The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
GDF15 Induces Anorexia through Nausea and Emesis
Open accessAbstract
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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Cites
Cisplatin in cancer therapy: Molecular mechanisms of action
Dasari, S., & Bernard Tchounwou, P. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.07.025 · Cited by 5,537
Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update
Basch, E., Prestrud, A. A., Hesketh, P. J., Kris, M. G., Feyer, P., Somerfield, M. R., Chesney, M., Clark-Snow, R. A., Flaherty, A. M. C., Freundlich, B., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.34.4614 · Cited by 1,058
Conditioned Aversion to Saccharin Resulting from Exposure to Gamma Radiation
García, J., Kimeldorf, D. J., & Koelling, R. A. (1955) · Science · doi:10.1126/science.122.3160.157 · Cited by 1,011
Chemotherapy-Induced Nausea and Vomiting
Hesketh, P. J. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0706547 · Cited by 833
GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates
Mullican, S. E., Lin-Schmidt, X., Chin, C.-N., Chavez, J. A., Furman, J. L., Armstrong, A. A., Beck, S. C., South, V. J., Dinh, T. Q., Cash-Mason, T. D., et al. (2017) · Nature Medicine · doi:10.1038/nm.4392 · Cited by 774
The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL
Emmerson, P. J., Wang, F., Du, Y., Liu, Q., Pickard, R. T., Gonciarz, M. D., Coskun, T., Hamang, M. J., Sindelar, D. K., Ballman, K. K., et al. (2017) · Nature Medicine · doi:10.1038/nm.4393 · Cited by 675
GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand
Yang, L., Chang, C.-C., Sun, Z., Madsen, D., Zhu, H., Padkjær, S. B., Wu, X., Huang, T., Hultman, K., Paulsen, S. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4394 · Cited by 668
Non-Homeostatic Body Weight Regulation Through a Brainstem-Restricted Receptor for GDF15
Hsu, J.-Y., Crawley, S., Chen, M., Ayupova, D. A., Lindhout, D. A., Higbee, J., Kutach, A., Joo, W., Gao, Z., Fu, D., et al. (2017) · Nature · doi:10.1038/nature24042 · Cited by 616
Tumor-induced anorexia and weight loss are mediated by the TGF-β superfamily cytokine MIC-1
Johnen, H., Lin, S., Kuffner, T., Brown, D. A., Tsai, V. W.-W., Bauskin, A. R., Wu, L., Pankhurst, G., Jiang, L., Junankar, S., et al. (2007) · Nature Medicine · doi:10.1038/nm1677 · Cited by 612
GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans
Patel, S., Alvarez-Guaita, A., Melvin, A., Rimmington, D., Dattilo, A., Miedzybrodzka, E. L., Cimino, I., Maurin, A.-C., Roberts, G. P., Meek, C. L., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.12.016 · Cited by 509 · cited 6×
“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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GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease
Wang, D., Day, E. A., Townsend, L. K., Djordjevic, D., Jørgensen, S. B., & Steinberg, G. R. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00529-7 · Cited by 543
Area postrema cell types that mediate nausea-associated behaviors
Zhang, C., Kaye, J. A., Cai, Z., Wang, Y., Prescott, S. L., & Liberles, S. D. (2021) · Neuron · doi:10.1016/j.neuron.2020.11.010 · Cited by 263
Zhong, W., Shahbaz, O., Teskey, G., Beever, A., Kachour, N., Venketaraman, V., & Darmani, N. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115797 · Cited by 291
GDF15: a hormone conveying somatic distress to the brain
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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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