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GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans
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 t...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408327/ https://www.ncbi.nlm.nih.gov/pubmed/30639358 http://dx.doi.org/10.1016/j.cmet.2018.12.016 |
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author | Patel, Satish Alvarez-Guaita, Anna Melvin, Audrey Rimmington, Debra Dattilo, Alessia Miedzybrodzka, Emily L. Cimino, Irene Maurin, Anne-Catherine Roberts, Geoffrey P. Meek, Claire L. Virtue, Samuel Sparks, Lauren M. Parsons, Stephanie A. Redman, Leanne M. Bray, George A. Liou, Alice P. Woods, Rachel M. Parry, Sion A. Jeppesen, Per B. Kolnes, Anders J. Harding, Heather P. Ron, David Vidal-Puig, Antonio Reimann, Frank Gribble, Fiona M. Hulston, Carl J. Farooqi, I. Sadaf Fafournoux, Pierre Smith, Steven R. Jensen, Jorgen Breen, Danna Wu, Zhidan Zhang, Bei B. Coll, Anthony P. Savage, David B. O’Rahilly, Stephen |
author_facet | Patel, Satish Alvarez-Guaita, Anna Melvin, Audrey Rimmington, Debra Dattilo, Alessia Miedzybrodzka, Emily L. Cimino, Irene Maurin, Anne-Catherine Roberts, Geoffrey P. Meek, Claire L. Virtue, Samuel Sparks, Lauren M. Parsons, Stephanie A. Redman, Leanne M. Bray, George A. Liou, Alice P. Woods, Rachel M. Parry, Sion A. Jeppesen, Per B. Kolnes, Anders J. Harding, Heather P. Ron, David Vidal-Puig, Antonio Reimann, Frank Gribble, Fiona M. Hulston, Carl J. Farooqi, I. Sadaf Fafournoux, Pierre Smith, Steven R. Jensen, Jorgen Breen, Danna Wu, Zhidan Zhang, Bei B. Coll, Anthony P. Savage, David B. O’Rahilly, Stephen |
author_sort | Patel, Satish |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6408327 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64083272019-03-21 GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans Patel, Satish Alvarez-Guaita, Anna Melvin, Audrey Rimmington, Debra Dattilo, Alessia Miedzybrodzka, Emily L. Cimino, Irene Maurin, Anne-Catherine Roberts, Geoffrey P. Meek, Claire L. Virtue, Samuel Sparks, Lauren M. Parsons, Stephanie A. Redman, Leanne M. Bray, George A. Liou, Alice P. Woods, Rachel M. Parry, Sion A. Jeppesen, Per B. Kolnes, Anders J. Harding, Heather P. Ron, David Vidal-Puig, Antonio Reimann, Frank Gribble, Fiona M. Hulston, Carl J. Farooqi, I. Sadaf Fafournoux, Pierre Smith, Steven R. Jensen, Jorgen Breen, Danna Wu, Zhidan Zhang, Bei B. Coll, Anthony P. Savage, David B. O’Rahilly, Stephen Cell Metab Article 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. Cell Press 2019-03-05 /pmc/articles/PMC6408327/ /pubmed/30639358 http://dx.doi.org/10.1016/j.cmet.2018.12.016 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Patel, Satish Alvarez-Guaita, Anna Melvin, Audrey Rimmington, Debra Dattilo, Alessia Miedzybrodzka, Emily L. Cimino, Irene Maurin, Anne-Catherine Roberts, Geoffrey P. Meek, Claire L. Virtue, Samuel Sparks, Lauren M. Parsons, Stephanie A. Redman, Leanne M. Bray, George A. Liou, Alice P. Woods, Rachel M. Parry, Sion A. Jeppesen, Per B. Kolnes, Anders J. Harding, Heather P. Ron, David Vidal-Puig, Antonio Reimann, Frank Gribble, Fiona M. Hulston, Carl J. Farooqi, I. Sadaf Fafournoux, Pierre Smith, Steven R. Jensen, Jorgen Breen, Danna Wu, Zhidan Zhang, Bei B. Coll, Anthony P. Savage, David B. O’Rahilly, Stephen GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans |
title | GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans |
title_full | GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans |
title_fullStr | GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans |
title_full_unstemmed | GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans |
title_short | GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans |
title_sort | gdf15 provides an endocrine signal of nutritional stress in mice and humans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408327/ https://www.ncbi.nlm.nih.gov/pubmed/30639358 http://dx.doi.org/10.1016/j.cmet.2018.12.016 |
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