Association of Serum Angiopoietin-Like Protein 7 With Ferroptosis-Related Proteins in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has been increasing globally, and data indicate that ferroptosis participates in the pathogenesis of MAFLD. Angiopoietin-like protein 7 (ANGPTL7) is a novel secretory glycoprotein that participates in the pathogenesis of many metabolic diseases. However, the role of ANGPTL7 in MAFLD has been poorly investigated. A total of 194 participants were enrolled, including 104 participants with MAFLD (MAFLD) and 90 healthy controls (Cons). Baseline characteristics and serum biochemical parameters were collected. Serum levels of ANGPTL7, inflammatory factors, and ferroptosis-related proteins were measured by enzyme-linked immunosorbent assay (ELISA). Liver biopsy tissues were obtained from six participants with nonalcoholic steatohepatitis and the trimmed liver tissues from five healthy liver transplant donors; H&E, Masson, Perls Prussian blue, and immunohistochemical staining were performed. Compared with healthy Con, BMI, SBP, and DBP were significantly increased, and ALT, AST, TC, TG, LDL-C, GLU, HbA1c, INS, Hcy, and UA levels were all significantly increased, while HDL-C levels were decreased in MAFLD patients (MAFLD vs. Con, p < 0.05 or p < 0.001). Serum levels of ANGPTL7, TNF-α, IL-6, ACSL4, Keap-1, HO-1, and ferritin were significantly increased, while IL-10, GPX4, and Nrf2 levels were decreased in MAFLD patients when compared with the Con group (MAFLD vs. Con, all p < 0.001). Immunohistochemical staining showed that the expression of ANGPTL7, Keap-1, and HO-1 was significantly increased, while Nrf2 expression was significantly decreased in liver tissue from the MAFLD group (MAFLD vs. Con, all p < 0.05). ROC analysis showed that the optimal cut-off value of serum ANGPTL7 for MAFLD was 9.75 ng/mL, suggesting it could serve as a potential biomarker for the diagnosis of MAFLD. ANGPTL7 may participate in the pathogenesis of MAFLD, and serum ANGPTL7 has predictive value for the diagnosis of MAFLD.