Induction of Cyp2e1 contributes to asparaginase-induced hepatocyte sensitization to lipotoxicity
Year: 2024
Type: article
Abstract: studies in mouse and human WAT suggest that PEG-ASNase induces the expression of adipose triglyceride lipase (ATGL), activates the lipase, and stimulates adipose tissue lipolysis, suggesting that the FFAs from WAT may contribute to the observed liver injury. Moreover, treatment with PEG-ASNase sensitizes hepatocytes to FFA-induced lipotoxicity. Mechanistically, our RNA-sequencing (RNA-seq) analyses reveal that PEG-ASNase-induced sensitization to lipotoxicity is accompanied by the induction of Cyp2e1. We demonstrated that this sensitization effect is attenuated by both pharmacological and genetic inhibition of Cyp2e1. Our findings suggest that PEG-ASNase therapy induces WAT lipolysis and sensitizes hepatocytes to hepatic lipotoxicity in a Cyp2e1-dependent manner.
Source: Acta Pharmaceutica Sinica B
Authors: Yin Zhu, Yuyin Wang, Keito Hoshitsuki, Da Yang, Lauren Kokai, Xiaochao Ma, Wen Xie, Christian A. Fernandez
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,600
OpenAlex ID: W4404135372