Bisphenol A and its Analogues Alter Appetite Control in Zebrafish

The regulation of appetite is of growing interest due to the significant rise in global obesity rates. Hunger and satiety are controlled by two hormones with functional activity in the brain; leptin, which is produced in adipocytes and suppresses food intake, and ghrelin, which is produced and released mainly by the stomach and functions as an appetite-stimulatory signal. In this study, zebrafish-based in vivo assays were used to examine whether BPA and five of its analogues, BPAF, BPE, BPC, BPC-CL, and BPS affect appetite regulation. The effect of bisphenol exposure on eating behavior was first examined. Four to six days old zebrafish larvae were exposed to a concentration range of the bisphenols and 17{beta}-estradiol, followed by being fed a stained egg yolk powder at day six. After an hour of feeding, the feed in the gut was imaged by microscopy. Quantitative PCR was used to analyze the gene expression of leptin and ghrelin, as well as eleven other genes involved in appetite control. Exposures to BPA, BPAF, BPE, BPC, BPC-Cl and BPS, resulted in increased amounts of feed in the gut of the larvae in a concentration dependent manner. The qPCR results suggested that leptin mRNA expression was downregulated with the increasing concentrations of BPA, BPAF and BPC-Cl, whereas ghrelin mRNA expression was upregulated. The expression of several additional anorexigenic genes were downregulated by BPAF and BPC-Cl exposure, whereas orexigenic genes were upregulated. In conclusion, bisphenol exposures resulted in an increased eating behavior in zebrafish larvae, which correlated to increased mRNA expression of appetite-stimulatory genes and decreased expression of satiety-inducing genes. In addition, the results suggest that zebrafish larvae can be used to efficiently assess obesogenic capacity of environmental pollutants.