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Suppl. Mater.: 

CLC number: 

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2022-12-15

Cited: 0

Clicked: 1912

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Hui CHANG

https://orcid.org/0000-0003-0305-5237

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Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.12 P.1042-1056

http://doi.org/10.1631/jzus.B2100798


Differential bone metabolism and protein expression in mice fed a high-fat diet versus Daurian ground squirrels following natural pre-hibernation fattening


Author(s):  Xuli GAO, Shenyang SHEN, Qiaohua NIU, Weilan MIAO, Yuting HAN, Ziwei HAO, Ning AN, Yingyu YANG, Yu ZHANG, Han ZHANG, Kenneth B. STOREY, Hui CHANG

Affiliation(s):  Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi’an 710069, China; more

Corresponding email(s):   changhui@nwu.edu.cn

Key Words:  High-fat diet, Pre-hibernation fattening, Bone formation, Bone loss, Wnt signaling



Abstract: 
This study compared the effects on bone metabolism and morphology of pathological obesity induced by excessive fat intake in a non-hibernator (mice) versus healthy obesity due to pre-hibernation fattening in a hibernator (ground squirrels). Kunming mice were fed a high-fat diet to provide a model of pathological obesity (OB group). Daurian ground squirrels fattened naturally in their pre-hibernation season (PRE group) were used as a healthy obesity model. Micro-computed tomography (micro-CT) and three-point bending tests were used to determine the microstructure and mechanical properties of bone. Western blots were used to analyze protein expression levels related to bone metabolism (Runt-related transcription factor 2 (RunX2), osteocalcin (OCN), alkaline phosphatase (ALP), osteoprotegerin (OPG), receptor activator of nuclear factor-‍κB ligand (RANKL), cathepsin K, matrix metallopeptidase 9 (MMP9), patched protein homolog 1 (Ptch1), phosphorylated β‍-‍catenin (P‍-‍β‍-‍catenin), and glycogen synthase kinase-3β(GSK-3β)). Compared with controls, there was no obvious bone loss in the OB mice, and the stiffness of the femur was increased significantly. Compared with summer active squirrels, bone formation was enhanced but the mechanical properties did not change in the PRE group squirrels. In OB mice, western blots showed significantly increased expression levels of all proteins except RunX2, OPG, and Ptch1. PRE ground squirrels showed significantly increased expression of most proteins except OCN and Ptch1, which decreased significantly, and P‍-‍β‍-‍catenin and OPG, which did not change. In conclusion, for non-hibernating mice, moderate obesity had a certain protective effect on bones, demonstrating two-way regulation, increasing both bone loss and bone formation. For pre-hibernating ground squirrels, the healthy obesity acquired before hibernation had a positive effect on the microstructure of bones, and also enhanced the expression levels of proteins related to bone formation, bone resorption, and wnt signaling.

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