| First Author | Nguyen AD | Year | 2018 |
| Journal | Bone | Volume | 106 |
| Pages | 167-178 | PubMed ID | 26055106 |
| Mgi Jnum | J:256980 | Mgi Id | MGI:6113099 |
| Doi | 10.1016/j.bone.2015.05.037 | Citation | Nguyen AD, et al. (2018) Uncoupling protein-1 is protective of bone mass under mild cold stress conditions. Bone 106:167-178 |
| abstractText | Brown adipose tissue (BAT), largely controlled by the sympathetic nervous system (SNS), has the ability to dissipate energy in the form of heat through the actions of uncoupling protein-1 (UCP-1), thereby critically influencing energy expenditure. Besides BAT, the SNS also strongly influences bone, and recent studies have demonstrated a positive correlation between BAT activity and bone mass, albeit the interactions between BAT and bone remain unclear. Here we show that UCP-1 is critical for protecting bone mass in mice under conditions of permanent mild cold stress for this species (22 degrees C). UCP-1(-/-) mice housed at 22 degrees C showed significantly lower cancellous bone mass, with lower trabecular number and thickness, a lower bone formation rate and mineralising surface, but unaltered osteoclast number, compared to wild type mice housed at the same temperature. UCP-1(-/-) mice also displayed shorter femurs than wild types, with smaller cortical periosteal and endocortical perimeters. Importantly, these altered bone phenotypes were not observed when UCP-1(-/-) and wild type mice were housed in thermo-neutral conditions (29 degrees C), indicating a UCP-1 dependent support of bone mass and bone formation at the lower temperature. Furthermore, at 22 degrees C UCP-1(-/-) mice showed elevated hypothalamic expression of neuropeptide Y (NPY) relative to wild type, which is consistent with the lower bone formation and mass of UCP-1(-/-) mice at 22 degrees C caused by the catabolic effects of hypothalamic NPY-induced SNS modulation. The results from this study suggest that during mild cold stress, when BAT-dependent thermogenesis is required, UCP-1 activity exerts a protective effect on bone mass possibly through alterations in central NPY pathways known to regulate SNS activity. |
