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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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Molecular mechanisms of metabolic syndrome with focus on new hormones produced by adipose tissue, liver and skeletal muscle
Kloučková, Jana ; Haluzík, Martin (advisor) ; Šenolt, Ladislav (referee) ; Bužga, Marek (referee)
1 Abstract The cluster of obesity, insulin resistance and other associated comorbidities represents a significant health risk for the affected individuals as well as the whole population. Chronic low-grade inflammation of adipose tissue is considered one of the main mechanisms respon- sible for the progression from simple obesity to a fully developed metabolic syndrome. The aim of our study was to explore two different approaches that could potentially ameliorate adipose tissue inflammation - therapeutic hypothermia and the adipocytokine clusterin. In the first part, we showed that a period of deep hypothermia associated with the an- oxic phase of cardiac surgery significantly delayed the onset of systemic inflammatory re- sponse induced by surgery. The relative gene expression of the studied genes was not altered during the hypothermic period, but was significantly increased in five out of ten studied genes (IL-6, MCP-1, TNF-α, HIF1-α, GLUT1) and decreased in two genes (IRS1, GPX1) at the end of surgery. We conclude that deep hypothermia delays the onset of local adipose tissue hy- poxia and inflammation. These results could partially explain the positive effects of therapeu- tic deep hypothermia on postoperative morbidity and mortality in cardiac surgery patients. In the second part, we examined plasma...
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Endocrine role of adipose tissue in the pathogenesis of chronic inflammation in obesity and type 2 diabetes mellitus
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Taxová Braunerová, Radka (referee)
Adipose tissue as an active endocrine organ is explored in a number of processes associated with metabolic disorders. This work is aimed on studying the effect of endoscopically implantable weight-reducing device - duodeno-jejunal bypass liner - on subclinical inflammation of adipose tissue in obese patients, which contributes to the development of type 2 diabetes mellitus. Specifically, for patients implanted with duodeno- jejunal bypass liner we determined anthropometric, biochemical and hormonal characteristics, and mRNA expression of subcutaneous adipose tissue proinflammatory (TNF-α, leptin, CCL- 2, CX3CL1, CD40, CD80, CD86, CD206, CD163 and IL-6) and anti-inflammatory genes (Adiponektin, IL-10) before, one month and ten months after the intervention. The implantation of duodeno-jejunal bypass liner significantly decreased body weight, waist circumference, and improved metabolic and glycemic control. In addition, C-reactive protein a highly sensitive indicator of inflammatory processes in the body was reduced ten months after implantation. In the case of mRNA expression of CD86 (a marker of activated B lymphocytes and macrophages) there was temporarily increase in adipose tissue one month after the surgery and the subsequent significant decrease after ten months. mRNA expression of other...
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