Microbial-Derived Daidzin (Eco-3) Inhibits Adipogenesis and Lipid Accumulation in Cellular and Zebrafish Models.

Daidzin is a soy-derived isoflavone with reported anti-obesity effects; however, the biological activity of microbial-derived daidzin remains poorly understood. In this study, we investigated the anti-adipogenic and anti-obesity potential of microbial-derived daidzin (hereafter referred to as Eco-3) in both in vitro and in vivo models. Eco-3 significantly suppressed adipocyte differentiation and lipid accumulation in 3T3-L1 preadipocytes and human adipose-derived stem cells (hASCs) without inducing cytotoxicity. Mechanistically, Eco-3 reduced the expression of key adipogenic regulators, including PPAR-γ and C/EBP-α, and modulated lipid metabolism-related proteins such as FAS and perilipin A. In addition, Eco-3 activated AMPK signaling while inhibiting the STAT-3 and STAT-5 pathway. In zebrafish models, Eco-3 significantly reduced lipid accumulation under both normal and diet-induced obesity conditions, as demonstrated by LipidGreen2 and Oil Red O staining. Collectively, these findings suggest that Eco-3 exerts anti-obesity effects through coordinated regulation of adipogenesis and lipid metabolism.