Abstract：
Obesity and type 2 diabetes cause a loss in brown adipose tissue (BAT) activity, but the molecular mechanisms that drive BAT cell remodeling remain largely unexplored. Using a multilayered approach, we comprehensively mapped a reorganization in BAT cells. We uncovered a subset of macrophages as lipid-associated macrophages (LAMs), which were massively increased in genetic and dietary model of BAT expansion. LAMs participate in this scenario by capturing extracellular vesicles carrying damaged lipids and mitochondria released from metabolically stressed brown adipocytes. CD36 scavenger receptor drove LAM phenotype, and CD36-deficient LAMs were able to increase brown fat genes in adipocytes. LAMs released transforming growth factor β1 (TGF-β1), which promoted the loss of brown adipocyte identity through aldehyde dehydrogenase 1 family member A1 (Aldh1a1) induction. These findings unfold cell dynamic changes in BAT during obesity and identify LAMs as key responders to tissue metabolic stress and drivers of loss of brown adipocyte identity.
摘要：
肥胖和2型糖尿病导致棕色脂肪组织（BAT）活性丧失，但是驱动BAT细胞重塑的分子机制在很大程度上仍未被探索。使用多层方法，我们全面绘制了BAT细胞中的重组图。我们发现了一部分巨噬细胞作为脂质相关巨噬细胞（LAMs），在BAT扩展的遗传和饮食模型中大量增加。LAM通过捕获携带从代谢应激的棕色脂肪细胞释放的受损脂质和线粒体的细胞外囊泡来参与这种情况。CD36清道夫受体驱动LAM表型，缺乏CD36的LAM能够增加脂肪细胞中的棕色脂肪基因。LAMs释放转化生长因子β1（TGF-β1），通过醛脱氢酶1家族成员A1（Aldh1a1）诱导促进棕色脂肪细胞身份的丧失。这些发现揭示了肥胖期间BAT的细胞动态变化，并将LAM鉴定为组织代谢应激的关键反应者和棕色脂肪细胞身份丧失的驱动因素。
