During obesity, tissue macrophages increase in number and become proinflammatory, thereby contributing to metabolic dysfunction. Lipoprotein lipase (LPL), which hydrolyzes triglyceride in lipoproteins, is secreted by macrophages. However, the role of macrophage-derived LPL in adipose tissue remodeling and lipoprotein metabolism is largely unknown. To clarify these issues, we crossed leptin-deficient Lep^ob/ob mice with mice lacking the Lpl gene in myeloid cells (Lpl^m−/m−) to generate Lpl^m−/m−;Lep^ob/ob mice. We found the weight of perigonadal white adipose tissue (WAT) was increased in Lpl^m−/m−;Lep^ob/ob mice compared with Lep^ob/ob mice due to substantial accumulation of both adipose tissue macrophages and collagen that surrounded necrotic adipocytes. In the fibrotic epidydimal WAT of Lpl^m−/m−;Lep^ob/ob mice, we observed an increase in collagen VI and high mobility group box 1, while α-smooth muscle cell actin, a marker of myofibroblasts, was almost undetectable, suggesting that the adipocytes were the major source of the collagens. Furthermore, the adipose tissue macrophages from Lpl ^m−/m−;Lep^ob/ob mice showed increased expression of genes related to fibrosis and inflammation. In addition, we determined Lpl ^m−/m−;Lep^ob/ob mice were more hypertriglyceridemic than Lep^ob/ob mice. Lpl^m−/m−;Lep^ob/ob mice also showed slower weight gain than Lep^ob/ob mice, which was primarily due to reduced food intake. In conclusion, we discovered that the loss of myeloid Lpl led to extensive fibrosis of perigonadal WAT and hypertriglyceridemia. In addition to illustrating an important role of macrophage LPL in regulation of circulating triglyceride levels, these data show that macrophage LPL protects against fibrosis in obese adipose tissues.

在肥胖期间，组织巨噬细胞数量增加并变得促炎，从而导致代谢功能障碍。脂蛋白脂肪酶 (LPL) 可水解脂蛋白中的甘油三酯，由巨噬细胞分泌。然而，巨噬细胞衍生的 LPL 在脂肪组织重塑和脂蛋白代谢中的作用在很大程度上是未知的。为了阐明这些问题，我们将缺乏瘦素的Lep ^ob/ob小鼠与骨髓细胞中缺乏Lpl基因的小鼠( Lpl ^m−/m− ) 杂交，以产生Lpl ^m−/m− ;Lep ^ob/ob小鼠。我们发现Lpl ^m−/m−中性腺周围白色脂肪组织 (WAT) 的重量增加；Lep ^ob/ob小鼠与Lep ^ob/ob小鼠相比，由于脂肪组织巨噬细胞和坏死脂肪细胞周围胶原蛋白的大量积累。在Lpl ^m−/m−的纤维化附睾 WAT ；Lep ^ob/ob小鼠中，我们观察到胶原蛋白 VI 和高迁移率组框 1 的增加，而肌成纤维细胞的标志物 α-平滑肌细胞肌动蛋白几乎检测不到，表明脂肪细胞是胶原蛋白的主要来源。此外，来自Lpl ^m−/m− ;Lep ^ob/ob小鼠的脂肪组织巨噬细胞显示与纤维化和炎症相关的基因表达增加。此外，我们确定了Lpl ^{m− / m−} ;Lep^ob/ob小鼠比Lep ^ob/ob小鼠具有更高的甘油三酯血症。Lpl ^m−/m−；Lep ^ob/ob小鼠的体重增加也比Lep ^ob/ob小鼠慢，这主要是由于食物摄入量减少。总之，我们发现骨髓Lpl的缺失导致性腺周围 WAT 广泛纤维化和高甘油三酯血症。除了说明巨噬细胞 LPL 在调节循环甘油三酯水平中的重要作用外，这些数据还表明巨噬细胞 LPL 可防止肥胖脂肪组织纤维化。