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High\u2010fat diet (HFD) consumption is one of the most important factors contributing to obesity. To elucidate and provide resources on how long\u2010term HFD to aging (LHA) affects the bone marrow and solid organs, we established an LHA mice model and demonstrated that LHA caused a shift from osteogenesis to adipogenesis in the bone marrow microenvironment. Single\u2010cell transcriptomics of bone marrow cells highlighted LHA\u2010driven perturbations in immune cell populations with distinct metabolic adaptations to LHA. We demonstrated that bone marrow macrophages of the LHA group upregulated Chil3 and Fabp4, which are associated with inflammatory response and regulation of adipocytes. Moreover, we identified the Ptn\u2013Sdc3 axis and Cxcl12\u2013Cxcr4 axis between bone marrow macrophages and brain epithelial cells as possible candidates for crosstalk between bone marrow and brain in LHA mice. Our findings indicated the bone marrow microenvironment as a central hub of LHA\u2010induced pathology, where adipogenic reprogramming and myeloid cell dysfunction collectively drive skeletal and systematic inflammation. This resource highlights therapeutic opportunities targeting bone marrow to mitigate obesity\u2010accelerated aging.<\/jats:p>","DOI":"10.1002\/mco2.70276","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T08:09:57Z","timestamp":1753085397000},"source":"Crossref","is-referenced-by-count":7,"title":["Long\u2010Term High\u2010Fat Diet Affected Bone Marrow Microenvironment During Aging at Single\u2010Cell Resolution"],"prefix":"10.1002","volume":"6","author":[{"given":"Yidan","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Institute of Microsurgery on Extremities and Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 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