Dataset Information

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

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.

SUBMITTER: Patel S

PROVIDER: S-EPMC6408327 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Patel Satish S Alvarez-Guaita Anna A Melvin Audrey A Rimmington Debra D Dattilo Alessia A Miedzybrodzka Emily L EL Cimino Irene I Maurin Anne-Catherine AC Roberts Geoffrey P GP Meek Claire L CL Virtue Samuel S Sparks Lauren M LM Parsons Stephanie A SA Redman Leanne M LM Bray George A GA Liou Alice P AP Woods Rachel M RM Parry Sion A SA Jeppesen Per B PB Kolnes Anders J AJ Harding Heather P HP Ron David D Vidal-Puig Antonio A Reimann Frank F Gribble Fiona M FM Hulston Carl J CJ Farooqi I Sadaf IS Fafournoux Pierre P Smith Steven R SR Jensen Jorgen J Breen Danna D Wu Zhidan Z Zhang Bei B BB Coll Anthony P AP Savage David B DB O'Rahilly Stephen S

Cell metabolism 20190110 3

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, ...[more]

PMID: 30639358

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Dataset Information

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

Publications

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

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