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.