Background
This study compared 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).
Methods
Kunming mice were fed a high-fat diet for 3 months 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. Body weight and adipose tissue wet weight were measured. Micro-computed tomography 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 formation (RunX2, OCN, ALP), bone resorption (RANKL, Cathepsin K, MMP9) and Wnt signaling (P-β-catenin, GSK-3β).
Results
Micro-CT showed that there was no obvious bone loss in the OB group, compared with controls, whereas bone formation in the PRE group was enhanced, compared to summer-active squirrels. Results of three-point bending tests showed that stiffness of the femur in OB mice was significantly enhanced, whereas the mechanical properties of bone in the PRE group did not change. Analysis of bone protein expression showed significantly increased expression levels of ALP, OCN, RANKL, MMP9, Cathepsin K, GSK-3β and P-β-catenin in OB mice, but RunX2 expression did not change. By contrast, PRE ground squirrels, showed significantly increased expression of most proteins except for OCN that decreased significantly, and P-β-catenin that did not change.
Conclusion
For non-hibernating mice, moderate obesity had a certain protective effect on bones, demonstrating two-way regulation, enhancing both bone loss and bone formation, so that bone metabolism was at a higher level of metabolic balance. 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.