氯膦酸鹽脂質(zhì)體清除附睪脂肪組織中的巨噬細(xì)胞，其分泌骨橋蛋白以調(diào)節(jié)骨穩(wěn)態(tài)

中文摘要：

在高脂飲食 （HFD） 誘導(dǎo)的肥胖中，附睪白色脂肪組織 （eWAT） 分泌一系列細(xì)胞因子來(lái)調(diào)節(jié)器官和組織的代謝，但其對(duì)骨代謝的影響尚不清楚。在這里，我們報(bào)道了 eWAT 中的巨噬細(xì)胞是骨橋蛋白的主要來(lái)源，骨橋蛋白選擇性地循環(huán)到骨髓并通過(guò)激活破骨細(xì)胞來(lái)促進(jìn)骨基質(zhì)的降解，以及調(diào)節(jié)骨髓衍生的巨噬細(xì)胞 （BMDM） 以吞噬小鼠骨髓中脂肪細(xì)胞釋放的脂滴。然而，骨橋蛋白調(diào)節(jié)誘導(dǎo)的乳酸積累通過(guò)限制溶酶體中 ATP6V0d2 的能量再生來(lái)阻斷 BMDMs 中的脂肪分解和破骨細(xì)胞生成。手術(shù)切除 eWAT 和局部注射氯膦酸鹽脂質(zhì)體 （用于清除巨噬細(xì)胞） 或骨橋蛋白中和抗體均顯示出對(duì) HFD 誘導(dǎo)的小鼠骨質(zhì)流失的改善。這些結(jié)果為開(kāi)發(fā)緩解肥胖相關(guān)骨骼疾病的治療策略提供了一條途徑。

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.

論文信息：

論文題目：Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis

期刊名稱(chēng)：Nature Communications

時(shí)間期卷：13, Article number: 427 (2022)

在線(xiàn)時(shí)間：2022年1月20日

DOI：doi.org/10.1038/s41467-021-27683-w

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱(chēng)：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology（靶點(diǎn)科技）

氯膦酸鹽脂質(zhì)體清除附睪脂肪組織中的巨噬細(xì)胞，其分泌骨橋蛋白以調(diào)節(jié)骨穩(wěn)態(tài)。氯膦酸鹽二鈉脂質(zhì)體清除巨噬細(xì)胞在高脂誘導(dǎo)的肥胖（HFD）模型附睪脂肪組織和破骨細(xì)胞功能研究，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見(jiàn)刊于Nature Communications：

ClodronateLiposomes清除附睪脂肪組織巨噬細(xì)胞緩解肥胖相關(guān)骨骼疾病的治療策略的研究

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

ATM(adipose tissue-derived macrophages： ATMs)depletion

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).