Bile acids in metabolic dysfunction-associated steatotic liver disease

Abstract

The liver is a central metabolic organ that regulates numerous physiological processes, including glucose and lipid metabolism, detoxification, and the synthesis of essential proteins and bile. Bile acids (BAs), synthesized from cholesterol in hepatocytes, not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease globally, closely linked with obesity, insulin resistance, and other components of metabolic syndrome. In MASLD, the metabolism of BAs is markedly disrupted, resulting in alterations in their synthesis, composition, and signaling activity. These changes contribute to hepatic steatosis, inflammation, and fibrosis, thereby exacerbating metabolic dysfunction and liver damage. The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity, but also as active mediators of its pathogenesis. Modulators of BA signaling pathways, especially FXR agonists, are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD. Recent research has yielded promising results, indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function. This minireview outlines the physiological roles of BAs, seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression, and highlights current and emerging therapeutic approaches. A deeper understanding of these complex interactions is essential for improving the diagnosis, prognosis and treatment of MASLD.

Keywords: Bile acids; Hepatic steatosis; Bile acid signaling, Farnesoid X receptor; Metabolic dysfunction; Therapeutic targets

Core Tip: Bile acids (BAs) play a central role in lipid metabolism, influencing lipid digestion, absorption, storage and oxidation. Through their actions, as signaling molecules, they regulate a wide range of metabolic processes, including lipid and glucose metabolism, fatty acid oxidation, energy expenditure, and composition of the gut microbiota. The dysregulation of bile acid metabolism is linked to various metabolic diseases, highlighting the importance of BAs in maintaining metabolic homeostasis. Understanding these mechanisms is of great importance and may be crucial for the development of new therapies for these diseases.