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 homeostasis 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 accumulation 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 demonstrated that high concentration of BHPF caused defects in 1,25(OH)D metabolic pathway through downregulation of cyp2r1, which further damaged pgc1a-mediated fatty acid oxidation and mitochondrial 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 administration of environmental pollutants.