Inhibition of hepatic lipogenesis and adipogenesis by cordyanhydride A isolated from <i>Cordyceps Militaris</i> cultivated on germinated soybeans

Regulation of lipid homeostasis requires coordinated control of fatty acid (FA) oxidation, lipogenesis, and adipocyte differentiation. Cordyanhydride A (CA) was isolated from Cordyceps militaris (CM) extract cultivated on germinated soybean through bioactivity-guided fractionation and structurally characterized using nuclear magnetic resonance (NMR) spectroscopy. The effect of CA was examined in mouse hepatocytes and adipocytes using gene expression analysis, immunoblotting, and lipid accumulation assays. In AML12 hepatocytes, CA upregulated the expression of enzymes and transcriptional regulators involved in FA oxidation and suppressed the lipogenic enzymes. In 3T3-L1 adipocytes, it markedly reduced lipid accumulation and downregulated the expression of transcription factors required for adipocyte differentiation. Molecular docking and dynamics simulations supported stable interactions between CA and key proteins involved in lipid metabolism. These results demonstrate that CA modulates lipid metabolism at the cellular level and underscore the value of integrated experimental and computational approaches in characterizing functional metabolites derived from fermented microorganisms.