C - Michigan Technological University

Reduced adiponectin levels were observed in the serum of hibernating bears(Tables 2.4 and 2.5). This reduction could be related to the increased mobilization oftriglycerides during hibernation [112]. Adiponectin is negatively correlated to serumtriglyceride levels in healthy human females [198]. This decrease in serum adiponectinmay also reduce bone turnover and protect bone during hibernation. Serum adiponectinhas a consistent inverse relationship to BMD [186, 199, 200], and adiponectin knockoutmice have increased trabecular bone volume and trabecular number at 14 weeks of age[201]. In cultured osteoblasts, adiponectin stimulates osteoblast proliferation,differentiation, and expression of BSALP [157, 158, 201, 202]. Furthermore, a positivecorrelation between BSALP and serum adiponectin has been discovered in men andpost-menopausal women [203-205]. These studies suggest that adiponectin promotesosteoblast activity. Conversely, adiponectin increases osteoblast gene expression of thepro-resorptive cytokine RANKL with a concurrent decrease in the decoy receptor ofRANKL, osteoprotegerin (OPG) [206]. There is an inverse correlation between serumlevels of high molecular weight adiponectin and serum OPG in post-menopausal women[207]. These studies suggest that adiponectin may promote osteoclast activity throughosteoblasts. In hibernating bears, reduced levels of adiponectin may result insuppression of osteoblast and osteoclast activities. In support of this idea, BSALP andTRACP were positively correlated to adiponectin in the serum of black bears (Table 2.8).Thus, suppressed adiponectin during hibernation may help conserve energy by reducingbone metabolism. Such a reduction in bone turnover during hibernation in bears hasbeen observed in histomorphometric analyses of cortical and trabecular bone [18, 20].These data are supported by the drops in serum BSALP and TRACP during hibernationin the current study.One limitation of the current study is that total serum osteocalcin (includingfragments) was quantified. Intact circulating OCN is quickly broken into fragments [208],and has a half-life of approximately five minutes. In patients with reduced renal function,fragments of OCN accumulate in the serum. Only 26% of total OCN in uremic serum isintact [209, 210]. Since hibernating bears can be compared to patients with reducedrenal function, it is likely that a large portion of the reported OCN was fragmented. Thebioactivities of such fragments are unknown, but some can promote osteoclastmaturation [211] or function as an indicator of bone resorption [212]. Quantification of32