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Regulatory mechanisms affecting etiopathogenesis of obesity, insulin resistance and type 2 diabetes mellitus.
Cinkajzlová, Anna ; Haluzík, Martin (advisor) ; Krčma, Michal (referee) ; Kříž, Jan (referee)
Subclinical inflammation plays a pivotal role in the development of obesity- related complications including type 2 diabetes mellitus, hypertension and cardiovascular diseases. Macrophages are considered important players participating in the initiation and progression of subclinical inflammation within as well as outside of adipose tissue. The first part of this dissertation thesis was focused on macrophage characterization and their quantitative and qualitative changes accompanying metabolic improvements after bariatric surgery. We have demonstrated that the number of macrophages in subcutaneous adipose tissue is reduced regardless of their M1 or M2 polarization manifested as positivity of both the M1- associated CD40 antigen and the M2-associated CD163 and CD206 antigens 6 months after bariatric surgery. Thus, as suggested by previously published data, subcutaneous adipose tissue macrophages seem to have a mixed phenotype. We further confirmed a higher number of non- classical monocytes, which play a role in the control of vascular integrity, in obese subjects as well as a classical monocyte-derived origin of CD163 positive monocytes. Our data also support the previous suggestion of the soluble form of CD163 antigen being a suitable marker of metabolic complications of obesity. The second part...
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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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Molecular cytogenetic analysis of mosaic chromosomal abnormalities
Cinkajzlová, Anna ; Kočárek, Eduard (advisor) ; Král, Jiří (referee)
The focus of this diploma thesis is on mosaic numerical and structural chromosomal aberrations. In its theoretical part, general problems of mosaicism, its phenotypic effect, mechanisms of origin, related epigenetic modifications, and diagnostic options are described. The methodical part of the thesis then primarily refers to fluorescence in situ hybridization (FISH) and its application in the diagnostics of mosaicism. This method was used in the examination of 29 patients with numerical as well as structural abnormalities of autosomes or gonosomes with proven or suspected mosaicism. On the basis of this analysis, possible errors of measurement were determined and data for statistic evaluation were retrieved. For the examinations of three patients an alternative of the comparative genomic hybridization, the array CGH technique, was applied. The FISH method, although being based on random selection and human factor, proved sufficient sensitivity as well as specificity in the field of low-frequency mosaicism diagnostics. The main critical factors responsible for potential misinterpretation of the data arose from inherent characteristics of the biological material, incorrect targeting of the analysis, probe instability, bleed through effect and absence of mitosis during the structural aberrations analysis.
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