Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

The cold exposure produced by standard housing conditions reduces bone mass in mice through a neuropeptide Y-mediated mechanism (#97)

Natalie K Wee 1 , Ron Enriquez 1 , Amy D Nguyen 2 , Herbert Herzog 2 , Paul A Baldock 1
  1. Skeletal Metabolism, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. Eating Disorders, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia

The thermoneutral temperature of mice (at which no energy is required to maintain body temperature) is 29°C, thus standard housing (~22°C) produces a continuous cold stress. The effect this has upon bone homeostasis is poorly defined. We have shown that neuropeptide Y (NPY) is involved in skeletal responses to chronic stress and to changes in uncoupling protein-1 (UCP-1), a key factor in the response to cold. UCP-1 upregulation in brown adipose tissue promotes heat generation and is anabolic to bone mass, whilst NPY levels are increased during negative energy balance, and is detrimental to bone.

We compared wild-type (WT) and NPY-null (NPYKO) mice at both thermoneutral (29°C-TN) and standard conditions (22°C) from 5 to 16 weeks of age.

Indicating the magnitude of the thermal stress, energy expenditure was significantly increased in WT (~43%) and NPYKO (~68%) mice exposed at 22°C compared to TN. This corresponded with 2 to 4-fold increases in UCP-1 levels in BAT, demonstrating that standard housing has a profound effect upon energy metabolism and thermogenesis. Coinciding with increased energy expenditure, both WT and NPYKO mice had increased calorie intake (~45% and ~60%) at 22°C, and no change in body composition.

WT mice at 22°C had reduced whole body and femoral BMC and BMD (~10% and ~18%) compared to TN, associated with reductions in cortical bone volume (~7%). NPYKO mice were not different between temperatures. Femoral cancellous bone was reduced in WT-22°C (~19%) mice and to a lesser degree in NPYKO-22°C mice (~5%). At cull, bone cell activity was not altered by temperature, suggesting a steady state had been reached.

This study demonstrates that standard housing is a marked thermal challenge to mice, inducing marked increases in energy expenditure, BAT activation and deleterious effects upon bone mass, though actions involving NPY.