Neuropeptide Y Regulation of Energy Partitioning and Bone Mass During Cold Exposure
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ORIGINAL RESEARCH
Neuropeptide Y Regulation of Energy Partitioning and Bone Mass During Cold Exposure Natalie K. Y. Wee1 · Amy D. Nguyen2 · Ronaldo F. Enriquez1 · Lei Zhang2 · Herbert Herzog2,3 · Paul A. Baldock1,3,4 Received: 13 January 2020 / Accepted: 4 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords Neuropeptide Y (NPY) · Skeleton · Uncoupling protein-1 (UCP-1) · Energy homeostasis · Brown adipose tissue (BAT) · Temperature Abbreviations BAT Brown adipose tissue BFR Bone formation rate BMD Bone mineral density BMC Bone mineral content Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00223-020-00745-9) contains supplementary material, which is available to authorised users. * Paul A. Baldock [email protected] 1
Bone Biology Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia
2
Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia
3
School of Medical Sciences, University of NSW, Sydney, NSW, Australia
4
School of Medicine Sydney, University of Notre Dame Australia, Sydney, Australia
DXA Dual x-ray absorptiometry MAR Mineral apposition rate MS Mineralising surface NPY Neuropeptide Y NPYKO Neuropeptide Y knockout PFA Paraformaldehyde RER Respiratory exchange ratio UCP-1 Uncoupling protein-1 WAT White adipose tissue WT Wild-type
Introduction A critical component of the response to cold exposure in mammalian systems is the ability to produce heat, mainly mediated in brown adipose tissu
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