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

Zhong, Chuanxin1,2,3,4; Li, Nanxi1,4; Wang, Shengzheng5; Li, Dijie1,6; Yang, Zhihua7; Du, Lin8; Huang, Guangxin9; Li, Haitian1; Yeung, Wing Sze1; He, Shan2; Ma, Shuting1; Wang, Zhuqian1; Jiang, Hewen10; Zhang, Huarui10; Li, Zhanghao1; Wen, Xiaoxin1; Xue, Song11; Tao, Xiaohui1; Li, Haorui8; Xie, Duoli1; Zhang, Yihao1; Chen, Zefeng1; Wang, Junqin2; Yan, Jianfeng2; Liang, Zhengming1; Zhang, Zongkang10; Zhong, Zhigang8; Wu, Zeting12; Wan, Chao13; Liang, Chao14; Wang, Luyao1,3,4; Yu, Sifan3,10; Ma, Yuan1,3; Yu, Yuanyuan1,3,4; Li, Fangfei1,3,4; Chen, Yang15; Zhang, Baoting3,10; Lyu, Aiping1,3,4,16; Ren, Fuzeng2; Zhou, Hong17; Liu, Jin1,3,4,15; Zhang, Ge1,3,4

2024-10-04

10.1038/s41467-024-52965-4

NATURE COMMUNICATIONS   影响因子和分区

2041-1723

["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 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-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 11 beta-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11 beta-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11 beta-HSD1 by using bone-targeted 11 beta-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11 beta-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity.","Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Here the authors show that elevated expression of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1), the enzyme driving local bone GC activation, is associated with bone loss and obesity mice."]

SCI

英语

通讯

Research Grants Council of Hong Kong SAR["T12-201/20-R","12106924","12136616","12103519","12102120","12102322","12100921","12102223","22102823"] ; Guangdong-Hong Kong-Macau Joint Lab[2020B1212030006] ; Interdisciplinary Research Clusters Matching Scheme of Hong Kong Baptist University[RC-IRCs/17-18/02] ; Research Matching Grant Scheme of Hong Kong Baptist University[RMGS2023 _15_03] ; Hong Kong Baptist University[RC-ICRS/19-20/01] ; International Science and Technology Corporation Key Program of Jiangxi Province[20232BBH80012] ; National Key R&D Program of China[2018YFA0800804] ; Youth's Project of Guangdong Basic and Applied Basic Research Fund[2022A1515110044] ; Young Scientists Fund of the National Natural Science Foundation of China[82304378] ; Guangdong-Hong Kong Technology Cooperation Funding Scheme["GHP/149/21GD","2023A0505010015"] ; National Natural Science Foundation of China[52371251] ; Fundamental and Applied Fundamental Research Fund of Guangdong Province[2022B1515120082] ; National Natural Science Foundation of China[82373733]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:001325885200003

NATURE PORTFOLIO

Web of Science

1.Hong Kong Baptist Univ, Law Sau Fai Inst Adv Translat Med Bone & Joint Dis, Sch Chinese Med, Hong Kong, Peoples R China
2.Southern Univ Sci & Technol, Dept Mat Sci & Engn, Shenzhen, Guangdong, Peoples R China
3.Guangdong Hong Kong Macao Greater Bay Area Int Res, Hong Kong, Peoples R China
4.Hong Kong Baptist Univ, Inst Syst Med & Hlth Sci, Sch Chinese Med, Hong Kong, Peoples R China
5.Fourth Mil Med Univ, Sch Pharm, Dept Med Chem, Xian, Shaanxi, Peoples R China
6.Guangxi Normal Univ, Guangxi Univ Key Lab Stem cell & Biopharmaceut Tec, Coll Life Sci, Guilin, Peoples R China
7.Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China
8.Shantou Univ, Affiliated Hosp 1, Sports Med Ctr, Med Coll, Shantou, Peoples R China
9.Southern Med Univ, Affiliated Hosp 3, Sch Clin Med 3, Dept Joint Surg, Guangzhou, Peoples R China
10.Chinese Univ Hong Kong, Fac Med, Sch Chinese Med, Hong Kong, Peoples R China
11.Peking Univ, Dept Sports Med & Rehabil, Shenzhen Hosp, Shenzhen, Peoples R China
12.Shantou Univ, Int Med Serv Ctr, Med Coll, Shantou, Peoples R China
13.Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Key Lab Regenerat Med,Minist Educ, Hong Kong, Peoples R China
14.Southern Univ Sci & Technol, Dept Biol, Shenzhen, Peoples R China
15.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Phytochemistry & Nat Med, Dalian, Peoples R China
16.Guangdong Hong Kong Macau Joint Lab Chinese Med &, Hong Kong, Peoples R China
17.Univ Sydney, ANZAC Res Inst, Bone Res Program, Sydney, Australia

Zhong, Chuanxin,Li, Nanxi,Wang, Shengzheng,et al. Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity[J]. NATURE COMMUNICATIONS,2024,15(1).

Zhong, Chuanxin.,Li, Nanxi.,Wang, Shengzheng.,Li, Dijie.,Yang, Zhihua.,...&Zhang, Ge.(2024).Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity.NATURE COMMUNICATIONS,15(1).

Zhong, Chuanxin,et al."Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity".NATURE COMMUNICATIONS 15.1(2024).