Bile acids: New regulators of the cardiometabolic crosstalk

Obesity and associated metabolic disorders are major drivers of cardiovascular disease worldwide. Bile acids are now recognized as endocrine signaling molecules that coordinate metabolic, immune, and cardiovascular homeostasis, extending their traditional role in intestinal lipid absorption. They act through several membrane and nuclear receptors, including farnesoid X receptor and Takeda G protein-coupled receptor 5. Through these pathways, bile acids regulate glucose and lipid metabolism, energy expenditure, inflammation, and vascular tone across multiple organs, such as the liver, gut, adipose tissue, and heart. Altered bile acid pool composition and impaired receptor signaling contribute to the development of obesity, insulin resistance, atherosclerosis, and heart failure. Conversely, pharmacological modulation of bile acid signaling pathways has shown therapeutic potential. Agonists targeting farnesoid X receptor or Takeda G protein-coupled receptor 5 agonists, as well as hydrophilic bile acid derivatives, improve metabolic flexibility, endothelial function, and cardioprotection in experimental and clinical studies. This review summarizes the multifaceted roles of bile acids in inter-organ communication and highlights their emerging potential as therapeutic targets in cardiometabolic disease.