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Neuropeptide Y mediates the short-term hypometabolic effect of estrogen deficiency in mice

International Journal of Obesity volume 37, pages 390–398 (2013)Cite this article

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Abstract

Background:

Estrogen deficiency increases body weight or total and central adiposity and decreases energy expenditure. Hypothalamic neuropeptide Y (NPY) expression is altered by estrogen deficiency in rodents, but the long-term consequences on energy homeostasis are unknown.

Objective:

To investigate the role of NPY in the changes in energy expenditure and physical activity, as well as the associated changes in body weight and composition in response to short-term and long-term estrogen deficiency.

Design:

Sham and ovariectomy (OVX) operations were performed at 8 weeks of age in wild-type (WT) and NPY−/− mice. Energy expenditure, physical activity, body composition and weight, as well as food intake were measured at 10–18 days (short-term) and 46–54 days (long-term) after OVX.

Results:

OVX influences energy homeostasis differently at early compared with later time-points. At the early but not the late time point, OVX in WT mice reduced oxygen consumption and energy expenditure and tended to reduce resting metabolic rate. Interestingly, these effects of short-term estrogen deficiency were ablated by NPY deletion, with NPY−/− mice exhibiting significant increases in energy expenditure and resting metabolic rate. In addition to these hypermetabolic effects, OVX NPY−/− mice exhibited significantly lower body weight and whole-body fat mass relative to OVX WT controls at the short-term but not the long-term time point. Food intake and physical activity were unaltered by OVX, but NPY−/− mice exhibited significant reductions in these parameters relative to WT.

Conclusion:

The effects of estrogen deficiency to reduce energy metabolism are transient, and NPY is critical to this effect as well as the early OVX-induced obesity.

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Acknowledgements

We gratefully acknowledge the staff of the Garvan Institute Biological Testing Facility for facilitation of these experiments. AZ is supported by an Australian Postgraduate Award; IPLW is supported by the University of New South Wales Postgraduate Award; HH, PB and AS are supported by a Fellowship and Career Development Awards from the National Health and Medical Research Council (NHMRC) of Australia. The NHMRC has additionally supported this work with grant #596840. Author Contributions: AZ, HH, PAB and AS designed research; AZ, ADN, IPLW, RFE performed research; AZ and LZ analyzed data; AZ and AS wrote the paper and HH, LZ, JAE and PB provided critical review of the manuscript.

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Authors and Affiliations

  1. Osteoporosis and Bone Biology, Garvan Institute of Medical Research, St Vincent′s Hospital, Sydney, New South Wales, Australia

    A Zengin, I P L Wong, R F Enriquez, J A Eisman & P A Baldock

  2. Neuroscience Program, Garvan Institute of Medical Research, St Vincent′s Hospital, Sydney, New South Wales, Australia

    A Zengin, A D Nguyen, I P L Wong, L Zhang, R F Enriquez, H Herzog, P A Baldock & A Sainsbury

  3. Faculty of Medicine, University of NSW, Sydney, New South Wales, Australia

    J A Eisman, H Herzog & P A Baldock

  4. School of Medical Sciences, University of NSW, Sydney, New South Wales, Australia

    A Sainsbury

  5. Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia

    A Sainsbury

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  1. A Zengin
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Correspondence to A Sainsbury.

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Zengin, A., Nguyen, A., Wong, I. et al. Neuropeptide Y mediates the short-term hypometabolic effect of estrogen deficiency in mice. Int J Obes 37, 390–398 (2013). https://doi.org/10.1038/ijo.2012.71

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