0332 Reduced Tissue IL-10 in Obstructive Sleep Apnea Is Linked to Impaired Insulin Signaling

Introduction Obstructive sleep apnea (OSA) drives cardiometabolic disease in part through chronic, low-grade inflammation. While circulating interleukin-10 (IL-10) findings in OSA have been inconsistent, we hypothesized that local anti-inflammatory capacity is diminished at the tissue level, thereby sustaining systemic inflammation and metabolic dysfunction. We therefore examined whether IL-10 is reduced in human OSA tissues despite equivocal plasma data, and tested whether exogenous IL-10 can directly improve insulin signaling in human adipose cells, supporting a translational anti-inflammatory strategy. Methods We partnered with the MU OneHealth Biorepository to obtain adipose and colon tissues from adults with and without OSA. Tissues were homogenized and IL-10 concentrations quantified using a high-sensitivity ELISA (Human IL-10 Quantikine HS, R&D HS100C). Fresh OSA adipose tissue was used to isolate the stromal vascular fraction (SVF). Purified SVF was pre-treated with recombinant human IL-10 (10 ng/mL, 4 h) or vehicle and then applied to matched donor adipocytes ± exogenous insulin. Insulin pathway activation was assessed by p-Akt (Ser473) immunoblots and normalized to total Akt. Results IL-10 levels were significantly lower in OSA adipose tissue (~35% reduction; 1.25 ± 0.05 vs 1.93 ± 0.78 pg/mg; p ≈ 0.04; n = 5–6) and showed a pronounced decrease in OSA colon (~58% reduction; 3.86 ± 1.8 vs 9.24 ± 4.58 pg/mg; p = 0.057; n = 5) relative to non-OSA controls. In preliminary functional assays from two independent OSA adipose samples, IL-10–conditioned SVF augmented adipocyte insulin signaling compared with vehicle, with p-Akt/Akt ratios of 1.54 ± 0.22 vs 1.07 ± 0.21, respectively, following insulin stimulation, consistent with partial restoration of insulin pathway responsiveness. Conclusion Tissue IL-10 is reduced in adipose and colonic samples from OSA patients, indicating a localized anti-inflammatory deficit that may underlie heightened cardiometabolic risk. Exogenous IL-10 enhances insulin signaling in primary human adipose preparations from OSA donors, supporting IL-10–based or IL-10–inducing interventions as potential adjuncts to CPAP to mitigate OSA-related metabolic dysfunction. Support (if any) NIH grant HL166617