A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin
10.1016/j.jpha.2023.03.010
- Author:
Pan SHEN
1
;
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
Author Information
1. Department of Pharmaceutical Sciences,Beijing Institute of Radiation Medicine,Beijing,100850,China
- Keywords:
Bavachin;
Hepatotoxicity;
Scd1;
Lipid metabolism;
Single-cell RNA-Seq
- From:
Journal of Pharmaceutical Analysis
2023;13(7):806-816
- CountryChina
- Language:Chinese
-
Abstract:
Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)syn-thesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that mul-tiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.
