Neuropeptide Y regulation of energy partitioning and bone mass during cold exposure

Natalie K. Y. Wee, Amy D. Nguyen, Ronaldo F. Enriquez, Lei Zhang, Herbert Herzog, Paul A. Baldock*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)510-523
Number of pages14
JournalCalcified Tissue International
Issue number5
Early online date17 Aug 2020
Publication statusPublished - Nov 2020
Externally publishedYes


  • Brown adipose tissue (BAT)
  • Energy homeostasis
  • Neuropeptide Y (NPY)
  • Skeleton
  • Temperature
  • Uncoupling protein-1 (UCP-1)


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