Liver immune and lipid metabolism disorders in mice induced by triphenyl phosphate with or without high fructose and high fat diet. (December 2022)

• Record Type: Journal Article
• Authors: Cui, Haiyan; Chang, Yeqian; Cao, Jing; Jiang, Xiaofeng; Li, Mei
• Is Part Of: Chemosphere. Volume 308:Part 3(2022)
• Publication Date: 2022-12
• Subjects: Triphenyl phosphate -- Liver damage -- High fructose and high fat -- Immune damage -- Cytochrome P450; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2022.136543
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Organophosphorus flame retardants (OPFRs) are frequently detected in food and human samples, and epidemiological studies have found that human exposure to aryl-OPFRs (triphenyl phosphate, TPP) is associated with lipid metabolism. Although toxicity studies suggest a potential obesity risk from TPP exposure, the molecular mechanism remains unclear. This study investigated the subchronic dietary effects on mouse liver significantly changed proteins (SCPs) and elucidated the underlying molecular mechanisms of TPP with or without a high-fructose and high-fat (HFF) diet. Male C57BL/6J mice were exposed to low-dose TPP (corresponding to the oral reference dose, 10 μg/kg body weight (bw)/day) and high-dose TPP (1000 μg/kg bw/day) for 12 weeks. The results showed that exposure to TPP generated changes of liver function and organelle damage as well as increases in total cholesterol and triglyceride levels. TPP exposure at a low dose damaged the liver immune system via major histocompatibility complex-related proteins involved in antigen processing and presentation. TPP exposure at a high dose caused disorders of the biosynthesis of unsaturated fatty acids and steroid hormones, thereby inducing lipid accumulation in the liver. Although 10 μg/kg TPP did not cause serious lipid metabolism disorders in the liver, significant overexpression of fatty acid-binding protein 5, malic enzyme 1, and other related SCPs was observed, which led to disorders of cholesterol metabolism and lipogenesis to activate the proliferator-activated receptor signaling pathway and thus induced potential obesity risks. In addition, lipid metabolism disorders related to TPP were aggravated under the HFF diet, impairing liver mitochondrial and endoplasmic reticulum function in mice by altering the activity of cytochrome P450 enzyme subfamilies. These findings provide an in-depth understanding of the molecular toxicity mechanisms and health risks associated with subchronic exposure to TPP under different dietary regimes. Graphical abstract: Image 1 Highlights: The adverse effects of TPP on HFF (high fructose and high fat)-fed mice were evaluated. Exposure to TPP of oral reference dose disrupted liver immune system by MHC-related proteins. TPP induced obesity risk by FABP5 and ME1 involved in cholesterol metabolism and lipogenesis. CYP450 was the specific enzyme that TPP aggravated lipid metabolism disorders induced by HFF.