Article abstract

Nature Medicine 13, 803 - 811 (2007)
Published online: 1 July 2007 | Corrected online: 24 July 2007 | doi:10.1038/nm1611

Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome

Lydia E Kuo1, Joanna B Kitlinska1, Jason U Tilan1, Lijun Li1, Stephen B Baker2, Michael D Johnson3, Edward W Lee1,8, Mary Susan Burnett4, Stanley T Fricke5, Richard Kvetnansky6, Herbert Herzog7 & Zofia Zukowska1

The relationship between stress and obesity remains elusive. In response to stress, some people lose weight, whereas others gain. Here we report that stress exaggerates diet-induced obesity through a peripheral mechanism in the abdominal white adipose tissue that is mediated by neuropeptide Y (NPY). Stressors such as exposure to cold or aggression lead to the release of NPY from sympathetic nerves, which in turn upregulates NPY and its Y2 receptors (NPY2R) in a glucocorticoid-dependent manner in the abdominal fat. This positive feedback response by NPY leads to the growth of abdominal fat. Release of NPY and activation of NPY2R stimulates fat angiogenesis, macrophage infiltration, and the proliferation and differentiation of new adipocytes, resulting in abdominal obesity and a metabolic syndrome-like condition. NPY, like stress, stimulates mouse and human fat growth, whereas pharmacological inhibition or fat-targeted knockdown of NPY2R is anti-angiogenic and anti-adipogenic, while reducing abdominal obesity and metabolic abnormalities. Thus, manipulations of NPY2R activity within fat tissue offer new ways to remodel fat and treat obesity and metabolic syndrome.

  1. Department of Physiology & Biophysics, Georgetown University Medical Center, 3900 Reservoir Rd. NW, BSB 234, Washington, DC 20057, USA.
  2. Department of Plastic Surgery, Georgetown University Medical Center, 3900 Reservoir Rd. NW, 1 PHC, Washington, DC, 20007, USA.
  3. Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Rd., NW W326A NRB, Washington, DC 20007, USA.
  4. Cardiovascular Research Institute, MedStar Research Institute, 108 Irving Street NW, Room 214, Washington, DC 20010, USA.
  5. Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd., NW WB-01 NRB, Washington, DC 20007, USA.
  6. Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06, Bratislava, Slovak Republic.
  7. Garvan Institute of Medical Research, 384 Victoria St., NSW 2010 Darlinghurst, Sydney, Australia.
  8. Present address: Department of Radiology, David Geffen School of Medicine at the University of California, Los Angeles, 10833 Le Conte Ave., Box 951721, Los Angeles, California 90095, USA.

Correspondence to: Zofia Zukowska1 e-mail:

* Nat. Med. 13, 803-811 (2007); published online 1 July; corrected after print 24 July 2007. The version of this article initially published contained several typographical errors affecting figure citations, units of measure and figure legends, none of which change the scientific conclusions of the manuscript in any way. In addition, the authors incorrectly stated that they had no competing financial interests. A proper description of these competing interests, as is required by journal policy, has now been attached to the HTML version of the article, and the typographical errors have been corrected in the HTML and PDF versions.


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Stress, diet and abdominal obesity: Y?

Nature Medicine News and Views (01 Jul 2007)