Anorexigenic and anxiogenic effects of the plasticiser DEHP (di-2-ethylhexyl phthalate) in goldfish: Involvement of PPAR signalling and feeding-related neuropeptides

Di-2-ethylhexyl phthalate (DEHP), a widely used plasticiser, is a pervasive environmental contaminant with potential detrimental effects on aquatic organisms. The objective of this study was to provide an integrative analysis of how DEHP alters energy balance, temporal homeostasis and fish welfare - interrelated aspects critical to animal survival - to address critical gaps in our understanding of its toxicological effects. Goldfish (Carassius auratus) were chronically (14 days) treated with DEHP. Energy balance was assessed through locomotor activity, metabolic rate, feed intake, and growth indices. Daily of locomotor and metabolic rate rhythms were examined to explore potential circadian disruptions. Anxiety-like behaviours were also examined to assess welfare. DEHP decreased feed intake and food-anticipatory activity (FAA), suggesting an anorexigenic effect, which may have been mediated by increased expression of anorexigenic genes in the hypothalamus and liver, along with decreased expression of orexigenic npy (neuropeptide Y) gene in the hypothalamus. Growth parameters remained unchanged, probably due to compensatory reductions in energy expenditure, as indicated by decreased locomotor activity and metabolic rate. Daily rhythms in these two parameters were preserved, suggesting no disruption in temporal homeostasis. DEHP increased hepatic expression of peroxisome proliferator-activated receptor (PPAR)-related genes, suggesting that PPARs activation is a potential mode of action for DEHP in fish. Anxiety levels were elevated, as evidenced by increased thigmotaxis and scototaxis in behavioural tests, which may be mediated by changes in hypothalamic neuropeptides. These findings highlight the adverse effects of DEHP on energy regulation and animal welfare, providing novel insights into its broader physiological consequences in fish.