Bisphenol A reveals its obesogenic effects through disrupting glucose tolerance, oxidant–antioxidant balance, and modulating inflammatory cytokines and fibroblast growth factor in zebrafish

Abstract

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 μm BPA), and high-dose BPA groups (10 μm 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, tnfα, 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.

Dose Dependent Effects of Bisphenol A Exposure on Locomotor Activity, Acetylcholinesterase and Redox System Parameters in Zebrafish Embryos

“…There is growing evidence that BPA organ toxicity is greatly influenced by the generation of reactive oxygen species (ROS) and/ or a diminished ability of antioxidant defense, which changes the oxidative equilibrium in the mitochondria and throughout the cell (14). The effects of BPA on increasing oxidative stress in zebrafish and zebrafish embryos have been demonstrated in previous studies (15,16).…”

Diethylhexyl phthalate exposure amplifies oxidant and inflammatory response in fetal hyperglycemia model predisposing insulin resistance in zebrafish embryos

“…We have previously shown obesogenic effects of BPA exposure through increased body weights, expressions of Il1ß, tnf, Il-6, lepa, fgf21 , and dnmt3a , reduced glucose tolerance, and disrupted oxidant-antioxidant status in adult zebrafish. BPA-exposed groups showed hepatocyte deterioration, lipid vacuolization, and vasocongestion demonstrating that the BPA-induced obesity model in zebrafish is related to altered glucose tolerance, oxidant-antioxidant balance, elevated inflammatory response, fgf21 expression, and dnmt3a expression (Beler et al, 2022).…”