ANGPTL7 Exacerbates Hepatic Steatosis by promoting Inflammatory and Oxidative Stress Responses in MASLD 

Abstract The prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has been increasing. Angiopoietin - like proteins 7 (Angptl 7) plays an important role in inflammatory responses, angiogenesis and oxidative stress. However, the role of Angptl 7 on MASLD has never been investigated. Liver tissues were collected from MASLD patients (MASLD group) and normal liver tissue were chose as controls(CON). The protein expressions of Angptl 7, STAT3, iNOS, and COX-2 were detected by immunohistochemical staining. HepG2 cells were treated by OA/PA medium, lipid levels were assessed by oil red O staining. Then HepG2 cells were divided into pcDNA3.1(+) (CON), Angptl 7 overexpression (Angptl 7 OE), and Angptl 7 OE with STAT3 knockdown (Angptl 7 OE + si-STAT3) groups, while IL-6, TNF-α, ROS, MDA, SOD, and GSH levels were measured using kits. Angptl 7, STAT3, iNOS, and COX-2 expression was evaluated by RT-PCR and western blot. Compared to CON group, expressions of Angptl 7, STAT3, iNOS, and COX-2 in liver tissue were significantly increased in MASLD patients(P < 0.05). In vitro, compared to CON group, the Angptl 7 overexpression led to increased cellular ROS, MDA, IL-6, and TNF-α levels, and increased expressions of STAT3, iNOS, and COX-2 could be alleviated by STAT3 knockdown (P < 0.05). Angptl 7 participated in the pathogenesis of MASLD by increasing oxidative stress and inflammation via targeting STAT3, which might be a potential therapeutic target for MASLD therapy.