Siglec-E modulates adipogenic and inflammatory markers to induce adipose tissue inflammation during obesity 2380

Abstract Description Over the last five decades, the prevalence of obesity increased drastically, becoming a global epidemic. Obesity is characterized by low-grade chronic inflammation in the adipose tissue (AT). Adipocytes secrete several adipokines and chemokines, which further attract macrophages into the obese AT to induce inflammation. Reportedly, Siglec-E is expressed by macrophages and dendritic cells (DCs), orchestrates immune function. However, the role of Siglec-E in AT inflammation during obesity is not well known. To explore the role of Siglec-E in AT inflammation, we fed normal diet (ND) and high-fat diet (HFD) to wild-type (WT) and Siglec-E knockout mice (Siglec-E-/-) for 12 weeks. HFD induction increased the body weight, AT inflammation, and other metabolic markers in both WT and Siglec-E-/- mice as compared to ND. The expression of adaptor molecules of non-canonical NF-κB signaling, including TRAF3 is increased in the epididymal white AT (eWAT) and suprascapular WAT in the HFD-fed Siglec-E-/- mice as compared to WT mice. We also observed a greater increase in CD11b+CD11c+ and CD11b+F4/80+ population in BMDMs in Siglec-E-/- as compared to HFD-fed WT mice. Further, we noticed that inhibition of Siglec-E using siRNA in vitro altered the expression of adipogenic and inflammatory markers in differentiated 3T3-L1 adipocytes and RAW264.7 macrophages. Collectively, our data suggests that modulating the Siglec-E is critical for regulating AT inflammation and adipogenesis during obesity. Funding Sources This study was supported by grants from NIH (NIAID R01 AI140405) Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)