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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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Effects of PrRP (prolactin-releasing peptide) and NPFF (neuropeptide FF) analogs in vitro and in vivo
Tichá, Anežka ; Ryšlavá, Helena (advisor) ; Železná, Blanka (referee)
Prolactin-releasing peptide (PrRP) and neuropeptide FF (NPFF) belong to the RF-amide family. These peptides have identical C-terminal amino acid sequence (R-F-NH2) and similar biological activities. PrRP was identified as an endogenous ligand of an orphan receptor GPR10 able to stimulate PRL-secretion in vitro and in vivo, but soon it was discoverd that this is not the primary function of this peptide. PrRP is thought to be an anorexigenic peptide as PrRP and GPR10 are found in several parts of the brain responsible for food intake regulation and because both GPR10 and PrRP deficient mice suffer from hyperphagia and late-onset obesity. In this study, relationship between PrRP and NPFF was studied using both in vitro binding and sell signaling and in vivo food intake and analgesia test in mice. In vitro experiments showed that PrRP bound to rat pituitary RC-4B/C cells containing GPR10 receptor with high affinity and NPFF, its stable analog 1DMe and its antagonist RF9 up to 10-5 M concentration did not bind to GPR10. NPFF, 1DMe and PrRP were bound to cell membranes with transfected NPFF2 receptor with high affinity, but RF9 with low affinity in a range of 10-7 M, in contrast to published literature. In vivo experiments with fasted mice confirmed that centrally injected PrRP and NPFF significantly...
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Ghrelin analogs in food intake regulation
Pýchová, Miroslava ; Ryšlavá, Helena (advisor) ; Sofrová, Danuše (referee)
Ghrelin analogs in food intake regulation Ghrelin, to date the only known peripherally produced and centrally acting peptide that stimulates food intake, is mainly synthesized in the stomach and acts through growth- hormone-secretagogue receptor (GHS-R). In addition to its orexigenic effect, ghrelin stimulates growth hormone (GH) release, gastric motility and acid secretion. The diverse functions of ghrelin raise the possibility of its clinical application for GH deficiency, eating disorders, and gastrointestinal diseases. Ghrelin agonists could be a promising therapeutics in cachexia occurring at cancer or chronic inflammatory diseases. Octanoylation of Ser3 is crucial for preservation of ghrelin activity. In this study, biological properties (binding to GHS-R, food intake stimulation in mice) of full length and shorter ghrelin analogues with octanoic acid coupled to diaminopropionic acid (Dpr) replacing Ser3 or without octanoic acid were followed. This substitution resulted in a prolonged stability and orexigenic effect of above mentioned ghrelin analogues. Importance of N-terminal part of ghrelin and octanoylation peptide was also confirmed.
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Peptide hormones affecting the food intake and their analogs as potential drugs for treatment of obesity
Nagelová, Veronika ; Maletínská, Lenka (advisor) ; Vybíral, Stanislav (referee)
Obesity is nowadays a major global health problem. Every year amount of obese (BMI > 30 kg . m-2 ) and overweight (BMI > 25 kg . m-2 ) people increases. Obesity is not just a cosmetic problem, but it leads to many serious health complications, particularly cardiovascular diseases, metabolic diseases etc. We can define obesity as an excessive amount of body fat. The development of obesity is often influenced by energy intake, which overrides the energy expenditure. Many studies are currently describe the influence of various substances that could potentially act as antiobesity drugs. Peptide hormones, which are engaged in this work, can be divided to the long-term (leptin, insulin, ghrelin) and short-term (e.g. cholecystokinin, glucagon like peptide 1, peptide YY, CART peptides, melanocortin system, neuropeptide Y and melanin concentrating hormone) acting. Peptides can be also divided according to their effect on food intake to the anorexigenic and orexigenic. Anorexigenic peptides reduce food intake, orexigenic do the reverse.
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Neuropeptide Y and food intake regulation
Váchová, Barbora ; Telenský, Petr (referee) ; Nedvídková, Jara (advisor)
Neuropeptide Y (NPY) is a 36-amino acid member of NPY family. Its biosynthesis occurs in the hypothalamus and its expression also in adipose tissue was described in 2007. NPY is an ubiquitous hormone with central and peripheral effects which lead to the maintenance of homeostasis; NPY is also one of the most significant orexigenic hormones. NPY utilizes G-protein coupled receptors Y1, Y2 and Y5 for its food intake regulation; owing to serious side effects of currently used anti-obesity drugs, the ligands of these receptors (Y1R and Y5R antagonists and Y2R agonists) are considered as targeting molecules for a new therapeutic strategy for obesity treatment. This work is focused on the characteristic of NPY as an orexigenic agent and the possibility of using NPY-based drugs for obesity treatment.
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Water temperature influence on the success of intensive farming of burbot (Lota lota L.)
CHOTĚBORSKÝ, Michal
The aim of this work was to realize the first intensive rearing of juvenile fish of burbot in the Czech Republic (TL = 165.79 +- 18.87, W = 32.91 +- 10.27 g) in recirculation aquaculture system (RAS) at different water temperatures. A total of 9 tanks were used in the three separate RAS systems. For a period of 12 weeks survival (S), specific growth rate (SGR), feed conversion ratio (FCR) and the condition of the fish (FC) was observed at 3 week intervals. The best values of survival (98 +- 0.4%) were achieved in burbots kept at a water temperature of 15 ° C. Survival in the group of fish kept at a water temperature of 18 °C did not statistically differ from the group of fish reared at 15 °C and 21 °C. The SGR value for the fish at a water temperature of 15 °C was (0.7 +- 0.09%.d-1) at 18 °C the SGR value was (0.45 +- 0.1%.d-1) and fish kept at a water temperature of 21 °C reached SGR values of 0.33 +- 0.04%.d-1. The best FCR values (1.27 +- 0.35) were reached also in the group of fish kept at 15 °C. For burbot kept at a water temperature of 21 °C, the FCR value was 2.78 +- 1.17. Based on our results we can conclude that the most appropriate water temperature for rearing juvenile burbot was 15 °C.
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Adaptation of Intensively Bred Juvenile Fish of Pikeperch (\kur{Sander lucioperca}) to a Pond Condition
CHOTĚBORSKÝ, Michal
The aim of this study was to evaluate the adaptability of juvenile fish of pikeperch (Sander lucioperca) artificially bred in the recirculation system, which were planted to experimental ponds. Within this study of adaptability, the survival rate of planted fish and their growth in determined period was observed. Later, after several months of breeding the pikeperch in experimental ponds, the returnable adaptability was evaluated, when the fish from ponds were returned to the recirculation system, where they were adapted back to the controlled breeding conditions and artificial feed. Again, the survival rate and growth of adapted fish was evaluated.
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Food intake of bream during the spawn period
ZEMAN, Jan
The main objective of this thesis was to assess food intake by bream, depending on the onset and end of spawning period. To meet the objectives of a practical experiment was carried out. This experiment was run on the dams Hamry and Brno in the years 2008 and 2009. Subsequently it was determined by standard methods. These methods (indirect, food frequency, filling index, index of superiority and gonadosomatic index. Subsequently, an analysis of stomach.
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Food Intake of Roach (Rutilus rutilus) During the Spawning Season
ŠAMPALÍK, Jan
The main objective of the diploma thesis was defined as the consideration of the hypothesis that food intake structure of adult roach changes significantly during the spawning period. The practical experiment was conducted to reach the defined aim. The experiment was performed on the Brno and Hamry Reservoirs in 2008 and 2009. The acquired data were analysed by standard tools used for gut contents analyses (Indirect Method, Frequency of Occurrence, Index of Fullness, Index of Preponderance) related to the Gonadosomatic Index.
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