biostudies-literatureHuang MKey Research and Development Program of Hunan ProvinceCentral South University Research Program of Advanced Interdisciplinary StudiesMajor Basic Research Projects in Hunan ProvinceNatural Science Foundation of HunanChina Postdoctoral Science FoundationNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaScience and Technology Innovation Program of Hunan Provincee2502634https://www.ebi.ac.uk/biostudies/studies/S-EPMC12302596biostudies-literatureUnknown12(28)Obesity is associated with skeletal deterioration and increased fracture risk, but the underlying mechanism is unclear. Herein, it is shown that obese gut microbiota promotes skeletal deterioration by inducing bone marrow macrophages (BMMs) senescence and grancalcin (GCA) secretion. Obese mice and those receiving obese fecal microbiota transplants exhibit increased senescent macrophages and elevated GCA expression in the bone marrow. In a study of 40 participants, it is found that obese patients are associated with higher serum GCA levels. It is further revealed that obese gut-microbiota derived lipopolysaccharides (LPS) stimulate GCA expression in senescent BMMs via activating Toll-like receptor 4 pathway. Mice with depletion of the Gca gene are resistant to the negative effects of obesitAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Gut Microbiota Modulates Obesity-Associated Skeletal Deterioration Through Macrophage Aging and Grancalcin Secretion.PMC123025962023QYJC011822611603972022RC10092024JC00042024M7637222022SK2023824725212023JJ409652023RC10272022YFC3601900822725602022YFC20096042025JJ60562819220172023JJ308962022RC3075He CHe WZLiu LChen KXHuang MChen HLYang FJiao YRLi XZeng CHou JLi CJSun YCWei JLei GHTang XfalseGut Microbiota Modulates Obesity-Associated Skeletal Deterioration Through Macrophage Aging and Grancalcin Secretion.Obesity is associated with skeletal deterioration and increased fracture risk, but the underlying mechanism is unclear. Herein, it is shown that obese gut microbiota promotes skeletal deterioration by inducing bone marrow macrophages (BMMs) senescence and grancalcin (GCA) secretion. Obese mice and those receiving obese fecal microbiota transplants exhibit increased senescent macrophages and elevated GCA expression in the bone marrow. In a study of 40 participants, it is found that obese patients are associated with higher serum GCA levels. It is further revealed that obese gut-microbiota derived lipopolysaccharides (LPS) stimulate GCA expression in senescent BMMs via activating Toll-like receptor 4 pathway. Mice with depletion of the Gca gene are resistant to the negative effects of obesit2025-01-01T00:00:00Z2025 Jul2026-07-15T09:48:38.968Z2025-08-17T03:06:05.762ZS-EPMC123025964034916310.1002/advs.202502634