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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.
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.
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.
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.
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.
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.
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
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
Faculty of Medicine, University of NSW, Sydney, New South Wales, Australia
School of Medical Sciences, University of NSW, Sydney, New South Wales, Australia
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
Supplementary Information accompanies the paper on International Journal of Obesity website
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