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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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).”
BackgroundResultInfluential
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–254 of 254
Yano‐Nashimoto, S., Shinozuka, K., Kurachi, T., Kagawa, K., Sakamoto, K. Q., Shigeno, Y., Niimi, K., Kuroda, K. O., & Yamaguchi, S. (2026) · Scientific Reports · doi:10.1038/s41598-026-41314-8 · Cited by 1
Xu, H., Li, M., Liu, Y., Nie, G., Li, M., & Meng, Z. (2026) · Toxicon · doi:10.1016/j.toxicon.2026.109152 · Cited by 1
Alanazi, M., Al‐kuraishy, H. M., Mohamed, A. A., Abass, S. A., Shokr, M. M., Alruwaili, M., & Batiha, G. E. (2026) · Current Nutrition Reports · doi:10.1007/s13668-026-00773-1 · Cited by 1
Wang, Z., Wang, X., Zheng, W., Lu, W., Hao, L., Wang, X., Huang, C., Wang, R. L., Hu, Y., Wang, Z., et al. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158600 · Cited by 1
Peng, B., Zhao, W., Kong, M., Chen, Y., & Sun, C. (2026) · British Journal of Biomedical Science · doi:10.3389/bjbs.2026.16085 · Cited by 1
GDF15: A Novel Insight Into Its Biology and Therapeutic Potential in Obesity
Ahmed, K., Saturnino, A., & Pozzilli, P. (2026) · Journal of Diabetes Research · doi:10.1155/jdr/3024772 · Cited by 1
Hong, H. J., Lee, M. H., Park, M., Kim, J. T., Kim, J., Ju, S.-H., Lee, J. H., Sohn, J.-W., Shong, K. E., Setoyama, D., et al. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102939 · Cited by 1
Yang, C., Chen, L., Xiao, H., Wei, W., Liang, J., Chen, T., Yang, T., & Ma, Y. (2026) · Journal of Cellular Biochemistry · doi:10.1002/jcb.70113 · Cited by 1
Lu, Z., Cui, D., Liu, J. Y. H., Jiang, B., Ngan, M. P., Sakata, I., Takemi, S., Sakai, T., Lin, G., Chan, S. W., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.858522 · Cited by 1
Humans without GDF15 reassure drug developers
Breit, S. N., & O’Rahilly, S. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01136-2 · Cited by 1
Cancer and Disordered Eating Behavior: The Issue of Anorexia
Molfino, A., Amabile, M. I., Imbimbo, G., Giorgi, A., & Muscaritoli, M. (2021) · Springer eBooks · doi:10.1007/978-3-030-81174-7_19 · Cited by 1
Therapy-Induced Toxicities Associated with the Onset of Cachexia
Huot, J. R., Pin, F., & Bonetto, A. (2022) · Springer eBooks · doi:10.1007/978-3-031-09518-4_8 · Cited by 1
GDF15 in Vascular and Liver Metabolic Disorders: A Novel Therapeutic Target
Fiorucci, S., & Urbani, G. (2022) · Recent Advances in Inflammation & Allergy Drug Discovery · doi:10.2174/277227081602221221113442 · Cited by 2
Gut-brain Axis Regulation of Food Intake and Visceral Illness
Patel, A. R. (2021) · Deep Blue (University of Michigan) · doi:10.7302/1469 · Cited by 1
Lü, Y., Wang, R., Wu, Y., Cui, Q., Tian, X., Zhang, Z., Yi, H., Liu, T., Gong, P., & Zhang, L. (2022) · Research Square · doi:10.21203/rs.3.rs-2020767/v1 · Cited by 1
Morning sickness-like changes during pregnancy in non-human primates and rodentsPreprint
Yano‐Nashimoto, S., Shinozuka, K., Kurachi, T., Kagawa, K., Sakamoto, K. Q., Shigeno, Y., Niimi, K., Kuroda, K. O., & Yamaguchi, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.14.668061 · Cited by 1
Protection from vomiting and β-cell death
Wong, W. (2020) · Science Signaling · doi:10.1126/scisignal.abb4981
Genome-wide association and transcriptome analysis reveals serum ghrelin to be linked with GFRALPreprint
Wittekind, D. A., Scholz, M. R., Kratzsch, J., Löffler, M., Horn, K., Kirsten, H., Witte, A. V., Villringer, A., & Kluge, M. (2020) · arXiv (Cornell University) · doi:10.48550/arxiv.2009.11549
Lee, C. W., Kim, I., Koh, Y., Shin, D., Hong, J., Kim, D., Park, M.-R., Hong, S.-M., Lee, Y., & Seo, K. S. (2021) · Research Square · doi:10.21203/rs.3.rs-1065861/v1
Borner, T., Geisler, C. E., Fortin, S. M., Cosgrove, R., Alsina‐Fernandez, J., Dogra, M., Doebley, S. A., Sanchez-Navarro, M. J., Leon, R. M., Gaisinsky, J., et al. (2021) · doi:10.2337/figshare.15125112
Self-citationIdentifying and characterising blood biomarkers associated with migraine risk
Tanha, H. M. (2023) · Queensland University of Technology · doi:10.5204/thesis.eprints.238337
Central Control of Glucose Homeostasis
Alonge, K. M., Francis, K. L., Richardson, N. E., & Schwartz, M. W. (2024) · Wiley eBooks · doi:10.1002/9781119697473.ch10
Chang, C., Liu, F., Deng, S., Militi, S., Hester, S. S., Rendek, A., Soonawalla, Z. F., Huang, W. C., Fischer, R., & Pauklin, S. (2024) · Research Square · doi:10.21203/rs.3.rs-3994602/v1
GENETIC AND MATERNAL FACTORS IN HYPEREMESIS GRAVIDARUM: A SYSTEMATIC REVIEW
Zainuddin, N., Nisfu, F. R. M., Roslan, M., & Arifin, S. R. M. (2023) · Journal of Health and Translational Medicine · doi:10.22452/jummec.vol26no1.8
Dai, Y., Hu, W., Han, J., Zhao, Y., Wu, X., Liao, X., & Nie, K. (2024) · Journal of Holistic Integrative Pharmacy · doi:10.1016/j.jhip.2024.05.002
Research Progress of Correlation between GDF15 and Female Hyperemesis Gravidarum
冯, 志. (2024) · Advances in Clinical Medicine · doi:10.12677/acm.2024.1461943
Melanocortin-4 receptor antagonist TCMCB07 alleviates chemotherapy-induced anorexia and weight lossPreprint
Zhu, X., Potterfield, R., Gruber, K. A., Zhang, E. Q., Newton, S., Norgard, M. A., Levasseur, P. R., Bai, P., Chen, X., Gu, Q., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.14.613069
Regulation of food intake by Connexin43 via adipocyte-sensory neuron electrical synapses
Chen, X., Fang, X., Zhou, H., Meng, J., He, Y., Straub, L. G., Lemoff, A. S., Crewe, C., Zhao, S., Xu, Y., et al. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102247
Yun, D., Luo, Y., Li, R. P., Li, W., Wan, C., Huang, Q., Du, J., Zeng, S., & Wang, G. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1627353
Dyck, L. V., Gunst, J., Casaer, M. P., Peeters, B., Derese, I., Wouters, P. J., de Zegher, F., Vanhorebeek, I., & Van den Berghe, G. (2020) · Figshare · doi:10.6084/m9.figshare.12955871
Dyck, L. V., Gunst, J., Casaer, M. P., Peeters, B., Derese, I., Wouters, P. J., de Zegher, F., Vanhorebeek, I., & Van den Berghe, G. (2020) · Figshare · doi:10.6084/m9.figshare.12955868
Liu, X., & Fan, F. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.29.702667
Bannitz, R. F., Pei, L., Wang, H., OZTURK, B., Querol, P. C., da Cruz, A. G., Cook, T. M., Saeed, H., Osterwalder, L., Poulos, L., et al. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102656
Sekine, S., Konishi, R., & Koyama, S. (2026) · Acupuncture & Electro-Therapeutics Research · doi:10.1177/03601293261430926
Fujii, R., Kawai, H., Kai, M., & Kondo, M. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.153812 · Cited by 1
Context-Specific Hypermetabolism In Humans With Mitochondrial Energy Transformation DefectsPreprint
Shaulson, E. D., Sercel, A. J., Rausser, S., Leonard, S. J., Whyte, K., Zuraikat, F. M., Seid, H., Huang, Q., Junker, A., Kapri, D., et al. (2026) · medRxiv · doi:10.64898/2026.05.30.26354528
Self-citationMorusin targeting GDF15 enhances ferroptosis and overcomes cisplatin resistance in NSCLC
Zhang, L., Liu, H., Jiang, S., Li, D. D., Li, X., Xu, M., Fei, J., & Zhou, L. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1803939
Functional segregation of body-brain signals in the area postremaPreprint
López-Cruz, A., Burgos, N. S. F., Hakimi, A. M., Xie, K., Mao, M., Kaur, M., Spina, A., Choi, K., Qiu, L., Lever, T. E., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.15.732473 · Cited by 1
Peptide hormone-based combinational pharmacotherapies for chronic metabolic diseases
Chui, Z. S. W., Xue, Y., Wu, X., & Xu, A. (2026) · Pharmacological Reviews · doi:10.1016/j.pharmr.2026.100150
GDF15: A Hijacked Metabo-Hormone Orchestrating Cachexia and Immunosuppression in Cancer
Qi, D.-Y., Wang, Y., & Jin, W. (2026) · Biomolecules · doi:10.3390/biom16071070
Yin, R., Sun, R., Gong, B., Shan, Z., & Zhao, D. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1854594
The nervous system as a systemic organizer of cancer-associated cachexia
Weng, Z., Cai, S., Zhu, H., Jiang, L., Zhang, S., Zhang, Z.-G., & Jiang, S. (2026) · Trends in Neurosciences · doi:10.1016/j.tins.2026.08.002
Li, B., Zhuang, X., Zhao, Y., Wang, J., Si, W., Lin, Y., Huang, X., Shao, K., & Ji, K. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2026.168463
Bonaventura, I., Weigand, I., Isidori, A. M., Kroiß, M., & Reincke, M. (2026) · Endocrine Reviews · doi:10.1210/endrev/bnag035
The causes of cachexia: key signals and the brain
Daly, A., Yin, S. L., & Coll, A. P. (2026) · Nature Reviews Endocrinology · doi:10.1038/s41574-026-01302-4
Aberrant microglial responses shape hypothalamic circuits in anorexia nervosaPreprint
Xu, J., Erskine, E., Eramo, B., Zimmer, K., Camoglio, C., Chaudhary, M., Feng, T., Orhan, F., Welch, E., Selander, L., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.18.748216
From stress cytokine to drug target: The translational landscape of growth differentiation factor 15
Najjar, N. R., Jonghe, B. C. D., Hayes, M. R., & Doyle, R. P. (2026) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2026.105036
Self-citationSanchez-Navarro, M. J., Zhang, C., Fortin, S. M., & Hayes, M. R. (2026) · Diabetes Obesity and Metabolism · doi:10.1111/dom.71415
Self-citationContext-specific hypermetabolism in humans with mitochondrial defects
Shaulson, E. D., Sercel, A. J., Rausser, S., Leonard, S., Whyte, K., Zuraikat, F. M., Seid, H., Huang, Q., Junker, A., Kapri, D., et al. (2026) · Cell Press Blue · doi:10.1016/j.cpblue.2026.100129
Self-citationPînzariu, A. C., Șerban, I. L., Soroceanu, R. P., Vlăsceanu, V. I., Maxim, M., Miler, A. A., Leonte, S. M., Atodiresei, C., Moscalu, M., Manole, L. M., et al. (2026) · Cells · doi:10.3390/cells15191823
Association of Serum GDF-15 with Bone and Muscle Parameters in Community-Dwelling Individuals
Profili, N. I., Makrogiannis, S. K., Castelli, R., Benelli, M., Orrù, V., Marongiu, M., Fiorillo, E., Cucca, F., & Delitala, A. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1920342
Integrating computational and experimental approaches to identify antigen–specific antibodies
Abbate, M. F., Pereira, P., Toxe, P., Maestrali, N., Gagnaire, M., Vigne, E., Shahsavarian, M. A., Mora, T., & Walczak, A. M. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1951538
Biological functions and emerging interplay of FGF21 and GDF15 in metabolic diseases and aging
Salmón‐Gómez, L., Keipert, S., Catalán, V., Rodrı́guez, A., Becerril, S., Frühbeck, G., & Gómez‐Ambrosi, J. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00627-w
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
