Exploring Organ-Specific Extracellular Vesicles in Metabolic Improvements Following Bariatric Surgery in Youth With Obesity.

Objective: Vertical sleeve gastrectomy (VSG) promotes significant metabolic improvements, though the underlying molecular mechanisms are not fully understood. Emerging evidence suggests that small extracellular vesicles (sEVs) contribute to metabolic improvements post VSG, such as improved fatty liver disease or adipose tissue function; however, it is unclear how different organ-specific sEVs interact with various metabolic parameters. The objective of this study is to establish the role of organ-specific sEVs in the metabolic improvements post VSG.

Methods: Demographic and anthropometric data, metabolic parameters, and sEV samples were collected pre VSG and 3-6 months post VSG in youth with obesity. sEV RNA was sequenced for bioinformatics analyses.

Results: A significant reduction of the liver-enriched mRNA cargo in sEVs was observed post VSG, whereas adipose-enriched mRNA cargo showed no such reduction. Liver-enriched mRNA cargo correlated with BMI, leptin, and resistin 6 months post VSG. Analysis of delta values (post minus pre surgery) revealed that adipose-enriched mRNA cargo correlated with markers of liver damage, whereas liver-derived mRNA cargo correlated with branched-chain amino acids.

Conclusions: Following VSG, significant changes occur in the liver-enriched mRNA cargo of sEVs. Liver-derived sEVs appear to influence adipose metabolism, whereas adipose-derived sEVs are linked with liver function, suggesting dynamic intertissue cross talk that shapes systemic metabolic outcomes.