司美格鲁肽，如何发挥功效逆转脂肪肝？

Core Viewpoint - The article discusses the significant role of GLP-1 receptor agonists, particularly semaglutide, in treating metabolic dysfunction-associated steatohepatitis (MASH) and its mechanisms beyond weight loss [6][12]. Group 1: Mechanism of Action - Semaglutide shows a strong effect on blood sugar control and weight loss, rapidly gaining recognition as a "miracle drug" for weight management [6]. - A recent study published in Nature Medicine reveals that semaglutide not only aids in weight loss but also has direct effects on liver tissue, indicating multiple pathways of action [6][12]. - Mediation analysis indicates that approximately 69.3% of the total effect on MASH relief can be attributed to weight loss, while the contribution to combating liver fibrosis drops to only 25.1%, suggesting other mechanisms are at play [7][12]. Group 2: Protein Analysis - The study identified 72 proteins associated with MASH relief and semaglutide treatment, many of which are linked to metabolic, fibrotic, or inflammatory pathways [9]. - In a separate cohort, these proteins were found to be abnormally expressed in MASH patients, and their levels normalized after semaglutide treatment, indicating a "reset" of pathological protein profiles [9][11]. Group 3: Animal Studies - Animal models demonstrated that semaglutide can inhibit fibrosis independently of weight loss, with significant reductions in liver fibrosis markers observed even in models that did not gain weight [10][11]. - The gene expression profiles in liver tissues showed downregulation of genes related to inflammation and collagen synthesis, confirming direct anti-fibrotic mechanisms [10][11]. Group 4: Future Implications - The research presents a comprehensive view of semaglutide's action against MASH, highlighting that while weight loss is a crucial mechanism, there are additional molecular effects that contribute to its efficacy [12][14]. - If future trials validate the predictive value of the identified protein markers, they could serve as dynamic biomarkers for early identification, personalized treatment, and efficacy monitoring in MASH patients [12][14].