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- Title
Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis.
- Authors
Dai, Bingyang; Xu, Jiankun; Li, Xu; Huang, Le; Hopkins, Chelsea; Wang, Honglian; Yao, Hao; Mi, Jie; Zheng, Lizhen; Wang, Jiali; Tong, Wenxue; Chow, Dick Ho-kiu; Li, Ye; He, Xuan; Hu, Peijie; Chen, Ziyi; Zu, Haiyue; Li, Yixuan; Yao, Yao; Jiang, Qing
- Abstract
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. Visceral adipose tissue secretes cytokines to regulate the homeostasis of organs. Here, the authors show that epididymal white adipose tissue-secreted osteopontin induces lipophagocytic mobilization of macrophages and promotes bone matrix degradation via activating osteoclasts.
- Subjects
ADIPOSE tissues; OSTEOPONTIN; WHITE adipose tissue; HOMEOSTASIS; ADIPOSE tissue physiology; MACROPHAGES; BONE marrow; BONE resorption
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-27683-w