Assessing the Impact of STX4 Knockdown on the Transcriptome of Brown Adipose Tissue

In this study, we investigate the effects of Syntax 4 (STX4) knockdown in brown adipocytes and its role in age-related changes in brown adipose tissue (BAT). Our focus was to understand the mechanisms preceding the significant loss of BAT mass observed with aging. By comparing transcriptomic profiles before the onset of this massive tissue loss, we identified a notable increase in markers indicative of pyroptotic cell death. These findings suggest a potential link between STX4 activity, cellular death pathways, and age-related alterations in BAT, providing insights into the molecular underpinnings of BAT aging and loss. We isolated total RNA from the BAT of four male mice with Ucp1 promoter-driven STX4 knockdown (Ucp1STX4KO) and four male wild-type littermates, serving as controls. Following RNA extraction, these samples were submitted for high-throughput RNA sequencing to analyze differential gene expression and related transcriptomic changes.本研究旨在探究突触融合蛋白4（Syntax 4，STX4）在棕色脂肪细胞中的敲低效应，及其在棕色脂肪组织（brown adipose tissue，BAT）年龄相关变化中的作用。本研究的核心目标是阐明衰老过程中观察到的棕色脂肪组织大量流失之前的潜在分子机制。通过在该大量组织流失发生前比较转录组学特征，我们发现焦亡细胞死亡标志物水平显著升高。上述结果提示，STX4活性、细胞死亡通路与棕色脂肪组织的年龄相关改变之间存在潜在关联，为阐明棕色脂肪组织衰老与流失的分子基础提供了新视角。我们从4只携带解偶联蛋白1（uncoupling protein 1，Ucp1）启动子驱动的STX4敲低（Ucp1STX4KO）的雄性小鼠，以及4只作为对照的雄性野生型同窝仔鼠的棕色脂肪组织中提取总RNA。RNA提取完成后，将所有样本提交进行高通量RNA测序，以分析差异基因表达及相关转录组学变化。