Effect of Leptin Deficiency on the Skeletal Response to Hindlimb Unloading in Adult Male Mice

Abstract

Based on body weight, morbidly obese leptin-deficient ob/ob mice have less bone than expected, suggesting that leptin plays a role in the skeletal response to weight bearing. To evaluate this possibility, we compared the skeletal response of wild type (WT) and ob/ob mice to hindlimb unloading (HU). Mice were individually housed at 32 °C (thermoneutral) from 4 weeks of age (rapidly growing) to 16 weeks of age (approaching skeletal maturity). Mice were then randomized into one of 4 groups (n = 10/group): (1) WT control, (2) WT HU, (3) ob/ob control, and (4) ob/ob HU and the results analyzed by 2-way ANOVA. ob/ob mice pair-fed to WT mice had normal cancellous bone volume fraction (BV/TV) in distal femur, lower femur length and total bone area, mineral content (BMC) and density (BMD), and higher cancellous bone volume fraction in lumbar vertebra (LV). HU resulted in lower BMC and BMD in total femur, and lower BV/TV in distal femur and LV in both genotypes. Cancellous bone loss in femur in both genotypes was associated with increases in osteoclast-lined bone perimeter. In summary, leptin deficiency did not attenuate HU-induced osteopenia in male mice, suggesting that leptin is not required for bone loss induced by unweighting.