Uncoupling protein-1 is protective of bone mass under mild cold stress conditions
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 and bone mass, albeit the interactions between BAT and bone remain unclear. Here we show that UCP-1 is critical for protecting bone mass under conditions of permanent mild cold stress (22oC), since UCP-1-/- mice showed significantly reduced cancellous bone mass, with reduced trabecular number and thickness, a decreased bone formation rate and mineralising surface area, but unaltered osteoclast number, compared to wild type mice also exposed to mild cold stress. UCP-1-/- mice also displayed shorter femurs than wild types, with smaller cortical periosteal and endosteal perimeters. Importantly, these altered bone phenotypes where not observed when UCP-1-/- and wild type mice were housed in thermo-neutral conditions (29oC). When housed under conditions of mild cold stress, UCP-1-/- mice showed elevated hypothalamic expression of neuropeptide Y relative to cold-stressed wild types. This finding is consistent with the reduced bone formation and mass of UCP-1-/- versus wild type mice and the known bone catabolic effects of hypothalamic NPY induced by SNS modulation. The results from this study collectively suggest that UCP-1 exerts a protective effect on bone mass during cold mild stress, when BAT-dependent thermogenesis is required, possibly through alterations in central neuropeptide pathways known to regulate SNS activity.
|Authors||Nguyen, A.D.; Lee, N.J.; Enriquez, R.F.; Khor, E.C.; Wee, N.K-Y.; Zhang, L.; Sainsbury, A.; Baldock, P.A.; Herzog, H.|