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Adipose tissue‐derived small extracellular vesicles and blood–brain barrier function in adults with overweight and obesity
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Adipose tissue‐derived small extracellular vesicles and blood–brain barrier function in adults with overweight and obesity
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Journal Article
Adipose tissue‐derived small extracellular vesicles and blood–brain barrier function in adults with overweight and obesity
2026
Overview
Obesity is associated with adverse changes in brain structure and function, in part, through crosstalk between adipose tissue (AT) and the brain. AT releases small extracellular vesicles (sEV) that can cross the blood–brain barrier (BBB) and modulate multiple pathophysiological pathways, including BBB function; however, this has never been investigated. We characterized circulating adipose tissue‐derived sEV (sEVAT) in adults with overweight and obesity and examined their effects on the BBB. The impact of adiposity and weight loss on these outcomes was also examined. sEVAT were isolated from the plasma of 29 adults (79% male; 93% White; mean age 66.2 ± 7.0 years; mean body mass index 36.0 ± 6.8 kg/m2) randomized to cardiac rehabilitation (CR) alone or CR plus a behavioural weight loss intervention (CR+WL). Following characterization of sEVAT size, concentration and total protein content, we assessed their effect on BBB permeability using an in vitro model. hCMEC/D3 cells were treated with sEVAT, and transendothelial electrical resistance (TEER) was measured at 0, 24, 48 and 72 h. Our findings show that sEVAT treatment decreased TEER by 40%, with a significantly lower TEER at 72 h compared with controls (23.138 ± 1.209 vs. 28.724 ± 1.613 Ω cm2, p = 0.012). TEER was also lower in participants with higher body mass index and body fat. However, we found no difference in TEER between the CR and CR+WL groups and no significant intervention effects on sEVAT characteristics or TEER. In conclusion, higher plasma sEVAT concentrations in adults with overweight and obesity are associated with greater adiposity, which might contribute to reductions in BBB function. What is the central question of this study? Small extracellular vesicles secreted from adipose tissue (sEVAT) might impair blood–brain barrier function. We developed an in vitro model to assess the effect of sEVAT on the blood–brain barrier in adults with overweight and obesity randomized to one of two lifestyle interventions. What is the main finding and its importance? Treatment of hCMEC/D3 cells with sEVAT decreased transendothelial resistance in both groups, with no significant intervention‐related effects. Higher plasma sEVAT concentrations were associated with greater adiposity, suggesting that sEVAT might contribute to the adverse effects of obesity on brain health.
Publisher
John Wiley & Sons, Inc,Wiley
