Bone Biology Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia.
Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia.
Calcif Tissue Int. 2020 Nov;107(5):510-523. doi: 10.1007/s00223-020-00745-9. Epub 2020 Aug 17.
The maintenance of whole body energy homeostasis is critical to survival and mechanisms exist whereby an organism can adapt to its environment and the stresses placed upon it. Environmental temperature and thermogenesis are key components known to affect energy balance. However, little is known about how these processes are balanced against the overall energy balance. We show that even mild cold exposure has a significant effect on energy expenditure and UCP-1 levels which increase by 43% and 400%, respectively, when wild-type (WT) mice at thermoneutral (29 °C) were compared to mice at room temperature (22 °C) conditions. Interestingly, bone mass was lower in cold-stressed WT mice with significant reductions in femoral bone mineral content (- 19%) and bone volume (- 13%). Importantly, these cold-induced skeletal changes were absent in mice lacking NPY, one of the main controllers of energy homeostasis, highlighting the critical role of NPY in this process. However, energy expenditure was significantly greater in cold-exposed NPY null mice, indicating that suppression of non-thermogenic tissues, like bone, contributes to the adaptive responses to cold exposure. Altogether, this work identifies NPY as being crucial in coordinating energy and bone homeostasis where it suppresses energy expenditure, UCP-1 levels and lowers bone mass under conditions of cold exposure.
全身能量稳态的维持对生存至关重要，生物体存在适应环境和应对压力的机制。环境温度和产热是已知影响能量平衡的关键因素。然而，人们对这些过程如何与整体能量平衡相平衡知之甚少。我们表明，即使轻度寒冷暴露也会对能量消耗和 UCP-1 水平产生显著影响，当野生型（WT）小鼠处于热中性（29°C）时，与处于室温（22°C）条件下的小鼠相比，分别增加了 43%和 400%。有趣的是，寒冷应激的 WT 小鼠的骨量较低，股骨骨矿物质含量（-19%）和骨体积（-13%）显著减少。重要的是，缺乏 NPY 的小鼠（能量平衡的主要控制器之一）没有出现这些冷诱导的骨骼变化，这突出表明 NPY 在这个过程中的关键作用。然而，在寒冷暴露的 NPY 缺失小鼠中，能量消耗显著增加，这表明抑制非产热组织（如骨骼）有助于对寒冷暴露的适应反应。总之，这项工作确定 NPY 对于协调能量和骨骼稳态至关重要，它在寒冷暴露条件下抑制能量消耗、UCP-1 水平并降低骨量。
