Exposure to environmental pollutant bisphenol A causes oxidative damage and lipid accumulation in Zebrafish larvae: Protective role of WL15 peptide derived from cysteine and glycine‐rich protein 2

Humans are exposed to obesity causing Bisphenol A in various ways, especially through diet and food containers. Bioactive peptides are already reported to have antioxidant, antidiabetic, and antiobesity properties, which can mimic the role of mediators involved in obesity prevention. The protective effect of a short molecule or peptide, WL15 from cysteine and glycine‐rich protein 2 of a teleost of aquatic resource on Bisphenol A (BPA)‐induced lipid accumulation in zebrafish larvae was investigated. BPA exposure disrupted the antioxidant enzymes, apoptosis, and nitric oxide and led to changes in biochemical markers including alkaline phosphatase, lactate dehydrogenase, lipid peroxidation, glutathione S‐transferases, glutathione peroxidase, and reduced glutathione. However, WL15 inhibited the overproduction of oxidative stress, which correlates with its lipid‐lowering potential. BPA‐induced lipid accumulation in zebrafish showed an increase in triglyceride, cholesterol, and glucose level; simultaneously, WL15 treatment significantly reduced such accumulation in zebrafish. Evidenced by Oil red O staining and Nile red assay, WL15 inhibited lipid accumulation. At the same time, WL15 at 50 µM increases 2‐(N‐[7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl]amino)‐2‐deoxy‐d‐glucose (2NBDG) glucose uptake in zebrafish. In addition, gene expression studies in zebrafish larvae demonstrated that the WL15 peptide could play a crucial role in preventing lipid accumulation by downregulating the expression of lipogenesis‐specific genes. These results revealed an interesting and novel property of WL15, suggesting its potential application in preventing lipid accumulation through the hypolipidemic and antioxidant properties. WL15 peptide exhibited lipid accumulation inhibition through downregulation of CCAAT/enhancer binding protein‐α (C/EBP‐α), sterol regulatory binding protein 1 (SREBP1), and fatty acid synthase (FAS) gene and improving antioxidant level in bisphenol A exposed zebrafish larvae.