Deoxycholic Acid at the Interface of Bile Acid Metabolism and Adipose Tissue Remodeling: From Endogenous Signaling to Injectable Adipocytolysis
Kyu-Ho Yi, Han Earl Lee, Hong Seok Kim, Thanya TechapichetvanichDeoxycholic acid (DCA) occupies an unusual position at the boundary between endogenous metabolism and therapeutic tissue ablation. Under physiological conditions, DCA is a gut microbial secondary bile acid that enters the enterohepatic circulation, contributes to the composition of the bile-acid pool, and participates in receptor-dependent signaling. When delivered as a concentrated injectable drug into subcutaneous fat, however, DCA acts primarily as an amphipathic cytolytic molecule that disrupts cell membranes, initiates adipocyte death, and provokes an organized inflammatory and reparative response. These two biological identities are often conflated, leading to imprecise descriptions of injectable DCA as a lipolytic, receptor-targeted, or metabolically selective treatment. This critical review integrates evidence from bile-acid biochemistry, microbiology, membrane biophysics, adipose-tissue biology, human histology, pharmacokinetics, and clinical trials. We describe the microbial formation, transport, conjugation, and signaling actions of endogenous DCA; distinguish physiological receptor signaling from concentration-dependent detergent injury; and examine the temporal sequence of adipocytolysis, innate immune recruitment, lipid clearance, fibrovascular remodeling, and volume reduction after local injection. We also assess systemic exposure, clinical efficacy, anatomic determinants of safety, and the limitations of extrapolating submental data to large-volume or non-submental treatment. Finally, we propose a translational metabolomics and lipidomics framework that combines local interstitial sampling, plasma bile-acid profiling, lipid mediator analysis, imaging, and tissue phenotyping. The central conclusion is that injectable DCA is best understood as a controlled local cytolytic perturbation superimposed on a tightly regulated endogenous bile-acid system. Framing the intervention in this way clarifies terminology, identifies measurable biomarkers, and creates a rational path toward dose optimization, patient selection, and safer clinical translation.