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Title: Obesity-related changes in bone structural and material properties in hyperphagic OLETF rats and protection by voluntary wheel running

Author
item HINTON, PAMELA - University Of Missouri
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)
item EATON, LYNN - University Of Missouri
item RECTOR, R - University Of Missouri

Submitted to: Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/24/2015
Publication Date: 5/1/2015
Citation: Hinton, P.S., Shankar, K., Eaton, L.M., Rector, R.S. 2015. Obesity-related changes in bone structural and material properties in hyperphagic OLETF rats and protection by voluntary wheel running. Metabolism. 64(8):905-916. doi: 10.1016/j.metabol.2015.04.004.

Interpretive Summary: Obesity is associated with increased risk of a host of other diseases including diabetes, metabolic syndrome and cardiovascular disease. Recent studies also suggest that greater weight and fat mass may decrease bone mass. Conversely, increased physical activity is considered to be beneficial to the skeleton. In the present report using an established rat model, we examined the influence of obesity development on morphological and biomechanical properties of the bone, and further examined the impact of voluntary wheel running on mitigating effects of obesity. Groups of obese animals were provided access to running wheels or were kept under sedentary conditions. The strength and mineral content of long bones of the legs (femur and tibia) was assessed using quantitative computerized tomography periodically until 40 weeks of age. These studies confirmed that obesity had negative effects on the bone which worsened with age and obesity development. More importantly, obese rats provided access to exercise did not develop the negative consequences of bone loss. These findings suggest that exercise can potentially protect against obesity-associated skeletal changes with marked benefits on the biomechanical properties of bone.

Technical Abstract: We conducted a study to examine how the development of obesity and the associated insulin resistance affect bone structural and material properties, and bone formation and resorption markers in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model. This was a 36-week study of sedentary, hyperphagic, male OLETF rats (OLETF-SED), exercise-treated OLETF rats (OLETF-EX) and sedentary non-hyperphagic controls (LETO-SED) with data collection at 13, 20, and 40 weeks of age (n = 5–8 animals per group per time point). We found that body mass and fat (%) were significantly greater in OLETF-SED versus controls. OLETF-SED were insulin resistant at 13 and 20 weeks, with overt diabetes by 40 weeks. At 13 weeks, OLETF-SED had lower total body BMC and BMD and serum P1NP compared with LETO-SED. Differences in total body BMC and BMD between OLETF-SED and LETO-SED persisted at 20 weeks, with reductions in total and cortical BMD of the tibia. OLETF-SED also had lesser femur diameter, cross-sectional area, polar moment of area, and torque at fracture than LETO-SED. By 40 weeks, OLETF-SED had elevated bone resorption and reduced intrinsic bone strength. OLETF-EX did not show the excessive weight gain, obesity, insulin resistance or diabetes observed in OLETF-SED. OLETF-EX had greater BMD than OLETF-SED, and structural and material properties of the femur were significantly increased in OLETF-EX relative to OLETF-SED and LETO-SED. The negative skeletal effects of excessive adiposity and insulin resistance were evident early in the progressive obesity with lasting negative impacts on intrinsic and extrinsic bone strength. Exercise protected against obesity-associated skeletal changes with marked benefits on the biomechanical properties of bone.