Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Down-regulation of AGXT2L1 promotes the development of nonalcoholic fatty liver disease

Articles in Press

Document Type : Original Article

Authors
Yue Yu
Lu Wu
Department of Radiation Oncology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
10.22038/ijbms.2026.89567.19546
Abstract
Objective(s): To investigate the role of alanine-glyoxylate aminotransferase 2-like1 (AGXT2L1) in Nonalcoholic fatty liver disease (NAFLD) and its underlying mechanisms.
Materials and Methods: Changes in AGXT2L1 expression during NASH progression were analyzed using tissue samples, cell experiments, and animal models. RNA sequencing was performed on experimental mice to explore potential mechanisms by assessing inflammatory factors, cell apoptosis, and endoplasmic reticulum stress.
Results: Compared with normal tissues, AGXT2L1 expression was reduced in multiple liver diseases. Both in vitro and in vivo experiments confirmed that down-regulation of AGXT2L1 exacerbated NASH severity. RNA sequencing initially indicated that abnormal AGXT2L1 expression primarily affects phospholipid metabolism. Additionally, animal experiments showed that AGXT2L1 deficiency increased the number of apoptotic hepatocytes and elevated the expression of endoplasmic reticulum stress markers.
Conclusion: Decreased AGXT2L1 expression is an evident alteration in liver injury. It has been indicated that down-regulation of AGXT2L1 promotes NAFLD development, possibly through three pathways: activation of inflammatory responses, promotion of hepatocyte apoptosis, and enhancement of endoplasmic reticulum stress.
Keywords
Alanine-glyoxylate-aminotransferase 2-like1- (AGXT2L1)
Apoptosis
ER stress
Inflammation
Nonalcoholic fatty liver disease (NAFLD)
Phospholipid metabolism
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 14 July 2026