image: Osteopontin (OPN) / integrin signaling mediates the effects of KIAA1199 on adipocyte differentiation of hBMSC. a, b Human bone marrow stromal stem cells (hBMSC) were transfected with specific siRNAs for KIAA1199 (siR-KIAA1199), OPN (siR-OPN), both or control siRNAs (siR-Ctrl), and were induced to adipocyte (AD) differentiation. Mature adipocytes stained by Oil red (a) and expression levels of KIAA1199, OPN, and adipocyte marker genes (FBAP4 and PPARG2) determined by qPCR, n = 4 (b). c–f hBMSC were transfected with siR-KIAA1199 or siR-Ctrl. Cells were treated with an integrin β1 (ITGB1) blocking antibody, or an isotype control, or CD44 blocking antibody (each at 10 mg/ml) during AD differentiation. Oil Red staining (c, e) and gene expression analysis of adipocyte marker genes (PPARG2, FABP4) analyzed by qPCR (d, f), n = 4. g KIAA1199-OPN axis regulates AD differentiation through ERK and AKT signaling. hBMSC were transfected with siR-KIAA1199 or siR-OPN or siR-Ctrl for 48 h, cells were starved for 6 h, followed by AD induction up to 0, 0.5, 1, 2 h. Western blot analysis for AKT and ERK activation was performed, and beta-tubulin was used as a loading control. h A schematic diagram of the possible mechanisms of KIAA1199 interacts with OPN/integrin/AKT/ERK axis on regulating adipogenesis and osteogenesis. Scale bar = 100 µm. All the experiments were performed at least for three times, data are expressed as means ± SD, statistical difference was determined by one-way ANOVA with Dunnett’s multiple tests, *P < 0.05, **P < 0.01 and ***P < 0.001.
Credit: bone research
A recent study has revealed that KIAA1199, a secreted protein produced by bone marrow cells, plays a crucial role in regulating both fat formation and overall energy metabolism. The protein's impact extends beyond bone remodeling, influencing glucose and lipid metabolism. Mice lacking KIAA1199 showed reduced fat mass, improved insulin sensitivity, and a decreased risk of obesity-related diseases. These findings suggest that targeting KIAA1199 could lead to new therapeutic strategies for combating metabolic disorders like obesity and type 2 diabetes.
Historically, bone has been recognized primarily for its structural role in the body, but emerging research suggests that it also acts as an endocrine organ influencing metabolic processes. Proteins secreted by bone cells, such as osteocalcin, have been found to regulate energy balance. Recently, KIAA1199 has emerged as a key player in this biological cross-talk, influencing both bone formation and fat storage. Given its complex effects on adipogenesis and overall metabolic health, understanding KIAA1199’s function could open the door to new treatments for obesity and insulin resistance. Due to these challenges, further research into KIAA1199’s mechanisms is essential to harness its potential therapeutic applications.
In a pivotal study (DOI: 10.1038/s41413-025-00415-2) published in Bone Research in April 2025, researchers led by Professor Li Chen from Guilin Medical University (China) and Professor Moustapha Kassem from the University of Southern Denmark explored the role of KIAA1199, a protein secreted by bone marrow cells, in regulating fat tissue formation and energy metabolism. The findings highlight how KIAA1199 influences insulin sensitivity and underscore the interplay between bone and fat tissue. This discovery holds promise for new therapeutic approaches to address metabolic diseases, particularly obesity and insulin resistance, providing a fresh perspective on how we treat these conditions.
The study uncovers a dual role for KIAA1199 in regulating both bone and fat tissue. In mice lacking KIAA1199, researchers observed notable reductions in bone marrow adipose tissue (BMAT) and other fat depots, such as subcutaneous and visceral fat. These KIAA1199-deficient mice also showed significant improvements in metabolic health, including enhanced insulin sensitivity, lower blood glucose levels, and a reduced risk of developing obesity. Remarkably, these mice were also protected from the adverse effects of high-fat diets, such as insulin resistance and liver steatosis. KIAA1199 regulates adipocyte differentiation via the osteopontin-integrin pathway, a complex mechanism involving AKT and ERK signaling pathways. These findings emphasize KIAA1199’s potential as a therapeutic target for treating metabolic disorders, showcasing its pivotal role in linking fat formation with overall energy metabolism.
Prof. Li Chen, co-author of the study, explains, ＂Our research underscores the crucial role KIAA1199 plays in bridging bone and fat tissue metabolism. By unraveling the molecular pathways involved, we are opening the door to targeted therapies that could enhance insulin sensitivity and combat obesity. This discovery has the potential to change the treatment landscape for metabolic diseases, offering new hope for individuals battling conditions like obesity and type 2 diabetes.＂
The findings from this study suggest that KIAA1199 could serve as a promising target for the development of treatments for metabolic disorders, including obesity and insulin resistance. Modulating KIAA1199’s activity may improve insulin sensitivity, regulate fat tissue formation, and alleviate the detrimental effects of high-fat diets. Further investigation into KIAA1199 inhibitors or monoclonal antibodies could lead to innovative therapies that not only enhance bone health but also address metabolic dysfunction, ultimately reducing the risk of chronic diseases. As research progresses, KIAA1199 could become a cornerstone in the fight against obesity and related metabolic conditions.
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References
DOI
Original Source URL
https://doi.org/10.1038/s41413-025-00415-2
Funding Information
The project got supports from Odense University Hospital PhD fellowship (2014), the NovoNordisk Foundations (NNF15OC0016284, NNF19OC0057449), the Innovation Foundation of Denmark (5166-00002B), National Natural Science Foundation of China (No. 32060155, 82260284) and Guangxi Medical and Health Key Discipline Construction Project.
About Bone Research
Bone Research was founded in 2013. As a new English-language periodical, Bone Research focuses on basic and clinical aspects of bone biology, pathophysiology and regeneration, and supports the foremost discoveries resulting from basic investigations and clinical research related to bone. The aim of the Journal is to foster the worldwide dissemination of research in bone-related physiology, pathology, diseases and treatment.
Journal
Bone Research
Subject of Research
Not applicable
Article Title
KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism
Article Publication Date
2-Apr-2025
COI Statement
The authors declare that they have no competing interests.