GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Satish Patel, Wellcome Trust-MRC Stem Cell Institute
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  • Anna Alvarez-Guaita, Wellcome Trust-MRC Stem Cell Institute
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  • Audrey Melvin, Wellcome Trust-MRC Stem Cell Institute
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  • Debra Rimmington, Wellcome Trust-MRC Stem Cell Institute
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  • Alessia Dattilo, Wellcome Trust-MRC Stem Cell Institute
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  • Emily L. Miedzybrodzka, Wellcome Trust-MRC Stem Cell Institute
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  • Irene Cimino, Wellcome Trust-MRC Stem Cell Institute
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  • Anne Catherine Maurin, Université Clermont Auvergne
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  • Geoffrey P. Roberts, Wellcome Trust-MRC Stem Cell Institute
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  • Claire L. Meek, Wellcome Trust-MRC Stem Cell Institute
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  • Samuel Virtue, Wellcome Trust-MRC Stem Cell Institute
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  • Lauren M. Sparks, Florida Hospital
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  • Stephanie A. Parsons, Florida Hospital
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  • Leanne M. Redman, Pennington Biomedical Research Center
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  • George A. Bray, Pennington Biomedical Research Center
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  • Alice P. Liou, Pfizer Inc.
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  • Rachel M. Woods, Loughborough University
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  • Sion A. Parry, Loughborough University
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  • Per B. Jeppesen
  • Anders J. Kolnes, Oslo University Hospital-Rikshospitalet
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  • Heather P. Harding, Wellcome Trust-MRC Stem Cell Institute, 1] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
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  • David Ron, Wellcome Trust-MRC Stem Cell Institute, 1] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
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  • Antonio Vidal-Puig, Wellcome Trust-MRC Stem Cell Institute
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  • Frank Reimann, Wellcome Trust-MRC Stem Cell Institute
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  • Fiona M. Gribble, Wellcome Trust-MRC Stem Cell Institute
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  • Carl J. Hulston, Loughborough University
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  • I. Sadaf Farooqi, Wellcome Trust-MRC Stem Cell Institute
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  • Pierre Fafournoux, Université Clermont Auvergne
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  • Steven R. Smith, Florida Hospital
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  • Jorgen Jensen, Department of Physical Performance, Norwegian School of Sport Sciences
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  • Danna Breen, Pfizer Inc.
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  • Zhidan Wu, Pfizer Inc.
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  • Bei B. Zhang, Pfizer Inc.
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  • Anthony P. Coll, Wellcome Trust-MRC Stem Cell Institute
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  • David B. Savage, Wellcome Trust-MRC Stem Cell Institute
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  • Stephen O'Rahilly, Wellcome Trust-MRC Stem Cell Institute

GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress.

Original languageEnglish
JournalCell Metabolism
Volume29
Issue3
Pages (from-to)707-718.e8
ISSN1550-4131
DOIs
Publication statusPublished - 2019

    Research areas

  • conditioned taste aversion, GDF15, GFRAL, integrated stress response, overnutrion

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