Ticagrelor, but Not Clopidogrel, Attenuates Hepatic Steatosis in a Model of Metabolic Dysfunction-Associated Steatotic Liver Disease

Author:

Lee Eun Jeoung1ORCID,Lee Seung Min1ORCID,Oh Ju Hee2ORCID,Kim Hye Young1,Saeed Waqar Khalid3,Kim Hyun Sung4ORCID,Jun Dae Won15ORCID

Affiliation:

1. Department of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Republic of Korea

2. Department of Obstetrics and Gynecology, Institute of Women’s Medical Life Science, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

3. Department of Biomedical Sciences, Pak-Austria Fachhochschule—Institute of Applied Sciences and Technology, Mang 22621, Pakistan

4. Department of Pathology, Hanyang University School of Medicine, Seoul 04763, Republic of Korea

5. Department of Internal Medicine, Hanyang University School of Medicine, Seoul 04763, Republic of Korea

Abstract

Background: Previous studies have suggested that platelets are associated with inflammation and steatosis and may play an important role in liver health. Therefore, we evaluated whether antiplatelet agents can improve metabolic disorder-related fatty liver disease (MASLD). Methods: The mice used in the study were fed a high-fat-diet (HFD) and were stratified through liver biopsy at 18 weeks. A total of 22 mice with NAFLD activity scores (NAS) ≥ 4 were randomly divided into three groups (HFD-only, clopidogrel (CLO; 35 mg/kg/day), ticagrelor (TIC; 40 mg/kg/day) group). And then, they were fed a feed mixed with the respective drug for 15 weeks. Blood and tissue samples were collected and used in the study. Results: The TIC group showed a significantly lower degree of NAS and steatosis than the HFD group (p = 0.0047), but no effect on the CLO group was observed. Hepatic lipogenesis markers’ (SREBP1c, FAS, SCD1, and DGAT2) expression and endoplasmic reticulum (ER) stress markers (CHOP, Xbp1, and GRP78) only reduced significantly in the TIC treatment group. Inflammation genes (MCP1 and TNF-α) also decreased significantly in the TIC group, but not in the CLO group. Nile red staining intensity and hepatic lipogenesis markers were reduced significantly in HepG2 cells following TIC treatment. Conclusion: Ticagrelor attenuated NAS and hepatic steatosis in a MASLD mice model by attenuating lipogenesis and inflammation, but not in the CLO group.

Funder

Hanyang University

Publisher

MDPI AG

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