Waterborne fluoxetine disrupts feeding and energy metabolism in the goldfish Carassius auratus

Fluoxetine (FLX) is one of the most commonly detected pharmaceuticals in wastewater and bioaccumulates in wild-caught fish, especially in brain, liver and muscle tissues. Previous studies indicated that FLX is pharmacologically active in fish species exerting anorexigenic effects, but it is not clear whether waterborne FLX has any potential effects on regulating food intake and energy metabolism. In this study, we investigated the effect of two doses of FLX, an environmental concentration of 540 ng/L, and 100-times this concentration (54 μg/L), on feeding and key metabolic parameters in goldfish. Fish were exposed for a period of 28 days and changes in food intake and body mass were assessed. Pair-fed groups were maintained to discern primary FLX-induced effects from secondary metabolic responses induced by the decreased food intake. Additionally, an untreated control group and a fasted group were used to further compare physiological changes in the context of nutritional status of the animals. Significant decreases in food intake and weight gain were recorded in goldfish exposed to 54 μg/L FLX. Furthermore a significant decrease occurred in circulating glucose levels in the group exposed to 540 ng/L FLX. To elucidate potential mechanisms, we investigated gene expression of feeding neuropeptides in the neuroendocrine brain of goldfish as well as gene expression and enzymatic activity of glycolytic and gluconeogenetic enzymes in liver and muscle tissues. The results confirm brain gene expression patterns in line with potential anorexigenic effects in the hypothalamus, with increased expression in corticotropin-releasing factor (CRF) and decreased expression of neuropeptide Y (NPY). With respect to glucose metabolism, liver gene expression of the gluconeogenic enzyme fructose-1,6-bisphosphatase decreased and muscle hexokinase activity increased in fish exposed to 540 ng/L FLX. Overall, this study demonstrated anorectic properties of FLX at a dose of 54 μg/L FLX and moderate but significant effects on glucose metabolism in goldfish exposed to 540 ng/L FLX. Future studies investigating the importance of these changes in fish are warranted.