Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity

Chuanxin Zhong, Nanxi Li, Shengzheng Wang, Dijie Li, Zhihua Yang, Lin Du, Guangxin Huang, Haitian Li, Wing Sze Yeung, Shan He, Shuting Ma, Zhuqian Wang, Hewen Jiang, Huarui Zhang, Zhanghao Li, Xiaoxin Wen, Song Xue, Xiaohui Tao, Haorui Li, Duoli Xie, Yihao Zhang, Zefeng Chen, Junqin Wang, Jianfeng Yan, Zhengming Liang, Zongkang Zhang, Zhigang Zhong, Zeting Wu, Chao Wan, Chao Liang, Luyao Wang, Sifan Yu, Yuan Ma, Yuanyuan Yu, Fangfei Li, Yang Chen, Baoting Zhang, Aiping Lyu (), Fuzeng Ren (), Hong Zhou (), Jin Liu () and Ge Zhang ()
Additional contact information
Chuanxin Zhong: School of Chinese Medicine, Hong Kong Baptist University
Nanxi Li: School of Chinese Medicine, Hong Kong Baptist University
Shengzheng Wang: School of Pharmacy, Fourth Military Medical University
Dijie Li: School of Chinese Medicine, Hong Kong Baptist University
Zhihua Yang: The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
Lin Du: The First Affiliated Hospital of Shantou University Medical College
Guangxin Huang: The Third Affiliated Hospital of Southern Medical University, The Third School of Clinical Medicine, Southern Medical University
Haitian Li: School of Chinese Medicine, Hong Kong Baptist University
Wing Sze Yeung: School of Chinese Medicine, Hong Kong Baptist University
Shan He: Southern University of Science and Technology, Shenzhen
Shuting Ma: School of Chinese Medicine, Hong Kong Baptist University
Zhuqian Wang: School of Chinese Medicine, Hong Kong Baptist University
Hewen Jiang: Faculty of Medicine, The Chinese University of Hong Kong
Huarui Zhang: Faculty of Medicine, The Chinese University of Hong Kong
Zhanghao Li: School of Chinese Medicine, Hong Kong Baptist University
Xiaoxin Wen: School of Chinese Medicine, Hong Kong Baptist University
Song Xue: Peking University Shenzhen Hospital
Xiaohui Tao: School of Chinese Medicine, Hong Kong Baptist University
Haorui Li: The First Affiliated Hospital of Shantou University Medical College
Duoli Xie: School of Chinese Medicine, Hong Kong Baptist University
Yihao Zhang: School of Chinese Medicine, Hong Kong Baptist University
Zefeng Chen: School of Chinese Medicine, Hong Kong Baptist University
Junqin Wang: Southern University of Science and Technology, Shenzhen
Jianfeng Yan: Southern University of Science and Technology, Shenzhen
Zhengming Liang: School of Chinese Medicine, Hong Kong Baptist University
Zongkang Zhang: Faculty of Medicine, The Chinese University of Hong Kong
Zhigang Zhong: The First Affiliated Hospital of Shantou University Medical College
Zeting Wu: The First Affiliated Hospital of Shantou University Medical College
Chao Wan: Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong
Chao Liang: Southern University of Science and Technology
Luyao Wang: School of Chinese Medicine, Hong Kong Baptist University
Sifan Yu: Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery
Yuan Ma: School of Chinese Medicine, Hong Kong Baptist University
Yuanyuan Yu: School of Chinese Medicine, Hong Kong Baptist University
Fangfei Li: School of Chinese Medicine, Hong Kong Baptist University
Yang Chen: Dalian Institute of Chemical Physics, Chinese Academy of Sciences
Baoting Zhang: Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery
Aiping Lyu: School of Chinese Medicine, Hong Kong Baptist University
Fuzeng Ren: Southern University of Science and Technology, Shenzhen
Hong Zhou: ANZAC Research Institute, The University of Sydney
Jin Liu: School of Chinese Medicine, Hong Kong Baptist University
Ge Zhang: School of Chinese Medicine, Hong Kong Baptist University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11β-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11β-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11β-HSD1 by using bone-targeted 11β-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11β-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-52965-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52965-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-52965-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().