ECEESPE2025 Poster Presentations MTEabolism, Nutrition and Obesity (125 abstracts)
CASP3-mediated PARP1 cleavage promotes hepatocyte apoptosis in non-alcoholic fatty liver disease
Fengyi Zhang 1 , Xinhe Wang 1 , Yahui Li 2 , Wenlu Ma 2 , Yaxin Chen 1 , Yufeng Zhang 1 , Jiayi Zhang 1 , Xin Wang 1 , Jingjing Pan 1 , Yu Zhang 1 , Ziyang Cheng 1 , Wenbo Wang 2 & Yujie Li 2
1Shandong University of Traditional Chinese Medicine, Jinan, China; 2Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
JOINT553
Introduction: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic triglyceride (TG) accumulation and is commonly associated with obesity and metabolic syndrome. Due to the lack of effective pharmaceutical treatments, lifestyle interventions, such as dietary control and exercise, remain fundamental for NAFLD management. Studies have shown that obesity-related NAFLD is closely linked to mitochondrial stress and hepatocyte apoptosis, with excessive hepatocyte apoptosis being a critical factor in the progression to non-alcoholic steatohepatitis (NASH). Therefore, identifying targets and drugs that inhibit hepatocyte apoptosis may help alleviate obesity and slow the progression from NAFL to NASH. Poly(ADP-ribose) polymerase 1 (PARP1) is a key regulator of cellular stress responses involved in various physiological and pathological processes. As a substrate of the caspase-3-dependent apoptotic pathway, its cleavage product cl-PARP1 (89 kDa) plays a significant role in apoptosis. However, the role of this mechanism in NAFLD remains poorly understood.
Methods: In this study, db/db mice were used as an animal model, and FFA-induced HepG2 cells were used for In vitro experiments. Western blot (WB), quantitative PCR (qPCR), immunohistochemistry (IHC), immunofluorescence, apoptosis staining, and plasmid transfection techniques were employed to investigate the role of the CASP3-PARP1 apoptotic pathway in NAFLD pathogenesis.
Results: In the db/db mouse model of fatty liver and FFA-induced HepG2 cells, CASP3 was activated, leading to increased cl-PARP1 (89 kDa), elevated Bax expression, and decreased Bcl2 expression. Additionally, enhanced TRITC-dUTP red fluorescence signals indicated aggravated hepatocyte apoptosis. In HepG2 cells, overexpression of CASP3 plasmid resulted in significantly increased cl-PARP1 (89 kDa), further confirming CASP3’s role in PARP1 cleavage.
Conclusion: This study demonstrates that CASP3 is activated in fatty liver, promoting hepatocyte apoptosis through the cleavage of PARP1 to generate cl-PARP1 (89 kDa). Pharmacological inhibition of CASP3 and PARP1 may slow down hepatocyte apoptosis, representing a promising therapeutic strategy for NAFLD. Further investigation into the CASP3-PARP1 pathway could provide new drug targets and therapeutic approaches for NAFLD.
1. Conflict of Interest: None disclosed.
2. Funding: Research relating to this abstract was funded by the Natural Science Foundation of Shandong Province (ZR2020MH361, ZR2023MH300) and Special funding for Mount Tai Scholar Project (tsqn202211356, tsqn202312377).
Volume 110
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Endocrine Abstracts
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