Uniting GDF15 and GFRAL: Therapeutic Opportunities in Obesity and Beyond
Abstract
Growth differentiation factor-15 (GDF15) is a circulating protein that has been implicated in multiple biological processes, including energy homeostasis, body weight regulation, and cachexia driven by cancer and chronic disease. The potential to target GDF15 in the treatment of energy-intake disorders, including obesity and anorexia, is an area of intense investigation, but has been limited by the lack of an identified receptor, signaling mechanism, and target tissue. GDNF family receptor α-like (GFRAL) was recently identified as the neuronal brainstem receptor responsible for mediating the anorectic actions of GDF15. Herein, we provide a brief overview of GDF15 biology with a focus on energy homeostasis, and highlight the implications of the recent receptor identification to this field and beyond.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Activation of GFRAL in the brain leads to activation of a neuronal network involving the nucleus of the solitary tract, the hypothalamus, and the central amygdala, reducing food intake and appetite.
“In the brain, activation of the GFRAL receptor leads to a complex activation of a neuronal network involving the nucleus of the solitary tract, the hypothalamus, and the central amygdala, reducing food intake and appetite ( Figure 1 ) (96).”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [96]
GDF15 binds with high affinity to GFRAL and its co-receptor RET, inducing phosphorylation of RET and downstream signaling through AKT, ERK1/2, and PLCγ pathways.
“GDF15 binds with high affinity to GFRAL and its co-receptor RET, which induces phosphorylation of RET, leading to downstream signaling through the AKT, ERK1/2, and phospholipase C (PLCγ) pathways [201,213,215].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [201]
GFRAL is exclusively expressed in the human brainstem and is responsible for the metabolic effects of GDF15 on regulating appetite.
“GFRAL is exclusively expressed in the human brainstem and is responsible for the metabolic effects of GDF15 on regulating appetite [201,215].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [201]
Administration of GDF15 to wild-type mice produced responses similar to transgenic mice, but these mice exhibited consistent reduction in food intake.
“Conversely, administration of GDF15 to wild-type mice produced responses similar to those in transgenic mice; however, these mice exhibited consistent reduction in food intake [201,213].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [201]
GDF15 is associated with numerous biological processes and diseases including cancer, cardiovascular disease, and obesity.
“Growth differentiation factor 15 (GDF15), also called macrophage inhibitory cytokine-1, is associated with numerous biological processes and diseases including cancer, cardiovascular disease, and obesity [[199], [200], [201], [202]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [201]
Cites
Definition and classification of cancer cachexia: an international consensus
Fearon, K., Strasser, F., Anker, S. D., Bosaeus, I. G., Bruera, E. D., Fainsinger, R. L., Jatoi, A., Loprinzi, C. L., Macdonald, N., Mantovani, G., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70218-7 · Cited by 5,800 · see citing works
Cancer Cachexia: Mediators, Signaling, and Metabolic Pathways
Fearon, K. C. H., Glass, D. J., & D, D. C. G. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.011 · Cited by 1,203 · see citing works
MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily
Bootcov, M. R., Bauskin, A. R., Valenzuela, S. M., Moore, A. G., Bansal, M., He, X. Y., Zhang, H. P., Donnellan, M., Mahler, S. M., Pryor, K., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11514 · Cited by 1,180 · see citing works
A guide to analysis of mouse energy metabolism
Tschöp, M. H., Speakman, J. R., Arch, J. R. S., Auwerx, J., Brüning, J. C., Chan, L., Eckel, R. H., Farese, R. V., Galgani, J. E., Hambly, C., et al. (2012) · Nature Methods · doi:10.1038/nmeth.1806 · Cited by 813 · see citing works
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 · see citing works
Self-citationThe 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 · see citing works
Maternal Nutrition and Birth Outcomes
Abu-Saad, K., & Fraser, D. (2010) · Epidemiologic Reviews · doi:10.1093/epirev/mxq001 · Cited by 672 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Kempf, T., Zarbock, A., Widera, C., Butz, S., Stadtmann, A., Rossaint, J., Bolomini-Vittori, M., Korf-Klingebiel, M., Napp, L. C., Hansen, B., et al. (2011) · Nature Medicine · doi:10.1038/nm.2354 · Cited by 518 · see citing works
Prognostic Utility of Growth Differentiation Factor-15 in Patients With Chronic Heart Failure
Kempf, T., von Haehling, S., Peter, T., Allhoff, T., Cicoira, M., Doehner, W., Ponikowski, P. P., Filippatos, G. S., Rozentryt, P., Drexler, H., et al. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.04.091 · Cited by 492 · see citing works
Adela, R., & Banerjee, S. K. (2015) · Journal of Diabetes Research · doi:10.1155/2015/490842 · Cited by 474 · see citing works
Baek, S. J., Kim, K. S., Nixon, J. B., Wilson, L. C., & Eling, T. E. (2001) · Molecular Pharmacology · doi:10.1124/mol.59.4.901 · Cited by 402 · see citing works
Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
Chung, H. K., Ryu, D., Kim, K. S., Chang, J. Y., Kim, Y. K., Yi, H.-S., Kang, S. G., Choi, M. J., Lee, S. E., Jung, S.-B., et al. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201607110 · Cited by 357 · see citing works
Review article: the role of gastric motility in the control of food intake
Janssen, P., Berghe, P. V., Verschueren, S., Lehmann, A., Depoortere, I., & Tack, J. F. (2011) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2011.04609.x · Cited by 347 · see citing works
Macrophage inhibitory cytokine‐1 (MIC‐1/GDF15): a new marker of all‐cause mortality
Wiklund, F. E., Bennet, A. M., Magnusson, P. K. E., Eriksson, U. K., Lindmark, F., Wu, L., Yaghoutyfam, N., Marquis, C. P., Stattin, P. E., Pedersen, N. L., et al. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00629.x · Cited by 290 · see citing works
Paralkar, V. M., Vail, A. L., GRASSER, W. A., Brown, T. A., Xu, H., Vukičević, S., Ke, H. Z., Qi, H., Owen, T. A., & Thompson, D. D. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.22.13760 · Cited by 289 · see citing works
Pancreatic signals controlling food intake; insulin, glucagon and amylin
Woods, S. C., Lutz, T. A., Geary, N., & Langhans, W. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1858 · Cited by 286 · see citing works
Unsicker, K., Spittau, B., & KRIEGLSTEIN, K. G. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.05.003 · Cited by 274 · see citing works
MIC-1 is a novel TGF-β superfamily cytokine associated with macrophage activation
Fairlie, W. D., Moore, A. G., Bauskin, A. R., Russell, P. K., Zhang, H.-P., & Breit, S. N. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.65.1.2 · Cited by 266 · see citing works
Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer
Bauskin, A. R., Brown, D. A., Kuffner, T., Johnen, H., Luo, X. W., Hunter, M., & Breit, S. N. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4067 · Cited by 251 · see citing works
Breit, S. N., Johnen, H., Cook, A. D., Tsai, V. W. W., Mohammad, M. G., Kuffner, T., Zhang, H. P., Marquis, C. P., Jiang, L., Lockwood, G., et al. (2011) · Growth Factors · doi:10.3109/08977194.2011.607137 · Cited by 247 · see citing works
NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism
Chrysovergis, K., Wang, X., Kosak, J., Lee, S.-H., Kim, J. S., Foley, J. F., Travlos, G., Singh, S., Baek, S. J., & Eling, T. E. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.27 · Cited by 241 · see citing works
Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys
Xiong, Y., Walker, K., Min, X., Hale, C., Tran, T., Komorowski, R., Yang, J., Davda, J., Nuanmanee, N., Kemp, D., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aan8732 · Cited by 236 · see citing works
PLAB, a novel placental bone morphogenetic protein
Hromas, R., Hufford, M. B., Sutton, J., Xu, D., Li, Y., & Lu, L. (1997) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(97)00122-x · Cited by 233 · see citing works
Kempf, T., Björklund, E., Olofsson, S., Lindahl, B., Allhoff, T., Peter, T., Tongers, J., Wollert, K. C., & Wallentin, L. C. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm465 · Cited by 227 · see citing works
de Jager, S. C. A., Bermúdez, B., Bot, I., Koenen, R. R., Bot, M., Kavelaars, A., de Waard, V., Heijnen, C. J., Muriana, F. J. G., Weber, C., et al. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20100370 · Cited by 222 · see citing works
Leptin treatment: Facts and expectations
Paz-Filho, G., Mastronardi, C. A., & Licinio, J. (2014) · Metabolism · doi:10.1016/j.metabol.2014.07.014 · Cited by 220 · see citing works
Macia, L., Tsai, V. W.-W., Nguyen, A. D., Johnen, H., Kuffner, T., Shi, Y.-C., Lin, S., Herzog, H., Brown, D. A., Breit, S. N., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034868 · Cited by 211 · see citing works
Concise Review: Growth Differentiation Factor 15 in Pathology: A Clinical Role?
Corre, J., Hébraud, B., & Bourin, P. (2013) · Stem Cells Translational Medicine · doi:10.5966/sctm.2013-0055 · Cited by 209 · see citing works
Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta
Lawton, L. N., Bonaldo, M. F., Jelenc, P. C., Qiu, L., Baumes, S. A., Marcelino, R. A., de Jesus, G. M., Wellington, S., Knowles, J. A., Warburton, D., et al. (1997) · Gene · doi:10.1016/s0378-1119(97)00485-x · Cited by 209 · see citing works
Lerner, L., Hayes, T. G., Tao, N., Krieger, B., Feng, B., Wu, Z., Nicoletti, R., Chiu, M. I., Gyuris, J., & Garcia, J. M. (2015) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12033 · Cited by 208 · see citing works
Mimeault, M., & Batra, S. K. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22196 · Cited by 208 · see citing works
Zimmers, T. A., Jin, X., Hsiao, E. C., McGrath, S. A., Esquela, A. F., & Koniaris, L. G. (2005) · PubMed · Cited by 199 · see citing works
Ding, Q., Mráček, T., González‐Muniesa, P., Kos, K., Wilding, J. P. H., Trayhurn, P., & Chen, B. (2008) · Endocrinology · doi:10.1210/en.2008-0952 · Cited by 193 · see citing works
Growth Differentiation Factor–15 and Risk of CKD Progression
Nair, V., Robinson‐Cohen, C., Smith, M. R., Bellovich, K. A., Bhat, Z. Y., Bobadilla, M., Brosius, F. C., de Boer, I. H., Essioux, L., Formentini, I., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016080919 · Cited by 192 · see citing works
MAP3K11/GDF15 axis is a critical driver of cancer cachexia
Lerner, L. R., Tao, J., Liu, Q. H., Nicoletti, R., Feng, B., Krieger, B., Mazsa, E. K., Siddiquee, Z., Wang, R., Huang, L., et al. (2015) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12077 · Cited by 191 · see citing works
TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator
Tsai, V. W.-W., Macia, L., Johnen, H., Kuffner, T., Manadhar, R., Jørgensen, S. B., Lee-Ng, K. K. M., Zhang, H. P., Wu, L., Marquis, C. P., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055174 · Cited by 188 · see citing works
Half‐Life Extension of Biopharmaceuticals using Chemical Methods: Alternatives to PEGylation
van Witteloostuijn, S. B., Pedersen, S. L., & Jensen, K. J. (2016) · ChemMedChem · doi:10.1002/cmdc.201600374 · Cited by 186 · see citing works
Exercise increases circulating GDF15 in humans
Kleinert, M., Clemmensen, C., Sjøberg, K. A., Carl, C. S., Jeppesen, J. F., Wojtaszewski, J. F. P., Kiens, B., & Richter, E. A. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2017.12.016 · Cited by 186 · see citing works
Vila, G., Riedl, M., Anderwald, C. H., Resl, M., Handisurya, A., Clodi, M., Prager, G., Ludvik, B. H., Krebs, M., & Luger, A. (2010) · Clinical Chemistry · doi:10.1373/clinchem.2010.153726 · Cited by 185 · see citing works
Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum
Fejzo, M. S., Sazonova, O. V., Sathirapongsasuti, J. F., Hallgrímsdóttir, I. B., Vacic, V., MacGibbon, K., Schoenberg, F. P., Mancuso, N., Slamon, D. J., Mullin, P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03258-0 · Cited by 184 · see citing works
Dostálová, I., Roubíček, T., Bártlová, M., Mráz, M., Lacinová, Z., Haluzíková, D., Kaválková, P., Matoulek, M., Kasalicky, M., & Haluzı́k, M. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0417 · Cited by 183 · see citing works
Moore, A. G., Brown, D. A., Fairlie, W. D., Bauskin, A. R., Brown, P. K., Munier, M. L. C., Russell, P. K., Salamonsen, L. A., Wallace, E. M., & Breit, S. N. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.12.7007 · Cited by 181 · see citing works
Bottner, M. B., Suter‐Crazzolara, C., Schober, A., & Unsicker, K. (1999) · Cell and Tissue Research · doi:10.1007/s004410051337 · Cited by 180 · see citing works
Kempf, T., Guba-Quint, A., Torgerson, J., Magnone, M. C., Haefliger, C., Bobadilla, M., & Wollert, K. C. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0466 · Cited by 176 · see citing works
Baek, S. J., Okazaki, R., Lee, S.-H., Martinez, J., Kim, J.-S., Yamaguchi, K., Mishina, Y., Martin, D. W., Shoieb, A., Mcentee, M. F., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.09.015 · Cited by 175 · see citing works
Bonaterra, G. A., Zügel, S., Thogersen, J., Walter, S., Haberkorn, U., Strelau, J., & Kinscherf, R. (2012) · Journal of the American Heart Association · doi:10.1161/jaha.112.002550 · Cited by 168 · see citing works
The diverse roles of nonsteroidal anti-inflammatory drug activated gene (NAG-1/GDF15) in cancer
Wang, X., Baek, S. J., & Eling, T. E. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.11.025 · Cited by 154 · see citing works
Baek, S. J., Horowitz, J. M., & Eling, T. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101814200 · Cited by 147 · see citing works
Huo, L., Maeng, L. Y., Bjørbæk, C., & Grill, H. J. (2007) · Endocrinology · doi:10.1210/en.2006-1572 · Cited by 142 · see citing works
Bauskin, A. R., Zhang, H., Fairlie, W. D., He, X. Y., Russell, P. K., Moore, A. G., Brown, D. A., Stanley, K. K., & Breit, S. N. (2000) · The EMBO Journal · doi:10.1093/emboj/19.10.2212 · Cited by 133 · see citing works
Tsai, V. W.-W., Manandhar, R., Jørgensen, S. B., Lee-Ng, K. K. M., Zhang, H. P., Marquis, C. P., Jiang, L., Husaini, Y., Lin, S., Sainsbury, A., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100370 · Cited by 124 · see citing works
Progressive Postnatal Motoneuron Loss in Mice Lacking GDF-15
Strelau, J., Strzelczyk, A., Rusu, P. M., Bendner, G., Wiese, S., Diella, F., Altick, A. L., von Bartheld, C. S., Klein, R., Sendtner, M., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1133-09.2009 · Cited by 121 · see citing works
Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease
Breit, S. N., Carrero, J. J., Tsai, V. W.-W., Yagoutifam, N., Luo, W., Kuffner, T., Bauskin, A. R., Wu, L., Jiang, L., Barany, P. F., et al. (2011) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfr575 · Cited by 111 · see citing works
Artz, A., Butz, S., & Vestweber, D. (2016) · Blood · doi:10.1182/blood-2016-01-696617 · Cited by 108 · see citing works
Casanovas, G., Spasić, M. V., Casu, C., Rivella, S., Strelau, J., Unsicker, K., & Muckenthaler, M. U. (2012) · Haematologica · doi:10.3324/haematol.2012.069807 · Cited by 107 · see citing works
hNAG-1 increases lifespan by regulating energy metabolism and insulin/IGF-1/mTOR signaling
Wang, X., Chrysovergis, K., Kosak, J., Kissling, G., Streicker, M., Moser, G., Li, R., & Eling, T. E. (2014) · Aging · doi:10.18632/aging.100687 · Cited by 106 · see citing works
Tsai, V. W.-W., Zhang, H. P., Manandhar, R., Lee-Ng, K. K. M., Lebhar, H., Marquis, C. P., Husaini, Y., Sainsbury, A., Brown, D. A., & Breit, S. N. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.258 · Cited by 101 · see citing works
Abulizi, P., Loganathan, N., Zhao, D., Mele, T. S., Zhang, Y., Zwiep, T., Liu, K., & Zheng, X. (2017) · Scientific Reports · doi:10.1038/s41598-017-00902-5 · Cited by 97 · see citing works
Lim, J. H., Park, J. W., Min, D. S., Chang, J., Lee, Y. H., Park, Y. B., Choi, K. S., & Kwon, T. K. (2006) · APOPTOSIS · doi:10.1007/s10495-006-0576-9 · Cited by 95 · see citing works
TGF-β contamination of purified recombinant GDF15
Olsen, O. E., Skjærvik, A., Størdal, B., Sundan, A., & Holien, T. (2017) · PLoS ONE · doi:10.1371/journal.pone.0187349 · Cited by 94 · see citing works
NAG-1/GDF15 accumulates in the nucleus and modulates transcriptional regulation of the Smad pathway
Min, K.-W., Liggett, J. L., SILVA, G. H. D. O., Wu, W., Wang, R., Shen, R.-F., Eling, T. E., & Baek, S. J. (2015) · Oncogene · doi:10.1038/onc.2015.95 · Cited by 90 · see citing works
A p53-type response element in the GDF15 promoter confers high specificity for p53 activation
Osada, M., Park, H. L., Park, M. J., Liu, J.-W., Wu, G., Trink, B., & Sidransky, D. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.01.089 · Cited by 90 · see citing works
Supraphysiologic Administration of GDF11 Induces Cachexia in Part by Upregulating GDF15
Jones, J. E., Cadena, S. M., Gong, C., Wang, X., Chen, Z., Wang, S. X., Vickers, C., Chen, H., Lach‐Trifilieff, E., Hadcock, J. R., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.01.044 · Cited by 85 · see citing works
Targeting Obesity and Cachexia: Identification of the GFRAL Receptor–MIC-1/GDF15 Pathway
Breit, S. N., Tsai, V. W.-W., & Brown, D. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.10.005 · Cited by 83 · see citing works
Anorexia/cachexia of chronic diseases: a role for the TGF‐β family cytokine MIC‐1/GDF15
Tsai, V. W.-W., Husaini, Y., Manandhar, R., Lee-Ng, K. K. M., Zhang, H. P., Harriott, K., Jiang, L., Lin, S., Sainsbury, A., Brown, D. A., et al. (2012) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1007/s13539-012-0082-6 · Cited by 81 · see citing works
Mazagova, M., Buikema, H., van Buiten, A., Duin, M., Goris, M., Sandovici, M., Henning, R. H., & Deelman, L. E. (2013) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00387.2013 · Cited by 80 · see citing works
Growth/differentiation factor-15: prostate cancer suppressor or promoter?
Vaňhara, P., Hampl, A., Kozubı́k, A., & Souček, K. (2012) · Prostate Cancer and Prostatic Diseases · doi:10.1038/pcan.2012.6 · Cited by 67 · see citing works
Bauskin, A. R., Jiang, L., Luo, X., Wu, L., Brown, D. A., & Breit, S. N. (2010) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2009.0052 · Cited by 66 · see citing works
GDF‐15 prevents platelet integrin activation and thrombus formation
Rossaint, J., Vestweber, D., & Zarbock, A. (2012) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12100 · Cited by 66 · see citing works
Identification, expression and functional characterization of the GRAL gene
Li, Z., Wang, B., Wu, X., Cheng, S., Paraoan, L., & Zhou, J. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03372.x · Cited by 63 · see citing works
Altena, R., Fehrmann, R. S. N., Boer, H., de Vries, E. G. E., Meijer, C., & Gietema, J. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0115372 · Cited by 56 · see citing works
Martinez, J. M., Sali, T. M., Okazaki, R., Anna, C. H., Hollingshead, M. G., Hose, C. D., Monks, A. P., Walker, N. J., Baek, S. J., & Eling, T. E. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.100081 · Cited by 56 · see citing works
Machado, V., Haas, S. J.-P., Halbach, O. V. B. U., Wree, A., KRIEGLSTEIN, K. G., Unsicker, K., & Spittau, B. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.12.016 · Cited by 56 · see citing works
Lerner, L., Gyuris, J., Nicoletti, R., Gifford, J., Krieger, B., & Jatoi, A. (2016) · Oncology Letters · doi:10.3892/ol.2016.5183 · Cited by 55 · see citing works
Loss of GDF-15 abolishes Sulindac chemoprevention in the ApcMin/+ mouse model of intestinal cancer
Zimmers, T. A., Gutierrez, J. C., & Koniaris, L. G. (2009) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-009-0691-4 · Cited by 43 · see citing works
Yoshioka, H., Kamitani, H., Watanabe, T., & Eling, T. E. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805248200 · Cited by 43 · see citing works
GDF15—From Biomarker to Allostatic Hormone
O’Rahilly, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.017 · Cited by 43 · see citing works
Dostálová, I., Kaválková, P., Papežová, H., Domluvilová, D., Zikán, V., & Haluzı́k, M. (2010) · Nutrition & Metabolism · doi:10.1186/1743-7075-7-34 · Cited by 35 · see citing works
Growth/differentiation factor-15 and its role in peripheral nervous system lesion and regeneration
Wang, X., Krebbers, J., Charalambous, P., Machado, V., Schober, A., Bosse, F., Müller, H.-W., & Unsicker, K. (2015) · Cell and Tissue Research · doi:10.1007/s00441-015-2219-3 · Cited by 33 · see citing works
Liu, D., Lü, J., Zhao, Q., Hu, C., & Mei, Y. (2016) · Scientific Reports · doi:10.1038/srep28653 · Cited by 32 · see citing works
Loss of neurturin in frog—Comparative genomics study of GDNF family ligand-receptor pairs
Hätinen, T., Holm, L. U., & Airaksinen, M. S. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2006.10.009 · Cited by 30 · see citing works
CXXC4 activates apoptosis through up-regulating GDF15 in gastric cancer
Han, M., Dai, D., Yousafzai, N. A., Wang, F., Wang, H., Zhou, Q., Lu, H., Xu, W., Feng, L., Jin, H., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.21581 · Cited by 29 · see citing works
Husaini, Y., Lockwood, G. P., Nguyen, T. V., Tsai, V. W.-W., Mohammad, M. G., Russell, P. J., Brown, D. A., & Breit, S. N. (2015) · PLoS ONE · doi:10.1371/journal.pone.0115189 · Cited by 27 · see citing works
Zhang, X., Kang, Y., Huo, T., Tao, R., Wang, X., Li, Z., Guo, Q., & Zhao, L. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.07.011 · Cited by 24 · see citing works
Degradation Paradigm of the Gut Hormone, Pancreatic Polypeptide, by Hepatic and Renal Peptidases
Cuenco, J., MINNION, J. S., Tan, T., Scott, R., Germain, N., Ling, Y., Chen, R., Ghatei, M., & Bloom, S. R. (2017) · Endocrinology · doi:10.1210/en.2016-1827 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint
Wischhusen, J., Melero, I., & Fridman, W. H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00951 · Cited by 506 · see citing works
GDF15 induces anorexia through nausea and emesis
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. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.12.004 · Cited by 255 · see citing works
Hepatokines and metabolism: Deciphering communication from the liver
Jensen-Cody, S. O., & Potthoff, M. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101138 · Cited by 252 · see citing works
Baek, S. J., & Eling, T. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.008 · Cited by 194 · see citing works
Benichou, O., Coskun, T., Gonciarz, M. D., Garhyan, P., Adams, A. C., Du, Y., Dunbar, J. D., Martin, J. A., Mather, K. J., Pickard, R. T., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2022.12.011 · Cited by 115 · see citing works
Li, M., Duan, L., Cai, Y.-L., Li, H.-Y., Hao, B.-C., Chen, J.-Q., & Liu, H.-B. (2020) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01092-7 · Cited by 71 · see citing works
GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin
Ouyang, J., Isnard, S., Lin, J., Fombuena, B., Peng, X., Chen, Y., & Routy, J.-P. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.581839 · Cited by 39 · see citing works
- Authors
- Mullican, S. E., & Rangwala, S. M.
- Corresponding author
- Rangwala, Shamina M.
- ORCID
- Mullican, Shannon E.
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 29
- Issue
- 8
- Pages
- 560-570
- ISSN
- 1043-2760 (ISSN-L)
- OpenAlex
- W2805288114
- Cited by
- 127
- References
- 88
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 10 · 2023: 18 · 2022: 18 · 2021: 16 · 2020: 30 · 2019: 18 · 2018: 2
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Keywords
- GDF15, GFRAL, growth differentiation factor 15, obesity, anorexia, energy homeostasis, appetite regulation, receptor identification, cachexia, brainstem, therapeutic target
- MeSH terms
- Animals, Anorexia, Humans, Obesity, Glial Cell Line-Derived Neurotrophic Factor Receptors, 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
