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Journal of Zhejiang University SCIENCE B
ISSN 1673-1581(Print), 1862-1783(Online), Monthly
2022 Vol.23 No.12 P.1042-1056
Differential bone metabolism and protein expression in mice fed a high-fat diet versus Daurian ground squirrels following natural pre-hibernation fattening
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.
Key words: High-fat diet; Pre-hibernation fattening; Bone formation; Bone loss; Wnt signaling
1陕西省秦岭珍稀濒危动物保育重点实验室，西北大学生命科学学院，中国西安市，710069
2西部资源生物与现代生物技术教育部重点实验室，中国西安市，710069
3卡尔顿大学生物系，加拿大渥太华，K1S 5B6
概要：本研究比较了非冬眠动物（昆明小鼠）过度摄入脂肪引起的病理性肥胖与冬眠动物（达乌尔黄鼠）冬眠前自然育肥导致的健康肥胖对骨代谢和形态的影响。研究将高脂饮食喂养的昆明小鼠作为病理性肥胖模型（OB组），冬眠前自然育肥的达乌尔黄鼠作为健康性肥胖模型（PRE组）。使用微计算机断层扫描和三点弯曲实验确定骨的微观结构和力学性能，并用蛋白质印迹分析与骨代谢相关的蛋白质（Runt相关转录因子2（Runt-related transcription factor 2，RunX2）、骨钙素（osteocalcin，OCN）、碱性磷酸酶（alkaline phosphatase，ALP）、骨保护素（osteoprotegerin，OPG）、核因子κB受体活化因子配体（receptor activator of nuclear factor-κB ligand，RANKL）、组织蛋白酶K（cathepsin K）、基质金属蛋白酶9（matrix metallopeptidase 9，MMP9）、蛋白修补同源1（patched protein homolog 1，Ptch1）、磷酸化β-连环蛋白（phosphorylatedβ-catenin，P-β-catenin)和糖原合酶激酶-3β（glycogen synthase kinase-3β，GSK-3β））的表达水平。结果显示，与对照（CON）组相比，OB组小鼠没有明显的骨质流失，但股骨的刚度明显增加。与夏季活跃（SA）组黄鼠相比，PRE组黄鼠的骨形成增强，但骨骼力学性能没有变化。在OB组小鼠中，蛋白质印迹显示除RunX2、OPG和Ptch1之外的所有蛋白质的表达水平显著增加。PRE组黄鼠大多数蛋白质的表达水平显著增加，但OCN和Ptch1显著下降，P-β-catenin和OPG没有变化。综上所述，对于非冬眠小鼠，适度肥胖对骨骼有一定的保护作用，表现为双向调节，既增加了骨质流失，又增加了骨形成。对于冬眠前黄鼠，冬眠前育肥对骨骼的微观结构有积极的影响，同时也提高了与骨形成、骨吸收和Wnt信号相关蛋白质的表达水平。
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DOI:
10.1631/jzus.B2100798
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On-line Access:
2022-12-15
Received:
2021-09-15
Revision Accepted:
2022-05-20
Crosschecked:
2022-12-15