter in assessing physical activity was a question about daily physical activity lasting at least 30 minutes. Patients who were physically active more than 30 minutes per day had significantly better HbA1c (50±9 vs. 60±15 mmol/mol, p<0.01), total cholesterol (3.7±0.8 vs....
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Nonlinear methods of heart rate variability analysis in metabolic syndrome
Vaňková, Eliška ; Kozumplík, Jiří (referee) ; Kubičková, Alena (advisor)
This work deals with the problematic of heart rate variability of patients with metabolic syndrome. Includes the theory, which describes the heart rate variability and the methods for its analysing. Especially it specifies nonlinear methods, particularly Lyapunov exponent and its calculation in Matlab software. Algorithm of the calculation is applicated to already measured tachogram of the healthy people and patients with the metabolic syndrome. Further, this work deals with general valorization of the results using Lyapunov exponent and her eis also done the statistical evaluation.
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Mechanisms of comorbidity of metabolic and neurodegenerative diseases
Tauchman, Martin ; Telenský, Petr (advisor) ; Brožka, Hana (referee)
In Czechia, number of people with neurodegenerative diseases is in the hundreds of thousands, and the lifetime health care costs and social impact of each patient's disease reach hundreds of thousands of euros, but these costs could be reduced by early and effective intervention. Its correct implementation could be helped by knowledge of causal links between neurodegenerative and metabolic diseases, whose prevalence is correlated in the population. One of the important factors is an increased pro-inflammatory immune response. In people with obesity and type 2 diabetes mellitus, systemic inflammation evolves into neuroinflammation, which subsequently leads to neurodegeneration. Another mechanism is hyperglycaemia, which is a consequence of insulin resistance. Hyperinsulinaemia and hyperglycaemia lead to impaired expression of glucose transporters and insulin-degrading enzyme, resulting in reduced clearance of amyloid beta. Genetic background is also recognized as a highly influential factor, affecting various mechanisms in both beneficial and harmful ways. Lifestyle is also an important factor. In general, smoking and alcohol consumption are harmful to health. Both increased consumption of alcoholic beverages and smoking tobacco products can lead to metabolic disorders as well as neurodegeneration. On the...
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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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Peptides regulating food intake and their role in metabolic syndrome
Buderová, Markéta ; Maletínská, Lenka (advisor) ; Hojná, Silvie (referee)
Unhealthy lifestyle together with genetic factors can lead to serious health problems like metabolic syndrome (MetS). MetS is a cluster of risk factors such as abdominal obesity, dyslipidemia, insulin resistance and hypertension. Each component of MetS contributes to cardiovascular diseases, type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease. Treatment of MetS is primarily focused on lifestyle modification, especially weight loss. In severe cases, pharmacological treatment is also used. Pharmacological treatment includes peptide analogues that regulate food intake. Anorexigenic (food- reducing) peptides are involved in the regulation of food intake, together with orexigenic (food- increasing) peptides, which thus play an important role in maintaining energy homeostasis. Several analogues of anorexigenic peptides regulating food intake are already used for the treatment of obesity or T2DM. Other peptide analogues are in preclinical stages of testing or in the development of stable analogues. Elucidating the physiology and pathology of both anorexigenic and orexigenic peptides in the regulation of food intake may contribute to finding potential treatments for metabolic, cardiovascular, and other disorders.
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Evaluation of antibody quality for Endoglin detection in liver
Kejzlarová, Eliška ; Svobodová, Zuzana (advisor) ; Tripská, Katarína (referee)
The diploma thesis deals with endoglin, a transmembrane glycoprotein that can be cleaved to form so-called soluble endoglin, which then circulates in the blood. The theoretical part of the thesis is devoted to cardiovascular and liver diseases related to changes in the expression or level of endoglin in the blood and summarizes current knowledge about endoglin and its relation to various diseases. The experimental part of the thesis describes the selection of a suitable antibody against endoglin intended for western blot (WB). We have four anti-endoglin primary antibodies available from three manufacturers. The purpose was to test the antibodies and determine, which one had the best ability to detect endoglin in mouse tissue samples such as liver or aorta on WB. Affiblot was used to verify their ability to bind endoglin and also to compare their affinities to this protein. Newly developed patented dot-blot-based device. The binding of the used antibodies to endoglin was verified using the WB method and then the results of both methods were compared. The obtained results showed that the Abcam antibody has the most suitable parameters regarding specificity and sensitivity for the identification of endoglin in mouse tissue on WB. Keywords: endoglin, soluble endoglin, NASH, cirrhosis, non-alcoholic...
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Effects of stable analogs of anorexigenic neuropeptides in models of metabolic syndrome
Mráziková, Lucia ; Maletínská, Lenka (advisor) ; Kříž, Jan (referee) ; Bardová, Kristina (referee)
Obesity is a worldwide health problem and an effective treatment is still scarce. Anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential for the treatment of obesity and its complications, but in their natural form they have several limitations such as poor bioavailability, low stability and inability to cross the blood-brain barrier after peripheral administration. Recently we have designed lipidized analogs of PrRP. Lipidization makes this peptide more stable and able to act centrally after peripheral administration. The aim of this study was to investigate the chronic effect of PrRP palmitoylated at position 11 (palm11 -PrRP31) on obesity and obesity-related metabolic parameters and to clarify mechanisms of its action. We used three rodent models of obesity: Wistar Kyoto (WKY) rats with high-fat diet-induced obesity (DIO) having intact leptin and leptin receptor as well as rodents with disrupted leptin function: leptin deficient ob/ob mice and fa/fa rats with a disturbed leptin signaling. Consumption of a high-fat diet in DIO WKY rats increased their body weight, caused strong glucose intolerance and increased liver mRNA expression of enzymes of de novo lipogenesis. Palm11 -PrRP31 treatment significantly decreased cumulative food intake, body weight, plasma...
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