Distinct T Cell Subset Profiles and T-Cell Receptor Signatures in Metabolically Unhealthy Obesity

Metabolically unhealthy obesity (MUO) is associated with increased inflammation and a higher risk of metabolic disorders compared to metabolically healthy obesity (MHO). T cell dysregulation in blood and adipose tissue may contribute to obesity-induced metabolic dysfunction, yet the characteristics of T cell subset profiles and T-cell receptor (TCR) repertoires in MHO and MUO remain unclear. We analyzed T cell subsets and TCR repertoires in peripheral blood and omental adipose tissue (oAT) from age- and BMI-matched MHO and MUO individuals using flow cytometry and high-throughput TCR sequencing. MUO individuals exhibited a higher proportion of memory CD4⁺ T cells in both compartments, with an increased frequency of central memory T cells. Circulating CD8⁺ T cells were increased in MUO, whereas CD8⁺ T cell subset composition remained unchanged in both blood and oAT. The TCR repertoire in oAT was significantly more restricted than in blood and showed greater skewing in MUO, with selective amplification of specific TRB V genes (TRBV12-4, TRBV18, TRBV7-9) and altered CDR3 length distributions. These findings suggest that distinct CD4⁺ T cell populations and specific TCR signatures may serve as potential biomarkers for metabolic dysfunction in obesity, providing insights into immune mechanisms underlying the transition from MHO to MUO.