Down-regulation of AGXT۲L۱ promotes the development of nonalcoholic fatty liver disease

Objective(s): To investigate the role of alanine-glyoxylate aminotransferase ۲-like۱ (AGXT۲L۱) in Nonalcoholic fatty liver disease (NAFLD) and its underlying mechanisms.Materials and Methods: Changes in AGXT۲L۱ 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, AGXT۲L۱ expression was reduced in multiple liver diseases. Both in vitro and in vivo experiments confirmed that down-regulation of AGXT۲L۱ exacerbated NASH severity. RNA sequencing initially indicated that abnormal AGXT۲L۱ expression primarily affects phospholipid metabolism. Additionally, animal experiments showed that AGXT۲L۱ deficiency increased the number of apoptotic hepatocytes and elevated the expression of endoplasmic reticulum stress markers.Conclusion: Decreased AGXT۲L۱ expression is an evident alteration in liver injury. It has been indicated that down-regulation of AGXT۲L۱ promotes NAFLD development, possibly through three pathways: activation of inflammatory responses, promotion of hepatocyte apoptosis, and enhancement of endoplasmic reticulum stress.

کلیدواژه ها:

Alanine-glyoxylate-aminotransferase ۲-like۱- (AGXT۲L۱) ، Apoptosis ، ER stress ، Inflammation ، Nonalcoholic fatty liver disease (NAFLD) ، Phospholipid metabolism