|
|
NMDA receptors outside CNS and their subunit composition
Hotovec, Matěj ; Kolcheva, Marharyta (advisor) ; Horáková, Olga (referee)
N-Methyl-D-Aspartate receptors (NMDARs) are a type of ionotropic glutamate receptor that is widely present in the central nervous system and in lesser numbers in other parts of the body, including the gastrointestinal tract. NMDARs play a crucial role in various physiological and pathological processes in the CNS, including synaptic plasticity, learning and memory, and excitotoxic damage. The role of NMDARs outside the CNS is still under investigation. This thesis aims to confirm the presence of NMDARs in the gastrointestinal tract and their subunit composition. Subunit specific NMDAR modulators showed effect on spontaneous phasic activity of ileum, indirectly confirming the presence of GluN1, GluN2A-D and GluN3 subunits. Attempt at direct evidence of protein expression by immunolabeling with monoclonal antibodies against NMDAR subunits was unsuccessful.
|
|
|
Effect of Exercise on Lipid Metabolism in White Adipose Tissue
Gazdová, Tatiana ; Horáková, Olga (advisor) ; Tauchmannová, Kateřina (referee)
Obesity and old age are more prevalent among the current human population than ever before. Increased fat accumulation and hormonal dysregulation are common hallmarks of both these states. It is well reported that both states are associated with impaired lipolysis and glucose homeostasis as a result of disrupted metabolic pathway signalling. Current research offers exercise as a possible remedy, which could improve substrate handling in obesity and old age. Increased energy expenditure, myokine production, and improved insulin sensitivity are all potential benefits of exercise that could mitigate the health risks associated with obesity and ageing. In this work we aim to explore the effect of acute endurance exercise protocol on lipolytic activity of visceral and subcutaneous white adipose tissue depots of lean and young, obese, and aged mice. By the addition of forskolin, isoproterenol, and insulin into the explant media we hope to assess the functionality of β-adrenergic signalling in our subjects. Post exercise lipolytic rate, measured as non-esterified fatty acid release, increased in both depots in all test groups. Glycerol release did not follow the same pattern. Additionally, lipolytic rate, measured as non-esterified fatty acid release, in visceral adipose tissue was higher in samples from...
|
|
|
The influence of gut microbiome on NAFLD development
Herbstová, Kateřina ; Horáková, Olga (advisor) ; Vodička, Martin (referee)
The composition of the intestinal microbiome (i.e. the set of microorganisms living in the intestines) can significantly contribute to the overall function of the host organism, its state of health and the development of diseases. The aim of this works is to describe the possible connections between the gut microbiome and the development of NAFLD (non-alcoholic fatty liver disease). NAFLD is a disease caused by excessive storage of fat hepatic cells not due to alcohol abuse.
|
|
|
Functional crosstalk between human adipose tissue and lymphatic system
Varaliová, Zuzana ; Rossmeislová, Lenka (advisor) ; Daňková, Pavlína (referee) ; Horáková, Olga (referee)
Both adipose tissue (AT) and lymphatic system (LS) are organs with a great influence on whole-body homeostasis and metabolism. Although the first evidence of a link between the AT and LS was provided already in the 19th century when immune clusters called "milk spots" were found in the omental AT, their functional crosstalk remained unexplored and therefore unappreciated for a long time. However, research in recent years has begun to clearly demonstrate the relationship between the two organs, thanks to the development of new tools for studying and visualizing the LS. Nevertheless, many questions about this crosstalk remain unanswered. This doctoral thesis therefore aimed to answer some of them: How do AT and adipocytes change in response to LS dysfunction ranging from worsened lymphatic drainage to chronic lymphedema? What is the trigger of massive AT expansion in lymphedema? Do adipocytes support lymphangiogenesis, and how? Do lymphatic endothelial cells (LECs) affect the metabolic activities of adipocytes? Although our experiments to answer these questions are ongoing, this work demonstrates several new facts. We showed that the lack of effective lymphatic drainage affects lipolytic reactivity in femoral AT and leads to significant differences in the distribution of AT metabolites between the...
|
|
|
Effect of metformin on glucose tolerance in relation to fat content in diet
Kuchaříková, Petra ; Horáková, Olga (advisor) ; Škop, Vojtěch (referee)
Prevalence of obesity and associated diseases like type 2 diabetes has increased rapidly during last years. These diseases closely relate to each other. Obesity leads to insulin resistence, which directly precedes type 2 diabetes. Metformin is the most prescribed medicament for type 2 diabetic patients and insulin resistant people. It improves glucose tolerance and insulin resistance. Enzyme AMP-activated protein kinase (AMPK) is strogly involved in metformin action. The latest studies using transgenic models lacking AMPK suggest, that notable part of mechanisms involved in metformin action is independent on AMPK. n-3 polyunsaturated fatty acids (n-3 PUFA), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are abundant in sea fish, have beneficial effects on metabolism. These fatty acids lower plasma lipids and exert cardioprotective effects. n-3 PUFA also prevent development of insulin resistence and type 2 diabetes in rodents. The aim of this thesis was to characterise acute effects of metformin on glucose homeostasis, impact of short term diet intervention with diet rich in n-3 PUFA on metformin action and the role of insulin stimulated signalling pathways and AMPK. Results suggest that early effect of metformin is dose dependent and that single dose of metformin...
|
|
|
Molecular mechanisms of insulin sensitivity in relation to fat content in diet
Kuchaříková, Petra ; Horáková, Olga (advisor) ; Klusoňová, Petra (referee)
Insulin resistance is a key component of the pathogenesis of metabolic syndrome and type 2 diabetes. Skeletal muscle is an important part of energy metabolism. It recieves, stores and uses most of the glucose from blood. Insulin stimulates glucose uptake, by promoting translocation of glucose transpoters to plasma membrane. It also increases the rate of protein, glycogen and triglyceride synthesis. When muscle is unable to respond to normal levels of circulating insulin, insulin resistance occurs. Insulin resistance leads to disruption of key metabolic processes. Fatty acid transport across the membrane is upregulated, whereas the ability to oxidize fatty acids is decreased. This imbalance leads to accumulation of lipid metabolites inside the cells. Lipid intermediates may interfere with insulin signalling. Inflammatory cytokines, particularly TNF, activate kinases that may inhibit the insulin signal transmission. Insulin resistance may be treated pharmacologically, but also physical activity and decrease of energy intake are important part of therapy. Also polyunsaturated fatty acids have beneficial effects on muscle insulin sensitivity.
|
|
|
Role of adiponectin and B-type natriuretic peptide in the regulation of adipose tissue lipolysis
Wedellová, Zuzana ; Štich, Vladimír (advisor) ; Kunešová, Marie (referee) ; Cahová, Monika (referee) ; Horáková, Olga (referee)
Obesity is a most common metabolic disorder worldwide. Prevalence of obesity is consistently growing in all continents during last years. Primarily the increase of incidence of obesity in children is alarming. Obesity is linked to elevated risk of type 2 diabetes, hyperlipidemia, cardiovascular diseases, some cancers and disorders of musculoskeletal system. The cost of the treatment of diseases linked to obesity is annually increasing and obesity represents very important part of costs of health system in developed - and recently also developing - countries. This fact shows the necessity of research in the area of preventive and therapeutic procedures. The development of metabolic disturbances linked to obesity is associated with dysfunction of adipose tissue. Its two main features are: 1) altered secretion of specific substance with hormonal or paracrinne charakter (called adipokines) and 2) elevated mobilization of non- esterified fatty acids (NEMK) from adipose tissue and subsequently their increased release into the circulation (1). In our studies we paid attention to the study of lipolysis. The rate of lipolysis is the primary factor that determines the release of NEFA from adipose tissue. We focused to a role of adiponectin and natriuretic peptid type B (BNP) in the regulation of lipolysis in...
|
|
|
Regulation of immunometabolism in white adipose tissue
Gazdová, Tatiana ; Horáková, Olga (advisor) ; Beňová, Andrea (referee)
High-fat diet promotes the development of diet-induced obesity, which leads to further complications such as insulin resistance and type II diabetes. The underlying cause for development of obesity associated pathologies is disruption of adipose tissue homeostasis. Excessive lipid accumulation and rapid white adipose tissue expansion stimulate infiltration, proliferation, and activation of immune cells involved in inflammation propagation. Immune cells within white adipose tissue have the ability to modulate adipocyte function as well as whole-body metabolism. These interactions and function modulations are the core topics of immunometabolism, a rapidly developing field of research focused on interpreting how immune system modulates metabolism on cellular as well as systemic level. In obesity, pro-inflammatory immune cells, for example M1 macrophages and neutrophils, outnumber homeostasis-promoting anti-inflammatory immune cells in white adipose tissue and alter the tissue environment. As a result, pro-inflammatory cytokines prevent adipocytes from adequately responding to extracellular stimuli. The resulting interactions between immune cells and adipocytes maintain inflammation and promote ectopic lipid accumulation. Experimental studies suggest that white adipose tissue inflammation can be...
|
|
|
Effect of regular physical exercise on metabolism of adipose tissue in elderly
Čížková, Terezie ; Šiklová, Michaela (advisor) ; Horáková, Olga (referee)
Ageing is associated with changes in body composition, which is caused by decreases in muscle mass and a progressive increase of fat mass. It is also associated with redistribution of adipose tissue with increased visceral and ectopic fat deposition. These changes are related to insulin resistance and other metabolic disturbances. Adipose tissue dysfunction is important contributor to the disturbed metabolic status of elderly and it is characterized by altered adipogenesis, metabolic flexibility and changes in secretory activity. Regular exercise is indisputably a key part of a healthy lifestyle. It was shown to improve muscle function, cardiovascular fitness and metabolic health of elderly. The aim of this thesis was to investigate whether a regular physical exercise can influence characteristics of an adipose tissue in elderly women, and if these changes in the adipose tissue can contribute to an improvement in an insulin sensitivity. In the two groups of elderly women, a long-term trained and a sedentary, the subcutaneous adipose tissue was analyzed for a gene expression of number of metabolic genes, an adipocyte size and a lipolytic rate at the basal state and after the isoproterenol stimulation. Anthropometric parameters and insulin sensitivity were also determined. Outcomes of this thesis...
|
|
|
Specification and differentiation of cells in pancreatic development
Malfatti, Jessica ; Pavlínková, Gabriela (advisor) ; Horáková, Olga (referee)
Pancreas is divided into exocrine and endocrine tissue. The exocrine part contains acinar cells, which produce digestive enzymes, and ductal cells that help with their transportation to the duodenum. The islets of Langerhans form the endocrine part and consist of 5 types of cells; α, β, δ, ε, and PP-cells, producing hormones glucagon, insulin, somatostatin, ghrelin and pancreatic polypeptide, respectively. Pancreas development is divided into primary, secondary and tertiary transition. Many transcription factors participate in the cell specification and differentiation processes. Pancreatic duodenal homeobox 1 specifies the pancreatic domain in primary transition. Pancreas-specific transcription factor 1A is important for the specification and differentiation of acinar cells. All endocrine cell precursors express Neurogenin 3, a key specification factor of endocrine cells. A large number of transcription factors regulate differentiation of endocrine cells as well as their function. Absence or dysfunction of some transcription factors have been associated with pathologies, for example diabetes mellitus, pancreatic carcinoma or pancreatitis. Key words Pancreas, islets of Langerhans, insulin, glucagon, development, differentiation, diabetes
|
guest ::
