Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Genetics and Etiopathology of Childhood Obesity, and Development of a Genetic Risk Calculation Panel Based on the Polygenic Risk Score Approach(01. Izmir Institute of Technology, 2023) Yurt, Dudu Seher; Sezgin, EfeObesity is the disease that significantly affects human life as a combination of genetic and physiological environment. The polygenic background of the disease causes of childhood or adulthood obesity are still not fully understood. Childhood obesity and adulthood obesity are usually expressed in terms of body fat mass and body mass index (BMI). Obesity is a comorbid disease that is often associated with T2D, cardiovascular diseases, fatty liver and various mental health problems. Therefore, examining the genetic background of the disease is also important for epidemiological studies. Obesity, which is one of the multi-gene diseases, is revealed by genome-wide research studies, candidate gene studies by SNP genotyping assays. SNP genotyping analyzes not only provide information about the transmission of childhood obesity, but also provide significant guidance on the biological pathways of the disease. Genome-wide association studies (GWAS) provide effective research in association studies between anthropometric body characteristics and the genome. The aim of this thesis is to investigate childhood related obesity variants, adulthood related obesity variants, to identify relationship of these two groups of genetic variants. In addition, the purpose of the thesis, is to understand effects of the variants on metabolic pathways, the difference of childhood and adulthood obesity related pathways and calculation of polygenic risk.Master Thesis Modulating Akkermansia Muciniphila by Probiotics for Obesity Management(Izmir Institute of Technology, 2021) Kamber, Aslıhan; Harsa, Hayriye Şebnem; Bulut Albayrak, ÇisemThe aim of this thesis is to investigate the potential of lactic acid bacteria (LAB) having probiotic properties to trigger Akkermansia muciniphila as anti-obesity candidate. Artisanal strains of LAB were evaluated in terms of stability in gastrointestinal conditions, mucin/mucus non-utilization properties, growth in the presence of mucin, adhesion to the mucin/mucus layer, biofilm formation, lactate production abilities, antimicrobial properties, HT-29 cell binding and mucin/mucus thickness increment abilities. Among 40 strains, 17 of LAB including 6 olive isolates were selected for their tolerance to gastrointestinal conditions and analyzed for further abilities e.g., mucin promotion potential. Most of them (13 of the 17 bacteria) remained viable in the range of 106-108CFU/mL in the simulated gastric juice, and these bacteria continued their viability in the range of 105-107 CFU/mL in the simulated intestinal fluid. Besides, 6 reference and 7 L. bulgaricus isolates did not utilize the mucin and showed no or negligible growth in the presence of mucin. Additionally, 13 of the 17 bacteria adhered to mucin layer with variable degree of binding between 41.03-65.37%. Furthermore, variable degree biofilm formation efficiencies can also support their existence and adhesion to intestinal cells. Varying amounts of lactate by 7 LAB were produced (6.51-18.17 g/L) and this ability is another important criteria for supporting mucus pathway. All those strains adhered to HT-29 cell line and they showed significant increase in mucin thickness by comparing the control. L. plantarum C47 and Lactobacillus AK50 isolates were selected as the antiobesity prototype candidates for their desirable attributes.Master Thesis Investigation of the Molecular and Genetic Response in Enterocytes of Duodenum During Elevated Intracellular Glucose Level(Izmir Institute of Technology, 2016) Boztepe, Tuğçe; Güleç, Şükrü; Seyrantepe, VolkanGlucose is one of the nutritional factor that involves in developing of obesity and type 2 diabetes in human. The studies indicated that enterocyte cells on intestine might play a role in dietary glucose sensing during obesity. Obese people are consumed high amount of dietary glucose and enterocyte cells consequently are exposed to high glucose. Thus, we aimed to find relevant physiological pathways and genome-wide mRNA expression profiles that can be regulated by glucose in fully differentiated human intestinal epithelial (CaCo-2). The cells were maintained two different glucose levels (5.5mM for control, 25mM for high glucose) at least three passages. The cells were grown on transwell system for 21 days to mimic human intestine system. Transepithelial electrical resistances (TEER) were measured to control monolayer formation and polarization. RNA isolation was performed and whole genome mRNA expression profile were determined following gene ontology analysis to find affected molecular pathways. Compared to control relative glucose level was found high in basolateral side of CaCo-2 cells that were under high glucose condition without effecting TEER. GLUT2, SGLT1, GLUT5 mRNA levels were significantly reduced during elevated glucose levels which is consistent with literature. Significant fold change analysis showed that 351 genes upregulated and 468 genes under high glucose condition. We found high glucose significantly leads changes of molecular pathways (downregulated; glycolysis and gluconeogenesis, adherens junction, fructose/mannose metabolism, pentose phosphate pathway and upregulated; protein export). These results provide us better understanding and open new window for glucose metabolism of enterocytes during obesity.
