Ginseng derived extracellular vesicles attenuate adipocyte hypertrophy and modulate gut microbiota and cholecystokinin responsiveness in high fat diet fed mice

Diet-induced obesity is associated with impaired satiety signaling and alterations in intestinal microbial communities. Plant-derived extracellular vesicles have recently emerged as bioactive dietary vesicles capable of influencing host physiology. However, the in vivo metabolic effects of Panax ginseng –derived extracellular vesicles (GDE) remain incompletely characterized. Male C57BL/6 mice were fed a low-fat diet, high-fat diet (HF), or HF supplemented with orally administered GDE (3 × 10⁹ particles, 3 times/week) for 9 weeks. Relative epididymal fat pad weight, adipose tissue histology, cholecystokinin (CCK)-mediated satiety responsiveness, gut microbiota composition, and selected intestinal inflammatory markers were evaluated. GDE administration reduced adipocyte diameter and normalized epididymal leptin mRNA expression in HF-fed mice despite comparable energy intake between HF and HF/GDE groups. HF feeding blunted the anorexigenic response to exogenous CCK, whereas GDE-treated mice showed significant CCK-induced suppression of food intake. Gut microbiota analysis revealed that GDE altered community composition, decreasing the relative abundance of Blautia , Colidextribacter , and Alistipes while increasing Anaerotruncus and Parabacteroides . Ileal TNF-α expression was elevated in HF mice and attenuated in HF/GDE mice, whereas plasma lipopolysaccharide-binding protein levels remained unchanged. Oral administration of ginseng-derived extracellular vesicles was associated with changes in adipocyte morphology, significant responsiveness to exogenous CCK, and alterations in gut microbial composition in high-fat diet–fed mice. These findings suggest that plant-derived extracellular vesicles from P. ginseng may influence multiple physiological features linked to diet-induced obesity, although the underlying mechanisms require further investigation. As only male mice were studied, extrapolation to females requires confirmation.