KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism
Abstract An increasing number of studies have characterized the bone as an endocrine organ, and that bone secreted factors may not only regulate local bone remodeling, but also other tissues and whole-body metabolic functions. The precise nature of these regulatory factors and their roles at bridgin...
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| Format: | Article |
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Nature Publishing Group
2025-04-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-025-00415-2 |
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| author | Li Chen Kaikai Shi Nicholas Ditzel Weimin Qiu Michaela Tencerova Louise Himmelstrup Dreyer Nielsen Florence Figeac Alexander Rauch Yuhang Liu Jiuyuan Tao Veronika Sramkova Lenka Rossmeislova Greet Kerckhofs Tatjana N. Parac-Vogt Sébastien de Bournonville Thomas Levin Andersen Mikael Rydén Moustapha Kassem |
| author_facet | Li Chen Kaikai Shi Nicholas Ditzel Weimin Qiu Michaela Tencerova Louise Himmelstrup Dreyer Nielsen Florence Figeac Alexander Rauch Yuhang Liu Jiuyuan Tao Veronika Sramkova Lenka Rossmeislova Greet Kerckhofs Tatjana N. Parac-Vogt Sébastien de Bournonville Thomas Levin Andersen Mikael Rydén Moustapha Kassem |
| author_sort | Li Chen |
| collection | DOAJ |
| description | Abstract An increasing number of studies have characterized the bone as an endocrine organ, and that bone secreted factors may not only regulate local bone remodeling, but also other tissues and whole-body metabolic functions. The precise nature of these regulatory factors and their roles at bridging the bone, bone marrow adipose tissue, extramedullary body fat and whole-body energy homeostasis are being explored. In this study, we report that KIAA1199, a secreted factor produced from bone and bone marrow, previously described as an inhibitor of bone formation, also plays a role at promoting adipogenesis. KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue, subcutaneous and visceral fat tissue mass, blood cholesterol, triglycerides, free fatty acids and glycerol, as well as improved insulin sensitivity in skeletal muscle, liver and fat. Moreover, these mice are protected from the detrimental effects of high-fat diet feeding, with decreased obesity, lower blood glucose and glucose tolerance, as well as decreased adipose tissue inflammation, insulin resistance and hepatic steatosis. In human studies, plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol, triglycerides, free fatty acids, glycerol, fasting glucose and HOMA-IR. Mechanistically, KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT / ERK signaling. These findings provide evidence for the role of bone secreted factors on coupling bone, fat and whole-body energy homeostasis. |
| format | Article |
| id | doaj-art-cdc36f647d4d45d0a67eadcac134d49a |
| institution | DOAJ |
| issn | 2095-6231 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj-art-cdc36f647d4d45d0a67eadcac134d49a2025-08-20T03:04:58ZengNature Publishing GroupBone Research2095-62312025-04-0113111310.1038/s41413-025-00415-2KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolismLi Chen0Kaikai Shi1Nicholas Ditzel2Weimin Qiu3Michaela Tencerova4Louise Himmelstrup Dreyer Nielsen5Florence Figeac6Alexander Rauch7Yuhang Liu8Jiuyuan Tao9Veronika Sramkova10Lenka Rossmeislova11Greet Kerckhofs12Tatjana N. Parac-Vogt13Sébastien de Bournonville14Thomas Levin Andersen15Mikael Rydén16Moustapha Kassem17Guangxi Key Laboratory of Tumor Immunology and Microenvironment Regulation, Guilin Medical UniversityDepartment of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital & University of Southern DenmarkDepartment of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital & University of Southern DenmarkDepartment of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital & University of Southern DenmarkDepartment of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital & University of Southern DenmarkDepartment of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital & University of Southern DenmarkDepartment of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital & University of Southern DenmarkDepartment of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital & University of Southern DenmarkGuangxi Key Laboratory of Tumor Immunology and Microenvironment Regulation, Guilin Medical UniversityGuangxi Key Laboratory of Tumor Immunology and Microenvironment Regulation, Guilin Medical UniversityDepartment of Pathophysiology, Centre for Research on Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles UniversityDepartment of Pathophysiology, Centre for Research on Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles UniversityBiomechanics Lab, Institute of Mechanics, Materials, and Civil Engineering, KU LeuvenBiomechanics Lab, Institute of Mechanics, Materials, and Civil Engineering, KU LeuvenBiomechanics Section, Department of Mechanical Engineering, KU LeuvenInstitute of Pathology, University of Southern DenmarkDepartment of Medicine (H7), Karolinska Institute, Karolinska University HospitalDepartment of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital & University of Southern DenmarkAbstract An increasing number of studies have characterized the bone as an endocrine organ, and that bone secreted factors may not only regulate local bone remodeling, but also other tissues and whole-body metabolic functions. The precise nature of these regulatory factors and their roles at bridging the bone, bone marrow adipose tissue, extramedullary body fat and whole-body energy homeostasis are being explored. In this study, we report that KIAA1199, a secreted factor produced from bone and bone marrow, previously described as an inhibitor of bone formation, also plays a role at promoting adipogenesis. KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue, subcutaneous and visceral fat tissue mass, blood cholesterol, triglycerides, free fatty acids and glycerol, as well as improved insulin sensitivity in skeletal muscle, liver and fat. Moreover, these mice are protected from the detrimental effects of high-fat diet feeding, with decreased obesity, lower blood glucose and glucose tolerance, as well as decreased adipose tissue inflammation, insulin resistance and hepatic steatosis. In human studies, plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol, triglycerides, free fatty acids, glycerol, fasting glucose and HOMA-IR. Mechanistically, KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT / ERK signaling. These findings provide evidence for the role of bone secreted factors on coupling bone, fat and whole-body energy homeostasis.https://doi.org/10.1038/s41413-025-00415-2 |
| spellingShingle | Li Chen Kaikai Shi Nicholas Ditzel Weimin Qiu Michaela Tencerova Louise Himmelstrup Dreyer Nielsen Florence Figeac Alexander Rauch Yuhang Liu Jiuyuan Tao Veronika Sramkova Lenka Rossmeislova Greet Kerckhofs Tatjana N. Parac-Vogt Sébastien de Bournonville Thomas Levin Andersen Mikael Rydén Moustapha Kassem KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism Bone Research |
| title | KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism |
| title_full | KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism |
| title_fullStr | KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism |
| title_full_unstemmed | KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism |
| title_short | KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism |
| title_sort | kiaa1199 cemip regulates adipogenesis and whole body energy metabolism |
| url | https://doi.org/10.1038/s41413-025-00415-2 |
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