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Molecular mechanisms of circadian clock entrainment by daily regime in food intake
Kapoun, Jiří ; Sumová, Alena (advisor) ; Červená, Kateřina (referee)
Circadian clocks form an endogenous time-keeping system present in most organisms, synchronizing physiological and behavioural processes with perodically changing environmental conditions. The system comprises of the master clock in the suprachiasmatic nuclei of the hypothalamus and numerous subsidiary clocks in peripheral tissues. Its molecular design is constituted by the clock genes, which are rhythmically expressed, form a series of transcriptional/translational feedback loops and influence the expression of various other genes involved in metabolic pathways. The peripheral clocks are dependent on the master clock, although they can be entrained with external cues like food intake timing and diet composition. This desynchronization leads to the distruption of clock gene oscillation, which can potentially have serious impact on metabolic processes and increase the risk of metabolic disorders. The aim of this thesis is to summarize current knowledge on the relationship of molecular chronobiology and nutrition with a focus on the molecular mechanisms through which can food, especially its intake timing and composition, influence the crosstalk between clock gene expression and cellular metabolism. The thesis also emphasises the potential effect of circadian clock disruption on the risk of metabolic...
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Nutritional condition and food intake in seniors living at home
CHARVÁTOVÁ, Pavla
Bachelor thesis entitled "Nutrition status and intake of food in seniors living at home" deals with nutrition of seniors, food intake and their nutritional status. The theoretical part deals first with the basic concepts of aging, important components of food - the need of energy, proteins, fats, carbohydrates, fiber, calcium and vitamin D as well as drinking and eating. Further, the theoretical work describes all changes of gastrointestinal tract from oral to thin and colon and any complications associated with them - malnutrition, obesity, osteoporosis and sarcopenia. The theoretical work also deals with evaluation of seniors' nutrition and especially with BMI, anamnesis, physical, anthropometric, laboratory and special examinations. The research question related to how the nutritional status of seniors living in a couple or seniors living single. A qualitative and quantitative method was used for processing the research part of the bachelor thesis. The research group created 5 seniors living at home aged 65 or higher. The seniors received a printed arc record at the beginning of the study in 14 days, each senior enrolling the type and amount of consumed diet, fluids, and also recording physical activity and time outdoors. For each senior, personal, family, medical history and basic height and weight data were initially identified. All consumed foods and beverages were entered into the "Nutriservis Professional" program, which calculated the intake of energy, protein, fat, carbohydrate, calcium, sodium, iron and vitamin D, then the averages of all results for each nutrient were calculated. These merits were compared with the merits for seniors. The ideal weight was determined using BMI for seniors. For each senior, bioimpedance (a special investigation method) was performed using Tanita bioimpedance scales at Nature House facilities in different cities. Using this special examination method, the ratio of fat, water and non-fat mass in the body of each senior was determined. In this facility, each senior was reconsidered. According to Harris Benedict's formula, the recommended amount of energy, proteins, fats and carbohydrates was calculated. Thereafter, these values were compared to the actual values of energy, protein, fat and carbohydrate taken from seniors' diet during the reference period. The data was processed into tables and plain text with short comments. Of all the results I have received, it can be seen that the nutrition in the elderly monitored does not reach the recommended values. Some seniors have failed to fulfill their daily nutritional needs. He buys and cooks food they taste for them. It does not look for sufficient intake of the necessary nutrients. They are not interested in healthy nutrition.
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New analogs of anorexigenic neuropeptides involved in food intake regulation
Pražienková, Veronika ; Maletínská, Lenka (advisor) ; Novotný, Jiří (referee) ; Skálová, Lenka (referee)
This work focuses on anorexigenic neuropeptides, cocaine- and amphetamine-regulated transcript (CART) and prolactin-releasing peptide (PrRP), which decrease food intake and body weight. CART peptide is an anorexigenic neuropeptide and, despite many efforts, its receptor has not yet been identified. We found CART peptide specific binding sites in pheochromocytoma PC12 cells. Cells differentiated to neurons increased significantly the number of binding sites. On the other hand, after differentiation to chromaffin cells the number of binding sites was so low that it was impossible to determine their density. To clarify the importance of each of the three disulfide bridges in the CART molecule, analogs with one or two disulfide bridges were synthetized. The biological activity was maintained in analog with two disulfide bridges in positions 74-94 and 88-101. Moreover, we demonstrated the stimulation of JNK and subsequently c-Jun activation in PC12 cells. Neuropeptide PrRP belongs to the RF-amide peptide family and has anorexigenic properties. PrPR has a high affinity to GPR10 and neuropeptide FF (NPFF2) receptor. In our laboratory lipidized analogs of PrRP were synthesized, which are able to decrease food intake after peripheral administration and may cross the blood-brain barrier. We tested biological...
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Supplementation and nutritional strategies in artistic gymnastics
Černák, Ján ; Petr, Miroslav (advisor) ; Šteffl, Michal (referee)
Title: Supplementation and nutritional strategies in artistic gymnastics Objectives: The aim of this thesis is to bring a critical view of the current state of nutrition and supplementation in gymnastics, as well as suggest ways to optimize nutrient intake and supplements in practice. Methods: For research I used primarily the database of electronic resources PubMed, EBSCO, ScienceDirect, Ovid and others. Based on informations from the articles and the available literature I created this review. Results: Low energy intake, especially in gymnasts, can cause degenerative disorder to health (menstrual problems, impact on growth). This is connected with inadequate nutrient intake. The aesthetic factor and the strength to weight ratio play a major role in reducing energy intake in gymnasts. Supplements are used by approximately 58% of gymnasts, who take them to improve the performance and because of physiological demands. Keywords: energy intake, food intake, gymnastics
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New analogues of prolactin-releasing peptide with prolonged effect on food intake
Tichá, Anežka ; Ryšlavá, Helena (advisor) ; Konvalinka, Jan (referee)
Prolactin-releasing peptide (PrRP) is a member of the family of RF-amide peptides. These peptides have typical C-terminal sequence -Arg-Phe-NH2 and similar biological effects. PrRP was discovered as an endogenous ligand of an orphan receptor GPR10 while searching for a factor responsible for a prolactin secretion. This effect was not later confirmed and nowadays, PrRP is mainly considered as an anorexigenic peptide. This is supported by a fact that PrRP and GPR10 deficient mice suffer from hyperphagia and late-onset obesity. Besides GPR10, PrRP is bound to NPFF2 receptor whose endogenous ligand is neuropeptide FF (NPFF). In this study, the PrRP's analogues modified at the N-terminus with fatty acids of different lenghts were tested in vitro on binding and activation MAPK/ERK1/2 signalling pathway. In in vivo experiments on food intake, the central anorexigenic effects of lipidized PrRP-analogues were tested provided their crossing blood brain barrier. Binding studies showed that all analogues bound to rat pituitary RC-4B/C cells with high affinity, analogues containing fatty acid with Ki of one order of magnitude lower than native PrRP. High affinity was also confirmed for binding to cells overexpressing GPR10 receptor and cell membranes with overexpressed NPFF2 receptor. All tested analogues...
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Impact of stable ghrelin receptor agonists and antagonists on food intake regulation
Holubová, Martina
The thesis is focused on the effect of ghrelin receptor (GHS-R1a) agonists and antagonist on food intake regulation. Ghrelin is the only known periferally produced orexigenic hormone and the only known acylated hormone. GHS-R1a agonists and antagonists could be useful in the treatment of cachexia and obesity, respectively. In the first part of the thesis, newly designed peptidic GHS-R1a agonists were characterized. The agonists were stabilized by replacing octanoylated Ser3 with a fatty acid coupled to diaminopropionic acid by a stable amide bond. Other noncoded amino acids were also incorporated. Ghrelin analogs were modified by replacing the octanoyl group with another fatty acid, incorporation of the second fatty acid or shortening the peptide chain. Most of the tested GHS-R1a agonists were found to possess high affinities for GHS-R1a (Ki = 10-9 - 10-10 nM) and to activate signaling pathways of ghrelin. After subcutaneous (SC) administration to mice, agonists showed significant and prolonged orexigenic effect. In the second part of the thesis, acute and long-term effects of pseudopeptide GHS- R1a agonist JMV1843 were tested in lean C57BL/6 mice. Acute SC administration of JMV1843 to fed mice increased food intake in a dose-dependent manner (ED50 = 1.94 mg/kg). JMV1843 was stable in blood serum...
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Impact of stable ghrelin receptor agonists and antagonists on food intake regulation
Holubová, Martina ; Maletínská, Lenka (advisor) ; Kopecký, Jan (referee) ; Sobotka, Luboš (referee)
The thesis is focused on the effect of ghrelin receptor (GHS-R1a) agonists and antagonist on food intake regulation. Ghrelin is the only known periferally produced orexigenic hormone and the only known acylated hormone. GHS-R1a agonists and antagonists could be useful in the treatment of cachexia and obesity, respectively. In the first part of the thesis, newly designed peptidic GHS-R1a agonists were characterized. The agonists were stabilized by replacing octanoylated Ser3 with a fatty acid coupled to diaminopropionic acid by a stable amide bond. Other noncoded amino acids were also incorporated. Ghrelin analogs were modified by replacing the octanoyl group with another fatty acid, incorporation of the second fatty acid or shortening the peptide chain. Most of the tested GHS-R1a agonists were found to possess high affinities for GHS-R1a (Ki = 10-9 - 10-10 nM) and to activate signaling pathways of ghrelin. After subcutaneous (SC) administration to mice, agonists showed significant and prolonged orexigenic effect. In the second part of the thesis, acute and long-term effects of pseudopeptide GHS-R1a agonist JMV1843 were tested in lean C57BL/6 mice. Acute SC administration of JMV1843 to fed mice increased food intake in a dose-dependent manner (ED50 = 1.94 mg/kg). JMV1843 was stable in blood serum in...
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The role of adipose tissue in the pathophysiology of obesity and anorexia nervosa
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Pavlišová, Jana (referee)
The view of adipose tissue and its significance in human pathophysiology has changed substantially in the recent couple of years. It has been shown that adipose tissue is not only a passive storage site for excess energy, but that it actively participates in the maintenance of whole-body homeostasis as an endocrine organ producing various hormones and other biologically active molecules, which by acting in an endocrine, paracrine as well as autocrine fashion affect different organs and systems. An intact regulation of adipose tissue processes plays an important role in sustaining the integrity of the organism, whereas its defects lead to the development of a number of diseases. This thesis focuses primarily on the significance of adipose tissue in the pathogenesis of obesity and anorexia nervosa. In the last years, the incidence of obesity rapidly increases ranking, along with its complications, among the world's leading health problems. Obesity is associated with endocrine dysfunction of adipose tissue characterized by disrupted production of adipose tissue hormones and cytokines resulting in the development of numerous disorders including type 2 diabetes mellitus and cardiovascular diseases. A completely opposite disorder, where, however, adipose tissue, or more precisely the absence of it, plays...
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New analogs of anorexigenic neuropeptides involved in food intake regulation
Pražienková, Veronika
This work focuses on anorexigenic neuropeptides, cocaine- and amphetamine-regulated transcript (CART) and prolactin-releasing peptide (PrRP), which decrease food intake and body weight. CART peptide is an anorexigenic neuropeptide and, despite many efforts, its receptor has not yet been identified. We found CART peptide specific binding sites in pheochromocytoma PC12 cells. Cells differentiated to neurons increased significantly the number of binding sites. On the other hand, after differentiation to chromaffin cells the number of binding sites was so low that it was impossible to determine their density. To clarify the importance of each of the three disulfide bridges in the CART molecule, analogs with one or two disulfide bridges were synthetized. The biological activity was maintained in analog with two disulfide bridges in positions 74-94 and 88-101. Moreover, we demonstrated the stimulation of JNK and subsequently c-Jun activation in PC12 cells. Neuropeptide PrRP belongs to the RF-amide peptide family and has anorexigenic properties. PrPR has a high affinity to GPR10 and neuropeptide FF (NPFF2) receptor. In our laboratory lipidized analogs of PrRP were synthesized, which are able to decrease food intake after peripheral administration and may cross the blood-brain barrier. We tested biological...
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Obesity its causes and cosequences
Ondráčková, Anna ; Vybíral, Stanislav (advisor) ; Kuda, Ondřej (referee)
Obesity is one of the most common health problems in the Word. Over 500 million adults and over 40 million children are obese. The aim of this work is to summarize findings of causes and consequences of this health problem. Even though in some cases only genetic mutations are responsible for obesity for example mutation in ob gene or Prader-Willi syndrome most cases are caused by lifestyle of people -excessive food intake and insufficient physical activity. There are many health problems accompanying obesity. The most serious problems are metabolic syndrome, diabetes mellitus, cardiovascular diseases and cancer. The consequences of obesity are, however, not confined only to health. We can also observe the economic consequences. Financial cost of treatment of obesity and related diseases are estimated in billions of dollars. Pharmacological treatment has so far proved to be ineffective. If drugs are effective, the side effects are so severe that their use is not possible. So far, the adipose tissue hormones that regulate food intake provide the best hope.
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