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Interplay between ghrelin and its novel endogenous antagonist LEAP2: possible role in the pathology of obesity
Holá, Lucie ; Maletínská, Lenka (advisor) ; Jurčovičová, Jana (referee) ; Malínská, Hana (referee)
The increasing number of overweight and obese individuals has become a major health issue in our society. The etiology of obesity often involves excessive hyperphagia, highlighting the importance of comprehensive understanding the regulation of food intake regulation in order to effectively treat this chronic condition. Ghrelin, a peripheral peptide hormone responsible for increasing food intake, directly affects the hypothalamus through the growth hormone secretagogue receptor (GHSR). Recently, it was found that liver expressed antimicrobial peptide 2 (LEAP2) naturally counteracts the effects of the GHSR as an inverse agonist. This makes LEAP2 a potential candidate for the development of anti-obesity treatment. This thesis explores the interaction between ghrelin and LEAP2 in the context of food intake regulation and obesity. Firstly, it focuses on modified N-terminal peptide LEAP2(1-14) and its lipidized analogs, examining their affinity to and activation of GHSR in vitro and in vivo. The results demonstrate that palmitoylated LEAP2(1-14) (palm-LEAP2(1-14)) exhibits the most pronounced affinity for GHSR, acts as GHSR inverse agonist, reduces food intake, inhibits growth hormone release, and shows increased stability in rat plasma. These findings suggest that palm-LEAP2(1-14) holds promise as an...
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Nutrigenetic analysis of metabolic syndrome: the role of spontaneously hypertensive rat chromosome 4
Petrů, Karolína ; Šeda, Ondřej (advisor) ; Malínská, Hana (referee)
Metabolic syndrome (MetS) is a complex condition with a number of interacting genes, epigenetic and environmental factors underlying its pathogenesis. The analysis of genetic component of MetS showed that number of defining parameters of the syndrome is linked to regions of rat chromosome 4. In order to verify these quantitative trait loci (QTL), a double congenic strain was derived with parts of chromosome 4 of spontaneously hypertensive rat (SHR, an inbred MetS model) origin introgressed onto genomic background of congenic Brown Norway strain (BN-Lx). The aim of the proposed thesis is comprise detail genetic mapping of differential segments of the above mentioned double congenic strain BN-Lx.SHR4 and comparison of its metabolic profile under different dietary conditions with varying carbohydrate and fat content. Utilizing DNA sequence and gene expression comparisons, candidate genes or polymorphisms for the MetS aspects and potential nutrigenetic interactions will be identified. Key words: nutrigenetics, experimental models, metabolic syndrome, congenic strain, genotyping, rat
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The role of fructose in hepatic fat accumulation
Justrová, Marie ; Kovář, Jan (advisor) ; Malínská, Hana (referee)
One of the metabolic disorders with an increasing incidence is non-alcoholic fatty liver disease (NAFLD). NAFLD is characterized by pathological accumulation of fat in the liver. According to some authors, excessive fructose consumption plays an important role in its pathogenesis. The thesis aims to interpret published findings of the relationship between fructose intake and fat deposition in the liver. In the first part the fructose metabolism is described and compared with the glucose metabolism. The other effects of fructose on fat, carbohydrate and nucleotide metabolism are mentioned. This is followed by definition of the term NAFLD, description of various stages and clinical characterization of the disease. In the final part of the thesis the results of studies concerned with the role of excessive fructose consumption in NAFLD development are summarized. Excessive consumption of fructose by healthy subjects during isocaloric diet doesn't result in hepatic fat accumulation due to effective compensatory mechanisms. However, the role of fructose in hypercaloric diet in the increase of hepatic fat content hasn't been definitely explained yet. It seems that excessive caloric intake per se is more important than the effect of fructose or its metabolites. More pronounced rise in hepatic fat content...
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The role of oxidative stress in the pathogenesis of metabolic syndrome and its complications
Malínská, Hana
The role of oxidative stress in the pathogenesis of metabolic syndrome and its complications Malínská Hana Abstract: Metabolic syndrome is a common disorder combining obesity, dyslipidemia, hypertension and insulin resistance and is primary risk factor for type 2 diabetes and cardiovascular disease. The pathogenetic mechanism is not fully clarified, but recent studies suggest that oxidative stress could play a key role in the pathogenesis of metabolic syndrome and could be common pathogenic factor underlying insulin resistance, diabetes type 2 and cardiovascular disease. The Thesis focus on oxidative stress in tissues and their metabolic consequences. Clustering of cardiovascular risk factors - hypertriglyceridemia, elevated FFA, impaired glucose tolerance and hypertension in HHTg rats as a model of metabolic syndrome increased lipoperoxidation and aggravated antioxidant system in arterial wall and myocardium. Obesity and growing age further potentiated these disturbances. Oxidative stress potentiated with glutathione depletion impaired glucose tolerance and reduced adipose tissue insulin sensitivity. Fat accumulation in the liver with increasing oxidative stress in SREBP-1a transgenic rats may play a causal role in the pathophysiology of non-alcoholic steatosis and may participate on progression to...
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Nutrigenomic analysis of diet influence in prenatal and early development on metabolic syndrome aspects manifestation in adulthood.
Školníková, Elena ; Šeda, Ondřej (advisor) ; Černá, Marie (referee) ; Malínská, Hana (referee)
16 Abstract The rising prevalence in noncommunicable diseases worldwide calls for the effort to determine their underlying causes. Common metabolic disorders in particular overwhelm the healthcare systems and are a one of the leading causes of poor quality of life of patients. Metabolic syndrome is represented by concurrence of several conditions - dyslipidaemia, obesity, hypertension or impaired glucose tolerance - altered metabolic phenotypes related to genetic and environmental factors. Recent studies suggest that early-life exposure to certain environmental stimuli is particularly capable of changing the mammalian phenotypes. Nutrition, as one of the major factors influencing health, is naturally a focus of research, which studies the link between parental diets and phenotypic alterations in offspring. The developmental origins of health and disease were historically more focused on maternal undernutrition, it is, however, more important to focus on surplus of macronutrients considering the westernization of modern diets. We propose the relevancy of not only the amount of macronutrients in maternal diet, but also their sources, as they may increase disease risk in offspring. Here we report, that sucrose as an alternative carbohydrate in maternal diet, has a marked impact on metabolism of the offspring...
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Nutrigenetic analysis of metabolic syndrome: the role of spontaneously hypertensive rat chromosome 4
Petrů, Karolína ; Šeda, Ondřej (advisor) ; Malínská, Hana (referee)
Metabolic syndrome (MetS) is a complex condition with a number of interacting genes, epigenetic and environmental factors underlying its pathogenesis. The analysis of genetic component of MetS showed that number of defining parameters of the syndrome is linked to regions of rat chromosome 4. In order to verify these quantitative trait loci (QTL), a double congenic strain was derived with parts of chromosome 4 of spontaneously hypertensive rat (SHR, an inbred MetS model) origin introgressed onto genomic background of congenic Brown Norway strain (BN-Lx). The aim of the proposed thesis is comprise detail genetic mapping of differential segments of the above mentioned double congenic strain BN-Lx.SHR4 and comparison of its metabolic profile under different dietary conditions with varying carbohydrate and fat content. Utilizing DNA sequence and gene expression comparisons, candidate genes or polymorphisms for the MetS aspects and potential nutrigenetic interactions will be identified. Key words: nutrigenetics, experimental models, metabolic syndrome, congenic strain, genotyping, rat
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Nutrigenetic interactions of dietary intake of carbohydrates in pathogenesis of type 2 diabetes
Turková, Michaela ; Šeda, Ondřej (advisor) ; Malínská, Hana (referee)
Type 2 diabetes is the most common metabolic condition caused by multiple factors comprising genetic predispositions, lifestyle including diet quality and quantity, environmental factors and others. Particular alleles of numerous genes taking part in pathogenesis of type 2 diabetes interact with dietary intake of specific carbohydrate or distinct ratio of carbohydrates and other macronutrients. The aim of this Bachelor thesis is to summarize the currently available data on nutrigenetic interactions involving carbohydrate intake and, at the same time, affecting risk of type 2 diabetes manifestation.
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The role of oxidative stress in the pathogenesis of metabolic syndrome and its complications
Malínská, Hana
The role of oxidative stress in the pathogenesis of metabolic syndrome and its complications Malínská Hana Abstract: Metabolic syndrome is a common disorder combining obesity, dyslipidemia, hypertension and insulin resistance and is primary risk factor for type 2 diabetes and cardiovascular disease. The pathogenetic mechanism is not fully clarified, but recent studies suggest that oxidative stress could play a key role in the pathogenesis of metabolic syndrome and could be common pathogenic factor underlying insulin resistance, diabetes type 2 and cardiovascular disease. The Thesis focus on oxidative stress in tissues and their metabolic consequences. Clustering of cardiovascular risk factors - hypertriglyceridemia, elevated FFA, impaired glucose tolerance and hypertension in HHTg rats as a model of metabolic syndrome increased lipoperoxidation and aggravated antioxidant system in arterial wall and myocardium. Obesity and growing age further potentiated these disturbances. Oxidative stress potentiated with glutathione depletion impaired glucose tolerance and reduced adipose tissue insulin sensitivity. Fat accumulation in the liver with increasing oxidative stress in SREBP-1a transgenic rats may play a causal role in the pathophysiology of non-alcoholic steatosis and may participate on progression to...
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Alkaline phosphatase as an indicator for the heat treatment of the milk for cheesemaking
Malínská, Hana ; Potůčková, Miroslava (advisor) ; Lidmila, Lidmila (referee)
Alkaline phosphatase as an indicator for the heat treatment of the milk for cheesemaking
Summary
The aim of this diploma thesis was to summarize current knowledge about the evaluation of alkaline phosphatase activity as an indicator of heat treatment of milk for production of dairy products in theoretical part. In experimental part were comparised 2 methods for this enzyme activity determination, the original according to ČSN EN ISO 11816-2 (2003), using pasteurized milk as an extracting agent, and ISO 11816-2/IDF 155-2 (2010), using extraction buffer. For comparison were used 110 cheese samples, 8 quarg products, 49 fresh cheese products, 9 spiced fresh cheese products, 7 white-brined cheese products, 7 Penicillium sp. flora cheese products, 5 coryneform flora cheese products and 25 semi-hard and hard cheese products.
Alkaline phosphatase (EC 3.1.3.1) is a hydrolase cleaving phosphate groups at the 5th and 3rdposition of many molecules including especially nucleotides and proteins. The enzyme has a pH optimum in the alkaline range (pH 10), their cofactors are ions Zn2+and inhibitors Cu2+. Dairy alkaline phosphatase derived from mammary epithelium and other cellular residua in milk. In this medium is the enzyme localized on the membrane of fat globules. Their amount depends on the stage of lactation (the highest concentration is in colostrum) and animal health (their concentration increases when disease, especially mastitis, starts). Due to its specific thermostability is alkaline phosphatase used for proof of milk and milk products pasteurization.
In the experimental part of the diploma thesis was found that the recommended substitution of pasteurized milk for buffer improves enzyme extraction process from cheese matrix and so enhances method sensitivity (p > 0.05). Method unsuitability for Penicillium sp. flora cheese (especially for blue-veined ones) was also confirmed (p > 0.05). This unsuitability could be explained by content of microbial alkaline phosphatase. For the same reason might not be this method suitable also for coryneform flora cheese. On the contrary, this analysis is suitable (p > 0.05) for white-brined cheese. For spiced fresh cheese were the results in terms of evaluation suitability ambiguous. Based on the obtained data was also confirmed the suitability of proposed limit (10 mU/g) for residual enzyme activity in products from pasteurized milk.
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