National Repository of Grey Literature 43 records found  beginprevious15 - 24nextend  jump to record: Search took 0.00 seconds. 
Impact of leptin and ghrelin on food intake and metabolic parameters in obese ovariectomized female mice
Matyšková, Resha ; Maletínská, Lenka (advisor) ; Jurčovičová, Jana (referee) ; Kuneš, Jaroslav (referee)
The thesis is focused on the effect of leptin and ghrelin receptor antagonists on food intake and metabolic parameters in ovariectomized (OVX) female mice on a high fat (HF) diet. In the first part of the thesis, diet-induced obesity was introduced in two strains of mice (NMRI and C57BL/6). Diet-induced obesity resulted from overconsumption of a HF diet containing 60 % of fat; a standard (St) diet contained only 9 % of fat. The strain C57BL/6 was more susceptible to a HF diet than the NMRI strain and was chosen for further experiments on food intake. In the second part of the thesis, OVX C57BL/6 female mice on a HF diet were introduced as a model of common obesity in women after menopause and overconsumption of high caloric food. OVX mice on a HF diet accumulated more than 4 times higher amount of the white adipose tissue compared to those on a St diet, had significantly elevated glucose, insulin and leptin levels and attenuated sensitivity to effect of centrally administered leptin, an adipokine that decreases food intake. Central leptin sensitivity and metabolic syndrome parameters were improved after 4 weeks of estradiol treatment. Because both ovariectomy and HF diet result in enhanced sensitivity to ghrelin, the hormone produced predominantly by the stomach that stimulates appetite, in the...
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...
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...
Impact of different types of antidiabetic interventions on the development of neurodegenerative changes in brains of diabetic mice and rats
Popelová, Andrea ; Maletínská, Lenka (advisor) ; Mareš, Pavel (referee) ; Hölscher, Christian (referee)
Alzheimer's disease (AD) is neurological disorder characterized by extracellular beta amyloid plaques and intracellular neurofibrillary tangles formed by hyper-phosphorylated Tau protein. Since type 2 diabetes mellitus (T2DM) is a risk factor of AD development, in the first part of the thesis, a potential relationship between hyper-phosphorylation of Tau protein and central insulin resistance was followed in hippocampi of two models of obesity-induced pre-diabetes, fa/fa rats, and mice with monosodium glutamate (MSG) induced obesity. In both 8-month-old fa/fa rats and 6-month- old MSG mice a decreased phosphorylation of insulin signaling cascade resulted in an increased activation of main Tau kinase glycogen-synthase kinase-3Beta (GSK-3β) and an increased Tau phosphorylation at epitopes Ser396 and Thr231. This phenomenon was less developed in 2-month-old animals. The second part of the thesis was focused on a potential neuroprotective anorexigenic neuropeptide, prolactin-releasing peptide (PrRP), designed at our Institute. Palmitoylation enabled PrRP to cross the blood-brain barrier and employ its central anorexigenic activity. In the third part of the thesis, an effect of 14-day-long SC administration of liraglutide, the most used anti-T2DM drug with central anorexigenic effect, and palmitoylated...
The analysis of mechanisms associated with beneficial metabolic effects of marine Omega-3 polyunsaturated fatty acids in different lipid forms.
Pavlišová, Jana ; Rossmeisl, Martin (advisor) ; Maletínská, Lenka (referee) ; Cahová, Monika (referee)
Obesity, one of the most serious health problems of the 21st century, often occurs as a result of an imbalance between energy intake and energy expenditure. Dietary lipids play an important role in the development of obesity, partly because they represent the richest source of energy amongst all macronutrients. It is, however, not only the amount of consumed lipids, but also the composition of fatty acids, which strongly influences health effects of a particular diet. Saturated fatty acids (SFA) are generally considered as unhealthy due to their pro-inflammatory and lipotoxic properties, while monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) represent a healthier alternative, as they are more readily oxidized and do not disrupt biochemical properties of cellular membranes. Amongst PUFA, PUFA of n-3 series (Omega-3) represent an utterly unique class of lipids that have been documented to protect against cardiovascular disease and dyslipidemia in men and improve insulin sensitivity and glucose tolerance primarily in animal models of obesity. Some molecular mechanisms of Omega-3 action have been already uncovered, such as the modification of biological membranes composition, activation of various transcription factors and membrane receptors, and their role as precursors for...
The role of stable analogs of prolactin-releasing peptide in obesity and hypertension.
Neprašová, Barbora ; Maletínská, Lenka (advisor) ; Poledne, Rudolf (referee) ; Rossmeisl, Martin (referee)
Anorexigenic neuropeptides have the potential to decrease food intake and ameliorate obesity and its complications such as high blood glucose or high blood pressure. However, they are not able to cross the blood-brain barrier after peripheral application. Recently, we have designed and synthesized lipidized analogs of prolactin-releasing peptide (PrRP), which resulted in stabilization of the molecule and allowed us to apply the peptide to the periphery to achieve its central biological effect, as it was demonstrated by increased neuronal activity shown by c-Fos in particular hypothalamus nuclei. The aim of this study was to choose the effective dose in acute food intake experiments and then to characterize the subchronic effect of palmitoylated PrRP analogs in mouse and rat models of obesity and diabetes. Several animal models were used: diet-induced obese (DIO) mice (C57Bl/6J), DIO Sprague-Dawley rats, and two rat models with leptin receptor-deficiency: Zucker diabetic (ZDF) rats and spontaneously hypertensive (SHROB) rats. Consumption of a high-fat diet in DIO mice and rats increased their body weight and blood pressure. Two-week intraperitoneal treatment with palmitoylated PrRP31 lowered the food intake, body weight, and returned the blood pressure to normal levels. This treatment also improved...
Effect of stable prolactin-releasing peptide analog in rat model of obesity
Pospíšilová, Kateřina ; Maletínská, Lenka (advisor) ; Bardová, Kristina (referee)
Obesity is a serious worldwide problem of modern society. Current state is at epidemic level not just in the developed world. It is no more "western disease" or "disease of affluence" as obesity used to be called. Determination of mechanisms that regulate energy balance in the human organism is necessary for further development of obesity drugs. Prolactin-releasing peptide (PrRP) is anorexigenic (food intake lowering) neuropeptide, which acts centrally in hypothalamus. Lipidized analogs of PrRP are promising tools in obesity and type-two diabetes mellitus treatment. This work is focused on impact of palmitoylated analog of prolactin-releasing peptide (palm11 -PrRP31) in a diet induced rat model of obesity after chronical administration. Body weight and cumulative food intake was monitored during the experiment. Administration of palm11 -PrRP31 markedly lowered food intake which caused decrease of body weight compared to obese control group on high-fat diet. This reduction correlated with significantly lower amount of intraperitoneal fat compared to group on high fat-diet. Also, high-fat diet worsened studied metabolic parameters including glucose tolerance. Palm11 -PrRP31 lowered leptin plasma level and improved glucose tolerance both compared to the high-fat fed. Therefore, palm11 -PrRP31 is...
Peptides regulating food intake and their lipidized analogs for possible treatment of obesity and cachexia
Buková, Anna-Marie ; Maletínská, Lenka (advisor) ; Janovská, Petra (referee)
In spite of good living conditions, the number of people in the state where the total food intake or individual nutrients is insufficient, unnecessary or unbalanced has increased in recent years. In case of superfluous food intake, amount of fat tissue increases and overweight and obesity appear, which is associated with an increased risk of type 2 of diabetes, cardiovascular disease or certain types of cancer. Insufficient intake of food may, for example, result in the function of the immune system, resulting in an increased risk of infection or poor wound healing. In addition to primary malnutrition, we can see malnutrition as the secondary manifestation of another illness. The state of weight loss and malnutrition caused by another disease is called cachexia. This is a serious complication of primary therapies. At present, in addition to established approaches to the treatment of these diseases, some studies address treatment options using compounds that influence the regulation of food intake. One group of these compounds is peptides able to reduce food intake (anorexigenic peptides) or increase it (orexigenic peptides). To these natural substances in the organism are also sought analogs with properties more favorable for use in practice. One of the possibilities are lipidized analogs, among...
Neuroprotective effects of food intake regulating peptides in vitro and in vivo
Kasperová, Barbora Judita ; Maletínská, Lenka (advisor) ; Vaněk, Ondřej (referee)
Nowadays, Alzheimer's disease (AD) is one of the most serious health problems among elder. To this day, pathogenesis of AD is still unknown and therefore no effective treatment has been found. AD is characterized by neuropathological features, the formation of extracellular senile plaques of amyloid β and intracellular neurofibrillary tangles of Tau protein. Numerous experimental studies have confirmed that metabolic disorders such as type 2 diabetes mellitus or obesity contribute significantly to the development of cognitive impairment and therefore the development of AD. In this diploma thesis, the potential neuroprotective effect of peptides regulating food intake was investigated in in vitro and in vivo experiments. The potential neuroprotective effect of liraglutide, a glucagon-like peptide-1 analog used as a type 2 diabetes mellitus treatment, a prolactin-releasing peptide (PrRP) and its palmitoylated analog, palm11 -PrRP31, was investigated on SH-SY5Y cell line. The peptides were used as a pretreatment on SH-SY5Y cells in methylglyoxal-induced cytotoxicity. It has been proven that the peptides themselves are not toxic and do not significantly reduce the viability of SH-SY5Y cells. The tested peptides showed prophylactic effects against cytotoxicity and apoptosis induced by toxic...

National Repository of Grey Literature : 43 records found   beginprevious15 - 24nextend  jump to record:
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