Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis
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香港中文大學研究人員
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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.
出版社接受日期04.11.2021
著者Dai B, Xu J, Li X, Huang L, Hopkins C, Wang H, Yao H, Mi J, Zheng L, Wang J, Tong W, Chow DHK, Li Y, He X, Hu P, Chen Z, Zu H, Li Y, Yao Y, Jiang Q, Qin L
期刊名稱Nature Communications
出版年份2022
月份1
日期20
卷號13
出版社Springer
文章號碼427
國際標準期刊號2041-1723
語言美式英語
