Lipid accumulation by triphenylphosphine oxide with simultaneous changes in neural dysregulation and microbiota changes

Organophosphorus flame retardants (OPFRs) pose various health risks. Their recently reported contribution to obesity prevalence has raised additional concerns about their hazards. In this study, the obesogenic effects of triphenylphosphine oxide (TPPO), a prevalent OPFR, were investigated in mice. TPPO increased levels of triglycerides and cholesterol. At low dose, TPPO stimulated high-density lipoprotein cholesterol (HDL-C) in serum and inhibited low-density lipoprotein cholesterol (LDL-C), while at high dose it inhibited both HDL-C and LDL-C. TPPO stimulated acyl-CoA oxidase 1, long-chain acyl-CoA synthetase, and adipose triglyceride lipase, while it inhibited glycerol-3-phosphate acyltransferase 1, long-chain fatty acid transport protein 1, and acetyl-CoA carboxylase. TPPO also reduced the expression of Grm3, Gnal, and Cebpa, but activated the expression of Ppara in liver. Notably, the effects of TPPO on Ppara expression were different between fat and liver tissues. In addition, TPPO significantly disturbed the levels of neurotransmitters including acetylcholine, dopamine, 5-hydroxytryptamine, and gamma-aminobutyric acid (GABA), and altered the composition of the gut microbiota (e.g., the ratio of Firmicutes to Bacteroidetes). In conclusion, TPPO induced obesogenic effects through multiple pathways including disturbances in enzyme activities, gene expression, neural regulation, and microbiota composition. Further studies are needed to elucidate the interactions among these multiple aspects.