Triclocarban Disrupts Hepatic Lipid Homeostasis and Promotes Endoplasmic Reticulum Stress in Mice: A Multiomics Investigation

Triclocarban (TCC) is an antiseptic ingredient incorporated into many skin-contact hygiene products, raising public health concerns for its frequent detection in the general population. As the central metabolic organ, the liver plays a key role in lipid synthesis and metabolism; however, the in vivo effects of TCC on hepatic lipid homeostasis remain largely unclear. Herein, a percutaneous TCC exposure model was established based on human-relevant concentrations. An integrated multiomics approach, including hepatic transcriptomics and lipidomics, was applied to explore TCC effects on the liver. We discovered that continuous dermal absorption of TCC significantly disturbed hepatic lipid profiles, as manifested by the decrease in energy storage lipid triacylglycerol (TG) and its synthetic precursor diacylglycerol (DG). Integrated analysis of transcriptomics and targeted validation revealed that TG reduction could result from the decline in lipogenesis, acceleration of fatty acid β-oxidation, and elevated secretion of very-low-density lipoproteins (VLDLs). Cell membrane homeostasis was also disrupted through altering hepatocellular phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels, which may be related to the activation of endoplasmic reticulum (ER) stress, resulting in the promotion of hepatocyte apoptosis. Together, this work provides novel insights into the causal relationship between TCC exposure and the hepatic metabolic homeostasis.