Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis.

Nature communications 2022 Jan 20

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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. © 2022. The Author(s).

Citation

Bingyang Dai, Jiankun Xu, Xu Li, Le Huang, Chelsea Hopkins, Honglian Wang, Hao Yao, Jie Mi, Lizhen Zheng, Jiali Wang, Wenxue Tong, Dick Ho-Kiu Chow, Ye Li, Xuan He, Peijie Hu, Ziyi Chen, Haiyue Zu, Yixuan Li, Yao Yao, Qing Jiang, Ling Qin. Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis. Nature communications. 2022 Jan 20;13(1):427