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Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity

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  • Daniel Kraus

    (Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    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.).)

  • Qin Yang

    (Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    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.).)

  • Dong Kong

    (Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Alexander S. Banks

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Lin Zhang

    (Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Joseph T. Rodgers

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Eija Pirinen

    (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
    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.).)

  • Thomas C. Pulinilkunnil

    (Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    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.).)

  • Fengying Gong

    (Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    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.).)

  • Ya-chin Wang

    (Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Yana Cen

    (Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA)

  • Anthony A. Sauve

    (Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA)

  • John M. Asara

    (Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, Massachusetts 02215, USA)

  • Odile D. Peroni

    (Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

  • Brett P. Monia

    (Isis Pharmaceuticals, 1896 Rutherford Road)

  • Sanjay Bhanot

    (Isis Pharmaceuticals, 1896 Rutherford Road)

  • Leena Alhonen

    (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
    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.).)

  • Pere Puigserver

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Barbara B. Kahn

    (Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA)

Abstract

Nicotinamide N-methyltransferase (NNMT) expression is increased in white adipose tissue and liver of obese and diabetic mice, Nnmt knockdown protects against diet-induced obesity by altering the availability of adipose S-adenosylmethionine and NAD+, rendering Nnmt a novel target for treating obesity and type 2 diabetes.

Suggested Citation

  • Daniel Kraus & Qin Yang & Dong Kong & Alexander S. Banks & Lin Zhang & Joseph T. Rodgers & Eija Pirinen & Thomas C. Pulinilkunnil & Fengying Gong & Ya-chin Wang & Yana Cen & Anthony A. Sauve & John M., 2014. "Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity," Nature, Nature, vol. 508(7495), pages 258-262, April.
    • Handle: RePEc:nat:nature:v:508:y:2014:i:7495:d:10.1038_nature13198
    DOI: 10.1038/nature13198
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    Cited by:

    1. Diego Sáenz de Urturi & Xabier Buqué & Begoña Porteiro & Cintia Folgueira & Alfonso Mora & Teresa C. Delgado & Endika Prieto-Fernández & Paula Olaizola & Beatriz Gómez-Santos & Maider Apodaka-Biguri &, 2022. "Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Rin Mizuno & Hiroaki Hojo & Masatomo Takahashi & Soshiro Kashio & Sora Enya & Motonao Nakao & Riyo Konishi & Mayuko Yoda & Ayano Harata & Junzo Hamanishi & Hiroshi Kawamoto & Masaki Mandai & Yutaka Su, 2022. "Remote solid cancers rewire hepatic nitrogen metabolism via host nicotinamide-N-methyltransferase," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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