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Molecular mechanisms linking adipose tissue dysfunction and atherosclerotic complications
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Bužga, Marek (referee) ; Cibičková, Ľubica (referee)
Obesity and its associated comorbidities increase the risk of mortality. The development of subclinical inflammation associated with obesity also plays a significant role in this. In our work, we focused on changes in the endocrine and mitochondrial function of adipose tissue and their relationship to cardiovascular complications. The first part of the thesis focuses on determining the expression of mitochondrial and endoplasmic reticulum genes in epicardial and subcutaneous adipose tissue, intercostal muscle or right myocardial atrium in patients with atherosclerotic coronary artery disease. Patients with coronary artery disease had reduced expression of several mitochondrial chain genes in epicardial adipose tissue compared to subcutaneous adipose tissue and other tissues, while no change in endoplasmic reticulum gene expression in the above-mentioned tissues has been demonstrated. Based on decreased mitochondrial gene expression in patients with coronary artery disease, we conclude that mitochondrial dysfunction of epicardial adipose tissue may contribute to the development of coronary atherosclerosis. The second part of the thesis is focused on neudesin, new potentional regulator of energy metabolism, in obese patients with type 2 diabetes mellitus (T2DM), who underwent various weight reduction...
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The role of RNA demethylase FTO in differentiation, regulation of energy metabolism and sensitivity to streptozotocin of neuronal and glial cell models
Čočková, Zuzana
Fat mass and obesity associated (FTO) demethylase is responsible for erasure of the most abundant epitranscriptomic mark in eukaryotic mRNA, the N6-methyladenosine (m6A) residue. Together with other m6A erasers, writers (methyltransferases) and readers it forms an m6A regulatory pathway that controls the amount, location and biological effect of m6A. The dynamic regulation of the brain's m6A methylome during neurodevelopment is essential for maintaining cerebral functions. In addition, preclinical research suggests that the m6A regulatory pathway regulates energy balance in a tissue- and cell type-specific manner. The FTO gene has been associated with lifelong risks of obesity and metabolic syndrome as well as regulation of total body energy intake and expenditure. However, little is understood about the function of the m6A pathway in control of brain energy metabolism. That is of interest in pursuit of understanding Alzheimer's disease, as this illness is characterized by profound disruptions in cerebral energy metabolism and mounting evidence suggests that disrupted brain bioenergetics may play a role in the disease's early genesis, before the appearance of clinical symptoms. In the present thesis we aimed to investigate the role of FTO in models of two brain cell types, neurons and astrocytes....
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Microplastics and their effects on the metabolism of animal cells
Fiedlerová, Gabriela ; Cajthaml, Tomáš (advisor) ; Černý, Jan (referee)
Microplastics are tiny particles smaller than 5 mm in size found in various environments, including seas, rivers and soil. These particles can be intentionally produced as part of cosmetic products or formed by the breakdown of larger plastic objects. Microplastics represent a serious threat to the environment and animals and could eventually reach humans through the food chain. This thesis deals with a critical and synthetic overview of the literature related to the influence of microplastics on the metabolism of animal cells. The thesis also considers the experimental conditions under which the data were obtained. In particular, factors such as the tested microplastics' shape, size and ageing are critically evaluated as these aspects are often neglected in the literature. Current knowledge shows that microplastics accumulate in the bodies of animals and cause physical and metabolic damage, inflammation, disruption of energy metabolism, protein metabolism and amino acid and lipid metabolism. The most serious effects of microplastics can be considered to be the formation of oxygen radicals, neurotoxicity, disruption of gametogenesis and offspring development.
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The role of RNA demethylase FTO in differentiation, regulation of energy metabolism and sensitivity to streptozotocin of neuronal and glial cell models
Čočková, Zuzana ; Novotný, Jiří (advisor) ; Horák, Martin (referee) ; Balík, Aleš (referee)
Fat mass and obesity associated (FTO) demethylase is responsible for erasure of the most abundant epitranscriptomic mark in eukaryotic mRNA, the N6-methyladenosine (m6A) residue. Together with other m6A erasers, writers (methyltransferases) and readers it forms an m6A regulatory pathway that controls the amount, location and biological effect of m6A. The dynamic regulation of the brain's m6A methylome during neurodevelopment is essential for maintaining cerebral functions. In addition, preclinical research suggests that the m6A regulatory pathway regulates energy balance in a tissue- and cell type-specific manner. The FTO gene has been associated with lifelong risks of obesity and metabolic syndrome as well as regulation of total body energy intake and expenditure. However, little is understood about the function of the m6A pathway in control of brain energy metabolism. That is of interest in pursuit of understanding Alzheimer's disease, as this illness is characterized by profound disruptions in cerebral energy metabolism and mounting evidence suggests that disrupted brain bioenergetics may play a role in the disease's early genesis, before the appearance of clinical symptoms. In the present thesis we aimed to investigate the role of FTO in models of two brain cell types, neurons and astrocytes....
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Úloha Adenylát kinázy 1 v aktivaci a metabolismu imunitních buněk larev \kur{Drosophila melanogaster}
KAISLEROVÁ, Nikola
The aim of this thesis was to study the role of Adenylate kinase 1 (Ak1) in the immune system of Drosophila melanogaster larvae upon the infection by parasitoid wasp Leptopilina boulardi. Using the immune specific Ak1 RNA interference, it was analyzed the effect of Ak1 reduction on the immune response and viability of Drosophila. The importance of Ak1 was also evaluated within the metabolism of immune cells. It has been shown that Ak1 is crucial in energy metabolism of immune cells and important for the proper functioning of immune system.
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Pentoses as energy sources of Mastigamoeba balamuthi
Novotná, Monika ; Verner, Zdeněk (advisor) ; Čepička, Ivan (referee)
Mastigamoeba balamuthi is a free-living amoeba, a sister group to one of the most widespread parasitic agent Entamoeba histolytica. During its lifetime, M. balamuthi can utilize at least four different energy sources to produce ATP. In addition to glucose, a standard cultivation energy source, the amoeba can utilize pentoses xylose and arabinose, as well as an amino acid L-arginine. In this work, energy source preference was assessed. Morphological and physiological characteristics including cell growth and size, motility, number of nuclei and metabolic end products were evaluated. It was concluded that glucose appears to be a less preferred energy source than pentose upon evaluating statistically significant differences. Therefore, it was proposed to replace the commonly used hexose with the preferred xylose in the culture medium of M. balamuthi.
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Brain energy metabolism and its pathologies
Nová, Jana ; Telenský, Petr (advisor) ; Kolář, David (referee)
The brain belongs amongst metabolically most active organs and disturbances of brain energy metabolism are commonly cited as a critical factor predisposing to neurodegeneration. Brain metabolic substrates must be strictly regulated both spatially and temporarily to ensure the energy homeostasis of the brain. Research on energy metabolism of the brain identified several models revealing the interdependence of metabolic processes in the CNS. Powered by TCPDF (www.tcpdf.org)
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Characterization of energy metabolism of murine models of obesity
Irodenko, Ilariia ; Bardová, Kristina (advisor) ; Šilhavý, Jan (referee)
Energy metabolism involves processes of energy intake and energy expenditure, including storage of excessive energy in a form of lipids. White adipose tissue stores energy and plays an important role in maintenance of energy homeostasis. Animals obtain energy by oxidation of substrates from diet. Indirect calorimetry is a method for assessment of energy expenditure based on a measurement of oxygen consumption and carbon dioxide production. The VCO2/VO2 ratio (Respiratory Quotient) indicates oxidation of specific metabolic substrates. Metabolic flexibility is the ability of an organism to match substrate oxidation to its availability. The decrease of a metabolic flexibility is linked to inability to adapt to available substrate and with excessive lipid storage in the body. In this thesis we evaluated correlation between the metabolic flexibility defined by indirect calorimetry and the adipose tissue metabolism in two strains of mice, C57Bl/6J and AJ, that differ in their propensity to diet-induced obesity. Increased whole-body metabolic flexibility in A/J mice was connected to higher ability of adipose tissue to release and uptake lipids. The study of reaction to high-fat diet enables us to distinguish "metabolically healthy" and "metabolically unhealthy" adipose tissue. The knowlegde of these...
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Energy metabolism and apoptotsis markers in cold heart aclimated rat.
Pospíšilová, Barbora ; Horníková, Daniela (advisor) ; Knytl, Martin (referee)
Cold adaptation and her effects has been known for many decates. Positive or negative impact depends especially on its length and strength. The lower temperature can very often cause the stress for organism. On the other hand in expreriment with long-term adapatation were found positive consequences on cardiovascular system. We found the lack of studies devoted to the energy metabolism and apoptosis in heart tissue during long-term cold adaptation. In this work we used a model with milder conditions of the adaptation (10žC±1), so there wouldn't be damage of the experimental animals. We compared the resuls betwen control, cold and regressive group of rats. In this expreriment we used methods of electrophoresis and Western blot. The target of the work was found if we can find any differences betwen chosen HIF targeted genes. The next goal was to detect the differences betwen chosen pro-apoptotic and anti-apoptotic markers. Keywords: cold adaptation, heart, energetic metabolism, HIF, apoptosis
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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David ; Žurmanová, Jitka (advisor) ; Adamcová, Michaela (referee) ; Bardová, Kristina (referee)
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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