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    Bisphenol a reveals its obesogenic effects through disrupting glucose tolerance, oxidant–antioxidant balance, and modulating inflammatory cytokines and fibroblast growth factor in zebrafish
    (SAGE Publications Ltd, 2022) Beler, Merih; Cansız, Derya; Ünal, İsmail; Üstündağ, Ünsal Veli; Dandin, Esra; Ak, Esin; Alturfan, A. Ata; Emekli Alturfan, Ebru
    Obesogens affect lipid metabolism, and genetic or epigenetic factors may also contribute to the progression of obesity. Endocrine-disrupting chemicals (EDCs) are the most striking among obesogens. Bisphenol A (BPA) is an estrogenic EDC used in food containers, adhesives, dye powders, and dental fillers. We aimed to elucidate molecular mechanisms of BPA’s obesogenic effects focusing on obesogenic pathways in the liver including fibroblast growth factor (FGF) and Dnmt3a which is its epigenetic regulator, oxidant-antioxidant status, and inflammatory cytokines. Zebrafish were divided into three groups as control, low-dose BPA (1 ?m BPA), and high-dose BPA groups (10 ?m BPA). At the end of 30 days, oral glucose tolerance test (OGTT) was performed, fasting blood glucose levels were measured, and hepatopancreas tissues were taken. Malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione S-transferase (GST), and nitric oxide (NO) activities were examined in the hepatopancreas. Inflammatory cytokines, lepa, fgf21, and dnmt3a expressions were determined by RT-PCR. BPA exposure increased the body weights, il1ß, tnf?, il6, lepa, fgf21, and dnmt3a expressions, impaired glucose tolerance, and oxidant–antioxidant status in a dose-dependent manner. Hepatocyte degeneration, lipid vacuolization, and vasocongestion were observed in both BPA-exposed groups. Our study suggests impaired glucose tolerance, oxidant–antioxidant balance, increased inflammatory response, fgf21 expression, and dnmt3a expressions as the possible mechanisms for the BPA-induced obesity model in zebrafish.
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    Stevioside ameliorates hyperglycemia and glucose intolerance, in a diet-induced obese zebrafish model, through epigenetic, oxidative stress and inflammatory regulation
    (Elsevier Ltd, 2022) Dandin, Esra; Üstündağ, Ünsal Veli; Ünal, İsmail; Ateş Kalkan, Perihan Seda; Cansız, Derya; Beler, Merih; Ak, Esin; Alturfan, A. Ata; Emekli Alturfan, Ebru
    Obesity is an independent risk factor for type 2 diabetes and epigenetic regulatory mechanisms affect obesityrelated mechanisms. Due to weight gain concern in society, artificial sweeteners with no nutritional value have been increasingly consumed. Stevia is a sweet natural glycoside and a calorie-free sweetner extracted from the leaves of Stevia rebaudiana Bertoni and used as a substitute for artificial sweetners. This study evaluates the effects of stevioside on glucose tolerance, epigenetic and metabolic regulators of insulin resistance, oxidant-antioxidant status and tissue histology in a diet-induced obese (DIO) zebrafish model. After 15 days of overfeeding body weight, and fasting blood glucose, lipid peroxidation and nitric oxide levels and the expressions of fbf21, lepa, ll21, tnf alpha were elevated, where as there was impaired glucose tolerance and lower superoxide dismutase and glutathione S-transferase activities, dnmt3a expression which is an epigenetic tool of insulin resistance. Beneficial effects of stevioside were observed on glucose tolerance, oxidative stress and inflammatory mediators linking obesity to insulin resistance and its epigenetic regulation, in DIO model.
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    Stevioside improves brain oxidant-antioxidant status in overfed zebrafish
    (Istanbul University Press, 2023) Dandin, Esra; Ünal, İsmail; Beler, Merih; Üstündağ, Ünsal Veli; Cansız, Derya; Ateş Kalkan, Perihan Seda; Emekli Alturfan, Ebru
    Objective: An excessive buildup of adipose tissue is a defining feature of overnutrition, and a significant fraction of the world's population suffers from obesity. Overnutrition is associated with the deterioration of mitochondrial functions in the brain in the case of obesity. In this study, we evaluated the effects of stevioside (ST) which is a calorie-free, naturally occurring herbal sweetener made from Stevia rebaudiana (Bertoni) on the oxidant-antioxidant balance in the brain in cases of overnutrition. Accordingly, the effects of ST consumption on the oxidant-antioxidant balance in the brain was evaluated and determined in a case study of overfeeding adult zebrafish for 15 days. Materials and Methods: Zebrafish were placed in four groups; the control group (C); overfed group (OF); low-dose (1mg/L) ST treated OF group (OF+LDS); and the high-dose ST (5mg/L) treated OF group (OF+HDS). The levels of lipid peroxidation (LPO) were evaluated together with nitric oxide (NO) to determine the oxidant status. The antioxidant status from the activities of the superoxide dismutase (SOD) and glutathione S-transferase (GST) were determined in brain tissues. Results: The ST treatment decreased the increased LPO and NO levels in overfed zebrafish and increased SOD and GST activities in a dose-dependent manner. Conclusion: ST exerted an antioxidant effect on the possible damage mechanisms that could occur in the brain in case of overnutrition by decreasing oxidative stress and improving the antioxidant enzyme activities.