中文摘要:
在高脂饮食 (HFD) 诱导的肥胖中,附睾白色脂肪组织 (eWAT) 分泌一系列细胞因子来调节器官和组织的代谢,但其对骨代谢的影响尚不清楚。在这里,我们报道了 eWAT 中的巨噬细胞是骨桥蛋白的主要来源,骨桥蛋白选择性地循环到骨髓并通过激活破骨细胞来促进骨基质的降解,以及调节骨髓衍生的巨噬细胞 (BMDM) 以吞噬小鼠骨髓中脂肪细胞释放的脂滴。然而,骨桥蛋白调节诱导的乳酸积累通过限制溶酶体中 ATP6V0d2 的能量再生来阻断 BMDMs 中的脂肪分解和破骨细胞生成。手术切除 eWAT 和局部注射氯膦酸盐脂质体 (用于清除巨噬细胞) 或骨桥蛋白中和抗体均显示出对 HFD 诱导的小鼠骨质流失的改善。这些结果为开发缓解肥胖相关骨骼疾病的治疗策略提供了一条途径。
英文摘要:
Epididymal white adipose tissue (eWAT) secretes an array of cytokines to regulate the metabolism of organs and tissues in high-fat diet (HFD)-induced obesity, but its effects on bone metabolism are not well understood. Here, we report that macrophages in eWAT are a main source of osteopontin, which selectively circulates to the bone marrow and promotes the degradation of the bone matrix by activating osteoclasts, as well as modulating bone marrow-derived macrophages (BMDMs) to engulf the lipid droplets released from adipocytes in the bone marrow of mice. However, the lactate accumulation induced by osteopontin regulation blocks both lipolysis and osteoclastogenesis in BMDMs by limiting the energy regeneration by ATP6V0d2 in lysosomes. Both surgical removal of eWAT and local injection of either clodronate liposomes (for depleting macrophages) or osteopontin-neutralizing antibody show comparable amelioration of HFD-induced bone loss in mice. These results provide an avenue for developing therapeutic strategies to mitigate obesity-related bone disorders.
论文信息:
论文题目:Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis
期刊名称:Nature Communications
时间期卷:13, Article number: 427 (2022)
在线时间:2022年1月20日
DOI:doi.org/10.1038/s41467-021-27683-w
产品信息:
货号:CP-005-005
规格:5ml+5ml
品牌:Liposoma
产地:荷兰
名称:Clodronate Liposomes and Control Liposomes
办事处:Target Technology(靶点科技)
氯膦酸盐脂质体清除附睾脂肪组织中的巨噬细胞,其分泌骨桥蛋白以调节骨稳态。氯膦酸盐二钠脂质体清除巨噬细胞在高脂诱导的肥胖(HFD)模型附睾脂肪组织和破骨细胞功能研究,荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications:
ClodronateLiposomes清除附睾脂肪组织巨噬细胞缓解肥胖相关骨骼疾病的治疗策略的研究
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法:
The abdominal hair was shaved, and the skin was treated with betadine. ATMs were depleted by injecting clodronate liposomes (0.675 mg/unilateral/3 days, LIPOSOMA, Lot # C10E0218) into the bilateral eWAT under inhalation isoflurane without surgical incision every 3 days from 12 weeks of age. Mice were simultaneously fed an NFD or HFD for 8 weeks. The control group mice received the control liposome (LIPOSOMA, Lot# C14E0218).