Browsing by Subject "Obesity"
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Item Open Access Characterization of enteric nervous system response to disease conditions in intestine(Bilkent University, 2022-01) Gönüllü, Nagihan GizaySmall intestine is one of the vital organs in gastrointestinal tract that is responsible for absorption of food, amino acids and create barrier against microbial invasion. Whereas large bowel is involved in the reabsorption of water and minerals. Intestinal epithelium is a highly regenerative tissue that it can renew its cells in a span of 4-5 days. In homeostatic state, the turnover rate of the epithelial cells is stable however, in case of inflammation and disease, the rate of proliferation and differentiation increase to regenerate the damaged tissue. Primary cilia (PC) are non-motile, microtubule-based organelles that extrude from plasma membrane. It functions as a sensory element to detect environmental cues. One of the highly studied disease models is ulcerative colitis is mainly characterized by the inflammation of the intestinal mucosal layer and generated by DSS administration. Additionally, high fat diet induced obesity, as a metabolic disease model, was shown to affect intestinal stem cell activity such that higher fat composition of diet causes shortening of small intestine and decrease in weight of tissue. Enteric nervous system is the endogenous nervous network surrounding the gastrointestinal tract and it controls many vital functions including digestion, blood flow, intestinal motility. The initial aim of this study was to reveal the response of intestinal stem cell niche in those stated disease conditions. After detecting ACOT7 protein as a global marker for enteric nervous system of myenteric and submucosal plexus layers, we hypothesized that subpopulations of ENS cells have a connection with intestinal niche upon disease states. Our following goal was to identify subpopulations of ENS and ciliated cells. In order to assess our hypotheses, we conducted series of IHC experiments and confocal microscopy analyses. We found that ACOT7+ cells in ENS contain mainly distinct types of neuronal cell populations such as PHOX2B+ and HuCD+ cells. Further, we identified that glial cells are the main subpopulation of ENS changing their expression pattern in both colitis and obesity models. Also, we classified ciliated cells as a heterogenous population to be colocalized with several ENS and mesenchymal markers. Lastly, we analyzed the gut-brain axis response to DSS induced colitis in the brain of model animals with a focus on thalamus and insular cortex. We identified several thalamic regions showed similar expression pattern alterations which were observed in colon. Overall, the novelty of this thesis arises from the identification of ACOT7 as an ENS marker along with the detection of glial cell interaction with mesenchymal sub-populations. This interplay demonstrates a response upon disease states of both small intestine and colon.Item Open Access Effects of obesity on airway and systemic inflammation in asthmatic children(S. Karger AG, 2021-03-22) Vezir, Emine; Civelek, Ersoy; Dibek Misirlioglu, Emine; Toyran, Muge; Capanoglu, Murat; Karakus, Esra; Kahraman, Tamer; Ozguner, Meltem; Demirel, Fatma; Gürsel, İhsan; Kocabas, Can NaciObese asthma is a complex syndrome with certain phenotypes that differ in children and adults. There is no clear evidence regarding the presence of additive or synergistic pathological interaction between obesity and asthma in children. Objectives: Our aim was to demonstrate the interaction of obesity and asthma in children in terms of airway and systemic inflammation by a controlled observational study. Methods: Four groups were formed: asthma obese (AO), asthma nonobese (ANO), non-AO (NAO), nonasthma nonobese (NANO). Spirometry test, fractional exhaled nitric oxide (FeNO) test, skin prick test, serum inflammatory biomarkers (C-reactive protein, C3, C4, adiponectin, leptin, resistin, periostin, YKL-40, Type 1, and Type 2 cytokines) were conducted and evaluated in all participants. Sputum inflammatory cells (sputum eosinophils and neutrophils) were evaluated in patients who could produce induced sputum and obesity-asthma interactions were determined. Results: A total of 153 participants aged 6–18 years were included in the study, including the AO group (n = 46), the ANO group (n = 45), the NAO group (n = 30), and the NANO group (n = 32). IL-4 (p < 0.001), IL-5 (p < 0.001), IL-13 (p < 0.001), resistin (p < 0.001), and YKL-40 (p < 0.001) levels were higher in patients with asthma independent of obesity. The lowest adiponectin level was found in the AO group and obesity-asthma interaction was detected (p < 0.001). Sputum eosinophilia (p < 0.01), sputum neutrophilia (p < 0.01), and FeNO levels (p = 0.07) were higher in asthmatic patients independent of obesity. In the group with paucigranulocytic inflammation, resistin and YKL-40 levels were significantly lower than in the group without paucigranulocytic inflammation (p < 0.01). Conclusion: No interaction was found between obesity and asthma in terms of airway inflammation. Interaction between obesity and asthma was shown in terms of adiponectin level and resistin/adiponectin and leptin/adiponectin ratios. It was found that serum YKL-40 and resistin levels could be associated with airway inflammation.Item Open Access ER-mitochondrial communication gets stressful(American Association for the Advancement of Science, 2014) Erbay, EbruItem Open Access Identification of differentially expressed microRNAs during lipotoxic endoplasmic reticulum stress in RAW264.7 macrophages(Turkish Biochemistry Society, 2016-06) Nadir, M.; Tufanlı, Ö.; Erbay, E.; Atalay, A.Objective: Increased fatty acids in the circulation and their accumulation in non-adipose tissues play a significant role in the development of obesity related metabolic and inflammatory disorders such as insulin resistance, diabetes and atherosclerosis. While fat tissue has the ability to store excess fatty acids, uptake of excess fatty acids to other tissues burdens intracellular metabolic organelles such as mitochondria and endoplasmic reticulum (ER), leading to stress response and lipotoxic cell death. Unfolded protein response (UPR) is a key adaptation of the ER to stress. It is still not completely clear how lipids engage the UPR and how UPR manages both the adaptive and destructive consequences under its control. Increasing evidence point to the importance of miRNA regulation of the UPR as well as UPR’s role in miRNA biogenesis. In order to understand how lipids engage the UPR, we set forth to identify microRNAs regulated by lipotoxic ER stress in macrophages. Methods: We stressed the mouse macrophage cell line (RAW 264.7) with a saturated fatty acid, 500μM palmitate, reflecting the levels found in the circulation of obese patients. We analyzed the microRNAome profiles of this cell line using QRT-PCR based miScript miRNA PCR array which contained all known mouse microRNAs in miRBase release16 and performed pathway analysis for potential targets. Results: 227 microRNAs showed altered expression levels; 43 microRNAs above 2 fold difference and 13 microRNAs 3-24 fold difference. Pathway analysis enriched the target mRNAs of these lipotoxic ER stress associated miRNAs. Conclusion: When exposed to high concentrations of saturated fatty acids that can induce ER stress, macrophages display a dynamic range of changes in their microRNAome profiles. Our findings reflect the consequences of lipotoxic stress on circulating monocytes and tissue-associated macrophages in obesity. Further studies are needed to deliniate which UPR arm is reponsible for the microRNA changes reported here.Item Open Access Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene(BMJ Group, 2008) Kaplan, Y.; Vargel, I.; Kansu, T.; Akin, B.; Rohmann, E.; Kamaci, S.; Uz, E.; Ozcelik, T.; Wollnik, B.; Akarsu, N. A.Aims: This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family. Methods: Both Xp11 and Xq26 loci were tested by linkage analysis. The 12 exons and intron-exon junctions of the FRMD7 gene were screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme, followed by PCR of the polymorphic CAG repeat of the androgen receptor gene. Results: The family contained 162 individuals, among whom 28 had NYS. Linkage analysis confirmed the Xq26 locus. A novel missense c.686C>G mutation, which causes the substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) in exon 8 of the FRMD7 gene, was observed. This change was not documented in 120 control individuals. The clinical findings in a female who was homozygous for the mutation were not different from those of affected heterozygous females. Skewed X inactivation was remarkable in the affected females of the family. Conclusions: A novel p.R229G mutation in the FRMD7 gene causes the NYS phenotype, and skewed X inactivation influences the manifestation of the disease in X linked NYS females.Item Open Access Spatial organization of functional groups on bioactive supramolecular glycopeptide nanofibers for differentiation of mesenchymal stem cells (MSCs) to brown adipogenesis(American Chemical Society, 2016-12) Caliskan, O. S.; Sardan, Ekiz M.; Tekinay, A. B.; Güler, Mustafa O.Spatial organization of bioactive moieties in biological materials has significant impact on the function and efficiency of these systems. Here, we demonstrate the effect of spatial organization of functional groups including carboxylate, amine, and glucose functionalities by using self-assembled peptide amphiphile (PA) nanofibers as a bioactive scaffold. We show that presentation of bioactive groups on glycopeptide nanofibers affects mesenchymal stem cells (MSCs) in a distinct manner by means of adhesion, proliferation, and differentiation. Strikingly, when the glutamic acid is present in the glycopeptide backbone, the PA nanofibers specifically induced differentiation of MSCs into brown adipocytes in the absence of any differentiation medium as shown by lipid droplet accumulation and adipogenic gene marker expression analyses. This effect was not evident in the other glycopeptide nanofibers, which displayed the same functional groups but with different spatial organization. Brown adipocytes are attractive targets for obesity treatment and are found in trace amounts in adults, which also makes this specific glycopeptide nanofiber system an attractive tool to study molecular pathways of brown adipocyte formation.Item Open Access Structural imaging of the brain reveals decreased total brain and total gray matter volumes in obese but not in lean women with polycystic ovary syndrome compared to body mass index-matched counterparts(Taylor and Francis Ltd, 2017) Saydam, B. O.; Has, A. C.; Bozdag, G.; Oguz, K. K.; Yildiz, B. O.Purpose: To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls. Methods: Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed. Results: Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p < 0.05 for both) whereas lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p < 0.05 for all), whereas lean patients with PCOS had lower GMV in the amygdala than lean controls (p < 0.05). No significant relations were detected between structural differences and measured hormone levels at baseline or during MTT. Conclusion: This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS. © 2017 Informa UK Limited, trading as Taylor & Francis Group.