A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin

• DOI: 10.1016/j.jpha.2023.03.010
• Publication Date: 2023-04-05T23:17:43Z
• Authors: Pan Shen; Zhi-Jie Bai; Lei Zhou; Ning-Ning Wang; Zhe-Xin Ni; De-Zhi Sun; Cong-Shu Huang; Yang-Yi Hu; Cheng-Rong Xiao; Wei Zhou; Bo-Li Zhang; Yue Gao
• Keywords: Steatosis

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs, such as bavachin (BV) Fructus Psoraleae, has a prolonged latency to overt drug-induced liver injury the clinic. Several studies have described BV-induced damage and underlying toxicity mechanisms, but little attention been paid deciphering of organisms cellular responses BV at no-observed-adverse-effect level, molecular mechanisms specific indicators are also lacking during asymptomatic phase, making it much harder for early recognition hepatotoxicity. Here, we treated mice with 7 days did not detect any abnormalities biochemical tests, found subtle steatosis BV-treated hepatocytes. We then profiled gene expression hepatocytes non-parenchymal cells single-cell resolution discovered three types hepatocyte subsets liver. Among these, hepa3 subtype suffered from vast alteration lipid metabolism, which was characterized enhanced apolipoproteins, carboxylesterases, stearoyl-CoA desaturase 1 (Scd1). In particular, increased Scd1 promoted monounsaturated fatty acids (MUFAs) synthesis considered be related polyunsaturated (PUFAs) generation, participates initiation ferroptosis. Additionally, demonstrated that multiple intrinsic transcription factors, including Srebf1 Hnf4a, extrinsic signals niche may regulate above-mentioned events Collectively, our study deciphered features response insult, decoded suggested could hub molecule prediction hepatotoxicity an stage.