Nature communications, 2022-01, Vol.13 (1), p.427-427, Article 427
2022
Details
- Autor(en) / Beteiligte
- Titel
- Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis
- Ist Teil von
- Nature communications, 2022-01, Vol.13 (1), p.427-427, Article 427
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2022
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-27683-wTitel-ID: cdi_doaj_primary_oai_doaj_org_article_cd1861519b2b4fda9aee7ace3bf268b9
- Format
- –
- Schlagworte
- Adipocytes, Adipose tissue, Adipose Tissue - diagnostic imaging, Adipose Tissue - metabolism, Adipose Tissue, White - diagnostic imaging, Adipose Tissue, White - metabolism, Animals, Antibodies, Biomedical materials, Bisphosphonates, Body fat, Body Weight, Bone and Bones - diagnostic imaging, Bone and Bones - metabolism, Bone diseases, Bone loss, Bone marrow, Bone matrix, Bone Resorption - pathology, Bone turnover, Cancellous Bone - diagnostic imaging, Cancellous Bone - metabolism, CD11b Antigen - metabolism, Clodronic acid, Cytokines, Degradation, Diet, High-Fat, Epididymis - metabolism, High fat diet, Homeostasis, Inflammation - pathology, Lactic acid, Lipid Metabolism, Lipids, Lipolysis, Lysosomes, Lysosomes - metabolism, Macrophages, Macrophages - metabolism, Male, Metabolism, Mice, Mice, Inbred C57BL, Models, Biological, Obesity, Organ Size, Organs, Osteoclastogenesis, Osteoclasts, Osteopontin, Osteopontin - metabolism, Protein Subunits - metabolism, Regeneration, Vacuolar Proton-Translocating ATPases - metabolism, X-Ray Microtomography