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Title: GDF15 provides an endocrine signal of nutritional stress in mice and humans
Authors: 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
Keywords: GDF15
GFRAL
Integrated stress response
Overnutrion
Conditioned taste aversion
Issue Date: 2018
Publisher: Elsevier © The authors
Citation: PATEL, S. ... et al, 2018. GDF15 provides an endocrine signal of nutritional stress in mice and humans. Cell Metabolism, 29, pp.1-12.
Abstract: 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.
Description: This is an Open Access Article. It is published by Elsevier under the Creative Commons Attribution 4.0 International Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/
Sponsor: HS6 is supported in part by a grant from the US Department of Agriculture: 2010-34323-21052. Mouse Studies 1, 2, and 3 are supported by The Disease Model Core, part of the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/5), and Wellcome Trust Strategic Award (100574/Z/12/Z). D.B.S. and S.O.R. are supported by the Wellcome Trust (WT 107064 and WT 095515/Z/11/Z), the MRC Metabolic Disease Unit (MRC_MC_UU_12012.1), and The National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and NIHR Rare Disease Translational Research Collaboration. A.P.C., D. Rimmington, and I.C. are supported by the Medical Research Council (MRC Metabolic Diseases Unit [MRC_MC_UU_12012.1]). D. Ron is supported by a Wellcome Trust Principal Research Fellowship (Wellcome 200848/Z/16/Z) and a Wellcome Trust Strategic Award to the Cambridge Institute for Medical Research (Wellcome 100140). A.V.-P. and S.V. are supported by the BHF (RG/12/13/29853) and MRC (MC_UU_12012/2). I.S.F. was supported by the Wellcome Trust (098497/Z/12/Z), European Research Council, NIHR Cambridge Biomedical Research Centre, and Bernard Wolfe Health Neuroscience Endowment. A.M. is supported by a studentship from the Experimental Medicine Training Initiative/AstraZeneca. G.P.R. was supported by an Addenbrooke’s Charitable Trust/Evelyn Trust Cambridge Clinical Research Fellowship (16-69), an EFSD project grant, and a Royal College of Surgeons Research Fellowship. C.L.M. is supported by the Diabetes UK Harry Keen intermediate clinical fellowship (17/0005712). F.M.G. and F.R. are supported by the MRC (MRC_MC_UU_12012/3), Wellcome Trust (106262/Z/14/Z and 106263/Z/14/Z), and research grants from Medimmune.
Version: Published
DOI: 10.1016/j.cmet.2018.12.016
URI: https://dspace.lboro.ac.uk/2134/36744
Publisher Link: https://doi.org/10.1016/j.cmet.2018.12.016
ISSN: 1550-4131
Appears in Collections:Published Articles (Sport, Exercise and Health Sciences)

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