Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis
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AbstractEpididymal 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.
Acceptance Date04/11/2021
All Author(s) ListDai 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
Journal nameNature Communications
Year2022
Month1
Day20
Volume Number13
PublisherSpringer
Article number427
ISSN2041-1723
LanguagesEnglish-United States

Last updated on 2024-27-02 at 00:36