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

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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., De Jonghe, Bart C.·2020·Cell Metabolism

DOI 10.1016/j.cmet.2019.12.004PMC PMC7161938

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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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“Since this cluster of findings, numerous reports and reviews have demonstrated promise for GDF15-GFRAL signaling in obesity treatment (Frikke-Schmidt et al., 2019; Patel et al., 2019; Tsai et al., 2018).”
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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)
ORCID: Borner, Tito
Shaulson, Evan D.
Horn, Charles C.
Doyle, Robert P.
Grill, Harvey J.
Hayes, Matthew R.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2020-02
Volume: 31
Issue: 2
Pages: 351-362.e5
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2019.12.004
PMC: PMC7161938
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: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Schweizerischer Nationalfonds zur FÃ¶rderung 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 › Cardiology and Cardiovascular Medicine › 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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GDF15 Induces Anorexia through Nausea and Emesis

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