Fluorene-9-bisphenol exposure decreases locomotor activity and induces lipid-metabolism disorders by impairing fatty acid oxidation in zebrafish

Aims: Fluorene-9-bisphenol (BHPF), as a substitute for bisphenol A, is used in many industries in daily life. Many studies have clarified its effects as an endocrine disruptor on organisms, but its effect on lipid metabolism of zebrafish larvae is not clear. Patients with non-alcoholic fatty liver disease (NAFLD) are more susceptible to external pollutants. It is not clear how BHPF perturbs lipid metabolism or promotes NAFLD progression.Main methods: We explored the biological effects of BHPF on locomotor activity, inflammatory response, endoplasmic reticulum (ER) stress and lipid metabolism in zebrafish, especially in the mechanism of lipid ho-meostasis disorder. In addition, the role of BHPF in the progression of non-alcoholic fatty liver disease (NAFLD) was further explored.Key findings: We found that high concentration (100 nmol/L) BHPF caused retarded growth, mild lipid accu-mulation and reduced the locomotive activity of zebrafish larvae, accompanied by a decrease in endogenous cortisol level. At the same time, it caused the full activation of inflammation and ER stress. Rescue experiments by 25(OH)D-3 demonstrated that high concentration of BHPF caused defects in 1,25(OH)(2)D-3 metabolic pathway through downregulation of cyp2r1, which further damaged pgc1a-mediated fatty acid oxidation and mitochon-drial function, resulting in lipid accumulation. In summary, exposure to BHPF could damage lipid homeostasis and worsen the diet-induced NAFLD.Significance: Our findings provide new insights into the role of BHPF in development of overweight and obesity and also improve understanding of its toxicological mechanism. Our results play a warning role in the admin-istration of environmental pollutants.

Automated summary

This study investigated the biological effects of BHPF on zebrafish, focusing on locomotor activity, inflammatory response, ER stress, and lipid metabolism. It was found that exposure to high concentration of BHPF disrupted lipid homeostasis and worsened the diet-induced NAFLD.