Exploring the Role of Bempedoic Acid in Metabolic Dysfunction Associated Steatotic Liver Disease: Actual Evidence and Future Perspectives

Int J Mol Sci. 2024 Jun 25;25(13):6938. doi: 10.3390/ijms25136938.

Abstract

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.

Keywords: ACLY; ATP-citrate lyase inhibitor; MASLD; bempedoic acid; dyslipidemia; lipid-lowering therapies.

Publication types

  • Review

MeSH terms

  • Animals
  • Dicarboxylic Acids* / pharmacology
  • Dicarboxylic Acids* / therapeutic use
  • Fatty Acids* / metabolism
  • Fatty Liver / drug therapy
  • Fatty Liver / metabolism
  • Humans
  • Lipid Metabolism* / drug effects

Substances

  • 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  • Dicarboxylic Acids
  • Fatty Acids

Grants and funding

This research received no external funding.