Cited by 255Regulation of Appetite and ObesityGDF15 and Related BiomarkersNausea and vomiting management

GDF15 induces anorexia through nausea and emesis

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Borner, Tito, Shaulson, Evan D., Ghidewon, Misgana Y., Barnett, Amanda B., Horn, Charles C., Doyle, Robert P., Grill, Harvey J., Hayes, Matthew R. +1 more·2020·Cell Metabolism

Abstract

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.

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Authors
Borner, T., Shaulson, E. D., Ghidewon, M. Y., Barnett, A. B., Horn, C. C., Doyle, R. P., Grill, H. J., Hayes, M. R., & De Jonghe, B. C.
Affiliations
  • University of Pennsylvania (US)
  • University of Pittsburgh (US)
  • SUNY Upstate Medical University (US)
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2020-02
Volume
31
Issue
2
Pages
351-362.e5
ISSN
1550-4131 (ISSN-L)
OpenAlex
W3000046815
Cited by
255
References
64
Citations by year
2026: 37 · 2025: 42 · 2024: 47 · 2023: 28 · 2022: 41 · 2021: 35 · 2020: 25
FWCI
16.56
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (P2ZHP3_178114, P400PB_186728)
  • National Institutes of Health (DK-112812, DK-115762, CA-201962, DK-021397)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
  • Health Sciences › Medicine › Surgery › Nausea and vomiting management
Keywords
GDF15, growth differentiation factor 15, anorexia, nausea, vomiting, pica, obesity treatment, feeding behavior, Suncus murinus, mice, rats
MeSH terms
Animals, Anorexia, Body Weight, Female, Humans, Hypoglycemic Agents, Male, Mice, Inbred C57BL, Nausea, Recombinant Proteins, Shrews, Vomiting, Rats, Sprague-Dawley, Mice, Rats, Growth Differentiation Factor 15

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