Core Viewpoint - Obesity is identified as a chronic metabolic disease characterized by excessive fat accumulation and is a major global public health concern, with nearly 50% of the adult population estimated to be overweight, leading to various non-communicable diseases [2] Group 1: Chronic Inflammation and Obesity - Chronic inflammation in adipose tissue is a key link between obesity and several chronic diseases, including type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular diseases [7] - The interaction between adipocytes and resident immune cells in adipose tissue plays a crucial regulatory role in this pathological process, although the underlying mechanisms remain largely unclear [7] Group 2: Research Findings - A recent study published in Signal Transduction and Targeted Therapy reveals that hypertrophic adipocytes mediate inflammation through a β2-microglobulin (B2M)-dependent mechanism, activating resident CD8+ T cells and macrophages in adipose tissue [4][5] - The study emphasizes the potential of targeting B2M in adipocytes as a therapeutic strategy for obesity-related chronic inflammation and metabolic disorders [5] Group 3: Mechanisms of Action - The research indicates that during obesity, the expression of B2M in hypertrophic adipocytes is upregulated, which not only activates CD8+ T cells but also promotes iron overload and ferroptosis in adipocytes, leading to M1 polarization of macrophages [7] - Specific knockout of B2M in adipocytes effectively inhibits the activation and accumulation of CD8+ T cells, as well as iron-induced cell death and M1 polarization, preventing obesity and related inflammation and metabolic disorders induced by a high-fat diet [7] Group 4: Correlation with Human Data - Bioinformatics analysis of human adipose tissue transcriptome data shows a strong correlation between B2M levels and obesity, with significantly elevated B2M expression found in adipocytes isolated from obese patients [9] - Overall, the findings highlight the critical role of adipocytes in obesity-related chronic inflammation and metabolic disorders through a B2M-dependent mechanism [9]