Abstract 15626: Novel Function Annotation Tool Revealed Obesity-Induced Inflammation is Exacerbated by miR-150 Regulated B Cell Receptor Signaling

03 medical and health sciences 0302 clinical medicine
DOI: 10.1161/circ.148.suppl_1.15626 Publication Date: 2023-12-19T08:08:02Z
ABSTRACT
B cells exacerbate obesity-induced metabolic dysfunction and become the second most abundant immune lineage in obese adipose tissue. However, high-resolution strategies to interrogate cellular dynamics driving cell responses under chronic obesity stress are lacking, stifling innovative cell-targeted therapies against health risk. Our previous work established potent role of miR-150 tissue B cells’ (ATB) pro-inflammatory obesity. This project aims elucidate mechanism of miR-150 regulated ATB actions that bolster inflammation. Method: We employed single-cell techniques decipher obesity-perturbed signaling networks cell-specific gain/loss function mouse models  vivo and  ex . utilized our novel annotation tool, B-RAY, to quantify B cytokine production, antibody secretion, antigen presentation from RNA-Seq. These strengths permitted several key findings: Result: A) overexpression mature alone improved systemic glucose tolerance obesity, despite similar body adiposity. In line, knock-out worsened tolerance. B) tissue, were skewed towards higher production away secretion compared lean Importantly, ATBs displayed increased activity direct targets, Myb, Etf1, Elk1, reduced expression miR-150. C) enriched receptor (BCR) downstream cascades. exhibited BCR-mediated Syk phosphorylation calcium influx, while yielded enhanced responses. Conclusion: results support hypothesis regulation limits inflammation tissue via modulating BCR prevent excessive presentation. Future will investigate activation in miR-150 mice across time diet-induced Collectively, this an important immunoregulatory network bolstering health risk.
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