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

Organophosphorus flame retardants (OPFRs) have various health risks. Their recently reported contribution to obesity prevalence earned even more concerns on their hazards. Presently, the obesogenic effects of triphenylphosphine oxide (TPPO), a prevalent OPFR, were investigated in mice. Despite of non-significant influences at 0.1 and 1 µg/(kg·day), TPPO at 10 and 100 µg/(kg·day) significantly increased the body weight gain by 44.5 % and 35.0 % compared with the control, respectively. TPPO at 0.1 µg/(kg·day) stimulated glucose tolerance, while at 100 µg/(kg·day) it declined glucose tolerance. TPPO increased levels of triglycerides and cholesterol. At the low dose, TPPO stimulated high-density lipoprotein cholesterol (HDL-C) in serum and inhibited low-density lipoprotein cholesterol (LDL-C), while at the 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-phosphateacyl transferases 1, long-chain fatty acid transport protein 1, and acetyl-CoA carboxylase. Simultaneously, TPPO reduced the expressions of Grm3, Gnal, and Cebpa but activated the expression of Ppara in liver. Especially, TPPO's effects on Ppara expressions were different in fat and liver tissues. Moreover, TPPO significantly disturbed the levels of neurotransmitters including acetylcholine, dopamine, 5-hydroxytryptamine and γ-aminobutyric acid and also the composition of the microbiota (e.g., ratio of Firmicutes to Bacteroidetes). Summing up, TPPO caused obesogenic effects through multiple aspects including disturbances on enzyme activities, genetic expression, neural regulation and microbiota composition. Further studies are needed to elucidate the interactions among the multiple aspects.