Hyocholic acid: A novel therapeutic strategy for metabolic syndrome

Abstract

<p>The outdated definition of bile acids (BAs) as a sort of metabolic adjuvant for lipid and lipidic solubility should be expired. Mammalian BAs are widespread, tautomeric, polyphyletic, and biosynthetic metabolites that extensively serve as bio-messengers and can be used to characterize various physiological states. Among these, hyocholic acid species (HCAs) have received considerable interest due to their strong potential to alleviate energy dysmetabolism, especially glucolipid metabolic disorder. Effective integration of gut microbiomics, glycolipidomics, and other omics contributes to establishing the regulation process of BA signaling on glucolipid metabolism. In a three-dimensional system, HCAs (1) remodel the structure of the gut microbiome, the pattern of reabsorbed secondary BAs, and intestinal lipid uptake efficiency by increasing the hydrophilicity of the total BA pool and reducing cytotoxicity; (2) dynamically shape the profile of hepatic lipometabolism and primary BA biosynthesis via enterohepatic circulation and feedback regulation-based network between gut microbiota and host, and (3) serve as a serious of output signals which are responsible for tuning energy physiology of peripheral tissue. These multidimensional influences allow HCAs to improve the gut microbiome, inhibit excessive lipid uptake, and remodel glucolipid metabolic flux distribution that enhances resistance to metabolic syndrome. Increasing attention to HCAs in clinical and animal studies emphasizes the vital potential of BAs in tracing the role of environmental factors in the evolutionary process of associated species and opens a novel perspective to develop BAs into clinically therapeutic strategies and variety breeding.</p>