Internal Medicine, Fondazione Policlinico Universitario "A.Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy.
CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A.Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy.
Int J Mol Sci. 2024 Jun 25;25(13):6938. doi: 10.3390/ijms25136938.
Metabolic dysfunction-associated steatotic liver disease (MASLD) involves excessive lipid accumulation in hepatocytes, impacting global healthcare due to its high prevalence and risk of progression to severe liver conditions. Its pathogenesis involves genetic, metabolic, and inflammatory factors, with cardiovascular events as the leading cause of mortality. This review examines the role of lipid-lowering therapies in MASLD, with a particular focus on bempedoic acid, a recently approved cholesterol-lowering agent for hypercholesterolemia and high cardiovascular-risk patients. It explores its potential in liver disease by modulating lipid metabolism and inflammatory pathways based on the most recent studies available. Bempedoic acid inhibits ATP-citrate lyase, reducing cholesterol and fatty acid synthesis while activating AMP-activated protein kinase to suppress gluconeogenesis and lipogenesis. Animal studies indicate its efficacy in reducing hepatic steatosis, inflammation, and fibrosis. Bempedoic acid holds promise as a therapeutic for MASLD, offering dual benefits in lipid metabolism and inflammation. Further clinical trials are required to confirm its efficacy and safety in MASLD patients, potentially addressing the multifaceted nature of this disease.
代谢相关脂肪性肝病（MASLD）涉及肝细胞内脂质过度蓄积，由于其高患病率和向严重肝脏疾病进展的风险，对全球医疗保健产生了影响。其发病机制涉及遗传、代谢和炎症因素，心血管事件是主要死亡原因。本综述探讨了降脂治疗在 MASLD 中的作用，特别关注了 bempedoic 酸，这是一种最近批准的用于高胆固醇血症和高心血管风险患者的降胆固醇药物。根据现有最新研究，它通过调节脂质代谢和炎症途径来探索其在肝脏疾病中的潜在作用。Bempedoic 酸抑制三磷酸腺苷-柠檬酸裂解酶，减少胆固醇和脂肪酸的合成，同时激活 AMP 激活的蛋白激酶以抑制糖异生和脂肪生成。动物研究表明，它在减少肝脂肪变性、炎症和纤维化方面具有疗效。Bempedoic 酸有望成为 MASLD 的一种治疗药物，在脂质代谢和炎症方面提供双重益处。需要进一步的临床试验来确认它在 MASLD 患者中的疗效和安全性，这可能有助于解决这种疾病的多方面性质。
