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

Change history

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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Acknowledgements

We thank J.F. Mill, A.K. Myers and P.C. Fox for editorial comments, M. Czarnecka for assisting with graphical aspects of the figures, A.-M. Hageny for assistance with catecholamine assays, M.D. Lane (Johns Hopkins) for 3T3-L1 preadipocytes, W. Rasband for NIH ImageJ and plug-ins, M. Abramoff for VolumeJ plug-in, and F. Bunz (Johns Hopkins) for pAdTrack-Cre. This work was supported by US National Institutes of Health (NIH) grants HL067357 and HL055310 to Z.Z., NIH grant DE016050 and PSEF National Endowment Grant to S.B.B., a Predoctoral Mid-Atlantic Fellowship from the American Heart Association to L.K., and Slovak Research and Development Agency grant APVV0148-06 to R.K.

Author information

Author notes

  1. Edward W Lee
    Present address: 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.,

Authors and Affiliations

  1. Department of Physiology & Biophysics, Georgetown University Medical Center, 3900 Reservoir Rd. NW, BSB 234, Washington, 20057, DC, USA
    Lydia E Kuo, Joanna B Kitlinska, Jason U Tilan, Lijun Li, Edward W Lee & Zofia Zukowska
  2. Department of Plastic Surgery, Georgetown University Medical Center, 3900 Reservoir Rd. NW, 1 PHC, Washington, 20007, DC, USA
    Stephen B Baker
  3. Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Rd., NW W326A NRB, Washington, 20007, DC, USA
    Michael D Johnson
  4. Cardiovascular Research Institute, MedStar Research Institute, 108 Irving Street NW, Room 214, Washington, 20010, DC, USA
    Mary Susan Burnett
  5. Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd., NW WB-01 NRB, Washington, 20007, DC, USA
    Stanley T Fricke
  6. Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, Bratislava, 833 06, Slovak Republic
    Richard Kvetnansky
  7. Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Sydney, Australia
    Herbert Herzog

Authors

  1. Lydia E Kuo
  2. Joanna B Kitlinska
  3. Jason U Tilan
  4. Lijun Li
  5. Stephen B Baker
  6. Michael D Johnson
  7. Edward W Lee
  8. Mary Susan Burnett
  9. Stanley T Fricke
  10. Richard Kvetnansky
  11. Herbert Herzog
  12. Zofia Zukowska

Contributions

L.E.K. carried out most of the experiments (as her PhD thesis work); developed stress models; established adipocyte-endothelial-neuronal co-cultures; together with S.T.F., adapted the MRI technique to the assessment of fat volumes; prepared most of the figures; and wrote major parts of the manuscript. J.U.T. contributed to many experiments using stress models, and assisted with harvesting tissues and adenoviral vectors. J.B.K. designed primers for RT-PCR; carried out molecular analyses; assisted with adipocyte-endothelial-neuronal co-cultures; and made major contributions to experimental design, data analyses, interpretation and presentation, and manuscript writing. L.L. performed NPY ELISA measurements, developed and carried out immunocytochemistry protocols, and contributed to data analyses and interpretation. S.B.B. provided human fat tissue derived from plastic surgeries that he had performed, together with M.D.J.; established a xenograft model of human fat growth in nude mice; and made major conceptual contribution to the clinical significance of the study for fat grafting and remodeling. M.D.J. contributed to all aspects dealing with human fat, and was instrumental in the adenoviral work by providing the vectors, measuring viral titers and training L.E.K. in experimental techniques. E.W.L. started the project and carried out experiments on genetically obese B6.V-Lep ob/J mice. M.S.B. carried out resistin analyses and contributed to discussions of stress effects on inflammation and metabolic syndrome. H.H. developed and provided the Npy −/− and _Npy2r_lox/lox mice for the study, trained J.U.T. in preparing adenoviral vectors, and contributed to discussion of the results. S.T.F. developed the MRI protocol for analyzing fat and contributed to discussion of the results. R.K. supervised catecholamine assays and contributed to analyses, interpretation and discussion of the data dealing with glucocorticoids and adrenergic system. Z.Z. developed the idea for and supervised the study, designed protocols, developed collaborations and wrote the manuscript.

Corresponding author

Correspondence toZofia Zukowska.

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Competing interests

Z.Z., L.E.K., S.B.B., M.D.J. and E.W.L. are listed as the inventors on the patent application “Compositions and Methods for Lipomodeling”, PCT/US2006/021873, filed 14 December 2006 by Georgetown University and based on the work described in this paper.

Supplementary information

Supplementary Fig. 1

Npy and Npy2r expression and actions in adipocytes and endothelial cells in vitro and in vivo. (PDF 428 kb)

Supplementary Fig. 2

Metabolic and neurohormonal effects of chronic stress, HFS and intra-fat Npy2r inhibition or deletion. (PDF 378 kb)

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Kuo, L., Kitlinska, J., Tilan, J. et al. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome.Nat Med 13, 803–811 (2007). https://doi.org/10.1038/nm1611

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