Exosomes from obese adipose contain dysregulated microRNAs linked to insulin signaling, as compared with lean controls, providing a direct connection between adiposity and insulin resistance. This study tested the hypotheses that gastric bypass surgery and its subsequent weight loss would normalize adipocyte‐derived exosomal microRNAs associated with insulin signaling and the associated metabolome related to glucose homeostasis.

African American female subjects with obesity (N = 6; age: 38.5 ± 6.8 years; BMI: 51.2 ± 8.8 kg/m²) were tested before and 1 year after surgery. Insulin resistance (HOMA), serum metabolomics, and global microRNA profiles of circulating adipocyte‐derived exosomes were evaluated via ANCOVA and correlational analyses.

One year postsurgery, patients showed decreased BMI (−18.6 ± 5.1 kg/m²; P < 0.001), ameliorated insulin resistance (HOMA: 1.94 ± 0.6 presurgery, 0.49 ± 0.1 postsurgery; P < 0.001), and altered metabolites including branched chain amino acids (BCAA). Biological pathway analysis of predicted mRNA targets of 168 surgery‐responsive microRNAs (P < 0.05) identified the insulin signaling pathway (P = 1.27E−10; 52/138 elements), among others, in the data set. The insulin signaling pathway was also a target of 10 microRNAs correlated to changes in HOMA (P < 0.05; r > 0.4), and 48 microRNAs correlated to changes in BCAA levels.

These data indicate that circulating adipocyte‐derived exosomes are modified following gastric bypass surgery and correlate to improved postsurgery insulin resistance.