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Effect of caloric restriction on neuroplasticity
Sonina, Alisa ; Málková, Petra (advisor) ; Kolář, David (referee)
Calorie restriction has been shown to have a wide range of beneficial effects on health and longevity, although its effects on brain function are not as well known. This paper reviews the current state of research on the effects of calorie restriction on neuroplasticity, including studies examining the molecular, structural, and behavioral effects of dietary restriction in animal and human models. Overall, the evidence suggests that caloric restriction promotes neuroplasticity. However, further research is needed to fully understand the mechanisms underlying these effects and to determine the optimal duration and intensity of caloric restriction. Key words: Caloric restriction, neuroplasticity, diet, cognition, neurogenesis, metabolism
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Relation between n-3 polyunsaturated fatty acids and cellular sensors of energetic state
Zouhar, Petr ; Flachs, Pavel (advisor) ; Pecina, Petr (referee)
The important factor in regulation of metabolic processes is regulatory proteins, which are able to react by feed-back to energetic state of the cell. Big attention is focused on the AMP activated kinase (AMPK) and NAD+ activated deacetylase SIRT1. These enzymes interact together and their stimulation increases mitochondrial biogenesis and fatty acid oxidation. Due to this it functions beneficially against the onset of obesity, insulin resistance and ageing. Fasting, exercise and some antidiabetogenic drugs act by these regulators. n-3 polyunsaturated fatty acids (PUFA) are also known because of their stimulative effects on mitochondrial biogenesis and -oxidation. Previous work of our group have showed that intake of higher dose of n-3 polyunsaturated fatty acids (PUFA) in diet lead to increase in activity of AMPK in white adipose tissue. New results presented in this thesis show that SIRT1 is essential for increase in expression of stimulators of -oxidation (PPAR etc) in response to n-3 PUFA in diet. n-3 PUFA futher improve the metabolic profile synergistically with calorie restriction probably through SIRT1.
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Effect of ectopic synthesis of mitochondrial uncoupling protein 1 in white adipose tissue on whole-body metabolism in mice
Janovská, Petra ; Kopecký, Jan (advisor) ; Drahota, Zdeněk (referee) ; Kalous, Martin (referee)
The prevention and treatment of obesity is a major problem of health care systems in affluent societies. Metabolism of adipose tissue belongs to the therapeutical targets, since accumulation of adipose tissue is the basis of obesity development. Experiments using transgenic mice with ectopic expression of brown- fat uncoupling protein 1 (UCP1) in white adipose tissue (WAT), verified a concept that obesity could be ameliorated by increasing energy expenditure in WAT. The goal of the experiments of this PhD Thesis was to characterize in detail the phenotype of this unique animal model of obesity resistance. We have shown that mitochondrial uncoupling in WAT resulted in increased oxidation of fatty acids (FA), in face of decreased lipogenesis and induced mitochondrial biogenesis in this tissue. In further studies, we aimed to modulate propensity to obesity be increasing FA oxidation in WAT in response to physiological stimuli. This could be accomplished in response to the combination treatment using n-3 polyunsaturated fatty acids (n-3 PUFA) and mild calorie restriction in mice fed high-fat diet. Synergistic induction of mitochondrial oxidative capacity and lipid catabolism in epididymal WAT was associated with suppression of low-grade inflammation of WAT, which is typical for obesity. The improvement of lipid...
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Interaction between adipocytes and immune cells in pathogenesis of obesity related pro-inflammatory state of adipose tissue
Mališová, Lucia ; Rossmeislová, Lenka (advisor) ; Flachs, Pavel (referee) ; Kazdová, Ludmila (referee)
Obesity is considered to be a worldwide epidemic disease characterized by an accumulation of AT. Increased adiposity can perturb normal metabolic functions and lead to the development of diseases like insulin resistance and other metabolic disorders. A large amount of clinical studies have been shown that changes in inflammatory signaling in adipose tissue cells, increased infiltration of immune cells into AT as well as stress of endoplasmic reticulum belong to the key molecular steps leading to the development of metabolic disturbances associated with this disease. Adverse metabolic effects of AT accumulation can be diminished by calorie restriction resulting in weight loss. In addition, stress of endoplasmic reticulum could be alleviated by chemical chaperones including bile acids. These two approaches for the treatment of obesity or the obesity-associated disturbances were basis for this PhD thesis. In the first part of this work, we studied inflammation status of gluteal in comparison with abdominal AT and differentiation and secretory capacity of adipocytes after weight loss in obese patients. We revealed that inflammatory profile of gluteal AT, estimated by mRNA level of macrophages and cytokines as markers of inflammatory status of the body, did not explain the different clinical impact of...
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Autophagy as a key mediator of beneficial effects of caloric restriction
Kačinská, Irena ; Novotný, Jiří (advisor) ; Funda, Jiří (referee)
Caloric restriction has long been known in the scientific world as a life-prolonging condition, and there is growing evidence that the effect of activation of non-selective autophagy is responsible for these effects. In this thesis, the molecular mechanisms of autophagy in the state of caloric restriction will be described, as well as its beneficial effects on the aging of the organism and various health problems associated with aging and the modern way of life will be summarized. Some risks that could result from unprofessional intervention in one's own body will also be mentioned. It is hypothesized that practicing caloric restriction under the supervision of an expert brings prevention of diseases of civilization diseases and diseases associated with aging and prolongs quality of life, which would, among other things, help reduce the cost of health and social care. Keywords: Autophagy, caloric restriciton, molecular mechanisms
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Role of post-translational modifications, O-GlcNAcylation and Phosphorylation, in neurodegenerative disorders and brain hypometabolism
Špundová, Tereza ; Růžička, Jiří (advisor) ; Čočková, Zuzana (referee)
Post-translational modifications are major mechanisms that highly increase the variability in protein function. O-GlcNAcylation and phosphorylation are among the most extensively studied post-translational modifications in research to date. In physiological conditions, O- GlcNAcylation acts as a metabolic sensor that links glucose metabolism to normal neuronal functioning. Reversible phosphorylation is one of the mechanisms that can downregulate metabolism by regulating the rates of flux through metabolic pathways. The impairments in the regulation of these modifications are linked to with neurodegenerative disorders and hypometabolism. This thesis focuses on the crosstalk and correlation between these two modifications, their reciprocal relationship and their mutual impact on their regulations in models of neurodegenerative diseases and disease non-related models. Keywords: hypometabolism, O-GlcNAcylation, phosphorylation, post- translational modifications, neurodegenerative disorders, hibernation, caloric restriction, memory, learning
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The longevity in mole rat.
Jelínková, Alena ; Schierová, Michaela (advisor) ; Španielová, Hana (referee)
Naked mole rat and blind mole rat are useful model organisms for human age-associated diaseases studies. Unlike human, their long lifespan is not accompanied by physical health impairment. In both species, the genes involved in aging process or carcinogenesis are under positive selection or their regulation differs from the regulatory pattern known in other rodents or human. Some genes are present in higher number of copies, missing or entirely new and not observed in other organisms. In naked mole rat, the degenerative development is reduced by elevated level of proteins which prevent amyloid β aggregation and contribute to oxidative damage tolerance. Their healthy aging is also caused by effective elimination of damaged proteins, natural caloric restriction or angiogenesis enhancement. High level of α-2-macroglobulin in blood, which is able to inhibit signal pathways required for tumor growth and malignancy, as well as the early contact inhibition repress tumorigenesis in naked mole rat. Many different mechanisms are involved in prolonged lifespan in both naked and blind mole rat species. The aim of this thesis is to present the most important genome and proteome differences contributing to their long lifespan. Key words: naked mole rat, blind mole rat, tumorigenesis resistance, senescence,...
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Interaction between adipocytes and immune cells in pathogenesis of obesity related pro-inflammatory state of adipose tissue
Mališová, Lucia ; Rossmeislová, Lenka (advisor) ; Flachs, Pavel (referee) ; Kazdová, Ludmila (referee)
Obesity is considered to be a worldwide epidemic disease characterized by an accumulation of AT. Increased adiposity can perturb normal metabolic functions and lead to the development of diseases like insulin resistance and other metabolic disorders. A large amount of clinical studies have been shown that changes in inflammatory signaling in adipose tissue cells, increased infiltration of immune cells into AT as well as stress of endoplasmic reticulum belong to the key molecular steps leading to the development of metabolic disturbances associated with this disease. Adverse metabolic effects of AT accumulation can be diminished by calorie restriction resulting in weight loss. In addition, stress of endoplasmic reticulum could be alleviated by chemical chaperones including bile acids. These two approaches for the treatment of obesity or the obesity-associated disturbances were basis for this PhD thesis. In the first part of this work, we studied inflammation status of gluteal in comparison with abdominal AT and differentiation and secretory capacity of adipocytes after weight loss in obese patients. We revealed that inflammatory profile of gluteal AT, estimated by mRNA level of macrophages and cytokines as markers of inflammatory status of the body, did not explain the different clinical impact of...
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NITRIC OXIDE AND REACTIVE OXYGEN SPECIES IN ACUTE CORONARY SYNDROME
Šnorek, Michal ; Herget, Jan (advisor) ; Ošťádal, Petr (referee) ; Al-Hiti, Hikmet (referee)
In cardiology, there are different conditions associated with the release of free radicals in some forms of hypoxia, such as ventilatory hypoxia or reduced perfusion. The role of free radicals during hypoxia in cardiology is the key point of our interest. In presented thesis, we have focused on hypoxia-induced pulmonary vasoconstriction and acute myocardial ischemia. Hypoxic pulmonary vasoconstriction (HPV), an important physiological mechanism, is regulated by changes in the production of and interactions among reactive oxygen species (ROS). There is controversy, however, over whether HPV is mediated by an increase or a decrease in ROS production. Also, the role of nitric oxide (NO) in HPV remains unclear. Our results indicate that inhibition of HPV by the superoxide dismutase mimetic tempol does not depend on either NO production or a decrease in basal vascular tone. The effect of three-day fasting on cardiac ischemic tolerance was investigated in another experimental model. Short-term fasting conclusively decreases ROS production. Three-day fasting effectively protected rat hearts against major endpoints of acute ischemia-reperfusion injury. It prevented severe ventricular arrhythmias and reduced the extent of myocardial infarction. These beneficial effects can be linked to altered mitochondrial redox...
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Effect of ectopic synthesis of mitochondrial uncoupling protein 1 in white adipose tissue on whole-body metabolism in mice
Janovská, Petra ; Kopecký, Jan (advisor) ; Drahota, Zdeněk (referee) ; Kalous, Martin (referee)
The prevention and treatment of obesity is a major problem of health care systems in affluent societies. Metabolism of adipose tissue belongs to the therapeutical targets, since accumulation of adipose tissue is the basis of obesity development. Experiments using transgenic mice with ectopic expression of brown- fat uncoupling protein 1 (UCP1) in white adipose tissue (WAT), verified a concept that obesity could be ameliorated by increasing energy expenditure in WAT. The goal of the experiments of this PhD Thesis was to characterize in detail the phenotype of this unique animal model of obesity resistance. We have shown that mitochondrial uncoupling in WAT resulted in increased oxidation of fatty acids (FA), in face of decreased lipogenesis and induced mitochondrial biogenesis in this tissue. In further studies, we aimed to modulate propensity to obesity be increasing FA oxidation in WAT in response to physiological stimuli. This could be accomplished in response to the combination treatment using n-3 polyunsaturated fatty acids (n-3 PUFA) and mild calorie restriction in mice fed high-fat diet. Synergistic induction of mitochondrial oxidative capacity and lipid catabolism in epididymal WAT was associated with suppression of low-grade inflammation of WAT, which is typical for obesity. The improvement of lipid...
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