GDF15 Induces Anorexia through Nausea and Emesis

Cell Metab. 2020 Feb 4;31(2):351-362.e5. doi: 10.1016/j.cmet.2019.12.004. Epub 2020 Jan 9.


Growth differentiation factor 15 (GDF15) is a cytokine that reduces food intake through activation of hindbrain GFRAL-RET receptors and has become a keen target of interest for anti-obesity therapies. Elevated endogenous GDF15 is associated with energy balance disturbances, cancer progression, chemotherapy-induced anorexia, and morning sickness. We hypothesized that GDF15 causes emesis and that its anorectic effects are related to this function. Here, we examined feeding and emesis and/or emetic-like behaviors in three different mammalian laboratory species to help elucidate the role of GDF15 in these behaviors. Data show that GDF15 causes emesis in Suncus murinus (musk shrews) and induces behaviors indicative of nausea/malaise (e.g., anorexia and pica) in non-emetic species, including mice and lean or obese rats. We also present data in mice suggesting that GDF15 contributes to chemotherapy-induced malaise. Together, these results indicate that GDF15 triggers anorexia through the induction of nausea and/or by engaging emetic neurocircuitry.

Keywords: GDF15; GFRAL; MIC-1; Suncus murinus; anorexia; chemotherapy; emesis; malaise; nausea; obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia / chemically induced*
  • Body Weight / drug effects*
  • Female
  • Growth Differentiation Factor 15* / administration & dosage
  • Growth Differentiation Factor 15* / adverse effects
  • Humans
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / adverse effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nausea / chemically induced*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Shrews
  • Vomiting / chemically induced*


  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Hypoglycemic Agents
  • Recombinant Proteins