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GDF15 Induces Anorexia through Nausea and Emesis
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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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“A recent study found that GDF15 induced anorexia through nausea and emesis in mice and musk shrews, respectively [216].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [216]
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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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Assessment and Management of Appetite Loss in Older Adults: An ICFSR Task Force Report
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Fc-GDF15 glyco-engineering and receptor binding affinity optimization for body weight regulation
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Single nuclei RNA sequencing of the rat AP and NTS following GDF15 treatment
Reiner, B. C., Crist, R. C., Borner, T., Doyle, R. P., Hayes, M. R., & Jonghe, B. C. D. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101422 · Cited by 26
Self-citationAlbuquerque, B., Chen, X., Hirenallur-Shanthappa, D. K., Zhao, Y. W., Stansfield, J. C., Zhang, B. B., Sheikh, A. Q., & Wu, Z. (2022) · Cells · doi:10.3390/cells11071073 · Cited by 24
The clinical potential of GDF15 as a “ready-to-feed indicator” for critically ill adults
Dyck, L. V., Gunst, J., Casaer, M. P., Peeters, B., Derese, I., Wouters, P. J., de Zegher, F., Vanhorebeek, I., & den Berghe, G. V. (2020) · Critical Care · doi:10.1186/s13054-020-03254-1 · Cited by 24
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Self-citationBrainstem BDNF neurons are downstream of GFRAL/GLP1R signalling
Feetham, C. H., Collabolletta, V., Worth, A. A., Shoop, R., Groom, S., Harding, C., Boutagouga Boudjadja, M., Coskun, T., Emmerson, P. J., D’Agostino, G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54367-y · Cited by 22
Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behavior
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Salimando, G. J., Tremblay, S., Kimmey, B. A., Li, J., Rogers, S. A., Wojick, J. A., McCall, N. M., Wooldridge, L. M., Rodrigues, A., Borner, T., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41407-2 · Cited by 19
Self-citationHe, L., Barreto, P. D. S., Sánchez‐Sánchez, J. L., Rolland, Y., Guyonnet, S., Parini, A., Lucas, A., Vellas, B. J., MAPT/DSA Group, Vellas, B. J., et al. (2022) · The Journals of Gerontology Series A · doi:10.1093/gerona/glac020 · Cited by 24
Cross-species comparison of pregnancy-induced GDF15
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Central mechanisms of emesis: A role for GDF15
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Self-citationTargeting the GDF15 Signalling for Obesity Treatment: Recent Advances and Emerging Challenges
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Mechanisms and pharmacotherapy of cancer cachexia‐associated anorexia
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Metabolic Messenger: growth differentiation factor 15
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Beneficial Effects of Low-Grade Mitochondrial Stress on Metabolic Diseases and Aging
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Neural pathways of nausea and roles in energy balance
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Tumor-immune-neural circuit disrupts energy homeostasis in cancer cachexia
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The development and benefits of metformin in various diseases
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Borner, T., Tinsley, I. C., Milliken, B. T., Doebley, S. A., Najjar, N. R., Kerwood, D. J., Jonghe, B. C. D., Hayes, M. R., & Doyle, R. P. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00667 · Cited by 18
Self-citationFood allergy: begin at the skin, end at the mast cell?
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Boccia, L., Borner, T., Ghidewon, M. Y., Kulka, P., Piffaretti, C., Doebley, S. A., Jonghe, B. C. D., Grill, H. J., Lutz, T. A., & Foll, C. L. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101444 · Cited by 18
Self-citation
Metadata
- 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)
- 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
- 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 › 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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