Background: TPT is an environmental endocrine disruptor that can interfere with endocrine function. However, whether TPT can cause damage to liver structure and function and abnormal lipid metabolism and whether it can cause ER stress is still unclear.
Objective: To explore the effect of TPT on liver structure, function and lipid metabolism and whether ER stress occurs.
Methods: Male SD rats were divided into 4 groups: control group (Ctrl group, TPT-L group (0.5 mg/kg/d), TPT-M group (1 mg/kg/d), and TPT-H group (2 mg/kg/d). After 10 days of continuous gavage, HE staining was used to observe the morphological structure of liver tissue, serum biochemical indicators were detected, gene expression and functional enrichment analysis were performed by RNA-seq, Western Blot was used to detect the protein expression level of liver tissue, and qRT-PCR was used to detect the gene expression.
Results: After TPT exposure, the liver structure damaged; serum TBIL, AST and m-AST levels were significantly increased in the TPT-M group, and serum TG levels were significantly decreased in the TPT-H group. TCHO and TG in liver tissues were significantly increased; transcriptomic analysis detected 105 differential genes. Enrichment analysis showed that TPT exposure mainly affected fatty acid metabolism and drug metabolism in liver tissue, and also affected the redox process of liver tissue; the protein expression levels of PPARα, PPARγ, AMPK, RXRα, IRE1α and PERK were significantly increased after TPT exposure; the expression levels of lipid metabolism-related genes Acsl1, Elovl5, Hmgcr, Hmgcs1 and Srebf1 were significantly increased in the TPT-L group, while in the TPT-M and TPT-H groups had no significant change.
Conclusions: TPT exposure can cause liver injury, lipid metabolism disorder and ER stress.
Keywords: ER stress; Lipid metabolism; Liver injury; TPT; Transcriptome.
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