Introduction: Obesity involves complex inter-organ communication, potentially mediated by gut microbiota-derived exosomes carrying molecular cargo. This study investigated whether these exosomes mediate signaling between the gut and metabolic tissues, contributing to obesity in a diet-induced model.

Methods: We isolated exosomes from the feces of diet-induced obese mice and lean controls. Their molecular cargo (miRNAs, proteins, lipids) was characterized using sequencing and proteomics. In vivo, exosomes from obese mice were administered to germ-free mice to assess their impact on weight gain, adiposity, and metabolic markers. In vitro studies exposed adipocytes and hepatocytes to these exosomes to investigate changes in gene expression and signaling pathways related to lipid metabolism and inflammation.

Results: Analysis identified distinct molecular cargo profiles in exosomes isolated from obese versus lean mice. The administration of obese-derived exosomes to germ-free recipients impacted metabolic parameters. In vitro experiments revealed that these exosomes influenced responses in target metabolic cells.

Conclusion: This research provides evidence suggesting that gut microbiota-derived exosomes function as molecular messengers affecting host metabolism in obesity. The findings support their potential role in inter-organ communication and highlight areas for further investigation into specific molecular targets and therapeutic strategies.