original data

Chronic inflammation in adipose tissue is considered a pivotal link between obesity and related chronic diseases, wherein the dysregulated interaction between adipocytes and adipose-resident immune cells plays a critical role; however, the underlying mechanisms remain largely unknown. In this study, we show that upregulated β2-microglobulin expression in hypertrophic adipocytes during obesity not only mediated activation of adipose-resident CD8⁺T cells in a cell contact-dependent manner, but also facilitated iron overload and ferroptosis of adipocytes, thereby promoting the M1 polarization of adipose tissue macrophages. Conversely, specific ablation of β2-microglobulin in adipocytes effectively suppressed the activation and accumulation of adipose-resident CD8⁺T cells, as well as adipocyte ferroptosis and M1 polarization, ultimately preventing obesity-related inflammation and metabolic disorders. Adeno-associated virus-mediated adipose-targeted knockdown of β2-microglobulin also effectively alleviates obesity-related chronic inflammation and metabolic disorders. Furthermore, our analysis of human adipose transcriptome data revealed a strong correlation between adipose β2-microglobulin<i> </i>and obesity. More importantly, β2-microglobulin is significantly upregulated in adipocytes isolated from patients with obesity. Thus, our findings highlight the pivotal role of adipocytes in obesity-associated chronic inflammation and metabolic disorders via β2-microglobulin-dependent mechanisms.