Chronic inflammation in adipose tissue is widely recognized as a pivotal link connecting obesity to a spectrum of related chronic diseases,including type 2 diabetes,non-alcoholic fatty liver disease,and cardiovascular...Chronic inflammation in adipose tissue is widely recognized as a pivotal link connecting obesity to a spectrum of related chronic diseases,including type 2 diabetes,non-alcoholic fatty liver disease,and cardiovascular disorders.In this pathogenic process,the dysregulated interaction between adipocytes and adipose-resident immune cells plays a critical regulatory role;however,the underlying mechanisms governing this abnormal interaction remain largely unknown.In this study,we showed that upregulatedβ2-microglobulin expression in hypertrophic adipocytes during obesity not only mediated the activation of adipose-resident CD8+T cells in a cell contact-dependent manner but also facilitated iron overload and the ferroptosis of adipocytes,thereby promoting the M1 polarization of adipose tissue macrophages.Conversely,specific ablation ofβ2-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 high-fat diet-induced obesity and its related inflammation and metabolic disorders.Additionally,adenoassociated virus-mediated adipose-targeted knockdown ofβ2-microglobulin has been demonstrated to therapeutically alleviate high-fat diet-induced obesity,as well as its related chronic inflammation and metabolic disorders.Furthermore,our bioinformatic analysis of human adipose transcriptome data revealed a strong correlation between adiposeβ2-microglobulin 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 viaβ2-microglobulindependent mechanisms.展开更多
基金financial support from the National Natural Science Foundation of China(No.32470987)the Special Program of the National Natural Science Foundation of China(No.32141005)+1 种基金the Major Program of the National Natural Science Foundation of China(No.82394410)We are also grateful for the technical support of the Central Laboratory of the Army Military Medical University。
文摘Chronic inflammation in adipose tissue is widely recognized as a pivotal link connecting obesity to a spectrum of related chronic diseases,including type 2 diabetes,non-alcoholic fatty liver disease,and cardiovascular disorders.In this pathogenic process,the dysregulated interaction between adipocytes and adipose-resident immune cells plays a critical regulatory role;however,the underlying mechanisms governing this abnormal interaction remain largely unknown.In this study,we showed that upregulatedβ2-microglobulin expression in hypertrophic adipocytes during obesity not only mediated the activation of adipose-resident CD8+T cells in a cell contact-dependent manner but also facilitated iron overload and the ferroptosis of adipocytes,thereby promoting the M1 polarization of adipose tissue macrophages.Conversely,specific ablation ofβ2-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 high-fat diet-induced obesity and its related inflammation and metabolic disorders.Additionally,adenoassociated virus-mediated adipose-targeted knockdown ofβ2-microglobulin has been demonstrated to therapeutically alleviate high-fat diet-induced obesity,as well as its related chronic inflammation and metabolic disorders.Furthermore,our bioinformatic analysis of human adipose transcriptome data revealed a strong correlation between adiposeβ2-microglobulin 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 viaβ2-microglobulindependent mechanisms.
