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 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…

• UD
  U.S. Department of Agriculture

  Award: 2010-34323-21052
• A
  AstraZeneca
• W
  Wellcome

  Awards: 100140, 106262/Z/14/Z, 107064, 098497/Z/12/Z, 106263/Z/14/Z, 095515/Z/11/Z, 100574/Z/12/Z
• WT
  Wellcome Trust

  Awards: MRC_MC_UU_12012/5, 100574/Z/12/Z, 100140, WT 095515/Z/11/Z, Wellcome 200848/Z/16/Z, 106263/Z/14/Z, 106262/Z/14/Z, WT 107064, MRC_MC_UU_12012/3
• NI
  National Institute for Health and Care Research

  Awards: 200848/Z/16/Z, 100574/Z/12/Z, MRC_MC_UU_12012/3
• BH
  British Heart Foundation

  Award: RG/12/13/29853
• DU
  Diabetes UK

  Award: 17/0005712
• EF
  European Foundation for the Study of Diabetes
• ET
  Evelyn Trust

  Award: 16-69
• M
  MedImmune
• MR
  Medical Research Council

  Awards: MRC_MC_UU_12012/3, MC_UU_00014/2, MC_UU_00014/3, MC_UU_00014/5, MC_UU_00014/1, MC_UU_12012/2, MRC_MC_UU_12012.1, MRC_MC_UU_12012/5
• CI
  Cambridge Institute for Medical Research, University of Cambridge

  Award: 100140
• NC
  NIHR Cambridge Biomedical Research Centre

  Award: 100574/Z/12/Z
• HE
  H2020 European Research Council