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lmportance of epicardial fat in heart diseases: new mechanism of action and their therapeutic implication
Matloch, Zdeněk ; Haluzík, Martin (advisor) ; Maruna, Pavel (referee) ; Lipš, Michal (referee)
It was documented earlier that epicardial fat is a source of pro-inflammatory mediators under basal conditions (Mazurek, Zhang et al. 2003, Baker, Silva et al. 2006). It was also found that during cardiac surgery there is an increased expression of mRNA for pro- inflammatory cytokines in both epicardial and subcutaneous adipose tissue (Kremen, Dolinkova et al. 2006). During advanced heart failure, an inflammation of adipose tissue and resistance to adiponectin was also discovered (Khan, Kato et al. 2012). As part of the project, we tested the hypothesis that changes in levels of pro-inflammatory and anti-inflammatory cytokines, including their expression in adipose, muscle and heart tissue, as well as changes in insulin resistance and lipid profile parameters, are dependent on the type of underlying disease of patients, either the presence of CAD or valve degeneration. The aim of our project was to investigate metabolic changes in various fat tissues, insulin resistance, pro-inflammatory and anti-inflammatory cytokines plasmatic levels and their mRNA expressions in patients with coronary artery disease (CAD) undergoing either elective coronary artery bypass surgery (CABG) or isolated valve replacement. Our patients underwent several blood tests and measurements like anthropometric, biochemical, and...
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Adipokines (leptin and adiponectin) as predictors of weight loss and weight regain during one year period following the 10-week low caloric diet (NUGENOB study)
Drahoš, Jan ; Polák, Jan (advisor)
In the Czech republic, about 20% of women and 16% of men are obese. The key role in the etiology of obesity plays the imbalance between energy intake and expenditure, which is influenced by many factors, including leptin and adiponectin. Leptin is secreted mainly from adipocytes and it's levels increase with cell fat content and body fat percentage. Leptin itself is supposed to lead to weight loss, both by decreasing appetite and increasing energy expenditure. But high levels of leptin can be a signal of so called leptin resistance, a state in which leptin is losing it's effects. Adiponectin is secreted exclusively from adipose tissue. In obese people, lower levels of adiponectin were proven (i.e. adiponectin levels are in a negative correlation with body fat percentage). That's consistent with the fact that adiponectin is affecting a range of metabolic prosesses and thus improves insulin sensitivity and metabolic profile. For evaluation, we used a database of almost 750 subjects, that was build under the Nugenob study, conducted in 8 cities in 7 european countries. Al the participants were measured their anthropometric and biochemical parameters at the baseline and after 10 weeks of a standardized weight reduction program. The czech center retested the patient once again 1 year after the initial...
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The role adipose tissue in development of insulin resistance and other metabolic disorders in patients with pheochromocytoma
Klímová, Judita ; Petrák, Ondřej (advisor) ; Kříž, Jan (referee) ; Mlíková Seidlerová, Jitka (referee)
Pheochromocytoma and functional paraganglioma (PPGL) are rare neuroendocrine tumors characterized by catecholamines overproduction, which give a rise to disorders of glucose, lipid, and energy metabolism. The role of adipose tissue in these processes remains unclear. Our aim was to determine the gene expression profile in subcutaneous and visceral adipose tissue of patients with PPGL focusing on endocrine functions of adipose tissue, occurrence of brown (BAT) and beige adipose tissue (BeAT), all in connection with other measured metabolic and energy parameters and levels of circulating adipokines. We demonstrate signs of UCP1-dependent norepinephrine induced thermogenesis connected with overexpression of DIO2 in retroperitoneal VAT of PPGL and higher expression of key transcriptional factors of brown/beige adipogenesis, namely PPARGC1α, CEBPB and PRDM16. However, classic murine BAT or BeAT gene signature in VAT of PPGL was not detected. In subcutaneous adipose tissue (SAT) of PPGL we found signs of possible BeAT transformation, however without simultaneously undergoing UCP1-dependent thermogenesis. We also demonstrate that patients with PPGL have higher serum levels of FGF21 compared to healthy controls and these levels do not differ from obese patients. Furthermore, successful tumor removal...
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Biomarkers of subchondral bone damage caused by inflammation in axial spondyloarthritis.
Bubová, Kristýna ; Pavelka, Karel (advisor) ; Horák, Pavel (referee) ; Hrnčíř, Zbyněk (referee)
Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease affecting primarily the spine and its adjacent structures. The disease is characterized not only by destructive joint changes but also by excessive osteoproduction, which can lead to gradual ankylosis of the spine and thus significantly reduce the mobility and quality of life. The pathogenesis of the disease is not yet fully understood, but a strong genetic background is suggested, along with dysregulation of tissue metabolism resulting from an imbalance of pro- and anti-inflammatory immune mechanisms. We are still lacking biomarker with sufficient sensitivity and specificity which could help to identify early diagnosis, to monitor subchondral damage, and to differentiate rapidly progressing patients. The aim of this work was to determine the levels of potential biomarkers of connective tissue metabolism, fat metabolism and new promising biomarkers for both disease subtypes, their relationship to disease activity and progressive structural changes. Results: We have shown increased serum/plasma levels of connective tissue metabolism biomarkers (especially matrix metalloproteinase mediated metabolites), which were able to differentiate patients with early and late forms of axSpA from healthy individuals (HC), were...
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Nutritional and movement intervention with breast cancer patients
Andrášková, Věra ; Matoulek, Martin (advisor) ; Tuka, Vladimír (referee)
Breast cancer the second most common cancers in women. A weight gain, higher amount of adipose tissue and lower physical activity are risk factors for breast cancer in terms of nutritional status. Recent studies document a negative effect of adipokines, adipose tissue hormones on the development and prognosis of cancer. Likewise, the positive effect of myokines, hormones of muscle tissue, has been increasingly discussed in recent years. Influencing the amount of adipose and muscle tissue in the body is possible through nutritional and physical intervention. A cooperation with a dietitian was offered to 81 patients in the Masaryk Memorial Cancer Institute. The offer of nutritional and physical intervention was accepted by 25 patients and 19 patients completed 3 months of therapy. The aim of the study was to analyze the development of weight in patients before and after the diagnosis of breast cancer, and futher to perform a nutritional intervention in the form of a 3 - month program using personal visits and online monitoring of diet and physical activity and to characterize the diet in patients with breast cancer after the intervention. From the obtained data it was not possible to perform an analysis of weight development in patients. The performed evaluation of eating habits based on a comparison...
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The role of demethylase FTO and adipokines in the heart: effect of chronic hypoxia
Benák, Daniel ; Hlaváčková, Markéta (advisor) ; Bardová, Kristina (referee)
Adaptace na chronickou hypoxii zvyšuje toleranci srdce k ischemicko-reperfuznímu poškození. Tato adaptace je umožněna řadou fyziologických změn na buněčné úrovni. Jednou z nich je změna v buněčném energetickém metabolismu. Tento proces může být regulován proteinem FTO (z angl. fat mass and obesity associated), demetylázou epigeneticky regulující buněčnou syntézu proteinů. Srdeční metabolismus může být také modulován adipokiny leptinem a adiponektinem. Cílem tohoto projektu bylo proto studovat roli FTO a adipokinů v chronicky hypoxickém srdci. Dospělí samci potkanů kmene Sprague Dawley byli adaptováni na dva modely kontinuální normobarické hypoxie (CNH; 12 % O2 a 10 % O2; 3 týdny). CNH (10 % O2) redukovala u těchto zvířat rozsah infarktu myokardu o 20 %. CNH (12 % O2) nebyla kardioprotektivní. Hladina proteinu FTO byla měřena v tkáni levých (LV) a pravých (RV) komor, stejně jako v játrech a koncovém mozku hypoxických i normoxických zvířat. Za normoxie je hladina FTO v RV o 50 % vyšší než v LV. Ve vysoce metabolicky aktivních tkáních jater a koncového mozku jsou pak hladiny FTO vyšší dokonce 6krát a 11krát. CNH (12 % O2) vedla k signifikantnímu nárůstu hladiny proteinu FTO v srdci. Jednalo se o 21% nárůst v LV a 27% v RV. Hladiny v játrech a koncových mozcích nebyly CNH ovlivněny. Silnější CNH (10 % O2)...
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The role of immune system in development of obesity and derived metabolic complications
Jindrová, Simona ; Bardová, Kristina (advisor) ; Cinkajzlová, Anna (referee)
Obesity is a chronic disease caused by an imbalance between energy intake and expenditure. Important source of energy is the body fat, stored in adipose tissue cells in the form of triacylglycerols. The adipose tissue does not only store triacylglycerols but also functions as an endocrine organ with the ability to secrete cytokines and adipokines - the molecules, participating in series of the metabolic proceses. The consequence of high-fat diet feeding is the growth of adipose cells and altered production od adipokines and cytokines. Majority of them have proinflammatory functions. Consequently inflammation of adipose tissue is increased as well as the activation of components of immune system, especially macrophages. The interplay between these and other aspects, including hight free fatty acid plasma levels, also associated with metabolic disorders caused by obesity, is connected with the development of insulin resistance, that means state, when the tissues are nonsensitive to insulin. Key words: obesity, adipokines, cytokines, immune system, adipose tissue, insulin resistance
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The role of adipose tissue in the pathophysiology of obesity and anorexia nervosa
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Pavlišová, Jana (referee)
The view of adipose tissue and its significance in human pathophysiology has changed substantially in the recent couple of years. It has been shown that adipose tissue is not only a passive storage site for excess energy, but that it actively participates in the maintenance of whole-body homeostasis as an endocrine organ producing various hormones and other biologically active molecules, which by acting in an endocrine, paracrine as well as autocrine fashion affect different organs and systems. An intact regulation of adipose tissue processes plays an important role in sustaining the integrity of the organism, whereas its defects lead to the development of a number of diseases. This thesis focuses primarily on the significance of adipose tissue in the pathogenesis of obesity and anorexia nervosa. In the last years, the incidence of obesity rapidly increases ranking, along with its complications, among the world's leading health problems. Obesity is associated with endocrine dysfunction of adipose tissue characterized by disrupted production of adipose tissue hormones and cytokines resulting in the development of numerous disorders including type 2 diabetes mellitus and cardiovascular diseases. A completely opposite disorder, where, however, adipose tissue, or more precisely the absence of it, plays...
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