Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis

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 and Ling Qin ()
Additional contact information
Bingyang Dai: The Chinese University of Hong Kong
Jiankun Xu: The Chinese University of Hong Kong
Xu Li: The Chinese University of Hong Kong
Le Huang: The Chinese University of Hong Kong
Chelsea Hopkins: The Chinese University of Hong Kong
Honglian Wang: Affiliated Traditional Medicine Hospital of Southwest Medical University
Hao Yao: The Chinese University of Hong Kong
Jie Mi: The Chinese University of Hong Kong
Lizhen Zheng: The Chinese University of Hong Kong
Jiali Wang: Sun Yat-sen University
Wenxue Tong: The Chinese University of Hong Kong
Dick Ho-kiu Chow: The Chinese University of Hong Kong
Ye Li: The Chinese University of Hong Kong
Xuan He: The Chinese University of Hong Kong
Peijie Hu: The Hong Kong Polytechnic University, Hung Hom
Ziyi Chen: The Chinese University of Hong Kong
Haiyue Zu: The Chinese University of Hong Kong
Yixuan Li: The Affiliated Hospital of Nanjing University Medical School
Yao Yao: The Affiliated Hospital of Nanjing University Medical School
Qing Jiang: The Affiliated Hospital of Nanjing University Medical School
Ling Qin: The Chinese University of Hong Kong

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-021-27683-w

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