Supplee Julianna G, Marmorstein Ronen, Wellen Kathryn E
Graduate Group in Biochemistry, Biophysics and Chemical Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Trends Endocrinol Metab. 2025 May 8. doi: 10.1016/j.tem.2025.04.002.
Disorders of lipid metabolism, including hyperlipidemia, atherosclerosis, and metabolic dysfunction-associated steatotic liver disease, are increasing across the globe. Bempedoic acid (BPA) is a first-in-class drug for the treatment of hypercholesterolemia and cardiac risk reduction, which may particularly benefit those who do not tolerate statins. Inhibition of hepatic ATP-citrate lyase (ACLY) is widely accepted as the main mediator of its observed clinical effects. However, BPA treatment also has ACLY-independent effects on lipid metabolism, as the structural similarity of BPA to endogenous fatty acids allows it to trigger multiple lipid-signaling pathways. Here, we review the molecular targets of BPA and related 'decoy fatty acid' drugs and identify areas where further study is warranted as these molecules are evaluated for clinical indications.
脂质代谢紊乱，包括高脂血症、动脉粥样硬化和代谢功能障碍相关脂肪性肝病，在全球范围内呈上升趋势。贝派地酸（BPA）是用于治疗高胆固醇血症和降低心血管风险的一流药物，对不耐受他汀类药物的患者可能特别有益。抑制肝脏ATP-柠檬酸裂解酶（ACLY）被广泛认为是其观察到的临床效果的主要介导因素。然而，BPA治疗对脂质代谢也有不依赖ACLY的作用，因为BPA与内源性脂肪酸的结构相似性使其能够触发多种脂质信号通路。在此，我们综述了BPA和相关“诱饵脂肪酸”药物的分子靶点，并确定了在对这些分子进行临床适应症评估时需要进一步研究的领域。
