No Adaptations in Bone of Leptin-Deficient ob/ob Mice in Response to Loading

Abstract

Leptin is a peptide hormone produced predominantly by white fat cells [1,47]. The mature protein, encoded by the obesity (ob) gene localized in human and mouse 7 and 6 chromosomes, respectively, is a 16 kDa non-glycosylated protein. Leptin levels in the blood are proportional to adipose tissue mass. Initially discovered as a central regulator of appetite and energy expenditure, leptin levels can be considered as a signal to the body regarding its energy reserves. Although elevated leptin levels are present in obesity, it is likely that the physiological importance of leptin is that low levels indicate a state of starvation [2]. Recent data suggest that leptin may regulate a variety of other physiological processes, such as insulin action [7], hemopoiesis [5], immune function [28], reproduction [40], angiogenesis [26], and bone development and remodeling [19]. However, it is not clear whether leptin is a stimulator or an inhibitor of bone growth in humans. Some investigators noted a positive relationship between serum leptin levels and bone mineral density (BMD). Iwamoto et al. described a weakly correlation of serum leptin level with bone mineral density of pelvis and left leg in the premenopausal women and Odebasi et al. found that there was no correlation between plasma leptin concentrations and BMD values in healthy postmenopausal woman but a weak correlation was observed in postmenopausal woman with osteoporosis [23,35]. Whereas others observed a negative relationship. Blum et al. suggest that for a given body weight, a higher proportion of fat and a higher serum leptin concentration have negative associations with bone mass in premenopausal women [6]. Sato et al. suggest that an increase in serum leptin reduces bone formation and decreases BMD in adult men [42]. Furthermore, no associations between serum leptin levels and BMD have been reported, which further confounds the interpretation of leptin's effect on bone mass. Martini et al. conclude that serum leptin have no direct effect on bone mass and bone turnover in healthy postmenopausal women [32] and Rauch et al. appear that leptin has less influence on the mature than on the growing skeleton [41]. Only a few studies in humans have examined the direct effect of leptin administration on BMD. Ogueh et al. [36] Leptin was found to be involved in regulation of bone development and remodeling. This study was performed to evaluate the effects of biomechanical loading due to body weight in leptin-defient ob/ob mice at the same pubertal stage. No significant difference was found between the two groups for all the parameters (p>0.05) suggesting that the presence of leptin may be an important pre-condition for positive correlation between loading and bone mass. Furthermore, concordance of bone formation was found among appendicular regions, but was not found between the axial and appendicular regions.

Differences in Trabecular Bone of Leptin-Deficient ob/ob Mice in Response to Biomechanical Loading

“…Fogelholm et al showed that the bone mineral density in the non-weight bearing bone of the distal radius was more strongly correlated with body weight than bone mineral density in the weight-bearing bones of the hip and spine 2. In our study we have shown the discrepancy in bone formation in the limbs and spine 3. This suggests that first body fat regulates bone metabolism by means of hormonal factors, and second the effects of muscle and loading are signaling factors in mechanotransduction 4, 5.…”

Osteoarthitis of Leptin-Deficient ob/ob Mice in Response to Biomechanical Loading in Micro-CT

“…In our own studies we were able to demonstrate differences in trabecular bone 41, 42 and the histomorphological progress of osteoarthritis in ob/ob-mice 43.…”