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Association of fatty acid composition in serum and / or adipose tissue lipids with lipid and carbohydrate metabolism in obese subjects of different age categories
Metelcová, Tereza ; Kunešová, Marie (advisor) ; Müllerová, Dana (referee) ; Štich, Vladimír (referee)
Obesity is a chronic disease that is caused by many factors. Excessive adipose tissue is involved in the development of metabolic and cardiovascular diseases. Prevention of cardiometabolic risks includes lifestyle arrangement, including an increased intake of omega 3 polyunsaturated fatty acids (PUFA). In additional to lifestyle factors, genetics factors also significantly contribute to influencing carbohydrate and lipid metabolism. In study A, we monitored 670 subjects (336 girls and 334 boys). Single-nucleotide polymorphisms (SNPs) in the FADS1 gene (rs174546, rs174537) was assessed using real-time PCR and then we determined the spectrum of fatty acids (FAs). The results show that SNPs in the FADS1 affect the efficiency of synthesis by affecting the activity of delta 5 desaturase. Abnormal FAs composition can affect cardiometabolic health. Study B examined a cohort of 215 individuals (131 women and 84 men) who participated in both rounds of the Childhood Obesity Prevalence And Treatment (COPAT) project. The individuals were divided into two groups: BMI≤25 kg/mš and BMI≥25 kg/mš. This model was evaluated regardless of sex because the variable sex did not correlate significantly with the variable weight status. The percentage of adipose tissue was used as the second parameter. The second parameter...
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Molecular mechanisms linking adipose tissue dysfunction and atherosclerotic complications
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Bužga, Marek (referee) ; Cibičková, Ľubica (referee)
Obesity and its associated comorbidities increase the risk of mortality. The development of subclinical inflammation associated with obesity also plays a significant role in this. In our work, we focused on changes in the endocrine and mitochondrial function of adipose tissue and their relationship to cardiovascular complications. The first part of the thesis focuses on determining the expression of mitochondrial and endoplasmic reticulum genes in epicardial and subcutaneous adipose tissue, intercostal muscle or right myocardial atrium in patients with atherosclerotic coronary artery disease. Patients with coronary artery disease had reduced expression of several mitochondrial chain genes in epicardial adipose tissue compared to subcutaneous adipose tissue and other tissues, while no change in endoplasmic reticulum gene expression in the above-mentioned tissues has been demonstrated. Based on decreased mitochondrial gene expression in patients with coronary artery disease, we conclude that mitochondrial dysfunction of epicardial adipose tissue may contribute to the development of coronary atherosclerosis. The second part of the thesis is focused on neudesin, new potentional regulator of energy metabolism, in obese patients with type 2 diabetes mellitus (T2DM), who underwent various weight reduction...
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Functions of Neuregulin 4
Majerčáková, Eva ; Žurmanová, Jitka (advisor) ; Haasová, Eliška (referee)
This work focuses on reviewing the function of Neuregulin 4 (Nrg4) and its receptor ErbB4 in various biological processes and disease states, including inflammation, cancer, metabolic diseases, and liver diseases. In metabolic diseases such as diabetes, Nrg4 may affect glucose metabolism and lipid homeostasis, but the exact mechanism of action is not yet well understood. Nrg4 and its receptor ErbB4 appear to be key factors in regulating inflammation and promoting cell survival. Moreover, in liver diseases, such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, Nrg4 and ErbB4 seems to play a protective role. Overall, these findings highlight complex roles of Nrg4 and ErbB4 in a multitude of biological processes and disease states. Further research is needed to fully understand these relationships and their potential as diagnostic or therapeutic targets.
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Effect of biological treatment and body constitution on in vitro osteoclastogenesis from peripheral precursors in axial spondylarthritisis
Beránková, Martina ; Daňková, Pavlína (advisor) ; Rossmeislová, Lenka (referee)
Introduction: Biological therapy is becoming a common approach to stop disease progression and suppress symptoms of axial spondyloarthritis, an inflammatory rheumatic disease characterized by bone loss due to dysregulation of bone turnover and increased osteoclast differentiation. Obesity likely affects bone metabolism through multiple mechanisms. It can promote adipocyte differentiation and fat accumulation while inhibiting osteoblast differentiation and bone formation. Additionally, obesity is closely associated with chronic inflammation, which can enhance osteoclast activity and bone resorption. This master's thesis aims to examine the potential influence of excessive adiposity on the osteoclastogenesis process among patients receiving biological therapy for axial spondyloarthritis. Materials and methods: Monocytes isolated from the peripheral blood of patients with axial spondyloarthritis undergoing biological therapy and healthy donors were stimulated in vitro with pooled sera from patients receiving biological treatment, patients with different type of treatment, and healthy controls for a duration of 7-14 days. Osteoclasts were evaluated as multinucleated, TRAP-positive cells, and their numbers were subjected to statistical analysis. Markers of bone metabolism and inflammation were assessed...
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Atherosclerosis risk factors and macrophage polarization in adipose tissue
Králová, Anna ; Poledne, Rudolf (advisor) ; Vrablík, Michal (referee) ; Zicha, Josef (referee)
Atherosclerosis is a major cause of cardiovascular disease, and the pro-inflammatory state stimulates the process of atherogenesis. Since the 1990s, it has become clear that adipose tissue has not only an endocrine function, but it is also a very important immune organ due to the presence of various immunocytes with high cytokine secretion. Local resident macrophages represent a major component in the development of this inflammation. Due to our inclusion in the unique transplantation program at IKEM, which ensured availability of peroperatively harvested adipose tissue and its subsequent and immediate analysis, we were able to characterize the different subpopulations of monocytes/macrophages and classify macrophages into pro- and anti-inflammatory populations based on the differential expression of surface markers. From subcutaneous (SCAT), perivascular (PVAT), and visceral (VAT) adipose tissue samples from healthy living kidney donors (LKD), we analyzed the macrophage phenotype after obtaining the stromal fraction by flow cytometry. At the beginning of the experiments, we chose the calprotectin molecule as a proinflammatory marker. However, in subsequent experiments described herein, we chose a different route and selected the CD16 receptor to determine the proinflammatory phenotype. This...
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Gamma-delta T lymphocytes in adipose tissue
Sztoláriková, Adéla ; Krulová, Magdaléna (advisor) ; Pačes, Jan (referee)
T lymphocytes are a unique type of T lymphocytes which, because of their innate-like qualities, belong to the so-called innate lymphocytes. Although they are a relatively rare population of T lymphocytes in peripheral blood, they are enriched in many peripheral tissues where they participate in immune responses to infectious pathogens and cell transformation. In addition, they play a role in the development of several autoimmune disorders. Recently, non- immune functions of T lymphocytes in tissue repair and tissue homeostasis have also been emphasized. This work focuses on the characterization of T lymphocytes, especially those residing in adipose tissue. T lymphocytes regulate adipose tissue homeostasis and overall energy metabolism. The roles of T lymphocytes under physiological and non-physiological conditions are described, including their impact on the development of obesity and metabolic syndrome. The possible applications of these lymphocytes in the treatment of these diseases are also briefly mentioned.
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Adipose tissue metabolism and genetically modified murine models
Irodenko, Ilariia ; Bardová, Kristina (advisor) ; Železná, Blanka (referee)
Adipose tissue plays an important role in energy and glucose homeostasis. Adipose tissue metabolism includes lipolysis and lipogenesis processes which control lipid mobilization, storage and distribution in the body. In addition to that adipose tissue is recognized as an endocrine organ which generates cytokines and adipokines for communication with other organs and tissues. The major process of lipogenesis is triacylglycerol synthesis which comprises such enzymes as monoacylglycerol acyltransferase and diglyceride acyltransferase for triacylglycerol storage in a form of lipid droplets. The other way around main enzymes of lipolysis adipose triglyceride lipase and hormone-sensitive lipase produce sufficient amount of energy for other tissues. Lipid combustion in brown adipose tissue produces heat in the body through the function of uncoupling protein 1. Signaling pathways of lipolysis and thermogenesis comprise adrenergic receptors. Study of thermogenic function of uncoupling protein and adipose tissue metabolism can be useful for the treatment of obesity and metabolic disorders.
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New regulatory metabolic factors in patients with obesity and type 2 diabetes mellitus
Matějková, Mirka ; Haluzík, Martin (advisor) ; Flachs, Pavel (referee)
Fibroblast growth factors are proteins with diverse biological function in development, tissue repair, and metabolism. The human FGF gene family consists of 22 members. FGF 19 subfamily includes FGF 19, FGF 21, and FGF 23. They act as systemic factors in an endocrine manner. FGF 19 subfamily requires klotho protein as a cofactor for its action. FGF 19 produced by intestine acts mainly in the liver through FGFR4, where it inhibits bile acid and fatty acid synthesis. FGF 21 is produced by the liver and contributes to the regulation of carbohydrate and lipid metabolism through modulation of glucose uptake in adipocytes. Serum FGF 21 levels are increased in patients with obesity and type 2 diabetes mellitus. Serum FGF 19 levels are on the contrary decreased in patients with obesity and type 2 diabetes mellitus and more probably depend on the nutritional status of the organism than on the glucose metabolism and insulin sensitivity. Key words: type 2 diabetes mellitus, FGF 19, FGF 21, obesity, adipose tissue
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Effect of physical exercise on adipose tissue characteristics: influence of obesity and aging
Čížková, Terezie ; Šiklová, Michaela (advisor) ; Horníková, Daniela (referee)
Obesity and ageing are associated with the changes in adipose tissue characteristics, which are con- sidered as one of important contributors to development of complications, such as cardiovascular diseases or type 2 diabetes. Physical exercise is known to be effective in prevention of diseases rela- ted to obesity and ageing. However, the effect of exercise on adipose tissue characteristics is only few elucidated in humans. The goal of this bachelor thesis is to summarize the main effects of exer- cise on adipose tissue characteristics. This thesis subsequently discuss detrimental changes (dysfunction) of the adipose tissue in obesity. Recent findings about the effects of some types of physical training on health of the elderly people are also mentioned. The initial chapter deals with adipose tissue in general, concretely the morphology, metabolism and endocrine function of the adipose tissue are described. Next part is focused on obesity, the concept of a chronic low-grade inflammatory state is introduced. The key section is the fourth chapter, in which the effects of exer- cise on adipose tissue, i.e. effects on metabolism of adipocytes and activation of immune cells, are reviewed. At the end of this thesis, the pathophysiological changes in inflammatory state and adi- pose tissue distribution associated...
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