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Neuropeptide Y Regulation of Energy Partitioning and Bone Mass During Cold Exposure

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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.

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Abbreviations

BAT:

Brown adipose tissue

BFR:

Bone formation rate

BMD:

Bone mineral density

BMC:

Bone mineral content

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

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Acknowledgements

NW was supported by an Australian Postgraduate Award (APA) administered by UNSW Australia. We would also like to thank the Biological Testing Facility at the Garvan Institute for assistance with the animal work.

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Authors and Affiliations

  1. Bone Biology Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia

    Natalie K. Y. Wee, Ronaldo F. Enriquez & Paul A. Baldock

  2. Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia

    Amy D. Nguyen, Lei Zhang & Herbert Herzog

  3. School of Medical Sciences, University of NSW, Sydney, NSW, Australia

    Herbert Herzog & Paul A. Baldock

  4. School of Medicine Sydney, University of Notre Dame Australia, Sydney, Australia

    Paul A. Baldock

Authors
  1. Natalie K. Y. Wee
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  2. Amy D. Nguyen
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  3. Ronaldo F. Enriquez
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  4. Lei Zhang
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  5. Herbert Herzog
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  6. Paul A. Baldock
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Contributions

Conception and design of study: NKW, HH, PAB. Acquisition of data: NKW, ADN, RFE. Analysis and interpretation: NKW, LZ, HH, PAB. Drafting and revising of the manuscript: NKW, HH, PAB. Final manuscript approved: NKW, ADN, RFE, LZ, HH, PAB.

Corresponding author

Correspondence to Paul A. Baldock.

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Conflict of interests

Natalie K. Y. Wee, Amy D. Nguyen, Ronaldo F. Enriquez, Lei Zhang, Herbert Herzog and Paul A. Baldock declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All experiments involving animals were approved by the Garvan Institute/St Vincent’s Animal Ethics Committee and conducted in accordance with the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes.

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Wee, N.K.Y., Nguyen, A.D., Enriquez, R.F. et al. Neuropeptide Y Regulation of Energy Partitioning and Bone Mass During Cold Exposure. Calcif Tissue Int 107, 510–523 (2020). https://doi.org/10.1007/s00223-020-00745-9

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  • DOI: https://doi.org/10.1007/s00223-020-00745-9

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