PPS29. Obesity-driven reprogramming of gastric cancer via adipocyte extracellular vesicles: Insights from metabolomic and transcriptomic profiling

Metabolic reprogramming is a hallmark of cancer, with adipocytes playing a key role through the release of bioactive cargo—especially under inflammatory conditions such as obesity. These factors are linked to metabolic syndrome and cancer progression, but the underlying mechanisms remain unclear. This study employs a multi-omics approach to characterize the transcriptome of adipocyte-derived extracellular vesicles (EVs) from the omentum of obese and lean gastric cancer (GC) patients, and to assess their impact on metabolic and transcriptomic reprogramming in GC cells.


Methods:

Adipocyte-derived EVs (Ad-EVs) were isolated from the omentum of lean and obese GC patients and characterized by size, morphology, and protein marker expression. Ad-EVs were co-cultured with GC cells for functional assays, metabolomic analysis, and bulk RNA sequencing, while their microRNA cargo was profiled separately. A murine peritoneal metastasis model was used, involving peritoneal injection of GC-luciferase cells with either lean or obese Ad-EVs.


Results:

Both lean and obese Ad-EVs enhanced GC cell proliferation, with obese Ad-EVs significantly increasing migration and invasion. We identified 30 differentially expressed microRNAs between lean and obese Ad-EVs. GC cells stimulated with Ad-EVs exhibited significant transcriptomic changes involving key biological pathways associated with tumor progression. In addition, treatment of GC cells with Ad-EVs increased glycolytic activity, with a more pronounced effect observed in cells treated with obese Ad-EVs. In immunocompromised mice, obese Ad-EVs led to higher metastatic rates compared to lean Ad-EVs.


Conclusions:

Integrated metabolomic and transcriptomic analysis revealed distinct metabolic and regulatory signatures linked to obesity-driven gastric cancer progression. This comparative approach highlights potential therapeutic targets, EV-derived biomarkers for intra-abdominal metastasis, and offers new insights into the biological links between obesity and cancer, supporting the development of more personalized interventions.