Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity (original) (raw)

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Gene Expression Omnibus

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The microarray data from adipose tissue of adipose-specific knockout and adipose-specific overexpression have been published by our laboratory and are available in NCBI Gene Expression Omnibus under accession number GSE35378.

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Acknowledgements

We thank R. Weinshilboum for NNMT antibody; P. Woster for DFMO; M. Yuan for tandem mass spectrometry; A. Karppinen, A. Korhonen, T. Reponen, A. Uimari, S. Pirnes-Karhu and T. Koponen for measurements of ODC and SSAT activity; C. Semenkovich and S. Fried for protocols for FAS activity measurements; and P. Aryal for assistance with real-time qPCR. D.Kr. is supported by the Deutsche Forschungsgemeinschaft (KR 3475/1-1) and American Heart Association (AHA) (09POST2250499); Q.Y. is a Klarman Scholar at the Beth Israel Deaconess Medical Center. This work is supported by grants from the NIH (R37 DK43051, P30 DK57521) and a grant from the JPB foundation to B.B.K.; grants from the NIH (KO8 DK090149, R01 DK100385, BNORC P30 DK046200 and NORCH P30 DK040561) to Q.Y.; grant RO1 DK69966 to P.P.; P01CA120964 and P30CA006516-46 to J.M.A.; AHA 13SDG14620005 and P&F P30 DK0460200 to D.K.; the Ellison Medical Foundation New Scholar in Aging Award to A.A.S.; and academy of Finland grant 118590 to L.A.

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Author notes

  1. Daniel Kraus, Qin Yang, Eija Pirinen, Thomas C. Pulinilkunnil, Fengying Gong & Leena Alhonen
    Present address: Present addresses: Division of Nephrology, Department of Internal Medicine I, Würzburg University Hospital, Oberdürrbacher Straße 6, 97080 Würzburg, Germany (D.K.); Department of Medicine, Physiology and Biophysics, Center for Diabetes Research and Treatment, and Center for Epigenetics and Metabolism, University of California, Irvine, California 92697, USA (Q.Y.); Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290, Helsinki, Finland (E.P.); Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie Medicine New Brunswick, Dalhousie University, Saint John, New Brunswick E2L4L5, USA (T.C.P.); Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China (F.G.); School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland (L.A.).,
  2. Daniel Kraus and Qin Yang: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA,
    Daniel Kraus, Qin Yang, Dong Kong, Lin Zhang, Thomas C. Pulinilkunnil, Fengying Gong, Ya-chin Wang, Odile D. Peroni & Barbara B. Kahn
  2. Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Alexander S. Banks, Joseph T. Rodgers & Pere Puigserver
  3. Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio Campus, PO Box 1627, FI-70211 Kuopio, Finland,
    Eija Pirinen & Leena Alhonen
  4. Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA,
    Yana Cen & Anthony A. Sauve
  5. Division of Signal Transduction, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, Massachusetts 02215, USA,
    John M. Asara
  6. Isis Pharmaceuticals, 1896 Rutherford Road, Carlsbad, 92008-7326, California, USA
    Brett P. Monia & Sanjay Bhanot

Authors

  1. Daniel Kraus
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  2. Qin Yang
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  3. Dong Kong
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  4. Alexander S. Banks
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  5. Lin Zhang
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  6. Joseph T. Rodgers
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  7. Eija Pirinen
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  8. Thomas C. Pulinilkunnil
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  9. Fengying Gong
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  10. Ya-chin Wang
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  11. Yana Cen
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  12. Anthony A. Sauve
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  13. John M. Asara
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  14. Odile D. Peroni
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  15. Brett P. Monia
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  16. Sanjay Bhanot
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  17. Leena Alhonen
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  18. Pere Puigserver
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  19. Barbara B. Kahn
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Contributions

Q.Y. discovered NNMT from the initial microarray analysis. D.Kr., Q.Y. and B.B.K designed the experiments, interpreted the data and wrote the paper. D.Ko. performed oxygen consumption experiments in adipocytes. A.S.B. performed CLAMS studies. L.Z., T.C.P., F.G., YC.W. and O.D.P. provided assistance with cell culture and animal experiments. O.D.P. also performed the microarray studies. J.T.R. and P.P. performed PGC-1α acetylation experiments. E.P. and L.A. provided expertise on polyamines and measured ODC and SSAT activity. Y.C. and A.A.S. measured nicotinamide and metabolites. J.M.A. performed metabolomics studies. B.P.M and S.B. provided Nnmt and control ASOs.

Corresponding authors

Correspondence toQin Yang or Barbara B. Kahn.

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Competing interests

B.B.K., Q.Y. and D. Kr. are inventors on a patent application related to NNMT. B.P.M. and S.B. are employees of Isis Pharmaceuticals Inc.

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Kraus, D., Yang, Q., Kong, D. et al. Nicotinamide _N_-methyltransferase knockdown protects against diet-induced obesity.Nature 508, 258–262 (2014). https://doi.org/10.1038/nature13198

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