Human dental pulp stem cell-derived exosomes inhibit adipogenesis and obesity by activating Wnt/β-catenin signaling

Obesity is a critical global health challenge linked to cardiovascular disease, type 2 diabetes, metabolic syndrome, and cancers. Current therapies often lack sustained efficacy, prompting interest in molecular strategies targeting adipogenesis. Exosomes, cell-derived extracellular vesicles, exhibit therapeutic potential due to high biocompatibility and ability to mediate intercellular communication. This study explored the anti-adipogenic effects of exosomes derived from human dental pulp stem cells (hDPSC-Exos). hDPSC-Exos were isolated from conditioned media and characterized by TEM, nanoparticle tracking analysis, and Western blotting. Their anti-adipogenic effects were evaluated in vitro using 3T3-L1 and OP9 preadipocytes via Oil Red O staining, RT-qPCR, western blotting and multi-omics analyses (RNA-seq, proteomics). Therapeutic efficacy was further validated in a diet-induced obesity mouse model. Treatment with hDPSC-Exos markedly suppressed adipocyte differentiation in vitro, reducing lipid accumulation and downregulating key adipogenic transcription factors and their downstream targets. Mechanistically, Wnt/β-catenin signaling activation mediated this inhibition. In vivo, hDPSC-Exos administration reduced body weight, fat mass, and adipogenic gene expression in obese mice. These findings reveal a novel regulatory function of hDPSC-Exos in adipogenesis, highlighting their potential as a cell-free therapy for obesity and related metabolic disorders.