{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:17:36Z","timestamp":1791901056901,"version":"4.3.4"},"reference-count":170,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016694","name":"Science and Technology Development Plan of Shandong Province","doi-asserted-by":"publisher","award":["M20241846"],"award-info":[{"award-number":["M20241846"]}],"id":[{"id":"10.13039\/100016694","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Osteosarcopenic obesity (OSO)\u2014the co-occurrence of osteoporosis\/osteopenia, sarcopenia, and excess adiposity\u2014is increasingly recognized in ageing populations and is strongly linked to frailty, fractures, disability, and cardiometabolic complications. However, heterogeneous operational definitions and population-specific cut-offs complicate risk stratification and mechanistic inference. Here, we propose a systems immunometabolic framework to explain coordinated deterioration of adipose tissue, skeletal muscle, and bone, focusing on chronic low-grade inflammation, trained immunity (innate immune memory), and senescence-associated signaling. Dysfunctional visceral adipose tissue emerges as an immune-active endocrine organ that sustains low-grade systemic inflammation through release of cytokines, adipokines, lipotoxic mediators, and damage-associated molecular patterns. A key mechanism potentially underpinning inflammatory persistence is trained immunity\u2014epigenetic and metabolic reprogramming of innate immune cells and their progenitors\u2014which establishes maladaptive inflammatory memory and amplifies inter-organ immune crosstalk. In skeletal muscle, this pro-inflammatory milieu promotes catabolic signaling and anabolic resistance, including NF-\u03baB activation and mTOR pathway dysregulation, thereby driving impaired proteostasis, fibrosis, and fatty infiltration. In bone, inflammatory and senescence-associated signals converge on osteoclastogenic pathways and disrupt the receptor activator of nuclear factor-\u03baB ligand (RANKL)\/osteoprotegerin (OPG) axis, leading to uncoupled bone remodeling and net bone loss. Collectively, we argue that OSO can be conceptualized as a fat-initiated, system-level immunometabolic remodeling process across the adipose-muscle-bone axis. This framework supports stratified, multimodal interventions combining lifestyle modification with mechanism-based anti-inflammatory and anti-resorptive therapies, while immuno-epigenetic and senescence-targeted approaches warrant further study. Notably, OSO-specific longitudinal and interventional evidence integrating immune phenotyping and multi-omics remains limited and is needed to test causality and validate actionable biomarkers and targets.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1808488","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:57:10Z","timestamp":1778129830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Immunometabolic mechanisms of osteosarcopenic obesity: chronic inflammation, trained immunity, and systemic immune dysregulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Haobo","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Traumatology of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]},{"name":"Department of Orthopaedics, The First Affiliated Hospital of Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zicheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyou","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangliang","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-014-0146-x","article-title":"Osteosarcopenic obesity: the role of bone, muscle, and fat on health","volume":"5","author":"Ormsbee","year":"2014","journal-title":"J Cachexia Sarcopenia 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