PUBLICATION
2-Ethylhexyl Diphenyl Phosphate Causes Obesity in Zebrafish by Stimulating Overeating via Inhibition of Dopamine Receptor D2
- Authors
- Yang, R., Zhang, Y., Deng, Y., Yang, Y., Zhong, W., Zhu, L.
- ID
- ZDB-PUB-230914-56
- Date
- 2023
- Source
- Environmental science & technology 57(38): 14162-14172 (Journal)
- Registered Authors
- Keywords
- 2-ethylhexyl diphenyl phosphate, dopamine receptor D2, feeding behavior, obesity, zebrafish
- MeSH Terms
-
- Molecular Docking Simulation
- Obesity/chemically induced
- Receptors, Dopamine
- Animals
- Hyperphagia/chemically induced
- Phosphates*
- Zebrafish*
- PubMed
- 37704188 Full text @ Env. Sci. Tech.
Citation
Yang, R., Zhang, Y., Deng, Y., Yang, Y., Zhong, W., Zhu, L. (2023) 2-Ethylhexyl Diphenyl Phosphate Causes Obesity in Zebrafish by Stimulating Overeating via Inhibition of Dopamine Receptor D2. Environmental science & technology. 57(38):14162-14172.
Abstract
Obesity is a popular public health problem worldwide and is mainly caused by overeating, but little is known about the impacts of synthetic chemicals on obesity. Herein, we evaluated the obesogenic effect caused by 2-ethylhexyl diphenyl phosphate (EHDPHP) on zebrafish. Adult zebrafish were exposed to 5, 35, and 245 μg/L of EHDPHP for 21 days. Results showed that EHDPHP exposure significantly promoted the feeding behavior of zebrafish, as evidenced by shorter reaction time, increased average food intake, feeding rate, and intake frequency (p < 0.05). Transcriptomic, real-time quantitative PCR, and neurotransmitter analyses revealed that the dopamine (DA) receptor D2 (DRD2) was inhibited, which interfered with the DA neural reward regulation system, thus stimulating food addiction to zebrafish. This was further verified by the restored DRD2 after 7 days of Halo (a DRD2 agonist) treatment. A strong interaction between EHDPHP and DRD2 was identified via molecular docking. As a consequence of the abnormal feeding behavior, the exposed fish exhibited significant obesity evidenced by increased body weight, body mass index, plasma total cholesterol, triglyceride, and body fat content. Additionally, the pathways linked to Parkinson's disease, alcoholism, and cocaine addiction were also disrupted, implying that EHDPHP might cause other neurological disorders via the disrupted DA system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping