Circulating Plasma Adiposomes as a Partial Lipidomic Readout of Matched Subcutaneous Adipose Tissue: Implications for Interorgan Communication

ABSTRACT Background Prior studies established adipose‐derived extracellular vesicles, or adiposomes, as mediators of interorgan communication with lipidomic signatures linked to cardiometabolic health. Because adiposomes signal to distant organs via the circulation, we examined whether circulating adiposome lipidomes reflect matched subcutaneous adipose tissue adiposomes. Methods This cross‐sectional paired lipidomic study included 22 subjects with matched circulating and subcutaneous adipose tissue adiposome samples. Untargeted lipidomics quantified 773 lipid features across 18 detected broad classes. Spearman correlation was the primary across‐subject species‐level metric; pooled and within‐subject Pearson and Spearman correlations, principal component analysis, Bland–Altman analysis, class composition, and matched‐versus‐mismatched similarity were complementary measures. Additional analyses evaluated sex, cardiometabolic phenotypes, and focused species‐clinical associations. Results Across 770 species with valid across‐subject estimates, the median plasma‐subcutaneous Spearman ρ was 0.101 and no species survived Benjamini‐Hochberg false‐discovery‐rate correction, although 553 (71.8%) correlations were positive. Mean broad‐class composition was highly conserved (Spearman ρ = 0.996; Pearson r on log 2 percentages = 0.996). Matched whole‐profile similarity was not greater than mismatched similarity (median ρ = 0.818 vs. 0.811; p = 0.620), and the matched sample was the closest pair for 0 of 22 participants. Neither sex nor any prespecified cardiometabolic phenotype explained matched‐profile similarity after correction, and no focused species‐clinical association survived full‐screen FDR correction. Conclusions Circulating and subcutaneous adiposome lipidomes share a highly conserved mean class architecture, but individual species, subject‐specific matching, and clinical‐association patterns are not interchangeable. Plasma adiposomes may therefore serve as complementary circulating readouts of adipose‐derived interorgan lipid signaling rather than direct tissue substitutes.